Veterinary Compounding - Cardiology

Veterinary: Cardiology/Hypertension

Amlodipine, atenolol, diltiazem, enalapril, and more are readily available for compounding at Phusion Pharmacy. Call one of our compounding pharmacists for details. 401-823-0000. (Download Rx Fax Form)

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 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.
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.
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
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).
Am J Vet Res 2002 Jun;63(6):833-9Effects of the calcium channel antagonist amlodipine in cats with surgically induced hypertensive renal insufficiency.
Click here to access the PubMed abstract of this article.
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.
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.
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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