Did You Know?
Our very own concoction of Triple Fish flavor brings cats running for their medications.

Finding Solutions for your Pet’s Health
Are you struggling to get your pet exactly the right dosage, and in a form they will accept? The Compounding Center has a solution.

The Compounding Center and Veterinarians work closely together to improve and maximize the medicinal treatments of pets, exotics, zoo animals and animals of all sizes. Our pharmacists work with the pet owner and veterinarian to prepare a medication that is unique to each pet’s health condition and size.

Getting a pet to take their medication can be quite a challenge. The Compounding Center can make this struggle simple by offering alternative dosage forms. Cats are lovely animals until you have to give one a pill. Many medications can be given in a topical form, such as a cream that is applied just inside the cat’s ear tip. If a cream is not the best option for your pet, maybe you need a beef or tuna flavored liquid. We offer many veterinary flavors and even vet treats to help in dosing your pet. From birds to horses and everything in between, The Compounding Center has the solution to your medication needs.

Using pure ingredients of the highest quality and following strict standards we are able to provide an excellent product that meets each individual pet’s unique needs. For more information or assistance, please contact one of our compounding pharmacists at 800-219-5433.

We provide and/or help treat:

Transdermal Medications

Have you ever thought about applying a transdermal preparation to the inside of an animal’s ear or another hairless area as an alternate route of systemic administration? It’s quick and easy, and many medications are compatible with transdermal bases. Transdermal delivery is particularly useful for animals who should not be stressed due to cardiovascular or hypertensive illness. Also, it is appreciated by owners who no longer have to deal with an animal who resists being medicated, and the resulting scratches! We can also prepare topical medications for application at the site of inflammation or infection.

Advantages of Transdermal Dosage Forms

Various alternative dosage forms permit medication to be absorbed via non-oral routes to meet an animal’s specific needs. Although the parenteral and rectal routes are traditional alternatives to oral administration, transdermal absorption offers many advantages.

For example:

  • When medication is absorbed directly into the bloodstream without first entering the gastrointestinal system, a smaller amount of active ingredient may be required for therapeutic effect.
  • Direct application and absorption at the target site can mean higher tissue levels and lower blood levels of various medications. Side effects such as GI irritation can be eliminated.
  • Various types of drug interactions may be avoided when one or more interacting medications are administered transdermally.

A substantial number of references exist in human medical literature with regard to the efficacy of transdermal administration of non-steroidal anti-inflammatory drugs and other types of analgesics, antiemetics, and other medications. We can compound transdermal and topical medications using a suitable base, and add penetrant enhancers if desired.

Transdermal Atenolol and Feasibility of Transdermal Administration

Oral administration of atenolol at a median dose of 1.1 mg/kg every 12 hours (range, 0.8 to 1.5 mg/kg) in cats induced effective plasma concentrations at 2 hours after treatment in most cats. Transdermal administration provided lower and inconsistent plasma atenolol concentrations. Further studies are needed to find an effective formulation and dosing scheme for transdermal administration of atenolol.

“In theory, the transdermal route of administering medications has many potential advantages. It is noninvasive and not demanding technically, avoids first-pass hepatic metabolism and gastrointestinal breakdown, has potential for sustained release formulations, and can be administered over a large surface area. Transdermal administration of medication has been shown to achieve blood concentrations of drug that are considered to be therapeutic (eg, fentanyl) or efficaciously affect physiologic surrogates (eg, methimazole, nitroglycerine, and lidocaine). Feasibility of transdermal medication varies on a drug-by-drug basis.”

Discussion: In spite of these results, investigators did not conclude that transdermally administered atenolol is not feasible.Because two cats did achieve therapeutic blood concentrations of atenolol after transdermal administration, the authors called for further research to find a transdermal formulation and dosing regimen for atenolol that will consistently result in plasma atenolol concentrations of >260ng/ml.Investigators offered several considerations for future studies. This study utilized a hydrophilic carbomer/propylene glycol/glycerin gel vehicle which has been used in human delivery of transdermal medications. As pluronic lecithin organogel (PLO) is the transdermal vehicle used almost exclusively in veterinary medicine, investigators encouraged future transdermal atenolol research utilizing PLO as the vehicle.Investigators also noted that higher doses of atenolol (3mg/kg) have been reported to consistently result in blood levels providing adequate adrenergic blockade at 12 hours in all cats studied.Since the median atenolol dose administered in this study was 1.1mg/kg, researchers suggest studying transdermal atenolol at the 3.3mg/kg dose.

Because daily oral administration of atenolol to cats is challenging and often results in a lack of compliance, a non-invasive dosage form such as transdermal atenolol will most likely result in better compliance, less stress to the cat, and reveal a positive therapeutic effect.

  1. Am J Vet Res. 2008 Jan;69(1): 39-44.
    Comparision of pharmacodynamic variables following oral versus transdermal administration of atenolol to healthy cats.
    Click here to read the PubMed abstract of this article.
Transdermal Carbimazole Gel for the Treatment of Feline Hyperthyroidism

The aim of a study conducted by Buijtels et al. of Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, The Netherlands, and presented at the 16th ECVIM-CA Congress, 2006, was to develop a carbimazole gel for application at the inner pinna of the ear and to study its effectiveness in cats with hyperthyroidism. The results of this study indicate that twice daily administration of carbimazole gel at the inner pinna of the ear is an effective treatment of cats with hyperthyroidism.

  1. Tijdschrift voor Diergeneeskunde. 2006; 131(13):478-82
    [Transdermal carbimazole for the treatment of feline hyperthyroidism] Click here to read the PubMed abstract of this article.

Anti-Infective Therapy

Penicillin Gelatin Guttural Pouch Lavage

Streptococcus equi is the bacterial pathogen responsible for a highly contagious equine disease known as strangles.  Strangles most commonly occurs in younger horses, but can be seen in horses of any age, particularly performance horses encountering sites where high density and high turnover of horses occurs (competition grounds, fairs, auctions, and boarding facilities). Infection by S. equi causes a severe inflammatory response manifesting as fever (102°-106°F), inappetance, lymphadenopathy with abscessation and resulting stridor, and a copious, mucopurulent nasal discharge. The guttural pouch has been identified as the site most likely to harbor S. equi organisms after infection due to draining abscesses from the mandibular lymph nodes.  While systemic beta-lactam therapy has proven very valuable in treatment of active disease, antibiotics do not achieve high enough concentrations in the guttural pouch to eliminate organisms.  Recently, the use of penicillin G sodium impregnated gelatin has been utilized to fill the guttural pouches following guttural pouch lavage in order to allow prolonged, bacteriocidal concentrations of penicillin in the guttural pouch after a single application.  The penicillin sodium gel should be prepared in an aseptic environment and refrigerated for at least 24 hours prior to administration. Our compounding pharmacists are able to provide this preparation for equine veterinary patients.

For further reading on equine strangles consult the American Association of Equine Practitioners at http://www.aaep.org/strangles.htm.

Clotrimazole 1% in Pluronic Gel for Nasal Aspergillosis

Nasal aspergillosis is a common fungal condition in dogs that results in massive turbinate destruction, pain and death or euthanasia due to lysis of surrounding skeletal structures such as the cribiform plate. Systemic treatment with oral antifungals is very expensive and often accompanied with serious adverse effects, and often is not successful (40-70% success).  Traditionally, the treatment of choice for nasal aspergillosis in dogs was a one-hour intranasal irrigation of 1% clotrimazole solution while the patient was anesthetized. The prolonged anesthesia was necessary to allow maximal contact time of the 1% clotrimazole solutions that immediately ran out of the sinuses once introduced. This therapy resulted in a success rate of almost 70% after a single treatment, but many dogs require multiple treatments for complete resolution.  Because of the expense and risk of multiple surgical and prolonged anesthetic procedures, a method to provide prolonged contact of 1% clotrimazole solutions in the nasal sinuses has been considered. A recent study assessed the retention, toxicity and stability of several viscous preparations of clotrimazole 1% in canine frontal sinus. Six compounds were evaluated including commercially available 1% clotrimazole cream, and 1% clotrimazole in varying concentrations of hydroxypropyl methylcellulose, carboxymethylcellulose, and poloxamer gel.  Results of this study indicate that clotrimazole 1% delivered in 25% poloxamer gel resulted in the least amount of sinus inflammation and was accompanied by a reasonable retention time.  Researchers concluded that use of poloxamer gels holds much promise for prolonged delivery of clotrimazole in nasal sinuses, potentially reducing anesthetic time as well as accomplishing fungal organism eradication after a single course of treatment. Veterinarians interested in pursuing use of this therapy for nasal aspergillosis can contact our compounding pharmacist to prescribe clotrimazole 1% in 25% poloxamer gel.

  1. Am J Vet Res 2009:70:640–647
    Assessment of clotrimazole gels for in vitro stability and in vivo retention in the frontal sinus of dogs.
    Click here to access the PubMed abstract of this article.
Antibiotic/Antifungal/Antiviral Therapy

Please scroll down for more information on the following topics:

  • Metronidazole
  • Esophageal Strictures Secondary to Administration of Doxycycline Tablets
  • Oral Itraconazole for Therapy of Dermatophytosis Caused by Microsporum can is
  • Chloramphenicol Suspension for Birds & Small Animals
  • Fluoroquinolone Antibiotics
  • Antibiotic Treats for Feline Abscess
  • Intranasal Clotrimazole for Treatment of Nasal Aspergillosis in Dogs
  • Azithromycin
  • Azithromycin for R. equi Infections in Foals
  • Idoxuridine Ophthalmic Drops for Cats
  • Feline Ocular Toxoplasmosis
  • Itraconazole/DMSO for Fungal Keratitis in Horses

Metronidazole
Metronidazole is effective against a variety of obligate anaerobic bacteria as well as anaerobic protozoa such as Giardia and Trichomonas. “Various salts of metronidazole with improved palatability are now available for veterinary patients… Cats and birds accept the benzoate salt much more willingly than they accept metronidazole HCl and do not seem to be stressed by its administration.”
Metronidazole should be used with caution in patients with hepatic dysfunction. Therapy should be promptly discontinued if abnormal neurological signs appear, including nystagmus, ataxia, seizures, and rigidity. All benzene moieties must be conjugated with glucuronide to facilitate elimination and this pathway is inefficient in cats. Therefore, doses of metronidazole benzoate above 200 mg/kg/day may produce signs of cumulative toxicity in cats within 48 to 72 hours.

  1. Compendium Dec. 2000: 22(12); pp. 1104, 1105, 1107, 1130

Esophageal Strictures Secondary to Administration of Doxycycline Tablets
“The most common causes of esophageal strictures in dogs and cats are gastroesophageal reflux during anesthesia, persistent vomiting, or ingestion of foreign bodies or caustic agents. In humans, esophageal retention of oral medication is a common cause of severe esophagitis. Of the medications proven to lead to esophageal ulceration, doxycycline is most often implicated. It has been suggested that pill-induced esophagitis also could occur in small animals…” Drug-induced esophageal ulceration usually occurs when tablets are taken with little or no water and adhere to the esophageal mucosa. Once this occurs, flushing with large quantities of liquid fails to wash the medication into the stomach. Melendez et al. of Colorado State University College of Veterinary Medicine report on three cases of presumptive doxycycline-induced esophagitis in cats, with resultant stricture formation. All cats had been administered fractions of doxycycline tablets one to three weeks before presenting with a chief complaint of regurgitation. “Two of the cases developed regurgitation within 7 days after initiation of therapy with doxycycline. One cat, which was treated while at an animal shelter, was noted to be regurgitating the day that it was adopted, approximately 2 weeks after being treated with doxycycline. No other cause of esophageal stricture formation could be identified.” If a pet that has received a doxycycline tablet shows sign of esophagitis (dysphagia, excessive salivation, inappetence, and regurgitation), the doxycycline tablets should be discontinued. Suggested therapy for esophagitis includes sucralfate slurries, a prokinetic agent (i.e. cisapride) to increase lower esophageal sphincter tone, and anti-inflammatory doses of glucocorticoids to prevent stricture formation.

Doxycycline can be compounded as a stable flavored liquid preparation or other palatable dosage form to meet the specific needs of each animal and owner.

  1. Feline Practice 28:2; 10-12 (Mar/Apr 2000)

Oral Itraconazole for Therapy of Dermatophytosis Caused by Microsporum canis
Itraconazole could be an effective alternative to griseofulvin that has toxic effects (particularly in puppies based on this author’s experience) and frequent therapeutic relapses. Itraconazole has also been used to successfully treat M. canis infection of cats and guinea pigs.

  1. J Am Vet Med Assoc 1998;213:993-995

Chloramphenicol Suspension for Birds & Small Animals
by J. Terry McGrath, VMD, Pennsylvania

Since chloramphenicol palmitate is no longer commercially available, we contacted our compounding pharmacist for an alternative for use in our avian and other small patients, such as rabbits and rodents. The pharmacist prepared a cola flavored suspension containing 30 mg/ml of chloramphenicol palmitate, which could be administered using a small oral syringe. However, birds did not like the taste and it was reformulated into a tutti fruitti and pina colada syrup. The “animal appropriate” flavor has really helped with compliance, because now the birds and small animals like to take their medicine!

Note: To avoid potential antagonism, chloramphenicol should not be administered simultaneously with penicillin or streptomycin. Chloramphenicol-containing preparations should not be administered in conjunction with, or two hours prior to, the induction of general anesthesia with pentobarbital.

When administered orally in dogs, chloramphenicol is well-tolerated, has high clinical efficacy, and a low incidence of side effects. The recommended canine dosage is 25 mg/lb of body weight every six hours.

Precautions: Chloramphenicol should be administered cautiously to animals with hematopoietic dysfunction, or impaired kidney or liver function.

Antibiotic Treats for Feline Abscess
Submitted by: Michael Briggs, Pharm.D. Veterinarian: Rich Marchetti, D.V.M.
Patient: One year old non-castrated short-haired male cat with abscess from wound received in fight. The owner reported that the cat, who is usually affectionate and friendly toward the owner and house dog, had been withdrawn, on guard, and growling for approximately three days. A thorn-like projection near the tail was found by the owner, who immediately took the cat to the veterinarian. The cat was anesthetized and the veterinarian cleaned, debrided, and shaved the area of the wound, and prescribed amoxicillin 100 mg daily for ten days. The owner was instructed to keep the cat inside for the duration of therapy, to minimize the risk of superinfection and avoid additional injury.
Medication Problem: The cat refused to take liquids, and was also resistant to taking tablets (“pilling”). The required dose of antibiotic was too high for transdermal treatment (due to the amount of gel that would need to be applied for each dose).

Solution: The veterinarian called our compounding pharmacy and asked if we could come up with a palatable dosage form. We formulated a fish-flavored chewable treat containing amoxicillin 100 mg to be given once daily for ten days. This dosage form offers the advantage of ease of administration, decreases the potential for dosing errors, and greatly increases patient compliance. The cat readily consumed the amoxicillin “treat”. The wound did not heal in a ten day period, so five additional days of therapy were required.
Comment: Our pharmacy has compounded this preparation more than ten times with a 100% success rate.

Intranasal Clotrimazole for Treatment of Nasal Aspergillosis in Dogs
“Treatment of nasal aspergillosis with systemic antifungal medications, such as thiabendazole, ketoconazole, and fluconazole, has been disappointing because the response rate is only 43 to 60%. Response to oral administration of itraconazole has been approximately 60 to 70%… Topical administration of the imidazoles, enilconazole, and clotrimazole is more effective than orally administered antifungal medications.”

Topical administration of clotrimazole resulted in resolution of clinical disease in 65% of dogs after 1 treatment and 87% of dogs after one or more treatments. Topical administration of clotrimazole, using either technique, was an effective treatment for nasal aspergillosis in dogs. Use of non-invasive intranasal infusion of clotrimazole eliminated the need for surgical trephination of frontal sinuses in many dogs and was associated with fewer complications. Nasal discharge ceased in most dogs 2 weeks after topical treatment, and the authors now recommend re-treatment with clotrimazole if nasal discharge has not improved 2 weeks after treatment.

“[Damage] of the cribriform plate may contraindicate use of topical treatment; complications arising from leakage of antifungal medications into the CNS in dogs with fungal rhinitis have not been evaluated.”

  1. J Am Vet Med Assoc 1998 Aug 15;213(4):501-6
    Comparison of topical administration of clotrimazole through surgically placed versus nonsurgically placed catheters for treatment of nasal aspergillosis in dogs: 60 cases (1990-1996).
    Click here to access the PubMed abstract of this article.
  1. J Am Anim Hosp Assoc 1998 Nov-Dec;34(6):487-92
    Management of nasal aspergillosis in a dog with a single, noninvasive intranasal infusion of clotrimazole.
    Click here to access the PubMed abstract of this article.

Azithromycin
is a form of erythromycin with improved action against gram-negative organisms, resistance to acid degradation, improved tissue penetration, and a prolonged elimination half-life. Azithromycin shows potential for use in veterinary medicine, particularly in cats and certain avian and exotic species.
“Lacking the prokinetic action of erythromycin, azithromycin appears to cause fewer GI side effects and is generally well tolerated after oral administration. Cats appear to tolerate the drug particularly well… Animals with a history of arrhythmias should be monitored while receiving the drug. Some reduction in dose may be warranted in patients with hepatic or biliary dysfunction, although no reduction appears necessary in patients with renal dysfunction.” Please consult our compounding pharmacist regarding dosing.

  1. Compendium of Continuing Education 23:3 (March 2001), pp. 242-7

Azithromycin for R. equi Infections in Foals
On the basis of pharmacokinetic values, minimum inhibitory concentrations of R. equi isolates, and drug concentrations in pulmonary epithelial lining fluid (PELF) and bronchoalveolar cells, a single daily oral dose of 10 mg/kg may be appropriate for treatment of R. equi infections in foals. Persistence of high azithromycin concentrations in PELF and bronchoalveolar cells 48 hours after discontinuation of administration suggests that after 5 daily doses, oral administration at 48-hour intervals may be adequate.

  1. Am J Vet Res 2001 Dec;62(12):1870-5
    Pharmacokinetics of azithromycin and concentration in body fluids and bronchoalveolar cells in foals.
    Click here to access the PubMed abstract of this article.
  1. The Capsule Report, Mixed Practice/Exotic Edition Jan 2002;15, 10: page 1

Itraconazole/DMSO for Fungal Keratitis in Horses
Fungal keratitis is a serious complication of trauma to the eye. Approximately one-half of the cases of fungal infections have involved the use of eye ointments containing corticosteroids after trauma to the globe of the eye.

“Itraconazole is a third generation triazole that has superior penetration properties and a wide spectrum of activity. A 1% solution of itraconazole in a 30% DMSO and petroleum base has been shown to reach high concentrations within the stroma of the cornea when administered every 4 to 6 hours. In general, every 6 hours is suitable for all but Fusarium sp which requires every 4 hour administration.”

Disease which is rapidly ulcerating “should also receive treatment that helps block the enzymes (collagenase) responsible for ulceration. A 5% acetylcysteine solution and autologous serum in which 4 mg/ml of EDTA has been added has been recommended. These need to be instilled hourly for best effect. The antimicrobial can be added to the serum.”

This information has been abstracted from an article by Robert N. Oglesby, DVM, which appears on his webpage, “The Horseman’s Advisor.”
For more information, references and complete text, see http://www.horseadvice.com/horse/messages/4/5506.html

Idoxuridine Ophthalmic Drops for Cats
The ocular signs of feline herpesvirus I (FHV-1) infection include bilateral conjunctivitis, serous ocular discharge which may become mucoid or mucopurulent, and blepharospasm. If corneal involvement is present, topical antivirals are prescribed. Research indicates that idoxuridine is effective against FHV-1. Prolonged contact with the infected tissue is required. The 0.1% solution must be applied five times daily. Previously marketed as Stoxil, the ophthalmic solution is not commercially available at this time.

  1. Michael Zigler, DVM, Cert.V.Ophthal  http://www.eyevet.ca/herpes.html
  1. Am J Vet Res 1989 Jan;50(1):158-60
    In vitro susceptibility of feline herpesvirus-1 to vidarabine, idoxuridine, trifluridine, acyclovir, or bromovinyldeoxyuridine.
    Click here to access the PubMed abstract of this article.

Feline Ocular Toxoplasmosis
“The anterior uveitis seen in cats with a positive serum titer to Toxoplasma gondii may result from immune-mediated mechanisms and not the presence or replication of the organism itself. As a result, it is unclear whether systemic antitoxoplasmic therapy is beneficial in these cases.” Michael G. Davidson, DVM, of North Carolina State University, College of Veterinary Medicine reports in Vet Clin N Amer, Sep 2000, that he “usually treats cats with ocular lesions and concurrent systemic findings of toxoplasmosis with systemic clindamycin (12.5 mg/kg PO twice daily for 14-21 days) and anti-inflammatory therapy. Other sources recommend clindamycin 10-12.5 mg/kg every 12 hours for 4 weeks. Oral trimethoprim-sulfonamide combination therapy (15 mg/kg every 12 hours for 2 to 4 weeks) can also be used to treat toxoplasmosis but is less suitable because of potential side effects caused by folic acid deficiency in cats.2 In T gondii seropositive cats exhibiting anterior uveitis alone and with no systemic signs, Dr. Davidson recommends topical steroids and atropine alone. If the cat fails to respond to topical therapy alone within 1-3 weeks, systemic clindamycin should be added to the treatment regimen. The rationale for the use of corticosteroids is to suppress the damaging inflammation in the retina, which may affect vision. Corticosteroids are typically administered 1-2 days after antibiotic therapy has been initiated to allow adequate tissue levels of the antimicrobial agent to be achieved. [Dr. Davidson] does not recommend systemic steroids in cats with suspected ocular toxoplasmosis because of the risk of exacerbating systemic replication of T gondii.”1
Swift and aggressive treatment of uveitis is necessary to avoid such secondary complications as glaucoma, cataract formation, and retinal degeneration or detachment.3

1 The Capsule Report 19:10 (Jan 2001), p. 4
2, 3 Compendium of Continuing Education 23:3 (March 2001), pp. 258-66

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Behavioral Medicine

Transdermal Treatment for Aggressive Cat

Donald Tummons, D.V.M.

An 11 year-old male cat showed aggressive behavior towards other cats and also started urinary spraying.  Buspirone 2.5mg/ml flavored suspension was tried.  It was extremely difficult for the owner to give the oral suspension and after a few days the cat was vomiting the medication.

Treatment
The owner was instructed to apply 0.1ml of transdermal buspirone 2.5mg/0.1ml pluronic lecithin organogel (PLO) topically inside the tip of the ear twice a day.

Outcome
After the first dose, the owner noticed the medication made the cat too sleepy and the dose was decreased to 0.05ml (1.25mg of buspirone).  The cat’s aggressive behavior has been controlled on the lower dose with a few exceptions and the owner then increased the dose to 2.5mg of buspirone for a couple of doses.  The owner is amazed how easy it is to apply the medication.

Amitriptyline for Behavioral and Urinary Disorders

Amitriptyline hydrochloride is one of the most widely used  tricyclic antidepressants (TCAs) in companion animal behavioral medicine, exerting antihistaminic, anti-inflammatory, analgesic, and antidepressant effects. Amitriptyline increases synaptic activity of serotonin and norepinephrine, has significant central and peripheral anticholinergic activity, and stimulates beta-adrenergic receptors in smooth muscle (e.g. the bladder), causing a decrease in smooth muscle excitability and a subsequent increase in bladder capacity and storage.

Although amitriptyline has been used successfully to treat behavior-related and urinary tract disorders in cats and dogs, the drug is not approved by the FDA for veterinary use and therefore is not available as a veterinary preparation.

Compendium 23(5) May 2001: 433-7

Imipramine

In animals, tricyclic antidepressants have actions similar to those of phenothiazines in altering avoidance behaviors. Imipramine has been used for the following indications:

Cats:  urethral incompetence

Dogs: treatment of separation anxiety and other behaviors, cataplexy, urethral incompetence

Horses:  narcolepsy and ejaculatory dysfunction

Naltrexone for Self-Mutilating Behavior

“Naltrexone may be useful in the treatment of self-mutilating or tail-chasing behaviors in dogs or cats… [A synthetic opiate antagonist,] naltrexone is generally considered to be contraindicated in patients physically dependent on opiate drugs, in hepatic failure or with acute hepatitis.”

Doses for Dogs:

As adjunctive therapy in behavior disorders:

For tail chasing or excessive licking: First give 0.01mg/kg SubQ of naloxone to determine if narcotic antagonists may be effective. If so, give naltrexone PO at 1 – 2 mg/kg daily. Long-term therapy may be required. (Crowill-Davis 1992)

For the adjunctive treatment of acral pruritic dermatitis:

2.2mg/kg PO once daily for one month trial. Some dogs exhibit drowsiness and minor changes in behavior. 50-60% of patients have benefited…    (Rosychuck 1991)

Canine Acral Lick Dermatitis

involves excessive licking of the paws or flank, even to the point of self-mutilation, and can produce ulcerations and infections that require medical treatment. Based on patterns of behavior and response to medication, veterinary scientists propose that canine acral lick dermatitis, also known as canine compulsive disorder (CCD), is an animal model of human obsessive-compulsive disorder. A randomized, placebo-controlled, double-blind crossover clinical study evaluated the efficacy of the medication clomipramine for treatment of CCD. Fifty one dogs with CCD were given clomipramine 3 mg/kg [1.3 mg/lb] of body weight orally every 12 hours for 4 weeks and then placebo for 4 weeks. While drug therapy can be helpful, therapy may need to include behavior modification to optimally manage CCD.

  1. J Am Vet Med Assoc 1998 Dec 15;213(12):1760-6
    Efficacy of clomipramine in the treatment of canine compulsive disorder.
    Click here to access the PubMed abstract of this article.
  1. Arch Gen Psychiatry 1992 Jul;49(7):517-21
    Drug treatment of canine acral lick. An animal model of obsessive-compulsive disorder.
    Click here to access the PubMed abstract of this article.
Fluoxetine for Refractory Owner-Directed Dominance Aggression

Evidence suggests that social dominance aggression may be modulated by serotonergic mechanisms. Fluoxetine (Prozac), a specific inhibitor of serotonin reuptake, is a popular human antidepressant which has been used successfully to decrease social aggression in dogs and monkeys.

  1. J Am Vet Med Assoc 1996;209:1585-1587
    Use of fluoxetine to treat dominance aggression in dogs.
    Click here to access the PubMed abstract of this article.
Fluoxetine for Urine Spraying in Cats

Administration of fluoxetine hydrochloride for treatment of urine spraying in cats can be expected to considerably reduce the rate of urine marking. Pryor et al. recommend that most cats should be treated more than eight weeks before treatment is withdrawn. Cats that vertically marked a mean of > or = 3 times per week were treated for 8 weeks with fluoxetine (1mg/kg PO daily- dosage individualized for each cat by a compounding pharmacy) or fish-flavored liquid placebo. When treatment was discontinued after 8 weeks, the spraying rate of cats that had received treatment varied. The main adverse reaction to the drug was a reduction in food intake, which was observed in 4 of 9 treated cats.

  1. J Am Vet Med Assoc 2001 Dec 1;219(11):1557-61
    Effects of a selective serotonin reuptake inhibitor on urine spraying behavior in cats.
    Click here to access the PubMed abstract of this article.

Inappropriate Elimination in Cats: Fluorescein to Find the Culprit

In a multi-cat household, it is important to determine which cat is inappropriately eliminating so that the proper intervention can be made. Even if one cat is observed marking or urinating outside the box, it does not rule out the possibility that other cats are also behaving inappropriately. When it is necessary to identify which cat in a multi-cat household is spraying or inappropriately eliminating, fluorescein can be orally administered once daily in the evening with food for three days. That cat’s urine will fluoresce under ultraviolet light for approximately 24 hours. To detect urine containing the fluorescein indicator, the client needs to scan the household with a commercial black light or black light purchased from a novelty store. Although urine will commonly glow, fluorescein treated urine fluoresces a characteristic bright yellow. Caution clients that they may reveal previously undiscovered sites of elimination; advise them not to become alarmed or angry. By administering the dye to different cats at two day intervals, the culprit can be identified.

Pharmacological support for urine spraying or marking is usually needed only for cases with underlying anxiety or problems with social interactions between cats (clomipramine), or for cats with interstitial cystitis (amitriptyline, doxepin). Administration of fluoxetine hydrochloride for treatment of urine spraying in cats may also considerably reduce the rate of urine marking.

Cyproheptadine to Control Urine Spraying and as an Antipruritic in Cats

A 10-year-old castrated male domestic cat was admitted to the hospital at the School of Veterinary Medicine, Tufts University. A diagnosis of territorial urine marking was made. Treatment included behavior modification and the administration of cyproheptadine, which resulted in the immediate arrest of undesirable urine marking. Cyproheptadine administration was adjusted to determine the lowest dosage that effectively maintained the cat’s consistent use of the litter box. It was recommended to continue cyproheptadine administration for at least 1 year before any attempt to withdraw its use. Another study recommended a dose of 2 mg, p.o., every 12 hours. This antihistamine, also prescribed for its appetite stimulant effects in cats, has antiandrogenic effects in other species.

  1. J Am Vet Med Assoc 1999 Aug 15;215(4):501-2, 482
    Use of cyproheptadine to control urine spraying in a castrated male domestic cat.
    Click here to access the PubMed abstract of this article.
  1. J Am Vet Med Assoc 1999 Feb 1;214(3):369-71, 351-2
    Use of cyproheptadine to control urine spraying and masturbation in a cat.
    Click here to access the PubMed abstract of this article.

Cyproheptadine hydrochloride was administered to 20 presumed or proven allergic cats to determine its efficacy in controlling pruritus. Each cat received 2 mg, orally, every 12 hours. The pruritus was satisfactorily controlled in 9 cats. Side effects were seen in 8 cats, and included polyphagia, sedation, vocalization, affectionate behavior, and vomiting.

  1. Can Vet J 1998 Oct;39(10):634-7
    Observations on the use of cyproheptadine hydrochloride as an antipruritic agent in allergic cats.
    Click here to access the PubMed abstract of this article.
Clomipramine for Feline Anxiety

A study of 11 cats assessed the clinical response to a treatment regimen that included clomipramine and behavior modification in cats diagnosed with anxiety-related or obsessive-compulsive disorders. Presenting signs were urine spraying in seven cases, overgrooming in three and excessive vocalization in one. Clomipramine was administered orally once daily, with a mean starting dose of 0.4 mg/kg. If necessary, the dose was adjusted according to the clinical response of each cat. The average maintenance dosage was 0.3 mg/kg once daily. The researchers concluded that clomipramine was effective in controlling the signs of anxiety-related and obsessive-compulsive disorders in 10 of 10 assessable cases when used in combination with behavior modification, and the drug was well tolerated.

  1. Aust Vet J 1998 May;76(5):317-21
    Use of clomipramine in the treatment of anxiety-related and obsessive-compulsive disorders in cats.
    Click here to access the PubMed abstract of this article.
Selegiline

is a monoamine oxidase (MAO) inhibitor indicated for use in dogs to control signs associated with canine cognitive dysfunction syndrome and uncomplicated pituitary-dependent hyperadrenocorticism (PDH). Studies suggest that selegiline may enhance survival rates. The recommended dose for cognitive dysfunction is 0.5 to 1 mg/kg, and for PDH is 1 mg/kg, orally each morning. If no improvement is seen after 2 months, the dose can be increased to the maximum of 2mg/kg/day. If there is no clinical improvement after 1 month at 2mg/kg/day, alternative therapy or further evaluation should be considered. “Overall, selegiline is well tolerated… Gastrointestinal disturbances, particularly vomiting and diarrhea, are the most common side effects reported. Diarrhea may resolve when the drug is discontinued or the dose decreased. Other adverse effects include hyperactivity, agitation, restlessness, and insomnia. A dose reduction or discontinuation of therapy also resolves these problems.”

Compendium March 2000; 22(3):204-5

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Cardiology / Hypertension

Transdermal Diltiazem for Treatment of Hypertrophic Cardiomyopathy in Cats

Diltiazem has direct coronary vasodilating properties, a beneficial therapeutic effect not provided by the beta-adrenergic blocking agents for the management of feline hypertrophic cardiomyopathy (HCM). “Orally administered diltiazem appears to have sustained beneficial effects on left ventricular filling and cardiac performance based on its ability to reduce resting heart rate, decrease blood lactate concentration, increase venous oxygen tension, improve echocardiographic parameters, and resolve radiographic abnormalities. Long-term diltiazem administration may also reverse myocardial hypertrophy in some patients. There appear to be few if any side effects of this drug. Diltiazem, therefore, provides a safe and effective approach for the management of feline HCM.”1

At North Carolina State University, College of Veterinary Medicine, analysis of diltiazem in Lipoderm® transdermal gel showed that diltiazem was stable at a concentration of 246 mg/ml for 30 days and at a concentration of 99.6 mg/ml for 60 days, no matter the storage conditions explored in the study.2

A formula is available for Diltiazem 5% for veterinary use.3

  1. 1 Vet Clin North Am Small Anim Pract. 1991 Sep;21(5):1023-34.
    Evidence for or against the efficacy of calcium channel blockers for management of hypertrophic cardiomyopathy in cats.
    Click here to access the PubMed abstract of this article.
  1. 2 J Pharm Biomed Anal. 2005 Jun 1;38(1):60-5. Epub 2004 Dec 25.
    Analysis of diltiazem in Lipoderm transdermal gel using reversed-phase high-performance liquid chromatography applied to homogenization and stability studies.
    Click here to access the PubMed abstract of this article.
  1. 3 International Journal of Pharmaceutical Compounding. Jan/Feb 2008; 12(1):67
    Diltiazem 5% in Lipoderm, Veterinary
    Click here to access the abstract of this article.
Transdermal Atenolol and Feasibility of Transdermal Administration
  1. Am J Vet Res. 2008 Jan;69(1): 39-44.
    Comparision of pharmacodynamic variables following oral versus transdermal administration of atenolol to healthy cats.
    Click here to read the PubMed abstract of this article.PMID: 18167085

Oral administration of atenolol at a median dose of 1.1 mg/kg every 12 hours (range, 0.8 to 1.5 mg/kg) in cats induced effective plasma concentrations at 2 hours after treatment in most cats. Transdermal administration provided lower and inconsistent plasma atenolol concentrations. Further studies are needed to find an effective formulation and dosing scheme for transdermal administration of atenolol.

“In theory, the transdermal route of administering medications has many potential advantages. It is noninvasive and not demanding technically, avoids first-pass hepatic metabolism and gastrointestinal breakdown, has potential for sustained release formulations, and can be administered over a large surface area. Transdermal administration of medication has been shown to achieve blood concentrations of drug that are considered to be therapeutic (eg, fentanyl) or efficaciously affect physiologic surrogates (eg, methimazole, nitroglycerine, and lidocaine). Feasibility of transdermal medication varies on a drug-by-drug basis.”

Discussion: In spite of these results, investigators did not conclude that transdermally administered atenolol is not feasible.Because two cats did achieve therapeutic blood concentrations of atenolol after transdermal administration, the authors called for further research to find a transdermal formulation and dosing regimen for atenolol that will consistently result in plasma atenolol concentrations of >260ng/ml.Investigators offered several considerations for future studies. This study utilized a hydrophilic carbomer/propylene glycol/glycerin gel vehicle which has been used in human delivery of transdermal medications. As pluronic lecithin organogel (PLO) is the transdermal vehicle used almost exclusively in veterinary medicine, investigators encouraged future transdermal atenolol research utilizing PLO as the vehicle.Investigators also noted that higher doses of atenolol (3mg/kg) have been reported to consistently result in blood levels providing adequate adrenergic blockade at 12 hours in all cats studied.Since the median atenolol dose administered in this study was 1.1mg/kg, researchers suggest studying transdermal atenolol at the 3.3mg/kg dose.

Because daily oral administration of atenolol to cats is challenging and often results in a lack of compliance, a non-invasive dosage form such as transdermal atenolol will most likely result in better compliance, less stress to the cat, and reveal a positive therapeutic effect.

Enalapril for Cardiomyopathy and CHF

“Enalapril maleate is an angiotensin-converting enzyme (ACE) inhibitor labeled to treat mild to severe heart failure in dogs.” Research has shown that enalapril in combination with diuretics – with or without digitalis glycosides – “produces statistically significant clinical improvement in dogs with advanced heart failure due to mitral regurgitation or dilated cardiomyopathy” and has demonstrated “beneficial hemodynamic and clinical effects of adding enalapril to conventional therapy for dogs with CHF… Dogs treated with enalapril and conventional CHF therapy survived two times as long as did those receiving standard therapy alone.”

Enalapril has also “been effective in treating cardiomyopathy and CHF in cats and ferrets, and its effects on blood pressure in horses and camels have been studied.” Because enalapril is a prodrug and can not be converted to its active form enalaprilat in patients with severe liver dysfunction, captopril or lisinopril might be a better choice in those patients. Renal function should be checked before starting enalapril therapy and at least every two months thereafter. The most common side effects are gastrointestinal, but there have been reports of enalapril-induced cough in dogs and a bird. Hypotension is a major concern if overdose occurs. NSAIDs, including aspirin, may reduce enalapril’s effect. The injectable form (enalaprilat) should not be given orally because it is very poorly absorbed.

“The recommended dose for enalapril in dogs is 0.5 mg/kg orally every 12 to 24 hours. The dose for cats is 0.25 to 0.5 mg/kg orally every 12 to 24 hours.”

Compendium, Dec. 1999

Amlodipine to Treat Feline Systemic Hypertension

Amlodipine, a calcium channel blocker, has an antihypertensive effect in cats with coexistent systemic hypertension and renal insufficiency. Its use may improve the prognosis for cats with systemic hypertension by decreasing the risk of ocular injury or neurologic complications induced by high blood pressure (BP). In a retrospective study, medical records from 69 cats with systemic hypertension and hypertensive retinopathy were reviewed. 68.1% of the cats were referred because of vision loss; retinal detachment, hemorrhage, edema, and degeneration were common findings. Amlodipine decreased BP in 31 of 32 cats and improved ocular signs in 18 of 26 cats. Primary hypertension in cats may be more common than currently recognized.

In a study at the Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, amlodipine was shown to be a safe and effective once-daily antihypertensive agent when administered to cats at a dosage of 0.18 +/- 0.03 mg/kg daily as monotherapy. Researchers at the Department of Medical Sciences, University of Wisconsin-Madison, administered amlodipine at an oral daily dosage of 0.625 mg per cat (range = 0.08 to 0.23 mg/kg body weight). Average indirect systolic blood pressure measurements in those 12 cases decreased significantly from 198 to 155 mmHg during amlodipine treatment. Significant changes in body weight and serum creatinine and potassium concentrations were not detected.

Relationship between ocular lesions and hypertension

Retinal lesions, caused predominantly by choroidal injury, are common in cats with hypertension. Hypertension should be considered in older cats with acute onset of blindness; retinal edema, hemorrhage, or detachment; cardiac disease; or neurologic abnormalities. Cats with hypertension-induced ocular disease should be evaluated for renal failure, hyperthyroidism, diabetes mellitus, and cardiac abnormalities. Blood pressure measurements and funduscopic evaluations should be performed routinely in cats at risk for hypertension (preexisting renal disease, hyperthyroidism, and age > 10 years).

  1. Am J Vet Res 2002 Jun;63(6):833-9
    Effects of the calcium channel antagonist amlodipine in cats with surgically induced hypertensive renal insufficiency.
    Click here to access the PubMed abstract of this article.
  1. J Am Vet Med Assoc 2000 Sep 1;217(5):695-702
    Ocular lesions associated with systemic hypertension in cats: 69 cases (1985-1998).
    Click here to access the PubMed abstract of this article.
  1. J Vet Intern Med 1998 May-Jun;12(3):157-62
    Amlodipine: a randomized, blinded clinical trial in 9 cats with systemic hypertension.
    Click here to access the PubMed abstract of this article.
  1. J Am Anim Hosp Assoc 1997 May-Jun;33(3):226-34
    Treatment of systemic hypertension in cats with amlodipine besylate.
    Click here to access the PubMed abstract of this article.

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Dermatologics / Allergies / Atopy

Alternative Therapies for Atopy

Dogs with atopic dermatitis (AD) often have concurrent allergies and are prone to relapsing skin and ear infections, which significantly contribute to their discomfort level. Much research has been done in recent years to identify effective and safe alternative treatments. Percutaneous absorption of allergens may be the most relevant route of exposure in dogs. Topical therapy may reduce the amount of allergen absorption through the skin. Several preparations, including glucocorticoids and anesthetics, can be used to reduce pruritus and provide analgesia.
Cyclosporine , misoprostol, pentoxifylline, and various antihistamines have been effective.

Compendium 2001 May 23(5):454-60

Tetracycline/Niacinamide for Dermatology

The combination of tetracycline and niacinamide is being used for a continually expanding list of dermatologic disorders thought to be of immune-mediated origin. Diseases that may be controlled with this combination include discoid lupus erythematosus, pemphigus erythematosus, vesicular cutaneous lupus erythematosus (idiopathic ulcerative dermatosis) in Collies and Shetland Sheepdogs, pemphigus foliaceus, lupoid onychodystrophy, metatarsal fistulae in German Shepherds, sterile panniculitis, sterile granulomatous/pyogranulomatous dermatitis, vasculitis, cutaneous histiocytosis, idiopathic lymphocytic/plasmacytic ear margin dermatitis, and nodular granulomatous episcleral keratitis.

The Capsule Report (Small Animal/Exotic Edition) 21:9, December 2002, reporting on Proceedings of the Friskies Pet Care Symposium 10:01

  1. J Am Anim Hosp Assoc 1997 Nov-Dec;33(6):540-3
    Tetracycline and niacinamide for the treatment of sterile pyogranuloma/granuloma syndrome in a dog.
    Click here to access the PubMed abstract of this article.
  1. J Am Vet Med Assoc 1992 May 15;200(10):1497-500
    Use of tetracycline and niacinamide for treatment of autoimmune skin disease in 31 dogs.
    Click here to access the PubMed abstract of this article.
Antihistamines in Horses

Practitioners may prefer to use antihistamines to reduce urticarial reactions and reduce pruritus in horses because these drugs usually have fewer side effects than steroids. The American Quarter Horse Association recommends a 10 day withdrawal prior to any competition.

Vet Prac News, Apr 2001

 

Prednisone Administered as a Transdermal Gel to Treat Allergic Dermatitis in a Cat

Submitted by Janna L. Love, Pharm.D.

A 5 y.o. female feline presented with allergic dermatitis accompanied by severe scratching and hair loss.

The cat had previously been treated with oral prednisone tablets. As the owner was unable to “pill the cat”, she had tried to crush the tablets and mix with milk or tuna juice, but the cat still would not take the medication.

It has been our experience that transdermal gels work wonderfully in cats. An owner does not have to fight the animal to get a tablet down the cat’s throat, and does not have to worry about whether the animal has received the correct dose, as the prescribed amount of gel can be massaged into the vascular surface inside the cat’s ear.

The veterinarian prescribed Prednisone 5 mg/0.1 ml in a transdermal gel. We dispensed 3 ml, with instructions to apply 0.1 ml (5 mg) daily to the inside of the cat’s ear. The benefits of transdermal administration include the ability to reliably administer the prescribed dose, and ease of administration to a calm, relaxed cat.

The therapy was very successful. The cat’s dermatitis resolved and the hair began to regrow within a few weeks. There were no complications and no modification in dosage was necessary. The owner periodically uses the preparation when she first notices signs of a relapse. Relapses have promptly resolved with transdermal prednisone therapy.

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Endocrinology – Diabetes, Thyroid, and Adrenal Disease

Low Dose Trilostane for Canine Cushing’s Disease

Cushing’s Disease (hyperadrenocorticism) is a common condition in older dogs, often mistaken for the aging process itself. Dogs get pot bellies, lose hair, drink and eat excessively, urinate in the house, and make owners begin to prematurely consider euthanasia. Yet, Cushing’s disease is treatable and that treatment can result in a longer, more comfortable life for the dog and its owner.

Trilostane is the most promising FDA-approved treatment for canine Cushing’s disease. Current FDA approved labeling for trilostane (Vetoryl™) lists the recommended dose at 3-6mg/kg body weight orally once daily, and Vetoryl™ capsules are available in strengths of 10mg, 30mg and 60mg.  Several studies conducted prior to US-approval of trilostane referenced effective doses ranging from 6-12mg/kg orally per day.  After noting that many dogs treated with trilostane at the labeled dose demonstrated symptoms of hypoadrenocorticism (Addison’s Disease), clinical endocrinologists at the University of California Davis College of Veterinary Medicine evaluated the safety and efficacy of lower doses of trilostane.  Investigators in this trial administered trilostane to dogs diagnosed with Cushing’s disease at doses ranging from 0.5-2.5mg/kg orally every 12 hours and evaluated dogs for therapeutic progress at 3 different treatment intervals over a total treatment period of 8-16 weeks. After 1 to 2 weeks, mean trilostane dosage was 1.4 mg/kg (0.64 mg/lb) every 12 hours (n = 22 dogs; good response [resolution of signs], 8; poor response, 14). Four to 8 weeks later, mean dosage was 1.8 mg/kg (0.82 mg/lb) every 12 or 8 hours (n = 21 and 1 dogs, respectively; good response, 15; poor response, 5; 2 dogs were ill). Eight to 16 weeks after the second reevaluation, remaining dogs had good responses (mean dosages, 1.9 mg/kg [0.86 mg/lb], q 12 h [n = 13 dogs] and 1.3 mg/kg [0.59 mg/lb], q 8 h [n =3]).

Since many dogs that develop Cushing’s disease are smaller breed dogs weighing less than 9kg (e.g. terriers and poodles), the commercially available capsules (10mg, 30mg and 60mg) are too large for appropriate therapy. As a result of the UC-Davis study, many veterinarians are requesting compounding pharmacists to compound smaller doses of trilostane as capsules or oral suspensions. On September 11, 2009, the Center for Veterinary Medicine division of the Food and Drug Administration issued a statement to veterinarians and pharmacists that “trilostane can only be legally compounded by using FDA-approved VETORYL™ as the starting material”, and that “…trilostane should not be imported from other countries or compounded from (the) bulk (chemical)”. As Vetoryl™ is only available for sale to licensed veterinarians in the US, and use of the bulk chemical to compound trilostane will not be tolerated by FDA, veterinarians and pharmacists are advised to collaborate to ensure availability of safe and legal compounded dosage forms of trilostane for dogs requiring lower doses than are commercially available.

  1. J Am Vet Med Assoc 2008;232:1321–1328.
    Evaluation of  twice-daily, low dose trilostane treatment in dogs with naturally occurring hyperadrenocorticism.
    Click here to access the abstract of this article.
  1. http://www.fda.gov/AnimalVeterinary/SafetyHealth/ProductSafetyInformation/ucm182038.htm
Phenoxybenzamine for Dogs with Pheochromocytoma

Some studies in dogs undergoing adrenalectomy for pheochromocytoma suggest that anesthetic complications and perioperative mortality are common. In humans, surgical outcome has improved with the use of phenoxybenzamine (PBZ) before adrenalectomy. Therefore, at the School of Veterinary Medicine, University of California, Davis, it was hypothesized that dogs treated with PBZ before adrenalectomy have increased survival compared with untreated dogs, and they conducted a retrospective medical record review of 48 dogs that underwent adrenalectomy for pheochromocytoma from January 1986 through December 2005. Twenty-three of 48 dogs were pretreated with PBZ (median dosage: 0.6 mg/kg PO q12h) for a median duration of 20 days before adrenalectomy. Duration of anesthesia and surgery, percentage of dogs with pheochromocytoma involving the right versus left adrenal gland, size of tumor, and presence of vascular invasion were similar for PBZ-treated and untreated dogs. Thirty-three (69%) of 48 dogs survived adrenalectomy in the perioperative period. PBZ-treated dogs had a significantly decreased mortality rate compared with untreated dogs (13 versus 48%, respectively). Additional significant prognostic factors for improved survival included younger age, lack of intraoperative arrhythmias, and decreased surgical time. Results from this retrospective study support treatment with PBZ before surgical removal of pheochromocytoma in dogs.

  1. J Vet Intern Med. 2008 Nov-Dec;22(6):1333-9.
    Predictive factors and the effect of phenoxybenzamine on outcome in dogs undergoing adrenalectomy for pheochromocytoma.
    Click here to access the PubMed abstract of this article.
Transdermal Carbimazole Gel for the Treatment of Feline Hyperthyroidism

The aim of a study conducted by Buijtels et al. of Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, The Netherlands, and presented at the 16th ECVIM-CA Congress, 2006, was to develop a carbimazole gel for application at the inner pinna of the ear and to study its effectiveness in cats with hyperthyroidism. The results of this study indicate that twice daily administration of carbimazole gel at the inner pinna of the ear is an effective treatment of cats with hyperthyroidism.

  1. Tijdschrift voor Diergeneeskunde. 2006; 131(13):478-82
    [Transdermal carbimazole for the treatment of feline hyperthyroidism] Click here to read the PubMed abstract of this article.
PZI and Low-Dose Insulin

The commercial production of traditional beef &/or pork insulins has declined as most human diabetic patients (the majority of the consumers) are being switched to human insulin products because of the reduced risk of allergic reactions. Protamine zinc insulin occurs as a sterile suspension of insulin modified by the addition of protamine sulfate and zinc chloride, and has a long duration of action (up to 30 hours). Therefore, treatment of many dogs and cats has been accomplished with once daily dosing of PZI.
U-20 and U-40 insulin allow for more accurate measurement of smaller doses required by many pets and birds. Use of U-100 insulin can result in morbidity or mortality caused by dosing errors.

Oral Anti-Diabetic Drugs

“may be appropriate for cats that are in good overall health with early or mild clinical signs of diabetes and those with owners who are unwilling or unable to administer insulin injections.”1 The oral hypoglycemic medication, glipizide, provides a viable therapeutic alternative to conventional insulin therapy with a positive therapeutic response in approximately 50% of diabetic cats with non-insulin-dependent disease. Response to glipizide therapy or lack thereof usually is evident within the first 4 to 6 weeks of treatment. Adverse side effects occurred in less than 10% of patients. The existence of residual beta cell function is necessary for response to glipizide therapy. Discontinuation of diabetogenic medications that may be contributing to insulin resistance is important.2

According to Deborah S. Greco, DVM, Ph.D., diplomate ACVIM, glipizide has been used successfully to treat diabetes mellitus in cats at a dosage of 2.5 to 5 mg two times daily, when combined with dietary fiber therapy. Dr. Greco recommends evaluating the patient weekly or every two weeks for a period of 2 to 3 months. If the fasting blood sugar decreases to less than 200 mg/dL, the glipizide should be continued at the same dosage and the cat reevaluated in 3 to 6 months. If the fasting blood glucose remains >200 mg/dL after 2 to 3 months of therapy and the cat is still symptomatic (polyuria, polydipsia, weight loss), glipizide should be discontinued and insulin therapy instituted. If the blood glucose remains >200 mg/dL and the cat becomes asymptomatic, glipizide should be continued indefinitely and the cat rechecked in 3-6 months.3

  1. 1 Compendium 23(7), July 2001, 633-640
  1. 2Vet Clin North Am Small Anim Pract 1995 May;25(3):599-615
    NIDDM in the cat: treatment with the oral hypoglycemic medication, glipizide.
    Click here to access the PubMed abstract of this article.
  1. 3 presented at the 1999 Southern California VMA Seminar and the 116th Indiana VMA Seminar
Methimazole for Feline Hyperthyroid Disease

“Methimazole is the drug of choice for the medical management of feline hyperthyroid disease. It is safer and more potent than propylthiouracil in blocking thyroid hormone synthesis. Use of the drug generally will bring serum T4 into normal ranges within 2 to 3 weeks… Adverse effects have been observed in approximately 15% of cats and generally are transient. Anorexia, vomiting, and transient lethargy have been reported. Serum antinuclear antibodies develop in many cats with long-term use of the drug. A glucocorticoid-responsive pruritus involving the face, ears, and neck may occur. In less than 2% of cases, thrombocytopenia or agranulocytosis have been reported in cats treated with [methimazole]. Withdrawal of the drug and provision of care for thrombocytopenia or agranulocytosis generally results in resolution… Cats on chronic methimazole therapy should be rechecked every 3 to 6 months to assay serum T4 levels and to check for signs of drug toxicity.”

Handbook of Veterinary Drugs, 2nd edition, ©1998, pp. 239-240

According to the International Journal of Pharmaceutical Compounding (Vol. 5, No. 2, March/April 2001, p. 96), “it could be theorized that transdermal administration would produce a … higher blood level of methimazole than that resulting from oral administration of the drug. A higher blood level of [methimazole] might result in a slightly greater risk of adverse effects, so drug therapy might need to be initiated at a slightly lower dose than that of the traditional oral dose.” The author of the article (GiGi Davidson, R.Ph., DICVP, North Carolina State University, College of Veterinary Medicine) states that anecdotal evidence indicates that this is true of “most transdermally administered doses of methimazole. The most measurable parameter for efficacy is the response of the serum T4 level.”

Note: Methimazole is also used to decrease renal toxicity of cisplatin in dogs.

Transdermal Methimazole Applied to Ear of Hyperthyroid Cats

Francis Arsenault, D.V.M., New Brunswick

The following six cats have received methimazole in a pluronic lecithin organogel (PLO) which the owners apply to the inner side of the ear. Overall, we have found this to be very effective therapy with good compliance. Transdermal administration can be particularly helpful for owners who have arthritis and those who have great difficulty “pilling” the cat. Methimazole doses have ranged from 2.5mg to 12.5 mg daily, divided into two doses.

Cat #1 (S.A.): 17 years old, has been on methimazole 1.25mg/0.1 ml PLO to inside of ear twice daily for nine months. The owner reports that the medicine is easy to administer and absorbs well. I am pleased with the clinical results.

Cat #2 (A.L.): 18 years old, has been using methimazole for six months. This cat was started on 3.5mg/0.1ml PLO BID. Several dosage adjustments were necessary. We increased the concentration of the transdermal gel to 5.0mg/0.1ml PLO, and the owner now applies 7.5mg/0.15ml PLO in the AM and 5mg/0.1ml in the PM. She places plastic wrap over her finger before applying the medication, which she has found to be much easier to use than pills, with no stress to the pet. She states the measurements on the topical dispenser are easy to read, and she needs to wash the cat’s ear to remove the coating left by the medication.

Cat #3 (B.M.): was started on methimazole eight months ago at 5mg/0.1ml PLO BID. The dose was decreased to 2.5mg BID. The cat’s owner stated the medication was very easy to use. B.M. improved clinically and gained weight, and is no longer on the med.

Cat #4 (S.O.): used medication once only.

Cat #5 (D.O.): same owner as cat #4, received methimazole 2.5mg/0.05ml PLO BID for two months. No longer on medication.

Cat #6 (M.B.): 19 years old, has received methimazole 1.25mg/0.1ml PLO BID for four months. The owner says the medication is easy to apply, and alternates ears. It is necessary to wipe the ear each day as the medication does leave a residue.

Adrenal Disease in Male Ferrets

Adrenal gland disease is a common problem in middle-aged to older ferrets. The disease results in one or both of the adrenal glands producing abnormal amounts of androgens and/or estrogens, and can cause hair loss, itching, vulvar enlargement in females, prostate enlargement in male ferrets which can block the flow of urine, and in rare cases, bone marrow suppression. Although not usually a serious health concern, ferrets may have no relief from the itching that is associated with this disease if it is not treated.
Flutamide is an androgen blocker that may help relieve prostatic enlargement. It is dosed at 10 mg/kg, PO, every 12-24 hours. Liver enzymes should be checked at one month and every six months thereafter. Mitotane may be effective in younger ferrets but may cause nausea and lethargy. Ketoconazole is usually ineffective.1

1 Evelyn Ivey, DVM, Dip ABVP, San Diego Co VMA Conf Procd, Sep 2000

Mitotane for Canine Hyperadrenocorticism

In veterinary medicine, mitotane is used primarily for the medical treatment of pituitary-dependent hyper-adrenocorticism (PDH) and palliative therapy of adrenal carcinoma, usually in dogs. Systemic drug availability has been found to be very poor from intact tablets in fasted dogs, and best when the powdered drug is mixed in oil and poured on dog food. The interaction between food and mitotane probably contributes to the variation in clinical response of dogs treated with the drug, because it appears that the efficacy is improved considerably when the drug is given with food. Because of the potentially severe toxicity associated with mitotane, clients should be instructed to wear gloves during and wash their hands after administering the medication, and to keep the medication out of reach of children or pets. Dogs with concurrent diabetes mellitus may have rapidly changing insulin requirements during the initial treatment period, and should be closely monitored until they are clinically stable. Clients should be advised of the symptoms of acute hypoadrenocorticism. Because of the potential severe toxicity associated with mitotane, clients should be instructed to wash their hands after administration and to keep the medication out of reach of children or pets.

  1. Res Vet Sci 1987 Sep;43(2):160-5
    Systemic availability of o,p’-DDD in normal dogs, fasted and fed, and in dogs with hyperadrenocorticism.
    Click here to access the PubMed abstract of this article.
  1. Veterinary Drug Handbook, 2nd Edition, by Donald C. Plumb

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Otitis

Therapy for Chronic Canine Otitis

Treatment errors, over and under treatment, or inappropriate use of antimicrobial medication can result in a chronically diseased ear. The key to successful management of chronic canine otitis is early intervention, identifying a cause of the condition, and employing specific and appropriate therapy.
Ears with highly proliferative, chronic disease require deep cleaning and flushing before any topical therapy can be expected to help resolve the condition. Should a myringotomy be performed, the contents of the middle ear can be aspirated as soon as rupture occurs, and the middle ear can be flushed with normal saline or Tris-EDTA using a feline, open-tipped urinary catheter. “Just before the animal wakes, Tris-EDTA and a topical antimicrobial solution should be instilled and a parenteral prednisolone administered.”
“The pathogens isolated most frequently from chronic external and middle-ear infections include Staphylococcus intermedius, Malassezia pachydermatis, Pseudomonas species, Proteus species, Escherichia coli, and enterococcus. Selection of both systemic and topical antimicrobial medication is based on cytologic evaluation and culture and sensitivity results. Systemic antibiotics are mandatory… Treatment should continue until the infection is resolved (a minimum of 4 weeks). It is not uncommon for treatment of otitis media to continue uninterrupted for 8 to 12 weeks.”
Patricia D. White, DVM, MS of Atlanta Veterinary Skin & Allergy Clinic suggests that several compounded preparations may be appropriate.

Compendium on Continuing Education 21:8 August 1999, pg 716-28

Importance of Medication Vehicle

“Topical antimicrobial therapy is an important part of the treatment regimen, and the vehicle is as important as the active ingredient. Most otic preparations are combination drugs (glucocorticoid plus antibiotic) in an oil or ointment base. Oils and ointments are occlusive, may hold or trap exudate, and may increase the risk of ototoxicity; such preparations are not desirable in cases of chronic otitis in which a moist exudate is present, the canal is stenotic, or the eardrum may be ruptured. The goal of treating a wet ear is to dry it. Solutions and suspensions are primarily composed of water; may contain an astringent (e.g., aluminum acetate); and are designed to evaporate over time, thus helping to dry the ear.” Topical antibiotics that are selected initially should be adjusted when the culture and sensitivity results are known.
“There is no single topical otic preparation that will satisfactorily treat all conditions. Practitioners tend to dispense a product based on clinical impressions or pick a favorite product rather than selecting one that has specific application for the current condition.” Direct application of medication to the ear canal will result in a higher concentration than that obtained with systemic medication.
Once you have identified the problem, we can compound an otic preparation to most appropriately treat each animal.

Compendium on Continuing Education 21:8 August 1999, pgs. 716-728

Antimicrobial/Anti-inflammatory Otic Suspensions Anhydrous Preparations without Aminoglycosides

It is desirable to move away from commercially available aminoglycoside-antifungal-steroid otic preparations to avoid animoglycoside induced ototoxicity. Use of a formulation that substitutes a fluoroquinolone for an aminoglycoside constitutes a more effective and less toxic therapy, and is preferred if a tympanum rupture is expected. The efficacy and tolerability of a fluoroquinolone-clotrimazole-dexamethasone (FCD) otic suspension (10 drops per affected ear once daily) was compared with a standard topical treatment containing polymyxin B, miconazole and prednisolone (PMP) in a total of 140 dogs with clinical signs of acute or subacute otitis externa, Staphylococcus, Pseudomonas, Enterobacteriaceae and Malassezia were isolated from samples taken at inclusion. Each group received treatment for 7 or 14 days according to the clinical outcome on day 7. Treatments were equally effective, with a cure rate of 58.3% for the FCD prep and 41.2% for the PMP combination. Both medications were equally well tolerated by dogs, but FCD was superior in terms of pain relief, decrease in pus quantity and smell, response rate and investigator’s assessment on day 14.

  1. Vet Dermatol 2005 Oct;16(5):299-307
    A comparative study of two antimicrobial/anti-inflammatory formulations in the treatment of canine otitis externa.
    Click here to access the PubMed abstract for this article.

While it is a common practice in some veterinary offices to add dexamethasone injection to clotrimazole solution to create an otic preparation with both antifungal and anti-inflammatory properties, it is more desirable to use an anhydrous preparation in the ear to reduce the risk of bacterial growth in the warm, moist environment. Anhydrous preparations also tend to have longer shelf lives. Avoid using products such as miconazole solution which has a high alcohol concentration to avoid irritating a sensitive ear.

Contact our compounding pharmacy for anhydrous otic preparations.

Helpful Hints Regarding Otitis Therapy

Ototoxicity manifested as deafness or vestibular toxicity is a potential adverse effect of some medications used to treat otitis, such as aminoglycosides (tobramycin, gentamicin, amikacin and neomycin) and chloramphenicol. Numerous alternatives exist.
Enrofloxacin, a fluoroquinolone effective against Pseudomonas species, can be compounded as a solution and applied to the ear canal twice daily. “Topical enrofloxacin may achieve a higher antibiotic concentration at the site more economically than systemic medication.”
Silver sulfadiazine is effective in vitro against Pseudomonas species, Staph aureus, Proteus species, and others; a 0.1% to 1% emulsion every 12 hours is adequate to kill Pseudomonas.
Topical otic products may contain potent glucocorticoids in ointment or oil bases. However, solutions may be a preferable vehicle, and it may be advisable to use a less potent steroid because the degree of absorption of topical steroids can not be controlled. We can compound a preparation containing your choice of steroid in the most appropriate vehicle to treat the condition.
“Commercial otic drying agents should be avoided in inflamed, chronically diseased ears because most contain isopropyl alcohol and varying concentrations of benzoic, acetic, salicylic, or boric acid. Each of these products individually can be extremely irritating to an already traumatized epithelium.”
Acetic acid solution can be used to decrease the bacterial population by lowering the pH within the ear canal. Pseudomonas can be killed by 1 minute of contact with a 2% solution. This treatment is especially beneficial when the organism is resistant to other antibacterials. Staph and Strep may be killed by 5 minutes of contact with a 5% solution, according to Kirk’s Current Veterinary Therapy XII Small Animal Practice. However, inflammation (which can be severe) is an occasional side effect of treatment with acetic acid concentrations higher than 2.5%.

Compendium on Continuing Education 21:8 August 1999, pgs. 716-728
Kirk’s Current Veterinary Therapy XII Small Animal Practice, 1995, Bonagura & Kirk, ed.

Treatment of Canine Otitis with Norfloxacin 1% & Ketoconazole 1%

by T. D. Flack, D.V.M. Scottsdale, AZ

The common therapy for fungal otitis externa in dogs utilizes an antifungal and topical steroid, sometimes in combination with systemic antibiotics. The three organisms which have been isolated and are thought to be the most common pathogens in recurrent canine otitis externa are Malassezia, Pseudomonas, and Proteus spp. Using a fluoroquinolone along with an antifungal, we are able to have good coverage on all virulent pathogens. For treatment of resistant infections, the synergism of norfloxacin and ketoconazole provides a broader spectrum of coverage than many other therapies, as ketoconazole is a more active antifungal than clotrimazole. We have utilized a compounded otic gel containing norfloxacin 1% and ketoconazole 1% more than 20 times with a very high success rate.
Infectious otitis externa is a common disease in dogs. Systemic antibiotic therapy is not always required. Thirty-six dogs of mixed sex, breed, and age were treated for… the purpose of evaluating the efficacy of a ketoconazole 1% and norfloxacin 1% otic gel… Treatment consisted of 0.5 to 1.0 ml of the otic gel in each affected ear twice a day for 7 days. Results showed 91.66% satisfactory responses at 7 and 14 days treatment… Failures (8.33%) were related to Staphylococcus associated with Proteus, Malassezia, and Candida… The 7-day treatment was successful in 21 cases. However, since 12 dogs required 14 days of treatment, it would be sensible to recommend a 14-day therapy.”

Canine Practice, Vol. 21, No. 2, pp. 26-28

Tris-EDTA Solution for Canine Otitis

Richard E. Wooley, D.V.M., Ph.D., Harry W. Dickerson, B.V.Sc., Ph.D., and William R. Engen, D.V.M.,
Department of Medical Microbiology, College of Veterinary Medicine, Univ. of Georgia, Athens

The authors reported the successful use of Tris-EDTA in the treatment of otitis externa. In 24 dogs with clinical otitis, the Tris-EDTA (tris[hydroxymethyl] aminomethane and ethylenediaminetetraacetate) combination was tested against Bacillus spp., Staphylococcus aureus, Candida spp., Pseudomonas aeruginosa, Esherichia coli, Proteus vulgaris, Trichosporon spp., and an a-streptococcus. “Fifteen of the 24 cases were acute; all were evaluated with bacterial culture before and after treatment. The treatment consisted of applying lavage solution to the ears t.i.d. until resolution or for three weeks if there was no clinical response. Dogs were examined for irritation of the ears after treatment… 23 of 24 cases were resolved; no adverse effects were seen, but duration of follow-up was not specified. The case that failed to respond was a chronic, mixed infection of E. Coli and Proteus spp.; inflammation was reduced, but the infection persisted. Most cases responded within one week, but P. aeruginosa infections required one to three weeks of treatment.”

Veterinary Forum, June 1999, p. 52

Tris-EDTA solution (buffered to pH 8.0) has a direct bactericidal effect on some bacteria by chelating metal ions in the cell wall. “Dogs with chronic disease (e.g. atopy, idiopathic seborrhea) will be predisposed to recurrent otitis; a topical antibiotic solution or Tris-EDTA used two to three times weekly may prevent an infection from occurring with each flare-up of the primary disease.”
The bactericidal effects of Tris-EDTA are synergistic with aminoglycosides. Although an antibiotic can be added to the Tris-EDTA solution, Patricia D. White, DVM, MS states that she prefers to use Tris-EDTA 5 to 10 minutes before the topical antibiotic. The Tris-EDTA/antibiotic combination is ineffective against yeast.

Compendium on Continuing Education 21:8 Aug. 1999, pgs. 716-728

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Pain Management

Transmucosal Buprenorphine: More is Better For Dogs and Horses

The pharmacokinetic profile of a buccally-administered (transmucosal) dose of buprenorphine to cats is almost identical to that of intravenously administered buprenorphine. The unusually alkaline salivary pH of cats prevents ionization of buprenorphine, allowing it to diffuse into systemic circulation in a non-ionized form. This discovery greatly facilitated outpatient feline pain relief, allowing owners to administer this drug to cats at home, without the need for hospitalization or injection.  Because the duration of analgesia from buprenorphine (4-12hrs) is longer than that provided by other opiates, buprenorphine is frequently used for provision of non-invasive, intermediate to long-term analgesia in cats.  It is typically administered at doses of 10-30mcg/kg applied to the oral mucosa (inside the cheek pouch) every 8 hours for up to 5 days (many cats experience anorexia after 5 days of therapy with buprenorphine). The commercially available 300mcg/ml solution for injection (Buprenex) works well for buccal administration with most cats receiving volumes of approximately 0.066ml/kg (e.g. 0.33ml for the average 5kg cat).1

Buccal absorption of buprenorphine has also been examined in dogs at approximately the same dose (20mcg/kg) utilized in cats. Absorption was low at this dose, but a dose of 120 mcg/kg administered transmucosally to dogs produced drug concentrations equivalent to an intravenous dose of 20 mcg/kg. Dogs have a relatively more acidic salivary pH than cats, resulting in more ionization of buprenorphine, reducing the amount of drug available for diffusion across membranes. At doses of 120mcg/kg, a 25kg dog would require 3000mcg or 10ml of the commercially available buprenorphine solution for injection.  A canine patient would likely swallow a large portion of 10ml administered buccally, and since the oral absorption of buprenorphine is extremely low, analgesic effect would not be achieved. Recent work at NC State University (unpublished) also demonstrates that buccal buprenorphine provides effective analgesia in horses when administered at doses of 6.6mcg/kg (e.g. 11ml of the commercially available injection for a 500kg horse). Again, a significant portion of this dose is likely to be swallowed by an equine patient, precluding a full analgesic effect.

For dogs and horses, a more concentrated solution of buprenorphine is greatly desirable for transmucosal use.  Compounded solutions of buprenorphine from 3-6mg/ml would allow for buccal administration of volumes of less than 1ml for both dogs and horses. Our compounding pharmacy can prepare concentrated solutions of buprenorphine for transmucosal use in dogs and horses.  Please call for more information.

  1. 1 J Vet Pharmacol Ther. 2005; 28(5):453-460.
    PK-PD modeling of buprenorphine in cats: intravenous and oral transmucosal administration
    Click here to access the abstract of this article.
  1. 2 Vet Ther. 2008 Summer;9(2):83-93.
    Pharmacokinetics of buprenorphine following intravenous and oral transmucosal administration in dogs.
    Click here to access the PubMed abstract of this article.
Gabapentin in a Xylitol-Free Formulation

Gabapentin is only approved for use in humans, but is widely used in veterinary medicine for both analgesia and neuroleptic indications.Dosed at 10-15mg/kg orally up to three times daily, this drug has become a valuable adjunct in veterinary therapies.Historically, gabapentin was available as a 100 mg scored tablet, enabling dosing of small animals (e.g. those weighing 5 kg or less) by quartering or halving tablets. Recently, gabapentin 100 mg tablets have been discontinued by all manufacturers, resulting in gabapentin 100 mg capsules being the smallest solid dosage form of gabapentin on the market.Because these capsules cannot be easily divided into smaller doses by pet owners, veterinarians have considered using Neurontin® (gabapentin) 50mg/ml oral solution to dose smaller patients.Unfortunately, Neurontin® Solution contains 300mg/ml of xylitol, an artificial sweetener which is known to cause profound hypoglycemia and hepatic necrosis in dogs at single doses of 100mg/kg. Dogs receiving doses of 0.3ml/kg of Neurontin® daily will be exposed to potentially toxic doses of xylitol.For this reason, veterinarians are turning to compounding pharmacists to compound patient-specific doses of gabapentin in capsules or treats, or compounded suspensions of gabapentin that do not contain xylitol.

Gabapentin is also used quite frequently in cats at small doses.  It is not known if cats have the same problems with xylitol that dogs do, but many cats dislike the strawberry taste of Neurontin® liquid, so the compounded preparation is often an appreciated alternative.

  1. Aust Vet J. 2005 Oct;83(10):602-8.
    Improving seizure control in dogs with refractory epilepsy using gabapentin as an adjunctive agent.
    Click here to read the PubMed abstract of this article.
  1. JAVMA  229: 1113-1117, 2006.
    Acute hepatic failure and coagulopathy associated with xylitol ingestion in eight dogs.
    Click here to read the PubMed abstract of this article.
  1. Vet Clin North Am Small Anim Pract. 2005 Jan;35(1):129-46
    Managing Pain in Feline Patients.
    Click here to read the PubMed abstract of this article.
Transmucosal Buprenorphine for Cats

The majority of an oral dose of buprenorphine is removed by hepatic first pass metabolism, therefore effective oral doses in dogs and cats may be cost prohibitive. Buprenorphines uniquely alkaline pKa (8.24) allows it to be administered transmucosally (buccally) to cats by virtue of the high salivary pH of this species (8-9). Administered on the tongue or in the cheek pouch at doses of 0.01-0.03mg/kg up to every 8 hours, buprenorphine has become a widely used and easy to administer analgesic for cats.

For cats, oral buprenorphine administration is not appropriate, as dosage forms such as oral suspensions encourage complete swallowing of the drug, delivering it to the gastrointestinal system where it will be almost entirely extracted by hepatic first pass metabolism and likely will NOT achieve analgesic blood levels. A preferable dosage form is a 0.3mg/ml solution for transmucosal administration; concentrations should not be lower than 0.3mg/ml as larger administered volumes risk being swallowed before absorption across buccal mucosa.

Some veterinarians also have reported anecdotal success by transdermal administration of buprenorphine at 0.03mg/kg every 8 hours. While there have been no scientific reports evaluating the efficacy of transdermally-administered buprenorphine in cats, a transdermal patch of buprenorphine is available in the United Kingdom and delivers buprenorphine transdermally to humans for up to 7 days.  Transdermal buprenorphine may prove to be a particularly effective analgesic for cats that have received extensive dental procedures and do not wish to have their mouths manipulated for buccal administration of drugs.

Pain Management in Cats

Pharmacokinetic data developed in other species cannot be safely extrapolated to the cat. Feline deficiency of glucuronidation pathways results in slow metabolism of several NSAIDs, which prolongs the duration of effect and may lead to drug accumulation and toxicity.

Meloxicam, a COX2 selective NSAID, has demonstrated clinical efficacy for chronic pain, musculoskeletal pain, and routine soft tissue surgery with few side effects. Based on clinical experience, Lascelles of NCSU College of Veterinary Medicine, now recommends oral meloxicam doses for cats that are less than previously reported in the literature (0.1 mg/kg PO on day 1 followed by 0.05 mg/kg PO daily for 4-6 days, then 0.025 mg/kg daily for 10 days, then lowest effective dose).1

Five days of oral treatment with meloxicam or ketoprofen for cats with painful locomotor disorders provided similar analgesia2, but meloxicam drops were more palatable than ketoprofen tablets. Appropriately flavored preparations in a convenient dosage form are easier for owners to administer and allow for accurate dosing.

According to Robertson and Taylor3, opioids have an unjustified reputation for causing mania in cats, but with refinements in dosing they are now used successfully in this species. The mu-opioid agonists are generally considered the best analgesics. Morphine (0.1 – 0.3 mg/kg) is effective in a clinical setting. Oxymorphone and hydromorphone (0.05 – 0.1 mg/kg) are widely used in the USA. These opioids are more potent (up to 10 times), and longer acting than morphine in cats. Buprenorphine (0.01 – 0.02 mg/kg), a partial mu-agonist, is the most popular opioid used in small animal practice in the UK, other parts of Europe, Australia and South Africa. In clinical studies it has produced better analgesia than several other opioids and appears to be highly suitable for perioperative pain management in cats.

Amitriptyline (starting dose 2.5 mg/kg PO, once daily) has been used to treat feline interstitial cystitis with few side effects, and there are anecdotal reports of its use for cancer and neuropathic pain management.

Some of the less conventional analgesics including the tricyclic anti-depressants and gabapentin may prove to play a useful role in chronic pain management, but controlled clinical trials are needed to establish the best doses for maximum efficacy. Other less traditional analgesics such as ketamine and local anesthetics are also used for clinical pain management. The transmucosal, transdermal and epidural routes offer novel methods for administration of analgesic drugs and have considerable potential for improving techniques in feline pain management.

  1. 1 http://www.vetmash.com/pdf_files/dr_duncan_lascelle04.pdf  (accessed June 2009)
  1. 2J Small Anim Pract 2001 Dec;42(12):587-93
    Evaluation of the clinical efficacy of meloxicam in cats with painful locomotor disorders.
    Click here to access the PubMed abstract of this article.
  1. 3Journal of Feline Medicine and Surgery; 6(5), Oct 2004: 321-333
    Pain management in cats—past, present and future. Part 2. Treatment of pain—clinical pharmacology
    Click here to access the PubMed abstract of this article.
Meloxicam for Analgesia in Dogs

A clinical trial was conducted to evaluate the safety and efficacy of  meloxicam in dogs with chronic osteoarthritis. A scoring system assessed specific lameness, general stiffness, painful rise, exercise intolerance, and behavior, and demonstrated significant reductions in clinical signs of osteoarthritis following 4 weeks of drug therapy. Side effects were minimal in extent and duration. The findings of this investigation suggest that the efficacy, tolerance, and formulation of meloxicam oral suspension make it well suited for the treatment of chronic osteoarthritis in the dog.

  1. Can Vet J 2000 Apr;41(4):296-300
    Clinical efficacy and tolerance of meloxicam in dogs with chronic osteoarthritis.
    Click here to access the PubMed abstract of this article.
Ketoprofen

is a potent anti-inflammatory and analgesic which can be used for the management of surgical pain or chronic pain. The drug should not be given to animals with GI ulceration, impaired renal or hepatic function, or coagulation disorders. Ketoprofen should not be used preoperatively when noncompressible bleeding may be a problem. Occasional vomiting has been reported. When an NSAID or other drug that is potentially irritating to the GI tract is needed, topical preparations offer an excellent alternative. Pharmaceutical Research, Vol. 13, No. 1, 1996 reports (in humans) “a topical formulation of ketoprofen has been developed for the temporary relief of minor aches and pains of muscle and joints and to minimize gastrointestinal side effects after oral administration.”

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Poisoning / Toxicosis

Xylitol Poisoning in Dogs

Compounding pharmacists are now receiving requests from veterinarians to compound oral medications for dogs and cats in vehicles that are known to be free of xylitol.  Xylitol is an artificial sweetener commonly used to sweeten human medications, gums, mouthwashes and candies, and while not toxic to humans, can be quite toxic to dogs.  Xylitol is not absorbed from the gastrointestinal tract of humans, but is easily absorbed in dogs.  Once in the bloodstream, xylitol acts like glucose, stimulating insulin secretion, which causes life-threatening hypoglycemia.  Profound hypoglycemia can last for 1-2 hours following xylitol ingestion, and has frequently resulted in death.  Many commercially available drugs labeled for humans, such as gabapentin oral suspension, contain xylitol as an inactive ingredient, and all human medications used in dogs should be scrutinized for xylitol content. Compounding pharmacists can play a valuable role for veterinarians and veterinary patients by providing xylitol-free suspensions of medications and by educating clients to avoid all xylitol-containing foods in their pets.  It is not currently known if xylitol is toxic in cats, but for the present, xylitol must also be assumed to be toxic to cats.  For more information, search “xylitol” at http://www.aspca.org/.

Apomorphine to Stimulate Vomiting

Emetic drugs are usually administered in emergency situations after ingestion of a toxin. “Apomorphine is an opiate drug that acts as a potent central dopamine agonist to directly stimulate the CTZ. It can be administered PO, IV, or SC; the IM route is not as effective. It can also be applied directly to conjunctival and gingival membranes, using the tablet formulation, which can easily be removed once emesis is initiated. Vomiting usually occurs in 5-10 min. Although apomorphine directly stimulates the CTZ, it has a depressant effect on the emetic center. Therefore, if the first dose does not induce emesis, additional doses are not helpful. Because the vestibular apparatus may also be involved in apomorphine-induced vomiting, animals that are sedate and motionless will not vomit as readily as animals that are active. Because it can cause CNS stimulation, apomorphine is used cautiously in cats. Opiate-induced excitement in cats can be treated with naloxone (an opiate antagonist).”
Apomorphine dosage for dogs: 4 mg/kg PO; 0.02 mg/kg IV; 0.3 mg/kg SC (from Merck Veterinary Manual, 8th edition, p. 1681); 0.25mg/kg (as a tablet) into the conjunctival sac (from Plumb’s Veterinary Drug Handbook, p.51)

Accidental Poisoning

“is not a rare event; and veterinarians need to have access to antidotes. However, there are relatively few products specifically labeled for use in these instances, so it has not really been legal for veterinarians to have previously prepared antidotes for poisonings on hand in emergency rooms. For example, if a case of lead poisoning is diagnosed and the veterinarian needs some calcium EDTA as an antidote, there is no product available labeled for use in animals… Compounding offers opportunities for facilities to have [items such as calcium EDTA] on hand … for emergency treatment, in anticipation of a legitimate prescription.”

Intl J of Pharm Comp 1997 July/Aug; 1(4): 240

N-acetylcysteine as an Antidote for Acetaminophen Toxicosis

   N-acetylcysteine (NAC) is the antidote of choice for the treatment of acetaminophen poisoning, one of the most common types of intoxication in dogs and cats. NAC acts principally by replenishment of intracellular glutathione stores and detoxification of the reactive metabolite (NAPQI). NAC acts as a scavenger of free radicals, blocks the conversion of hemoglobin to methemoglobin, and can reduce the extent of liver injury.
Although NAC is most effective if administered less than 12 hours after ingestion of acetaminophen, the use of NAC as an antidote is still recommended up to 36 to 80 hours after acetaminophen ingestion.
Oral NAC, IV NAC, and IV sodium sulfate were evaluated as treatments for cats who had received toxic sublethal doses of acetaminophen (APAP). At the dosage levels used, oral NAC, IV NAC, and IV sodium sulfate were equally effective antidotes, as measured by decreased methemo-globinemia, increased whole blood reduced glutathione, decreased APAP half-lives, and increased urinary excretion of the APAP-sulfate conjugate. All the antidotal treatments produced results significantly different from those in the control cats.
To determine if rectally administered N-acetylcysteine (NAC) is absorbed into the systemic circulation, NAC was administered into the rectal vault (2.0 g/kg) of swine via a balloon-tipped Foley catheter inserted into the animals’ rectums. NAC administered via the rectal route resulted in systemic absorption as determined by spectrophotometric methods in 5 of the 7 study animals. This study provides important information regarding the development of a potential alternative route for the administration of NAC to dogs.
In dogs and cats, NAC can be administered intravenously or orally, but has a pungent odor. Oral administration of NAC typically causes nausea and vomiting. The oral solution can be compounded as a chicken-flavored preparation to improve palatability.
Rapid intravenous administration of NAC can cause hypotension, bronchospasm, and flushing. Reactions can be minimized by slowing the rate of infusion.
Activated charcoal may absorb NAC and reduce its effectiveness, so NAC should not be administered within two hours of giving activated charcoal. “Administration of activated charcoal may exacerbate vomiting and lead to aspiration. A strong antiemetic agent (metoclopramide 0.4 mg/kg IV) may be necessary to prevent emesis.”
NAC is currently not approved by the FDA for use in dogs and cats, but is available in human formulations, and upon a prescription order, can be compounded to meet specific veterinary needs.

Compendium 2003 Apr;25(4):276-280

  1. Am J Vet Res 1985 Jul;46(7):1485-9
    Comparison of N-acetylcysteine and methylene blue, alone or in combination, for treatment of acetaminophen toxicosis in cats.
    Click here to access the PubMed abstract of this article.
  1. Vet Hum Toxicol 1997 Dec;39(6):329-31
    Rectal administration of N-acetylcysteine in swine: a pilot study.
    Click here to access the PubMed abstract of this article.

Vet Med 1997;92(2):158-165

Dimercaptosuccinic Acid for Lead Poisoning in Cats

Wright Veterinary Medical Center, Bethlehem, PA

The owners of two nine-year-old cats moved to a new house. One week after moving, both cats were vomiting and losing weight so the owners brought the cats to the veterinary clinic. The veterinarian began intravenous hydration. Blood work showed a very high level of nucleated RBC’s. The CBC revealed platelet clumps on feathered edge, few macrocytes, moderate anisocytosis, and occasional acanthocytes (54% and 45.1% NRBC). One cat had two seizures on the first day of hospitalization. Based on the initial signs and nucleated red cells, lead poisoning was suspected, although there was no radiographic evidence of lead ingestion. We tested for lead and began treatment with dimercaptosuccinic acid (DMSA) 40mg/cc.

The cats improved clinically within 24 hours. There were no more seizures and the cats began to eat. The blood lead levels were 164.8 and 210 (normal is 0-25). The cats were treated with 40mg (1cc) of DMSA given orally three times per day for a total of 10 days. DMSA is not commercially available in an injectable or liquid form. Therefore, we worked together with our compounding pharmacist to prepare a sterile formulation that would be suitable for intravenous or oral use.

The second day after therapy had begun, the owners informed us that they had been sanding the painted floors in their new house. The cats probably walked through the dust and in grooming themselves licked the lead paint off their paws. There have been no further problems with the cats to our knowledge. The owner declined to come in for a lead level recheck.

Penicillamine for Long-Term Treatment of Lead Poisoning

Penicillamine chelates a variety of metals, including copper, lead, iron and mercury, forming stable water-soluble complexes that are excreted by the kidneys. Used primarily for its chelating ability in veterinary medicine, it is the drug of choice for copper storage-associated hepatopathies in dogs at a dose of 15mg/kg PO twice daily. Penicillamine may also be used in cystine urolithiasis (penicillamine combines chemically with cystine to form a stable soluble complex that can be readily excreted) and in a different dose for the long-term oral treatment of lead poisoning. “This drug should preferably be given on an empty stomach, at least 30 minutes before feeding. If the animal develops problems with vomiting or anorexia, three remedies have been suggested. 1) Give the same total daily dose, but divide into smaller individual doses and give more frequently. 2) Temporarily reduce the daily dose and gradually increase to recommended dosage. 3) Give with meals (will probably reduce amount of drug absorbed).”

Veterinary Drug Handbook, 2nd edition, Donald C. Plumb, Ed.

4-Methylpyrazole for Ethylene Glycol (Antifreeze) Poisoning

Therapy for ethylene glycol poisoning is aimed at preventing absorption, increasing excretion, and preventing metabolism of ethylene glycol to its toxic metabolites. Inhibition of liver alcohol dehydrogenase (ADH), the enzyme responsible for the initial reaction in the metabolic pathway, can be accomplished by giving a compound that combines with the enzyme and renders it inactive. The most effective ADH inhibitor in the dog is 4-methylpyrazole (4-MP), which unlike most competitive inhibitors (ethanol, propylene glycol, and 1,3-butanediol) does not contribute to CNS depression and increased serum osmolality. The recommended dose of 5% (50mg/ml) 4-methylpyrazole is 20 mg/kg body weight IV initially, followed by 15 mg/kg IV at 12 and 24 hr, and 5 mg/kg at 36 hr. While 4-MP is the recommended therapy in dogs, it is not appropriate for use in cats. Although it is non-toxic, it does not effectively inhibit EG metabolism unless administered to a cat at the same time as consumption of EG.

Am J Vet Res 1995;56:825.

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Seizure Control

Potassium Bromide for Seizures
by Mollyann Holland, D.V.M., Oklahoma City, OK
Diplomate, American College of Veterinary Internal Medicine

Potassium bromide is frequently helpful in treating refractory seizures in animals. Because potassium bromide is excreted renally, it may also be preferable for use in animals that have developed hepatotoxicity while on other anticonvulsants. My compounding pharmacist prepares this as a liver flavored solution, which can easily be administered to dogs. I feel that it is important to inform my animal owners that potassium bromide solution is compounded from a reagent grade chemical, and is not a commercially available “drug.”

KBr is dosed on a weight basis. Maintenance doses range from 20-100 mg/kg body weight/day, and can be given as a single or divided dose. I usually dose at 30-40mg/kg/day as a single dose with food. Due to its long half-life, KBr can take up to four months to reach steady state; therefore, a loading dose may be required if therapeutic blood levels must be reached quickly. The loading dose is 400-600 mg/kg body weight and is administered orally over 30 to 60 minutes to avoid vomiting. A loading dose is not necessary if it is possible to keep the animal on other medications (as in a case of emerging hepatotoxicity) until levels of bromide are therapeutic (0.5-1.5 mg/ml), when the other anticonvulsant can be tapered off.

Potassium Bromide Chewable “Treats” for Seizure Control
Contributed by Steve Toney, R.Ph., Erin King, C.Ph.T. and Pam Woodin, D.V.M.

Case Report: 5 y.o. male Golden Retriever with seizure disorder. The owners called our compounding pharmacy to see what we could do as they were having difficulty administering medications to their dog. We suggested medicated canine treats that we have compounded many times with a 100% success rate. The veterinarian was consulted and we prepared potassium bromide (KBr) 150 mg treats coated with liver and beef flavored powder. The owner administers two treats two times daily, and the dog now loves to take his medicine!

Note: Chewable treats can be compounded to contain a variety of medications and flavored for the specific breed or pet. This dosage form has high patient acceptance and a low risk of owner misdosing.

Potassium bromide (KBr) can be also compounded as an oral solution which is easy to flavor and convenient for use as a loading dose. However, the risk of owner misdosing is greater than with a chewie or capsule.

Phenobarbital: Problems and Solutions

While phenobarbital is often used in veterinary medicine to treat seizure disorders, there are several concerns with its use:

  • there are no commercially available veterinary approved products
  • phenobarbital tablets for human use are small, hard, and unscored, making them difficult to divide for individualized dosing
  • phenobarbital elixir has a high alcohol content, which is problematic for cats or any species when chronically administered
  • phenobarbital induces CYP450 hepatic enzymes which can result in substantial drug interactions with oral anticoagulants, steroids, antibiotics, beta-blockers, theophylline, etc.
  • phenobarbital is contraindicated in dogs with hepatic disease

When you wish to prescribe phenobarbital, please be aware that our compounding pharmacy can prepare an alcohol-free, appropriately flavored oral suspension, which is highly bio-available and very easy to use when administering a loading dose or when a flexible dose is needed. Once the maintenance dose is established, the dosage form can be switched to a capsule (with a lower risk of misdosing by the owner) or a flavored chewable medicated “treat”, with the added benefit of high patient acceptance.

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Urology

Treating Feline Urethral Spasm

Feline lower urinary tract disease (FLUTD) is a spectrum of different diseases that present with a common set of clinical signs regardless of the underlying cause.  Cats with FLUTD, usually present with signs of dysuria (difficult urination), pollakiuria (increased frequency of urination), hematuria, agitation or vocalization (crying or howling) when unable to urinate due to urethral obstruction. Obstructive FLUTD can be a serious condition and may lead to post-renal azotemia, renal azotemia, hyperkalemia, hyperphosphatemia, hypocalcemia, and acidemia. These combined metabolic and renal disruptions can rapidly prove fatal. Therefore, cats presenting with lower urinary tract obstruction require immediate treatment. Acute renal failure and death can result in 1-3 day if urinary tract obstruction is left untreated.

Urethral spasm may occur in many cases of FLUTD, regardless of the underlying cause. Spasms may be initiated by local pain or inflammation, and may affect the smooth and/or skeletal muscle of the urethra. It may therefore be beneficial to give drugs to counter both smooth and skeletal muscle effects. While these drugs are rarely associated with side effects in young cats, the risk of concurrent renal or cardiac disease should be assessed before these drugs are given to older cats. Smooth muscle anti-spasmodics include prazosin 0.25-1.0 mg/cat PO q8-12h, and phenoxybenzamine  0.5-1.0 mg/kg PO q12h–give for 5 days before evaluating efficiency. The most commonly used skeletal muscle anti-spasmodic is dantrolene given at 0.5-2.0 mg/kg PO q12h.

There have been only a limited number of studies into the use of anti-spasmodic drugs in the relief of urethral spasm in cats; however, prazosin, phenoxybenzamine and dantrolene have been shown to be most beneficial.  Unfortunately, all of these drugs are commercially available in capsule forms that cannot be safely and accurately administered to cats. Because prazosin and phenoxybenzamine are smooth muscle alpha adrenergic antagonists, profound hypotension is a potential adverse effect.  For this reason, these drugs have a very narrow therapeutic index, and veterinary clinicians prefer to only use these drugs in carefully titrated doses. Our compounding pharmacy is able to provide these valuable anti-spasmodic drugs in palatable, appropriately-sized dosage forms and optimal individualized strengths.  While none of these drugs are stable for long periods of time in liquid dosage forms, we can compound capsules containing one or more of the anti-spasmodics individualized for a specific patient, or provide as medicated treats.  Due to the delayed onset of transdermal medications, this dosage form is not appropriate for use in treating this potentially life-threatening condition.

  1. AJVR 1995 Jul;56(7):919-23.
    Urethral pressure response to smooth and skeletal muscle relaxants in anesthetized, adult male cats with naturally acquired urethral obstruction.
    Click here to access the PubMed abstract of this article.
  1. AJVR 1992 Jul;53(7):1161-5.
    Urethral pressure response to alpha-adrenergic agonist and antagonist drugs in anesthetized healthy male cats.
    Click here to access the PubMed abstract of this article.
  1. AJVR 1996 Oct;57(10):1497-500.
    Effects of acepromazine maleate and phenoxybenzamine on urethral pressure profiles of anesthetized, healthy, sexually intact male cats.
    Click here to access the PubMed abstract of this article.
Treatment for Urinary Incontinence

Hormonal Therapy:
Diethylstilbestrol (DES) has been used to treat estrogen responsive incontinence in spayed female dogs. The use of DES is contraindicated in cats as daily use has resulted in pancreatic, hepatic, and cardiac lesions.

Dose for dogs:
Initially 0.1-1.0 mg PO daily for 3-5 days, followed by maintenance therapy of approximately 1 mg PO per week. Some animals may require much higher initial dosages to obtain a response. DES can be given PO to female dogs at 0.1-0.3 mg/kg/day for 7-10 days, followed by a similar dose once weekly. Dogs should be maintained at the lowest possible dose because bone marrow suppression can develop when diethylstilbestrol is given in high doses. 1,4 

When therapy is chronic or high dosages are used, packed cell volumes, white blood cell counts, and platelet counts should be done at least monthly. Liver function tests should be done at baseline, one month after therapy, and repeated 2 months after cessation of therapy if abnormal.

Clients should be informed to contact the veterinarian if signs and symptoms of lethargy, diarrhea, vomiting, abnormal discharge from vulva, excessive water consumption and urination or abnormal bleeding occur. DES is not for human consumption and should be dispensed only in child-resistant containers and stored in a secure location.1

DES is not currently commercially available; however, the medication can be prepared by a compounding pharmacy.

Adrenergic Agonists:
Phenylpropanolamine (PPA) is a weak alphaagonist that increases urethral sphincter tone and produces closure of the bladder neck, and is used to treat urethral sphincter hypotonus and resulting incontinence in dogs and cats.

Dose1:

Dogs:  1.1 mg/kg PO every 8 hours       Cats:  12.5mg PO every 8 hours

The effect is short-lived, and the dose needs to be titrated to effect. “Dogs that are older at the onset of clinical signs (median 5 years) and those with a longer period from the time of ovariohysterectomy to the onset of urinary incontinence (median 2.5 years) respond best. PPA is preferred to ephedrine because side effects are less severe; ephedrine has greater cardiovascular side effects and it tends to lose effectiveness over time.”2 In a multicenter, blinded, placebo-controlled trial, 50 dogs that presented with clinical signs consistent with urinary sphincter mechanism incontinence were treated for 28 days with either PPA (1 mg/kg three times daily) or placebo. At day 28, 85.7 per cent of PPA-treated cases had no episodes of unconscious urination compared with 33.3 per cent of placebo-treated cases.3

Potential side effects include restlessness, irritability, hypertension and anorexia. Numerous drug interactions exist.

In November2000, human PPA preparations were removed from the market due to reports of serious side effects in humans. PPA continues to be available as a bulk chemical for veterinary use only.

  1. 1 Veterinary Drug Handbook, 3rd edition, Donald C. Plumb, ed. pp.193-5, and 508-9
  1. 2Handbook of Veterinary Drugs, 2nd edition, pp. 277-8
  1. 3 J Small Anim Pract. 2002 Nov;43(11):493-6
    Evaluation of phenylpropanolamine in the treatment of urethral sphincter mechanism incompetence in the bitch.
    Click here to access the PubMed abstract of this article.
  1. 4http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/191024.htm&word=ppa

Per your prescription, we can compound customized dosage forms to meet the specific needs and flavor/texture preferences of each animal.

Piroxicam for Canine Bladder Cancer

Traditional chemotherapy (using cisplatin, carboplatin, adriamycin, and others) has been used in canine Transitional Cell Carcinoma (TCC). The response has been rather disappointing with <20% of dogs having remission.

Interest in non-steroidal anti-inflammatory (NSAID) therapy began when dogs with various forms of spontaneous cancer had remission while receiving the NSAID piroxicam for pain control, and no other therapy.  Two of the first dogs treated (one with metastatic carcinoma, one with undifferentiated sarcoma) had advanced cancer and had remission of their cancer when only receiving piroxicam. This has led to numerous studies of piroxicam in animals with cancer at Purdue University Veterinary Teaching Hospital (PUVTH). In an attempt to improve the response of TCC to therapy, PUVTH conducted a study comparing chemotherapy (cisplatin) alone to chemotherapy plus piroxicam. The combination of cisplatin and piroxicam was more effective against the cancer, but the combination treatment caused a rise in BUN. In several instances, the cisplatin therapy was withdrawn (so as to not cause renal damage) while the tumors were still shrinking.

In a phase I study of piroxicam in 62 dogs with various histopathologically confirmed, measurable tumors, gastrointestinal toxicity was dose-related and dose limiting, but anti-tumor activity occurred at lower, less toxic doses of piroxicam. Partial remission occurred in 8 dogs, including 3 of 10 dogs with TCC. A phase II clinical trial of piroxicam in dogs with histologically confirmed, measurable, nonresectable TCC was performed. The dogs lived at home with their owners and were evaluated at the PUVTH at monthly intervals. Piroxicam was given orally at a dosage of 0.3 mg/kg every 24 hours (the accepted canine dosage prior to this trial). Tumor response in 34 dogs included 2 complete remissions (CR), 4 partial remissions (PR), 18 stable disease (SD), and 10 progressive disease (PD). Piroxicam therapy was generally well tolerated, with gastrointestinal toxicity noted in six dogs and renal papillary necrosis in two dogs. The median survival was 180 days. Fifty-five additional dogs were treated with piroxicam, and tumor response included 2 CR, 7 PR, 32 SD, and 14 PD.

It is not known how long dogs with TCC that are not treated will live. Survival is affected by the growth rate of the tumor, the exact location of the tumor within the bladder, and whether the tumor has metasticized. The median survival in dogs treated with cisplatin or carboplatin at PUVTH was 130 days. Median survival with piroxicam treatment in 55 dogs with TCC was 190 days. The survival times in all of these studies, however, vary tremendously from only a few days to more than one year.  Longer survival times have been reached when chemotherapy is combined with piroxicam, but the optimal combination treatment is still being determined.

  1. Cancer Chemother Pharmacol 1992;29:214-218
    Phase I trial of piroxicam in 62 dogs bearing naturally occurring tumors.
    Click here to access the PubMed abstract of this article.
  1. J Vet Intern Med 1994;8:273-278
    Piroxicam therapy in 34 dogs with transitional cell carcinoma of the urinary bladder.
    Click here to access the PubMed abstract of this article.
  1. Cancer Chemother Pharmacol 2000;46:221-226
    Cisplatin versus cisplatin combined with piroxicam in a canine model of human invasive urinary bladder cancer.
    Click here to access the PubMed abstract of this article.
  1. Urologic Oncology 2000;5:47-59
    Naturally-occurring canine transitional cell carcinoma of the urinary bladder: A relevant model of human invasive bladder cancer.
Citrate Salts as Alkalinizing Agents

Citrate salts are a source of bicarbonate, but are much more palatable than bicarbonate preparations. “They are used as urinary alkalinizers when an alkaline urine is desirable and in the management of chronic metabolic acidosis accompanied with conditions such as renal tubular acidosis or chronic renal insufficiency. Potassium citrate alone has been used for the prevention of calcium oxalate uroliths. The citrate can complex with calcium thereby decreasing urinary concentrations of calcium oxalate… When urine is alkalinized by citrate solutions, excretion of certain drugs (e.g. quinidine, amphetamines, ephedrine, …tetracycline) is decreased, and excretion of weakly acidic drugs (e.g. salicylates) is increased. The solubility of ciprofloxacin and enrofloxacin is decreased in an alkaline environment [and patients] should be monitored for signs of crystalluria.” (Plumb’s Veterinary Drug Handbook, 2nd ed.)  In combination with potassium citrate preparations, these agents may lead to severe increases in serum potassium levels: NSAIDs, ACE-inhibitors, cyclosporine, digitalis, heparin and others.

Fludrocortisone Acetate
Fludrocortisone is a long-acting corticosteroid with potent mineralocorticoid and moderate glucocorticoid activity. It is used in small animal medicine for the treatment of adrenocortical insufficiency, where it promotes sodium retention and urinary potassium secretion. It is commercially available only as the human product, a tablet containing 0.1 mg  fludrocortisone acetate. The maintenance therapy for animals (particularly dogs) can require administration of multiple tablets for each daily dose.  Therefore, it may be more convenient for owner and animal to administer fludrocortisone acetate as a flavored suspension, or single flavored solid dosage form.

Aluminum Hydroxide for Hyperphosphatemia
For dogs and cats, aluminum hydroxide is initially dosed at 30 – 90 mg/kg orally one to three times daily. A preparation that can be mixed with food may be preferred as it is more easily dispersed throughout ingesta. Dosage must be individualized, and serum phosphate levels should be evaluated at 10-14 days to determine optimum dosage.

  1. Veterinary Drug Handbook, 3rd edition, Donald C. Plumb, editor. pp. 48-49
Calcitriol for Chronic Renal Failure

Submitted by Shirley Russman, D.V.M.

Our protocol for treating chronic renal failure includes a special diet, adequate hydration, potassium supplementation, stomach acid control and calcitriol therapy to control phosphorus levels. Calcitriol (a vitamin D3 metabolite) may also be used to prevent or reverse secondary hyperparathyroidism in dogs and cats with chronic renal failure.

Calcitriol is dosed in nanograms. Commercially available products are for humans, and the dose is much too high for dogs or cats (for example, the capsule contains 250 nanograms or 0.25 micrograms). Our compounding pharmacist has been able to prepare any capsule (8 nanograms and up) or liquid (i.e. 4 nanograms/0.25ml) necessary to meet our needs.  We have used this compounded remedy over one hundred times and have found it to be very successful in lowering phosphorus levels in our patients with chronic renal failure. Serum calcium levels should be monitored as hypercalcemia is a possible consequence of calcitriol administration.

Editor’s Note:

Calcitriol “has a rapid onset of action (1-4 days) and a short half-life (4-6 hours). Oral calcitriol is administered to patients after initial stabilization with fluid therapy, dietary protein and phosphorus restriction, the use of intestinal phosphate binders and H-2 blockers as needed. Serum phosphorus should be less than 6 mg/dL (1.9 mmol/liter) before initiating calcitriol.

“Hypercalcemia usually only occurs if calcitriol is used in conjunction with intestinal phosphate binders, especially calcium carbonate… Long-term use of phenytoin and the barbiturates may interfere with the action of the drug, necessitating higher doses of calcitriol… Thiazide diuretics may enhance the effects of calcitriol predisposing to hypercalcemia. Calcitriol-induced hypercalcemia may antagonize the antiarrhythmic effects of calcium channel-blocking agents.”

  1. Handbook of Veterinary Drugs, 2nd edition, pp. 105-106

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Wound Care

Would you like a topical medication that is difficult for an animal to lick off or that will adhere to a mucosal surface?

You can prescribe a medicated “polyox bandage” or “mucosal bandage”. When moistened, this medicated preparation will adhere to a wound or mucosal surface, thereby providing a protective barrier and increasing the contact between the medication and the affected area.

Wound and Incision Care – Prevent Licking

A common problem encountered by veterinarians and animal owners is preventing an animal from licking an incision or licking medication from the area to which it has been applied. In addition to injury to the wound, pharmacists and veterinarians must consider the consequences of internal consumption of an external preparation. To prevent an animal from licking, a medication can be compounded to contain an extremely bitter substance. Choices include diphenhydramine, quinine, or the non-therapeutic ingredient sucrose octaacetate. Sucrose octaacetate can be added at 1% to 5% to any topical dosage form and the bitterness usually prevents the animal from repeated licking of the area of application. Another way to protect a medicated area from licking is to incorporate the needed medication into CAP (Cellulose Acetate Hydrogen Phthlate) solution. Since CAP solution does not dissolve in an acidic pH, the animal’s saliva does not remove it from the skin. CAP solution can also be sprayed directly onto a wound or over stitches to protect them.

Phenytoin/Lidocaine Poly-Ox Bandage Used to Treat Leg Wound

Problem: Twenty-four hours after an automobile accident, an eight-month old female pit bull presented with a leg injury that appeared as if it would have difficulty healing. The dog had been hit by an automobile, which had scraped a hole in the right front leg. The wound, which extended from the elbow to the carpus, was approximately 3/4″ to 1″ wide.

Treatment: The tissue of the leg was stabilized using tension-relieving sutures. Because the veterinarian had prior successful experiences with other cases involving wound care, she requested we compound a topical preparation consisting of 2% phenytoin and 2% lidocaine in a methylcellulose/polyoxyethylene (poly-ox) bandage for the dog. The animal underwent hydrotherapy twice daily and the compounded medication was applied just before bandaging was secured.

Outcome: The wound was completely healed after 2 months of therapy and the animal has full use of her leg with no visible ill effects. According to the veterinarian, the animal healed much quicker than usual due to the increased contact time of the medications and she was satisfied with the treatment process.

We have also used this compound with the same positive success on a degloved feline after its paw had been caught in a fence overnight.

Reference:
Randy S. Carr, R.Ph., FIACP & Pamela Doskey, D.V.M.

Therapy for Severe Chemical Burns

by Barbara Espe, D.V.M., North Dakota

In April 1998, I was called to euthanize a 1 1/2 year old female miniature schnauzer that had been burned with hot water from the bath tub and washed in Woolite? 3-4 weeks earlier. The full thickness burns involved about 80% of the skin on the dorsal trunk from neck to tail and elbows to midthigh. The owners were using aloe vera to treat the burns and she had a severe infection, was emaciated (5 lb.) and had not eaten for one week. Since she had survived so long without treatment, I had the owners sign ownership over to me and I contacted the Central Dakota Humane Society. They agreed to take on this project despite the many hours of labor and the potential cost. The dog was immediately given an analgesic and antibiotics.

I literally stopped at the pharmacy with the dog so the compounding pharmacist could see what we were up against. At the pharmacist’s suggestion, a Poly-Ox bandage containing phenytoin base 2% and misoprostol 0.002% was compounded and applied in a layered manner. Telfa? pads were used to cover the wound, and a T-shirt was put on to protect the bandages. The dog started eating canned food that night and in several days she was eating four large cans of food daily. In addition to the Poly-Ox bandage, she remained on Cefadrops? and Rimadyl?. She seemed to be uncomfortable and analgesics did not appear to control her pain. The powder was returned to the pharmacy and lidocaine 2% was added. Although this helped somewhat, the dog was becoming non-compliant at the time of her dressing changes. The compound was again modified to contain bupivacaine 0.2% to obtain an extended analgesic effect. This was a significant improvement and therapy continued for several months. As healing occurred, the dog began to experience itching in the regranulated skin and wound areas. Diphenhydramine was given orally along with the Rimadyl? and we began rubbing her stretched skin with Emu oil to keep it moist. Shortly thereafter, the dog “became a schnauzer again.” Her activity level has increased greatly and we anticipate a complete recovery.

When I began treating this dog, I thought that skin grafting would be necessary. Due to the success of this therapy, no grafting will be needed. However, I don’t expect hair regrowth and the epithelium will remain scarred and easily bruised.

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Equine

Reserpine for Compulsory Stall Rest

Reserpine has clinical therapeutic value to sedate horses recovering from injuries that are confined to stall rest for long periods of time. Reserpine is a narrow therapeutic index drug. Recommended doses of reserpine range from 1-4mg/500kg horse once daily and may be administered orally or by intramuscular injection. Doses of 5-10mg/500kg horse have resulted in severe toxicity. Signs of toxicity can occur within three to six hours of administration. Initially, severe depression, sweating and flatulence are seen. There may be sporadic episodes of colic, sometimes violent, followed by somnolence. Injection frequently results in diarrhea, but both oral and parenteral routes may result in increased gastrointestinal sounds, muscle trembling, hypotension, decreased heart rate, arrhythmias, miosis, ptosis, and penile paralysis. Clinical signs will persist until norepinephrine stores are replenished which may be up to 60 hours after dosing.  Reserpine may be detected by drug assay for up to 5 days after administration.  No antidote is available for reserpine toxicity, although methamphetamine has been suggested as a possible therapy.

Drug interactions with reserpine can be life-threatening. Horses treated with reserpine within the previous 60 days may be at risk for profound hypotension (even death) when exposed to xylazine, detomidine or ketamine.

Reserpine is no longer commercially available as an injection, but is available in 0.1mg and 0.25mg tablets. However, reserpine has a bitter taste, and many horses will not accept these tablets voluntarily. Our compounding pharmacy is able to provide palatable oral gels and suspensions of reserpine as well as reserpine injection upon the order of a licensed veterinarian.

Equine Clinical Pharmacology. Editors Joseph Bertone, DVM, MS and Linda J. I. Horspool BVMS PhD. WB Saunders, p. 152.

Transmucosal Buprenorphine: More is Better For Dogs and Horses

The pharmacokinetic profile of a buccally-administered (transmucosal) dose of buprenorphine to cats is almost identical to that of intravenously administered buprenorphine. The unusually alkaline salivary pH of cats prevents ionization of buprenorphine, allowing it to diffuse into systemic circulation in a non-ionized form. This discovery greatly facilitated outpatient feline pain relief, allowing owners to administer this drug to cats at home, without the need for hospitalization or injection.  Because the duration of analgesia from buprenorphine (4-12hrs) is longer than that provided by other opiates, buprenorphine is frequently used for provision of non-invasive, intermediate to long-term analgesia in cats.  It is typically administered at doses of 10-30mcg/kg applied to the oral mucosa (inside the cheek pouch) every 8 hours for up to 5 days (many cats experience anorexia after 5 days of therapy with buprenorphine). The commercially available 300mcg/ml solution for injection (Buprenex) works well for buccal administration with most cats receiving volumes of approximately 0.066ml/kg (e.g. 0.33ml for the average 5kg cat).1

Buccal absorption of buprenorphine has also been examined in dogs at approximately the same dose (20mcg/kg) utilized in cats. Absorption was low at this dose, but a dose of 120 mcg/kg administered transmucosally to dogs produced drug concentrations equivalent to an intravenous dose of 20 mcg/kg. Dogs have a relatively more acidic salivary pH than cats, resulting in more ionization of buprenorphine, reducing the amount of drug available for diffusion across membranes. At doses of 120mcg/kg, a 25kg dog would require 3000mcg or 10ml of the commercially available buprenorphine solution for injection.  A canine patient would likely swallow a large portion of 10ml administered buccally, and since the oral absorption of buprenorphine is extremely low, analgesic effect would not be achieved. Recent work at NC State University (unpublished) also demonstrates that buccal buprenorphine provides effective analgesia in horses when administered at doses of 6.6mcg/kg (e.g. 11ml of the commercially available injection for a 500kg horse). Again, a significant portion of this dose is likely to be swallowed by an equine patient, precluding a full analgesic effect.

For dogs and horses, a more concentrated solution of buprenorphine is greatly desirable for transmucosal use.  Compounded solutions of buprenorphine from 3-6mg/ml would allow for buccal administration of volumes of less than 1ml for both dogs and horses. Our compounding pharmacy can prepare concentrated solutions of buprenorphine for transmucosal use in dogs and horses.  Please call for more information.

  1. 1 J Vet Pharmacol Ther. 2005; 28(5):453-460.
    PK-PD modeling of buprenorphine in cats: intravenous and oral transmucosal administration
    Click here to access the abstract of this article.
  1. 2 Vet Ther. 2008 Summer;9(2):83-93.
    Pharmacokinetics of buprenorphine following intravenous and oral transmucosal administration in dogs.
    Click here to access the PubMed abstract of this article.
Stability of Compounded Pergolide

Pituitary pars intermedia dysfunction (PPID) is the most common endocrine disorder in equine species.The most life-threatening clinical sign of PPID is laminitis, which is thought to be related to cortisol and other hormonal effects on glucose utilization by tissues of the hoof wall.

An integral part of PPID management is medical treatment.The most widely used drug is the dopamine agonist, pergolide. Unfortunately, pergolide was withdrawn from the human market in 2007 due to cardiovascular side effects in people. Pressured by the American Veterinary Medical Association, the American Association of Equine Practitioners, and thousands of horse owners in May 2007, the Food and Drug Administration decided to allow compounding of pergolide for horses utilizing the bulk chemical active pharmaceutical ingredient.As a result of this milestone decision, compounding pharmacists began providing various compounded dosage forms of pergolide for horses with PPID.Most horse owners prefer to utilize flavored oral suspensions of pergolide.This dosage form allows for both increased palatability to the patient, increased compliance by the horse owner, and allows for flexibility in dosage adjustment until an effective dosage is determined.Unfortunately, pergolide was never commercially available in a liquid oral dosage form.Commercial availability was limited to the tablet dosage form and until recently, no information was available to support the stability of a liquid dosage form of pergolide. In February 2009, researchers at the NC State College of Veterinary Medicine published results of a long-term stability study for aqueous suspensions of pergolide.In this study, pergolide was compounded into an aqueous formulation with a final target concentration of 1 mg/mL. Aliquots of the formulation were then stored at –20°, 8°, 25°, or 37°C without exposure to light or at 25°C with exposure to light for 35 days. Samples were assayed in triplicate by means of high-pressure liquid chromatography immediately after compounding and after 1, 7, 14, 21, and 35 days of storage.Results showed that samples exposed to light while stored at 25°C had undergone excessive degradation by day 14, samples stored at 37°C had undergone excessive degradation by day 21, and samples stored at 25°C without exposure to light had undergone excessive degradation by day 35. The decrease in expected concentration corresponded with the appearance of degradation peaks in chromatograms and with a change in color of the formulation.In light of these results, researchers concluded that compounded pergolide formulations in aqueous vehicles should be stored in a dark container, protected from light, and refrigerated and should not be used > 30 days after produced. It is also recommended that pharmacists and veterinarians do not add any excipients which would prevent an owner from detecting a color change in pergolide formulations.Formulations that have undergone a color change should be considered unstable and discarded. The results of this study should allow veterinarians and our compounding pharmacists to collaborate to provide more accurate control of this devastating equine disease.

  1. J Am Vet Med Assoc 2009;234:385–389
    Compounding and Storage Conditions on Stability of Pergolide Mesylate.
    Click here to access the abstract of this article.
Sugar-Free Medications For Horses with EMS

The term “equine metabolic syndrome” (EMS) has been adopted to describe a collection of clinical signs that contribute to the development of laminitis in horses, and has previously been described as peripheral equine Cushing’s syndrome, pseudo-Cushing’s syndrome, hypothyroidism, and insulin resistance syndrome. Causes of EMS are similar to those found to cause metabolic syndrome and insulin resistance in humans. Management and prevention of EMS primarily revolves around weight control and prevention of obesity. While there is no “cure” for EMS, there exist many supportive therapies including vitamin and mineral supplements, low starch feeds, and anti-inflammatory and analgesic medications. While the horse feed industry has quickly realized the need for sugar-free feeds, any change in drug formulation requires FDA approval, so the veterinary drug industry has not been able to respond quickly to the need for sugar-free medications and supplements for horses.

Our compounding pharmacy can contribute significantly to the care of EMS horses by working with veterinarians to convert all medications and supplements to sugar-free dosage forms. Sugar-free powders and pastes of phenylbutazone, flunixin, pergolide, and vitamins are particularly valuable to veterinarians treating horses with EMS.

Pergolide for Equine Cushing’s Disease

Pergolide has proven to be a safe and effective therapy in long term management of equine Cushing’s disease. The American Association of Equine Practitioners (AAEP) has been working with the FDA to develop options to provide veterinarians with continued access to pergolide to treat equine Cushing’s patients. FDA has indicated willingness to utilize regulatory discretion to allow compounding pharmacists to provide pergolide compounded from the bulk substance until a manufactured source of pergolide can be made available.

  1.  J Vet Intern Med. 2002 Nov-Dec;16(6):742-6.
    Treatment with pergolide or cyproheptadine of pituitary pars intermedia dysfunction (equine Cushing’s disease).
    Click here to access the PubMed abstract of this article.
Electrolyte Paste to Restore Fluid and Acid Base Balance in Horses

“Prolonged exercise in horses, particularly when performed in hot and humid conditions, brings about large fluid and electrolyte loses which, if not restored, may impair thermoregulatory responses and result in hyperthermia.” In horses, administration of oral rehydration solutions (ORS) is problematic, because many horses refuse to drink fluids containing electrolytes. Therefore, administration of ORS typically requires placement of a nasogastric tube with its inherent risks. An alternative is to give a concentrated electrolyte mixture as a paste. Leon et al. of Department of Veterinary Clinical Sciences, University of Sydney, NSW, Australia studied six Thoroughbred geldings to determine “whether oral administration of a concentrated electrolyte paste would promote the restoration of fluid, electrolyte, and acid base balance as well as fluid and electrolyte deficits induced by furosemide administration” (a standard model which induces significant contraction of plasma volume and consistent electrolyte deficit against which the effects of treatment could be measured).
“As a general conclusion, horses that received concentrated electrolytes [and had free access] to water consumed more water, regained more weight, lost considerably less electrolytes in urine, and maintained plasma electrolyte concentrations and acid base balance closer to baseline values than did those that had ad libitum access to water only.” Administration of electrolyte paste provided a more practical source than supplementation using feed or salt blocks.

  1. Am J Vet Res 1998 Jul;59(7):898-903
    Effects of concentrated electrolytes administered via a paste on fluid, electrolyte, and acid base balance in horses.
    Click here to access the PubMed abstract of this article.
Progesterone for Estrus Induction in Mares

According to Robert R. Foss, DVM, progesterone in sesame oil, 150 mg per day, IM is equally as efficacious as altrenogest. The optimal formulation is the combination of progesterone and estradiol 17-beta; the addition of estradiol provides a greater feedback than progesterone alone, so cessation produces a more dramatic response. The estradiol is somewhat protective against exacerbation of endometritis. Dr. Foss commonly uses this combination at 150 mg progesterone and 10 mg estradiol 17-beta, IM, daily for 10 days. Estrus will usually begin in 6-8 days with ovulation around day 10-12. This combination has been effective in situations where altrenogest has failed.

114th IL VMA Proceedings, February, 1996

Prednisone (Oral) Ineffective in Horses

Jackson et al. compared the effects of prednisone with environmental management to environmental management alone for the treatment of heaves (recurrent airway obstruction), and reported that oral prednisone has no additional benefit.1

To be effective, oral prednisone must be absorbed and metabolized to its active form prednisolone. Robinson et al. designed a study with two objectives:  1) to compare oral prednisone with intravenous dexamethasone for the treatment of horses with heaves; and 2) to measure serum prednisolone levels in horses after oral administration of prednisone and prednisolone. Each of five horses received five drug formulations (prednisone and prednisolone in tablet and liquid form, as well as intravenous prednisolone sodium succinate as a positive control, all at a dose of 2.2 mg/kg) in a Latin square design study. Severity of airway obstruction was measured, and there were no significant differences between prednisone administration and no medication at any time. Prednisolone was detectable in serum immediately after intravenous administration, peaking at around 1000 ng/ml at 12 min. Oral administration of prednisolone tablets or liquid yielded peak serum prednisolone concentrations of 377-1032 ng/ml at 30-45 min. When horses received oral prednisone tablets or liquid, prednisolone never reached detectable levels in the serum. The authors concluded, “In order for the drug prednisone to be effective after oral administration it must be absorbed from the gastrointestinal tract and converted to the active drug prednisolone by the liver. Although trace serum levels of prednisone were detected, prednisolone never appeared in the serum. Our data do not allow us to determine if prednisone is poorly absorbed, rapidly excreted, or not converted to prednisolone by the liver. However, it is clear that prednisone is unlikely to have any anti-inflammatory effect when administered by mouth. Oral administration of prednisolone is likely to be beneficial because it is rapidly absorbed and achieves serum levels close to those that result from intravenous administration.”2

Robert N. Oglesby, DVM (The Horseman’s Advisor, www.horseadvice.com) reports his reaction to hearing the above presentation at the November, 2000 meeting of the American Association of Equine Practitioners: “I was shocked and looking around me hundreds of other vets were also: oral prednisone doses are in every equine medicine text with many descriptions of its indications. Why has no one noticed the lack of effect before now? The reason is simple: no one believed it was possible that [prednisone] was not effective [in horses]. Its usefulness in other species was too well established… we did not even question its use. Looking back on it, it was the management changes that were responsible for the clinical improvement…”

  1. 1Equine Vet J 2000 Sep;32(5):432-8
  1. 2 AAEP Proceedings, Vol. 46, 2000, pp. 266-267
  1. Equine Vet J. 2002 May;34(3):283-7
    Prednisone per os is likely to have limited efficacy in horses.
    Click here for access to the PubMed abstract.

We can compound prednisolone into the most appropriate dosage form, including oral pastes or “chewies” that horses will love!

Pentoxifylline

In horses, a dose of 8.5 mg/kg orally two times daily is recommended for reducing the cytokine effects in endotoxemia. For the treatment of navicular disease, 6 g/day orally for 6 weeks should be used.

Anti-Diarrheals for Foals & Horses

Treatment of diarrhea should always be based on establishing a diagnosis and correcting the basic cause. Anti-diarrheal products are not a substitute for adequate fluid and electrolyte therapy when dehydration or shock threatens. When the veterinarian deems anti-diarrheal therapy is appropriate, the following options may be considered.

According to James L. Becht, D.V.M., M.S., Diplomat ACVIM, preparations containing bismuth subsalicylate seem superior to those containing kaolin, pectin, or activated charcoal for treating the foal with diarrhea. Bismuth subsalicylate neutralizes bacterial toxins, has some antibacterial activity, and may exert an antisecretory effect. It can be administered at a dosage of 4 oz q 6h; darkened feces will result. If no effect is seen within 48 hours, continued administration is probably not indicated. (105th Ohio VMA).

Wendy E. Vaala, V.M.D., Diplomate ACVIM reports (ACVIM 16th Veterinary Medical Forum) that delayed gastric emptying and gastroduodenal dysmotility can be improved  in some foals with  metoclopramide (0.25-0.6 mg/kg, PO q4-6h), erythromycin (1.0-2.0 mg/kg  PO q6h), or cisapride (10 mg/kg PO q6h). If colic, ileus, and gastric reflux are present, Dr. Vaala recommends an abdominal sonogram to rule out the presence of an intussusception prior to initiating prokinetic therapy. Diarrhea may be treated symptomatically with bismuth subsalicylate (1-2 ml/kg, PO, q4-6h) and may also respond to psyllium administration. Intestinal probiotics containing Lactobacillus bacteria … may be given to foals receiving antibiotics to help reestablish intestinal flora.

Adult horses may be treated with bismuth subsalicylate 1 oz per 8 kg of body weight PO TID-QID (Clark and Becht 1987).

Compendium 23(7), July 2001, 603-4

Headshaking in Horses

may include additional signs such as nose rubbing, striking at the nose with the forelegs, or active avoidance of light, warmth, or wind on the face. Newton et al studied 20 mature horses with typical headshaking of 2 week to 7 year duration, and concluded that the etiopathology may be a trigeminal neuritis or neuralgia. In 12 of 20 horses, drug therapy was initiated. Cyproheptadine (CP) alone was ineffective but the addition of carbamazepine (CM) resulted in 80-100% improvement in 80% of cases within 3 to 4 days of beginning drug therapy. Seven cases were treated with a combination of CM (4 mg/kg, three to four times daily) and CP (0.2-0.5 mg/kg  every 12 to 24 hours).

Carbamazepine alone has been effective in 88% of cases. Some headshaking horses have responded well to CM doses of 1.6 – 2.4 grams every six hours without apparent side effects. Horses are treated for 10 to 20 days and if they respond, the treatment is discontinued. If clinical signs of headshaking recur, treatment is restarted. In practice, there is a realistic possibility of controlling but not curing headshaking with carbamazepine therapy at the present time. Other studies have reported that cyproheptadine alone was beneficial in more than two thirds of treated horses.

  1. Equine Vet J  2000 May;32(3):208-16
    Headshaking in horses: possible aetiopathogenesis suggested by the results of diagnostic tests and several treatment regimes used in 20 cases.
    Click here for access to the PubMed abstract.
  1. Equine Vet J Suppl 1998 Nov;(27):28-9
    Characterisation of headshaking syndrome–31 cases.
    Click here for PubMed abstract.
  1. J Am Vet Med Assoc  2001 Aug 1;219(3):334-7
    Owner survey of headshaking in horses.
    Click here for access to the PubMed abstract. 
  1. ISU Vet Med  Sept 2000 
  1. The Pennsylvania State University Veterinary News, Dec 2000, pp 9-10
  1. Aust Vet J. 1991 Jul;68(7):221-4
    Use of phenytoin to treat horses with Australian stringhalt
    Click here for access to the PubMed abstract.

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Avian

Doxycycline Administered in Drinking Water for Treatment of Spiral Bacterial Infection in Birds

Spiral bacteria have been found in various portions of the respiratory tracts of cockatiels and lovebirds.  Common signs of infection with this bacterium include red clogged nares, sneezing, reddened and blunted choanal papillae and pharyngeal redness. Infected birds may also show signs of lethargy, anorexia and weight loss. Conjunctivitis, sinusitis and periorbital swelling may also be noted but are less common signs.  A survey of 148 cockatiels seen by a veterinary practice in New York indicated that 37 (25%) were found to be infected with spiral bacteria with most of these having clinical signs of upper respiratory tract infection and red choana. The infection rate was higher in birds <2yrs old and in birds fed poor diets, suggesting that spiral bacteria are opportunistic organisms that cause clinical signs in young and compromised birds.

Spiral bacterial infections in cockatiels have been successfully treated with oral administration of doxycycline hyclate at 25mg/kg orally every 12 hours for 3 weeks. However, this regimen requires twice-daily capture and forced administration of doxycycline liquid suspension, which is apparently not palatable to birds. The stress caused by this regimen to both birds and owners caused researchers at the North Carolina State University College of Veterinary Medicine to determine the feasibility of administering doxycycline via drinking water.  A group of 11 cockatiels naturally infected with spiral bacteria were offered solutions of doxycycline at 400mg per liter as the sole source of drinking water and 7 other naturally infected cockatiels acted as the control group receiving untreated tap water as the sole source of drinking water for a treatment period of 30 days.  For the first 14 days, spiral bacteria were isolated from all 18 birds in both the treatment and control group, but after day 21, spiral bacteria were no longer seen in the treatment group.

For this study, doxycycline drinking water was prepared by emptying the contents of 4 x 100 mg doxycycline hyclate capsules into a liter of deionized water and stirring with a magnetized stirrer for 4 minutes and made fresh every 24-36 hours.  As most bird owners do not have magnetic stirrers at home, and as the doxycycline hyclate capsules contain excipients other than doxycycline that do not go into solution and settle out at the bottom of the drinking bowl, our compounding pharmacy can provide bird owners with a more efficient method of doxycycline hyclate delivery by preparing 400mg capsules or packets of pure doxycycline hyclate, which the owner can stir into a 1 liter bottle of sterile water for irrigation (eliminating the possibility of contamination as well as preventing any binding of doxycycline by cations in tap water). It is interesting to note that doxycycline monohydrate is more palatable than doxycycline hyclate, but unfortunately, doxycycline monohydrate is not soluble in water and would not be a useful salt for this method of drug administration.

  1. J Am Vet Med Assoc. 2008 Feb 1;232(3):389-93
    Administration of doxycycline in drinking water for treatment of spiral bacterial infection in cockatiels.
    Click here to access the PubMed abstract of this article.
Antifungal Therapy for Avian Species

In avian species, the most frequent causes of infection have shifted from gram-negative bacteria to gram-positive bacteria and Candida (often non-albican) species. There is a decreased susceptibility of many non-albicans species to available antifungal drugs, perhaps as a consequence of nondiscriminate azole use.

The efficacy of terbinafine has been improved when administered in combination with azoles for treatment of azole resistant oral candidiasis and aspergillosis. Because terbinafine was administered successfully in an African gray parrot at 15 mg/kg every 12 hours for 30 days without adverse effects, it may have potential for use in systemic aspergillosis in these azole-sensitive species. Caution should be used in avian patients with liver or renal disease.

  1. Veterinary Clin North Am Exot Anim Pract. 2003 May;6(2):337-50, vi
    Antifungal drug therapy in avian species.
    Click here to access the PubMed abstract of this article.
Treatment of a Systemic Fungal Infection in a Parrot with Itraconazole Flavored Suspension and Nebulized Clotrimazole

Submitted by Michael Briggs, Pharm.D.

A Solomon Island Eclectus parrot, female aged 1.5 years, presented in a weakened state. Examination and culture revealed a systemic Aspergillus infection. Due to its significant cost as well as concern for the pet, the owner was highly motivated to treat the parrot.

Treatment posed a challenge because the parrot only eats brightly-colored foods, and there was no commercially available clotrimazole solution for nebulization for veterinary use. The veterinarian contacted the local compounding pharmacy to discuss how compounded medications might help solve this therapeutic dilemma. It was decided that an oral suspension flavored with equal parts orange, banana, and strawberry could mask the bitter flavor of itraconazole, and that a customized dosage (20mg/ml) could be compounded for the parrot. The veterinarian also prescribed clotrimazole 1% for nebulization.

The owner administered 0.2ml (4mg) of itraconazole suspension to the bird each day by mouth using an oral syringe. Therapy continued for three months. Clotrimazole 1% solution was nebulized (1ml BID to TID) by placing a pediatric nebulizer mask over the cooperative bird’s head. After 30 days, the bird still had a productive cough. Therefore, nebulizer therapy with clotrimazole continued after total resolution of signs and symptoms of infection, for a total of four months (one month after the oral itraconazole was finished).

The parrot fully recovered. This case represented the pharmacy’s first attempt at avian therapy, and was 100% successful. The same therapy was used later for another bird that also fully recovered from a systemic Aspergillus infection.

Enrofloxacin in Birds

Enrofloxacin is highly active against most gram-negative bacteria. Doses of 15 mg/kg orally twice daily have maintained effective drug concentrations in most of the psittacine species that have been tested. Senegal parrots have required TID dosing for moderately resistant organisms. Keven Flammer, DVM, Dip ABVP, reports successful treatment of E coli, Klebsiella, and Proteus infections. He states that oral administration is well tolerated, but that IM administration should be avoided, and never used for repeated dosing, due to irritation at the site of injection. The IM formulation can be given orally but is unpalatable, even when mixed with flavoring. Dr. Flammer notes that an oral suspension can be compounded and appropriately flavored.

  1. 10th U Wisc Exotic Pet Conf Procd 04:01
    The Capsule Report, Small Animal/Exotic Edition Jan 2002;20, 10: page 3
Haloperidol for Feather-Plucking and Self-Mutilation

Neuropeptides, particularly dopamine, are implicated in many self-mutilating disorders. The 1993 Proceedings of the Association of Avian Veterinarians (pg. 119-120) reports the dopamine antagonist  haloperidol is currently being used on cockatiels, lovebirds, ring-neck parakeets, African Greys, and several species of cockatoos and Amazon parrots.  The indications for use in these birds have included severe feather plucking, mutilation of skin and muscle over the back, chest and legs, wing web mutilation, and Amazon foot necrosis syndrome.  Side effects from the use of haloperidol have included depression, depressed appetite, excitability and anorexia. (In most birds, side effects disappeared after discontinuing the drug for several days and then retrying at a lower dose.)  One study reported normal behavior was maintained “by administering haloperidol at approximately 0.4 mg/kg body weight/day for approximately seven months.”

  1. Journal of Small Animal Practice 1993; 34:564-566
    Treatment of psychogenic feather picking in birds with a dopamine antagonist.
Haloperidol for Feather Plucking

by Stacie Fowler, D.V.M., Texas

Signalment:  “Echo”, adult male Eclectus Parrot

Chief Complaint:  Feather picking of 4-6 years duration

Diagnosis:  Previous veterinarian had done numerous tests in 1993 to rule out medical causes of feather picking and the final diagnosis was psychological behavioral feather picking.

Feather Picking:  This is a common syndrome in pet “parrot-type” birds that can have medical and/or psychological causes. It is  important to rule out all medical causes of this condition before initiating psychotropic drug therapy. It is also important to institute appropriate dietary and environmental changes as well as behavioral therapy along with psychotropic drug use.

Past History and Medications:  Echo first started picking at his feathers in 1991.  By November of 1994 he had pulled out all his feathers except those which he could not reach on his head. In December of 1994, Echo’s previous veterinarian started him on naltrexone (dose unknown) for behavioral feather picking. He failed to respond to this drug and was placed in an Elizabethan collar on 4/20/95 to prevent further plucking.  The author first saw this patient on 1/10/97. He had been wearing the collar almost constantly since 4/95 and all his feathers were in place (but ragged and unkempt looking) except under the collar. Anytime the collar was removed the patient would rip his feathers out.  The owners wished to try Prozac? for Echo’s problem but since this author has had little success with Prozac?, we started trials on other drugs. Along with changes in diet and environment and behavioral exercises, we started Echo on Aventyl? elixir at 1/4 teaspoon per 4 ounces of drinking water to be replaced with fresh twice daily. We also initiated every other daily misting of the feathers with a dilute Aloe and Penetran? suspension. By 3/8/97, Echo was still plucking too many feathers when the collar was removed.  To his Aventyl? therapy, we added naltrexone compounded to 5 mg/ml in a strawberry flavored base, 0.16 ml by mouth twice daily. By 3/20/97 he was still plucking badly when the collar was removed.

The Aventyl and naltrexone were discontinued and we did a brief trial on diazepam 2 mg per 4 ounces of drinking water. The diazepam is not meant to sedate and the owner was instructed to increase the dose to a maximum of 10 mg per 4 ounces of water if feather plucking continued but only if no sedation was noted. The diazepam produced no change in behavior and caused too much sedation for Echo.  On 4/10/97 we began a trial on haloperidol 2 mg/ml at .015 ml by mouth once daily. The owners were instructed that they could increase the dose to maximum of .06cc of 2 mg/ml haloperidol twice daily. By 5/7/97, Echo’s owners reported that they were giving .075 cc of 2 mg/ml haloperidol twice daily and he seemed to be responding nicely. On 5/17/97 the haloperidol was refilled and compounded to 1 mg/ml to facilitate easier measuring.  As of 9/2/98, Echo is receiving haloperidol 0.15 mg by mouth twice daily. This is a higher dose than I have seen published in the literature but the owners are pleased with Echo’s condition and do not wish to try a lower dose or even possibly wean him off the haloperidol. Echo is not experiencing any noticeable side effects from his haloperidol therapy. Currently, Echo never wears his Elizabethan collar and is totally feathered in except for his neck. I believe that 2 years of constant pressure from the collar has caused atrophy of the feather follicles around the neck.

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Miscellaneous

Low Dose Anti-platelet Therapies for Feline Arterial Thromboembolism (FATE)

Feline hypertrophic cardiomyopathy (HCM) is the most common form of heart disease in cats and is characterized by concentric thickening of the left ventricle. The clinical consequences of ventricular hypertrophy include arrhythmias, congestive heart failure, and feline aortic thromboembolism (FATE).  FATE carries an extremely poor prognosis with a 66% mortality rate.  The formation of aortic clots in FATE leads to paralysis, severe leg pain and, often, death.  There is no cure for HCM; hypertrophy of the heart wall is irreversible.  Therapies demonstrating benefit to HCM patients include beta-blockers, diuretics, ACE inhibitors, and antiplatelet drugs.  Because systemic warfarin therapy is associated with a high occurrence of hemorrhagic events, aspirin has historically been utilized as the primary oral antiplatelet therapy to prevent FATE in cats with HCM. It was initially dosed at 81mg every 72 hours as this was the smallest commercially available dosage form of aspirin. A study in 2003 revolutionized low dose aspirin therapy in cats through utilization of a compounded 5mg aspirin capsule administered orally every 72 hours. Results of this study indicated that the same degree of antiplatelet activity was achieved but the inhibition of endothelial production of prostacyclin (PGI), an antagonist to platelet aggregation and vasoconstriction, is not affected with the 5mg dose as is seen with the 81mg dose. This study also demonstrated a lower incidence of gastrointestinal adverse effects with the 5mg dose when compared to the 81mg dose of aspirin.
Clopidogrel (Plavix™) has been shown to be more effective than aspirin in preventing myocardial infarction, stroke and peripheral vascular events in humans. Clopidogrel has recently been evaluated in cats and has been shown to significantly inhibit multiple platelet functions. Investigators concluded that a low dose of 18.75mg of clopidogrel (1/4 of a commercially available 75mg tablet) given orally once daily was safe and effective anti-platelet therapy for cats.  Investigators also commented that a considerably lower compounded dose of clopidogrel may prove to be as effective, safer, and considerably less expensive than quartering the commercially available tablets and recommended that studies be performed with lower doses of clopidogrel as were done with aspirin in 2003. Some veterinary teaching hospitals are utilizing doses of 6mg and 7mg clopidogrel orally once daily in combination with low dose aspirin therapy although the efficacy of these therapeutic regimens have not been evaluated.  The multi-centric Feline Arterial Thromboembolism – Clopidogrel vs. Aspirin Trial (FAT-CAT) initiated at Purdue University College of Veterinary Medicine has been accepting FATE cats for enrollment for the last two years to determine if there is clinical superiority of either agent when prophylaxing against recurrence of FATE.  Initial results show a significant (41.6%) reduction of FATE recurrence in one of the two treatment groups; however, study coordinators will not unblind the treatment arms to investigators until the full enrollment of 30 cats per treatment group is achieved. Clinicians interested in learning more about the FAT-CAT study should visit http://www.vin.com/FATCAT/    Veterinarians interested in exploring use of low dose aspirin and low dose clopidogrel therapy can collaborate with our compounding pharmacists regarding formulation of patient-specific doses.

  1. J Vet Intern Med 2003;17:73-83
    Arterial thromboembolism in cats: acute crisis in 127 cases (1992-2001) and long-term management with low-dose aspirin in 24 cases.
    Click here to access the abstract of this article.
  1. J Am Vet Med Assoc 2004;225:1406–1411
    Antiplatelet effects and pharmacodynamics of clopidogrel in cats.
    Click here to access the PubMed abstract of this article.
  1. Cornell University and NC State University
Prednisone versus Prednisolone:  Which drug for which species?

While prednisone and prednisolone have historically been considered therapeutically equivalent when used in veterinary medicine, recent studies have proven that they are not.  It is now well-accepted in veterinary medicine that while prednisone and prednisolone may be therapeutically equivalent in dogs and humans, they are not in cats and horses.  Researchers Graham-Mize and Rosser administered 10 mg total dose of either prednisone or prednisolone to cats in order to determine comparative pharmacokinetics of each drug. The AUC (ng/ml/hr) and Cmax (ng/ml) of oral prednisolone was 5 fold and 11 fold higher following administration of prednisolone compared to an equivalent oral dose of prednisone: 3230 and 1400, respectively, following oral prednisolone compared to 672.63 and 122, respectively following oral prednisone. Although the study was not designed to discriminate differences in oral absorption versus hepatic conversion, the authors nonetheless demonstrate the superiority of oral prednisolone to prednisone in cats.  Until further studies are conducted, most veterinary clinicians agree that prednisolone (not prednisone) should be utilized in feline patients.

In 2002, researchers had demonstrated a superiority of prednisolone over prednisone in treating horses with recurrent airway obstruction (heaves). In this crossover study, 5 horses were given the following treatments: prednisone tablets, prednisone liquid, prednisolone tablets, prednisolone liquid and i.v. prednisolone sodium succinate (positive control). Blood samples were taken before drug administration and at selected time points during a 24 hour period. Serum concentrations of prednisone and prednisolone were determined in order to evaluate gastrointestinal absorption and hepatic metabolism. Serum concentrations of the endogenous glucocorticoid hydrocortisone were also determined as an indicator of the biological activity of the drugs. Both prednisolone tablets and liquid were absorbed rapidly, with prednisolone detectable in serum within 15 min of administration and with peak concentrations occurring within 45 min. Small amounts of prednisone were detected in the serum samples after administration of both prednisone tablets and liquid. The active metabolite prednisolone was not detected in serum samples after administration of prednisone liquid and was detected in serum samples from only one horse after administration of prednisone tablets. Endogenous hydrocortisone production was suppressed when horses received prednisolone. The results of these studies indicate that prednisone has poor efficacy for the treatment of heaves because it is poorly absorbed and the active metabolite prednisolone is rarely produced. In contrast, prednisolone tablets have excellent bioavailability and should be useful as a therapeutic agent in horses.

Consult our compounding pharmacist about customized dosage forms and strengths. Caution: Transdermal application of prednisolone (or other corticosteroids) to the ear is not recommended due to a high likelihood of epidermal atrophy of the ear pinnae with chronic use.  The ear tips will flop with time and may not return to normal shape even after withdrawal of the prednisolone.

  1. Veterinary Dermatology 15 (s1) 2004, pp 10.
    Bioavailability and activity of prednisone and prednisolone in the feline patient.
    Click here to access the PubMed abstract of this article.
  1. Equine Vet. J. 2002 May;34(3):283-7
    Prednisone per os is likely to have limited efficacy in horses.
    Click here to access the PubMed abstract of this article.
Safety and Efficacy of Ocular vs Parenteral Apomorphine for Induced Emesis in Dogs

A study published in October 2008 retrospectively evaluated the efficacy of a compounded 2mg ocular insert of apomorphine versus a compounded 1mg/ml apomorphine injection. Either parenteral or ocular apomorphine dosage forms were sent to veterinary clinics with a case study report form requesting case-specific information. Information collected included breed, body weight, time from placement of the insert until emesis, and any information available regarding the nature of the toxin and clinical signs. Clinicians were asked to grade the severity of adverse effects on a subjective scale of 0 to 5, with 5 being most severe and 0 being absent. The adverse effects listed included prolonged vomiting, tachycardia, excitation, respiratory depression, bradycardia, sedation, and ocular irritation. Hypotension was not specifically included because of the difficulty of monitoring this while treating the dog. The clinician was also asked to grade the ease of product use for each case. Case reports for more than 5000 dogs were ultimately reviewed.
For the ocular insert group, approximately 67% of dogs developed emesis between 3 and 10 minutes following placement of the insert. Approximately 83% of the dogs had emesis within the 15-minute time interval. Median time to emesis was 6 minutes, 7.2% of dogs experienced emesis after 15 minutes, and 9.3% did not have emesis at all. When the drug was administered IV, emesis occurred rapidly with a success rate of 90.6% and a median time to emesis of 1 minute. Difference in success rate between the IV and ocular insert groups was not significant (p=0.399).
The prevalence of adverse effects with the IV route was less than the ocular route; however, the prevalence of tachycardia and sedation were higher with the IV group. Tachycardia was detected in 0.6% of dogs treated with the ocular insert and 15.6% of those treated IV. In the ocular insert group, sedation occurred with a frequency of 11.1%, whereas the IV group had a frequency of 43.8%. For the ocular insert group, ocular irritation in 82% of dogs was also reported, but of these, 80% had severity scores of 1, which meant detected but not clinically relevant. If reports with a score of 1 were disregarded, the frequency of irritation decreased to 16.2%. In 6.3% of dogs, the clinician experienced some difficulty with use of the insert, either in placing the insert or in maintaining the insert in the conjunctival sac; and some dogs actively resisted placement of the insert while other dogs were successful in dislodging the insert once it had been placed, leading to discontinuous administration. The ease of use scores seemed to become better with time, suggesting that with experience, the clinicians became more skilled in using the inserts.
Researchers also observed that dogs weighing more than 25kg seemed less responsive to a 2mg ocular dose of apomorphine. Researchers concluded that an insert with a larger quantity of apomorphine should be utilized for larger dogs and that safeguards should be employed to prevent administration of larger dose inserts to smaller dogs.
Apomorphine has not been commercially available to veterinarians for several years. For this reason, compounding pharmacists have been supplying apomorphine to veterinarians in various dosage forms to have immediately available for emergency use. Dosage forms include compressed tablets, powders for reconstitution into ocular or injectable solutions, and injectable solutions for parenteral administration.  In light of the results of this study, it would appear that compounded ocular solutions might be superior to either injections or solid ocular tablets or inserts. Kits can be prepared containing apomorphine that can be reconstituted for use as an isotonic ophthalmic solution and subsequently can be administered as an injection if emesis is not successfully induced after ophthalmic administration. Veterinarians interested in obtaining these dosage forms or kits may contact our compounding pharmacy.

  1. Am J Vet Res. 2008 Oct;69(10):1360-5.
    Safety and efficacy of an ocular insert for apomorphine-induced emesis in dogs.
    Click here to access the PubMed abstract of this article.
Pyridostigmine Oral Liquid for Treatment of Myasthenia Gravis

Myasthenia gravis (MG) is a common cause of generalized weakness in dogs and cats. With optimal care, the prognosis for remission and a normal life are good. “Unfortunately, drugs used to diagnose and treat myasthenia gravis are frequently unavailable” but during manufacturer shortages, compounding pharmacists can provide needed medications.1

The drug used most commonly to treat MG is pyridostigmine bromide at a dose of 1-3 mg/kg orally two to three times daily. “It is extremely important to note, however, that pyridostigmine bromide should not be compounded with methylcellulose-containing vehicles, as methylcellulose has been shown to completely inhibit the oral absorption of pyridostigmine from the gastrointestinal tract.2 For animals not responding to pyridostigmine, corticosteroids (e.g., prednisone for dogs, prednisolone for cats) can be administered at 0.5 mg/kg orally every other day. Immunosuppressive doses of corticosteroids are not recommended as they may worsen muscle weakness.”3

  1. 1,3 International Journal of Pharmaceutical Compounding. Sep/Oct 2008; 12(5):398-401
    Veterinary Compounding for Myasthenia Gravis
    Click here to access the abstract of this article.
  1. 2 Neurology 1981; 31(2):145-149.
Compounding for Feline Lymphoma

Feline lymphoma is one of the most common cancers in cats and presents with a variety of lesions and symptoms. Feline lymphoma, like human lymphoma, is classified into low, medium and high-grade categories depending on the anatomic location and degree of malignant cell growth in affected organs. There are many clinical reports published describing the diagnosis, treatment and prognosis of cats with lymphoma; however, there has been little correlation between treatment, histologic grade and clinical outcome. Until 1999 there had only been one published study that followed treatment and outcomes for a group of cats with intestinal lymphoma.1Of 40 cats evaluated, 29 cats with low-grade lymphoma in this study had a significantly greater response (69%) to medical therapy (chlorambucil and prednisone) and underwent complete remission with a medical survival time of greater than 20.5 months.The 11 cats in the high-grade group (treated with a variety of multiple drug combinations) showed a much poorer response to therapy.

A retrospective study reviewed 667 cases of feline lymphoma and identified cats suffering from low-grade lymphoma.2This study concluded that 92% of cats treated with chlorambucil and prednisone responded to treatment for more than 2.5 years and showed a disease-specific median survival time of 967 days.Both of these studies indicate that the combination of oral chlorambucil and prednisone are excellent treatment modalities for cats suffering from low-grade lymphoma.

The dosage range for prednisone or prednisolone for treatment of feline lymphoma is 5-10mg daily. In spite of the success demonstrated by treatment with prednisone in the previously mentioned studies, recent pharmacokinetic work indicates that prednisolone has a much better oral bioavailability (i.e., higher levels of drug in the body) as compared to prednisone in cats.3 Veterinarians may find that providing prednisolone instead of prednisone with chlorambucil may further increase remission rates and survival times in cats with lymphoma. Both prednisolone and chlorambucil are extremely bitter drugs and many cats object strongly to the taste. By collaborating with veterinarians and pet owners, our compounding pharmacist can play an active role in providing palatable, individualized oral chemotherapeutic regimens of prednisolone and chlorambucil for cats with lymphoma.

  1. 1 Eur J Comp Gastroenterol 1999;4:5–11.
    Feline gastrointestinal lymphoma: 67 cases (1988–1996).
    Click here for more information.
  1. 2 J Am Vet Med Assoc. 2008 Feb 1;232(3):405-10.
    Outcome of cats with low-grade lymphocytic lymphoma: 41 cases (1995–2005)
    Click here to read the PubMed abstract of this article.
  1. 3 VetDermatology. 2004; 15 (Suppl. 1):9.
    Bioavailability and activity of prednisone and prednisolone in the feline patient.
    Click here for more information.
Managing Tracheal Collapse in Toy and Miniature-breed Dogs

Collapsing trachea is a commonly recognized problem with toy and miniature-breed dogs (e.g., Toy Poodles, Yorkshire Terriers, Pomeranians, Maltese, Chihuahuas) that is associated with weakness of the tracheal cartilage resulting in collapse of the airway.Tracheal collapse can sometimes be helped with surgery, but medical management remains the treatment of choice. Treatment strategies involve cough suppression, and the drug therapy of choice has historically been the combination of hydrocodone and homatropine used orally three to four times daily.As long as shortages of commercially available hydrocodone/homatropine products continue, our pharmacy can play a valuable role in providing compounded hydrocodone/homatropine oral suspensions, capsules and chewable treats in canine-friendly flavors for dogs with tracheal collapse.

  1. Vet Clin North Am Small Anim Pract. 2000 Nov;30(6):1253-66, vi.
    Tracheal collapse. Diagnosis and medical and surgical treatment.
    Click here to read the PubMed abstract of this article.
Cetirizine Pharmacokinetics in Cats

While chronic dosing studies and safety and efficacy studies in allergic cats still need to be conducted, that the pharmacokinetic profile of cetirizine suggests that it is a promising alternative to glucocorticoid therapy in allergic cats. Presently, commercially available forms of cetirizine are not easily adjusted to cats. Cetrizine tablets for adult humans are 10mg tablets and could be halved to achieve an appropriate dose for a 5kg cat.Cetrizine products labeled for human children are available in 5mg chewable grape-flavored tablets or a 1mg/ml grape-flavored syrup. Because of the flavoring and the volume of liquid that would have to be administered, cetirizine products labeled for human children would be very difficult to administer to cats.

Commercially-available cetirizine dosage forms are not particularly cat-friendly, and because cetirizine shows much promise for therapy of allergies in cats, veterinarians may wish to contact our compounding pharmacy to assist in preparing dosage forms of cetrizine that can be easily administered to cats.

  1. Am J Vet Res. 2008 May;69(5):670-4.
    Pharmacokinetics of cetirizine in healthy cats.
    Click here to read the PubMed abstract of this article.
Aspirin Therapy for Cats

A retrospective study in cats receiving high dose aspirin (> or = 40 mg/cat q72h) and cats receiving low-dose aspirin (5 mg/cat q72h) showed equally efficacious anti-platelet effect in either group but a significantly lower incidence of adverse effects in the low dose aspirin group.

Capsules containing 5mg of aspirin can be compounded in lactose, flavored with various powdered flavors. Pet owners can administer the capsules intact, or if the act of pilling is too stressful for the cat, the contents of the capsule can be sprinkled in a small amount of moist food for the cat to consume at will.

Clinical effects and plasma concentrations of fentanyl after transmucosal administration in three species of great ape.

“fentanyl can be administered transmucosally to captive orangutans and gorillas for sedation. With further study on formulation, it may also become useful in chimpanzee protocols. The transmucosal route may also be clinically useful for acute pain management.”

  1.  J Zoo Wildl Med. 2004 Jun;35(2):162-6
    Clinical effects and plasma concentrations of fentanyl after transmucosal administration in three species of great ape.
    Click here to access the PubMed abstract of this article.
Emergency Emetic Kits for Canine Drug Units

Canine members of police departments are frequently trained to detect drugs and other illicit substances. Although training techniques are now being modified to avoid ingestions, most dogs were historically trained to aggressively paw, mouth, or bite any object that was suspect. This behavior greatly increases the risk of oral ingestion of these very potent, very dangerous drugs.  Veterinarians are now offering training and emergency emetics to police officers so that they may provide life-saving decontamination measures.  Compounding pharmacists can work with local police and veterinarians to provide emesis kits to ensure that these valuable public servants are afforded the best chance for survival when faced with an accidental ingestion.

  1. JAVMA, 2006 Apr 1;228(7):1028-32
    Toxicologic hazards for police dogs involved in drug detection.
Efficacy of oral supplementation with L-lysine in cats latently infected with feline herpesvirus

Maggs et al. of the College of Veterinary Medicine, University of Missouri examined the effects of orally administered L-lysine on clinical signs of feline herpesvirus type 1 (FHV-1) infection and ocular shedding of FHV-1 in latently infected cats. Fewer cats and eyes were affected by conjunctivitis, and onset of clinical signs of infection was delayed on average by 7 days in cats receiving L-lysine 400 mg once daily for 30 days, compared with cats in the control group. Significantly fewer viral shedding episodes were identified in the treatment group cats, compared with the control group cats. This dose caused a significant but short-term increase in plasma L-lysine concentration without altering plasma arginine concentration or inducing adverse clinical effects.

  1. Am J Vet Res 2003 Jan;64(1):37-42
    Efficacy of oral supplementation with L-lysine in cats latently infected with feline herpesvirus.
    Click here to access the PubMed abstract of this article.
Dextromethorphan

Of the seven major human cough suppressants, only dextromethorphanis indicated for treating cough in small animals. If after reviewing the indications and contraindications, cough suppression is desired, the available human products must be screened carefully as a very limited number contain dextromethorphan without other potentially harmful ingredients. Typically, the dose in dogs and cats is 1 to 2 mg/kg three to four times daily. Human products are not flavored to an animals taste, and may require administering a significant volume (typical strength is 15 mg/5 ml) to adequately dose an average size dog.

Stool Softeners

Docusate (DSS) can be used to assist in the passage of hard or dry feces that may occur secondary to dehydration or use of opioid analgesics or metoclopramide. While capsules hide the bitter taste, they can not be divided for appropriate dosing in smaller animals. The recommended dose in dogs and cats is 2 mg/kg once daily. For more severe cases, appropriately dosed DSS enemas may offer an alternative to phosphate-solution enemas.

Merck Veterinary Manual, 8th Edition, pp. 1691

Ursodiol for Gallstones

The purpose of this study, reported in Am J Health-Syst Pharm (Vol. 52) was to prepare an oral dosage form of the bile acid ursodiol (also known as ursodeoxycholic acid) from commercially available capsules and to determine the short-term stability of this formulation.  The formula used for this extemporaneous compound was found to be stable for up to 35 days.

Ursodiol in a Dog with Chronic Hepatitis

A dog with severe cholestasis secondary to chronic hepatitis was treated with ursodeoxycholic acid (ursodiol) orally. After 2 weeks of daily treatment, the dog was more active and had an improved appetite. Monthly serum biochemical determinations and analysis of individual bile acid profiles documented improvement in hepatobiliary tests and a marked reduction in the concentrations of potentially hepatotoxic endogenous bile acids. These effects were maintained for approximately 6 months.

Studies have found an extemporaneously compounded ursodiol suspension to be stable for up to 35 days refrigerated. This drug is well absorbed orally and enters the liver directly from the portal system, and is then secreted into bile. Ursodiol should be administered orally as the first-pass effect is vital for effectiveness.

  1. J Vet Intern Med 1997 May-Jun;11(3):195-7
    Use of ursodeoxycholic acids in a dog with chronic hepatitis: effects on serum hepatic tests and endogenous bile acid composition.
    Click here to access the PubMed abstract of this article.
Aminocaproic Acid for Degenerative Myelopathy (DM) in Dogs

DM appears with relative frequency only in the German Shepherd breed (GSD); confirmation of the diagnosis is important in other breeds before assuming that they have DM of GSD. During the past two decades, R.M. Clemmons, DVM, Ph.D., and other researchers at the University of Florida have provided important new insights into the pathoetiology of DM. Recently, they have found that when combined with the history, neurologic signs, CSF protein concentration and EMG, an elevated CSF acetylcholinesterase level helps confirm the diagnosis. It is increasingly clear that DM is caused by an autoimmune disease attacking the nervous systems of patients, leading to progressive neural tissue damage. In many respects, DM is similar to Multiple Sclerosis in human beings.

The Integrative Medical Approach to Treatment of Degenerative Myelopathy involves four basic approaches: 1) exercise, 2) dietary supplementation, 3) medication, 4) other supportive measures. Conventional medicine has little to offer patients with DM. On the other hand, use of exercise, certain vitamins and selected drugs have delayed or prevented progression of DM in many afflicted dogs.

Clemmons et al have found 2 medications which appear to prevent progression or result in clinical remission of DM in up to 80% of patients – aminocaproic acid (EACA) and n-acetylcysteine (NAC). They propose that circulating immune-complexes lead to endothelial cell damage in the vessels of the CNS. Subsequently, fibrin is deposited in the perivascular spaces. When this degrades (point of action of aminocaproic acid), inflammatory cells are stimulated to migrate into the lesions. The inflammatory cells release prostaglandins and cytokines (point of action of vitamin E and C) which lead to the activation of tissue enzymes and the formation of oxygen free-radicals (point of action of acetylcysteine) which, in turn, leads to tissue damage.They recommend giving EACA as a flavored solution, 500 mg orally every 8 hours. A “source for EACA is to have a compounding pharmacy make the solution from chemical grade EACA.”  The only side effects that have been attributed to EACA have been occasional gastrointestinal irritation. This has presented a problem only in a few patients, typically those with pre-existing GI problems. The only known drug interaction is with high dose estrogen compounds.

N-Acetylcysteine is a potent anti-oxidant which has powerful neuroprotective effects. Clemmons et al give 75 mg/kg divided in 3 doses a day for 2 weeks; then, 3 doses every other day. The N-acetylcysteine must be diluted to a 5% solution; otherwise, it will cause stomach upset. “This new treatment is expensive unless purchased through compounding pharmacies.” NAC can produce vomiting (due to the sodium content of the pharmaceutical product, which requires high concentration of base to buffer) and may increase the bleeding time. Giving fresh ginger 30 minutes before NAC or administering NAC with food (or on a full stomach) often reduces this effect.

The chances of successful treatment are improved if the therapy is begun early in the course of DM rather than later. A response to the drugs should be evident within the first 7-10 days.

Chlorpromazine for Anti-Emesis

Chlorpromazine (Thorazine®) is a phenothiazine and works at the emetic center, the chemoreceptor trigger zone, and peripheral receptors; it is this veterinarian’s “all purpose anti-emetic of choice” for cats.1 Chlorpromazine may cause extrapyramidal symptoms in cats when administered at high doses. The drug may discolor urine pink or red-brown, cause mild sedation, and may potentiate hypotension in dehydrated patients. Phenothiazines should not be given within one month of worming with an organophosphate agent. The recommended oral doses in dogs and cats is 3.3 mg/kg PO one to four times daily. Due to extensive first pass metabolism2, it may be necessary to reduce the dose in animals with liver disease. A liquid concentrate can be appropriately flavored for dogs or cats.

1Todd R. Tams, DVM, Dip ACVIM in CA VMA C/E Conf Procd, 2000
2Veterinary Drug Handbook 3rd edition, Donald C. Plumb, ed.;  pp. 129-30

Managing Anorexia in Uremic Dogs and Cats

H2-receptor antagonists (cimetidine, ranitidine, and famotidine) can be useful to reduce gastric acid secretion. Increased gastrin concentrations in serum during chronic renal failure may stimulate excessive secretion of gastric acid and cause ulcer formation. Some uremic dogs and cats dramatically increase their interest in food and food intake after therapy with an H2 blocker. According to a presentation at the Atlantic Coast Veterinary Conference by Dennis J. Chew, DVM, Dip and C.A. Buffington, DVM, some uremic animals may need this medication for an extended period of time (months to rest of their lives). Much of the experience of these veterinarians has been either with cimetidine at an initial dose of 10 mg/kg, followed by 5 mg/kg PO BID or famotidine at 1 mg/kg daily.

The Capsule Report, Vol. 19, No. 10, Jan. 2001

Doxycycline for Prophylaxis and Treatment of Osteoarthritis in Dogs

Prophylactic administration of doxycycline (a tetracycline) has markedly reduced the severity of canine osteoarthritis (OA) in weight-bearing regions of the medial femoral condyle, and therapeutic administration of oral doxycycline has been shown to reduce the severity of articular cartilage breakdown in various animal models of OA. This disease modifying effect is associated with reductions in the levels of active and total collagenase and gelatinase in articular cartilage of the involved joint.

A prospective, clinical study of eighty-one dogs with OA secondary to spontaneous cranial cruciate ligament (CCL) rupture concluded that doxycycline inhibits nitric oxide production in cartilage in dogs with CCL rupture, and that doxycycline may have a role in the treatment of canine OA. Dogs with OA secondary to CCL rupture were divided into 2 groups before surgery. The Doxy-CCL group (n = 35) received 3 to 4 mg/kg doxycycline orally every 24 hours for 7 to 10 days. The CCL group (n = 46) received no treatment. Synovial fluid, articular cartilage, synovial membrane, and CCL samples were collected during surgery or immediately after euthanasia from healthy dogs (control group). Total nitric oxide concentrations measured in cartilage were significantly lower in the Doxy-CCL group than in the CCL group, but were not different from those measured in the control group.

In another study, ten healthy adult mongrel dogs underwent transection of the left anterior cruciate ligament, which resulted in a marked decrease in bone mass, with increased osteoclastic activity and increased bone formation. Doxycycline treatment did not significantly affect either bone formation or bone resorption. The authors concluded that doxycycline protects against joint breakdown in this OA model via inhibition of matrix metalloproteinases in articular cartilage, rather than through an effect on subchondral bone.

  1. Vet Surg 2001 Mar-Apr;30(2):132-9
    The effects of doxycycline on nitric oxide and stromelysin production in dogs with cranial cruciate ligament rupture.
    Click here to access the PubMed abstract of this article.
  1. J Rheumatol 1996 Jan;23(1):137-42
    Effects of oral doxycycline administration on histomorphometry and dynamics of subchondral bone in a canine model of osteoarthritis.
    Click here to access the PubMed abstract of this article.
  1. J Rheumatol Suppl 1995 Feb;43:149-51
    Modification by oral doxycycline administration of articular cartilage breakdown in osteoarthritis.
    Click here to access the PubMed abstract of this article.
  1. Vet Clin North Am Small Anim Pract 1997 Jul;27(4):863-81
    Slow-acting, disease-modifying osteoarthritis agents.
    Click here to access the PubMed abstract of this article.
  1. Arthritis Rheum 1992 Oct;35(10):1150-9
    Effect of stanozolol on body composition, nitrogen balance, and food consumption in castrated dogs with chronic renal failure.
    Click here to access the PubMed abstract of this article.
Cisapride: a Prokinetic Drug

Cisapride (Propulsid® - Janssen Pharmaceutica), was removed from the U.S. and Canadian markets by its manufacturer because of serious cardiac effects in humans. However, cisapride is now available as a bulk chemical for veterinary use only and can be compounded as per your prescription order.

Cisapride is chemically related to metoclopramide, but unlike metoclopramide, it does not cross the blood-brain barrier or have antidopaminergic effects or cause extrapyramidal reactions. Cisapride “is more potent and has broader prokinetic activity than metoclopramide, increasing the motility of the colon, esophagus (in cats and guinea pigs), stomach, and small intestine… [Cisapride] has been used in managing gastric stasis, idiopathic constipation, gastroesophageal reflux, and postoperative ileus in dogs and cats. Practitioners found cisapride especially useful in managing chronic constipation in cats with megacolon; in many cases, it alleviated or delayed the need for subtotal colectomy. Cisapride was also used in managing cats with hairball problems.”

“Cisapride appeared to be well tolerated by dogs and cats. Adverse reactions to cisapride have not been reported to the United States Pharmacopeia’s Veterinary Practitioners’ Reporting Program… Disorders of GI motility are common and frustrating clinical problems in dogs and cats. Cisapride, with its extensive prokinetic action, was a welcome addition to veterinary medicine.”

“Life after cisapride: Prokinetic drugs for small animals.” Patricia M. Dowling, DVM, MS, DACVIM, DACVCP    Veterinary Medicine, September 2000, pp. 678-685

Doses:
Dogs -
As a promotility agent: initially 0.5mg/kg three times daily
To reduce regurgitation associated with megaesophagus: 0.55mg/kg  orally one to three times daily, no less than 30 minutes before feeding.
As an antiemetic: 0.1-0.5mg/kg orally every 8 hours.

Cats -
For chronic constipation: initially, 2.5mg (for cats up to 10#) or 5mg
(cats 11-15#), or up to 7.5mg (for cats over 16#) three times daily, 30
minutes before food, in combination with stool softener and bulk agent.

Cisapride is contraindicated in patients in whom increased GI motility could be harmful (e.g., perforation, obstruction, GI hemorrhage). Absorption of other orally-administered drugs may be affected. Cisapride may enhance anticoagulants’ effects; additional monitoring and anticoagulant dosage adjustments may be required. Cisapride may enhance the sedative effects of benzodiazepines. Clients should be advised to monitor the animal and report any adverse effects.

Veterinary Drug Handbook, 3rd edition, Donald C. Plumb, editor. pp. 139-140

Hairball Remedy

Cat and ferret owners continually search for specialized foods and treats that their pets will readily consume and will also be effective for hairball prevention or elimination. Call us for a customized, flavored hairball remedy for your patients!

Stanozolol

In a study conducted at the Animal Health Unit and Gastrointestinal Sciences, University of Calgary, Alberta, ten healthy, intact, adult male sled dogs received either stanozolol tablets, 2 mg/dog PO, q12h, for 25 days or an intramuscular injection of stanozolol 25 mg on Days 7, 14, 21, and 28. A 15N amino acid (5.27 mmol) was infused intravenously into each dog on Day 0 (before stanozolol treatment) and on Day 31 (after stanozolol treatment). Both oral and injectable stanozolol resulted in significant increases in amino acid nitrogen retention compared to pretreatment values. Oral stanozolol increased nitrogen retention from 29.2 +/-8.2% to 50.3 +/- 9.2%, while stanozolol injection increased nitrogen retention from 26.6 +/- 9.9% to 67.0 +/- 7.5%. The nitrogen retention action of stanozolol may be beneficial in dogs under stress of surgical trauma and chronic disease.

In a separate blinded crossover trial at the College of Veterinary Medicine, Kansas State University, 22 castrated Beagles with experimentally induced chronic renal failure were treated with stanozolol. Cowan et al. concluded that for dogs with mild-to-moderate, nonuremic, experimentally induced, chronic renal failure, stanozolol had positive effects on nitrogen balance and lean body mass. Stanozolol did not have a significant effect on body fat, bone mineral content, or food consumption per kilogram of body weight.

Anabolic steroids such as stanozolol have been used to treat geriatric dogs. These drugs can increase nitrogen and mineral retention so that the body can better utilize dietary protein. As a result, the dog’s appetite may improve, resulting in more strength, energy, and weight gain. There is one reported case of the use of stanozolol (0.5 mg/kg, SQ, BID, PRN) to stimulate appetite in a rabbit. However, this class of drugs is not without potentially serious side-effects which must be considered before using them. Anabolic steroids should be used with caution in animals with heart, liver, or kidney problems, or in animals with breast or prostate cancer. Stanozolol should not be used in pregnant animals, during lactation, in young animals, or in male breeding animals. Anabolic steroids may increase the effects of warfarin and other anticoagulants.

In dogs, reported side effects are mainly androgenic, including increased aggression, increased activity, weight gain and mood alterations. However, in cats with and without chronic renal failure, there are reported cases of hepatotoxicity that appear to be related to the use of stanozolol.

  1. J Am Vet Med Assoc. 1997 Sep 15;211(6):719-22
    Effect of stanozolol on body composition, nitrogen balance, and food consumption in castrated dogs with chronic renal failure.
    Click here to access the PubMed abstract of this article.
  1. Can J Vet Res. 2000 Oct;64(4):246-8
    The effect of stanozolol on 15nitrogen retention in the dog.
    Click here to access the PubMed abstract of this article.
  1. Veterinary Forum. April 1999
    Effect of stanozolol on body composition, nitrogen balance, and food consumption in castrated dogs with chronic renal failure.
    Click here to access the PubMed abstract of this article.
Managing Tracheal Collapse Patients

Collapsing trachea is a commonly recognized disease of toy and miniature-breed dogs. Treatment strategies involve cough suppression, and the drug therapy of choice has historically been hydrocodone.

As long as shortages of commercially available hydrocodone/homatropine products continue, our pharmacy can play a valuable role in providing compounded hydrocodone/homatropine oral suspensions, capsules and chewable treats for tracheal collapse patients. While the ingredient homatropine may not play a significant role as a cough suppressant for dogs, inclusion of homatropine greatly discourages human abuse of hydrocodone by virtue of its anticholinergic side effects.We can compound as a canine-friendly flavor (e.g. liver).

  1. Vet Clin North Am Small Anim Pract. 2000 Nov;30(6):1253-66, vi.
    Tracheal collapse. Diagnosis and medical and surgical treatment.
    Click here to access the PubMed abstract of this article.
Compounding for Feline Lymphoma

Feline lymphoma is one of the most common cancers in cats and presents with a variety of lesions and symptoms resulting from various cell types, degrees of dissemination and rate of progression.Recent studies have shown cats treated with chlorambucil and prednisone responded to treatment for more than 2.5 years. Recent pharmacokinetic work indicates that prednisolone has a much better oral bioavailability as compared to prednisone in cats. Both prednisolone and chlorambucil are extremely bitter drugs and many cats object strongly to the taste. By collaborating with veterinarians and pet owners, our compounding pharmacist can play an active role in providing palatable, individualized oral chemotherapeutic regimens of prednisolone and chlorambucil for cats with lymphoma.

Eur J Comp Gastroenterol 1999;4:5–11.

  1. JAVMA, February 1, 2008; 232(3):405-410.
    Outcome of cats with low-grade lymphocytic lymphoma: 41 cases (1995–2005)
    Click here to access the PubMed abstract of this article.
  1. Veterinary Dermatology 15 (s1) 2004, page 10
Mirtazapine for Appetite Stimulation in Dogs and Cats

Mirtazapine (Remeron™-Organon) is approved as an antidepressant for use in humans and has activity both as an alpha2 receptor antagonist and as a potent 5HT3 antagonist.A side effect noted in humans taking this drug is appetite stimulation. Pharmacy faculty at the Mississippi State College of Veterinary Medicine used mirtazapine in a dog after all other attempts at appetite stimulation had failed, and were very pleased to find that mirtazapine restored appetite almost immediately in this dog.In another case, a physician used mirtazapine to treat anorexia and nausea in his Boston Terrier with chronic renal failure. Due to the vast improvement in the animal’s quality of life for one month preceding its death, the dog’s primary care veterinary clinic conducted a series of uncontrolled field trials using mirtazapine over the next 4 years in 24 dogs and 17 cats with GI symptoms that were marginally responsive or refractory to standard remedies. “Mirtazapine therapy led to a robust response in 12 animals, improvement compared with standard treatment in 16 cases, and an equivocal response in 13 animals. The most vigorous responses were observed in patients in chronic renal failure or receiving concurrent chemotherapy for neoplastic disease.”

Many veterinarians have started using mirtazapine to stimulate appetite in both dogs and cats.There have been no controlled studies and dosing is still empirical, but most dogs are dosed at 0.6mg/kg orally every 24 hours and cats are dosed at 3.75mg/cat orally every 48-72 hours. The terminal half-life of mirtazapine in humans is more than 40 hours, and mirtazapine is eliminated partially through conjugation with glucuronide. For this reason, dosing intervals of less than 48 hours are not recommended for cats, as accumulation is likely. Mirtazapine is not commercially available in an oral suspension; however, compounding pharmacists have formulated suspensions upon the request of veterinarians and have anecdotally reported success with this dosage form. For cats that are vomiting as well as anorectic and cannot swallow or retain oral medications, veterinarians have instructed compounding pharmacists to formulate transdermal gels of mirtazapine (3.75mg/0.1ml), which also have left veterinarians with a positive impression of clinical efficacy. Obviously, further studies are needed to determine stability, safety and efficacy of these compounded dosage forms, but until such evidence is available, veterinarians may wish to try these dosage forms in cases that are refractory to traditional methods of appetite stimulation.

Veterinary Forum, February 2006, pages 34-36

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