558 Small Animal/Exotics

Compendium June 2001

PHARM PROFILE

Email comments/questions to compendium@medimedia.com or fax 800-556-3288

AMLODIPINE
Rebecca Montgomery Arnold, PharmD Campbell University Buies Creek, North Carolina mlodipine, a dihydropyridine calcium-channel blocker, is commonly used to treat hypertension. The drug is long acting, vasoselective, and structurally related to nifedipine. Unlike other calcium antagonists, amlodipine has a high volume of distribution, low elimination rate, and prolonged half-life.

ter dosing).2 Pharmacokinetic studies have not been reported in cats, but oral administration in healthy cats does not result in hypotension, tachycardia, or any other adverse effects.3,4 In a recent study,5 average daily systolic blood pressure measurements suggested that the duration of action in cats is at least 24 hours. Amlodipine is slowly and almost completely absorbed from the gastrointestinal tract without regard to food. The drug undergoes extensive hepatic metabolism in humans; therefore, it is not recommended in cats with liver dysfunction.3

in humans treated with amlodipine are edema, dizziness, fatigue, and heart palpitations.10 No adverse effects, including hypotension, tachycardia, weight loss, or fatigue, were reported in cats3,5; some owners even reported improvement in their pets attitudes, appetites, and activity levels during treatment.3

PHARMACOLOGY Amlodipine inhibits the movement of calcium ions across the cell membrane. The drug decreases heart rate and has negative inotropic effects on the cardiovascular system. The overall effect is peripheral vasodilation, which results in reduced blood pressure. The major mechanism of action of calcium antagonists is a reduction in vascular smooth muscle tone. This is achieved by interfering with the excitationcontraction coupling process, which is dependent on intracellular calcium transport.1 In contrast to other dihydropyridines, amlodipine has a long plasma half-life (35 hours in humans; 30 hours in dogs) and high oral bioavailability (63% in humans; 88% in dogs) and can be given as once-daily treatment because of the slow onset of peak concentrations (3 to 8 hours af-

INDICATIONS Amlodipine is used to treat systemic hypertension in cats (defined as systolic pressure greater than 160 mm Hg and diastolic pressure greater than 100 mm Hg).6,7 Systemic hypertension in cats is usually secondary to hyperthyroidism or chronic renal failure. In patients with hyperthyroidism, treatment and maintenance of the hyperthyroid state are essential in the management of the hypertension. Amlodipine has been shown to cause the release of nitric oxide from blood vessels, consequently resulting in vasodilation.8 The drug also preserves left ventricular volume and function during healing after reperfused myocardial infarction in dogs.9 CAUTIONS The most common adverse effects

Use in Pregnancy Amlodipine is considered a pregnancy category C drug: Insignificant data exist to determine whether it can be safely administered to pregnant animals. No teratogenicity occurred when pregnant rats and rabbits were treated with up to 10 mg/kg PO of amlodipine during their respective periods of organogenesis. This is roughly 8 to 23 times the maximum recommended human dose based on mg/m2. Pregnant patients should only be treated when the benefit of treatment outweighs the risk.10 Acute Toxicity Single doses of 40 mg/kg in mice and 100 mg/kg in rats caused deaths. In dogs, a single dose of 4 mg/kg or higher caused marked peripheral vasodilation and hypotension. In cases of overdose, breathing and blood pressure should be monitored frequently. If hypotension is unresolved, vasopressors and intravenous calcium gluconate can be administered to reverse the effects of calcium entry blockade.10

Compendium June 2001

Small Animal/Exotics 559

Client Counseling Information

I Amlodipine is a safe, effective medication for reducing blood pressure in cats and dogs but must be administered exactly as prescribed. I This medication can be given once daily without regard to meals. I Cats given amlodipine must undergo periodic ophthalmic examinations to detect retinal lesions, a common complication of systemic hypertension. I Adverse reactions (e.g., weight loss, fatigue, lethargy, tachycardia) should be reported to the veterinarian immediately.

PO should be administered. The drug can be given without regard to meals. Blood pressure must be checked periodically to ensure the cat is not hypotensive. Cats given amlodipine must undergo routine ophthalmic examinations to check for retinal lesions. Usually referred to as hypertensive retinopathy, these lesions can be characterized by hemorrhage, detachment, and retinal edema.11

DRUG INTERACTIONS Administration of amlodipine in healthy individuals with thiazide diuretics, angiotensin-converting enzyme inhibitors, nitrates, sublingual nitroglycerin, NSAIDs, antibiotics, blockers, and oral hypoglycemic drugs has resulted in no drugdrug interactions.10 DOSAGE AND ADMINISTRATION The recommended dose of amlodipine in cats is 0.3125 to 0.625 mg/day PO.3 In dogs, a dose of 0.1 to 1 mg/kg/day

PREPARATIONS Amlodipine besylate, which is not labeled for veterinary use, is available as Norvasc (Pfizer, New York) in strengths of 2.5-, 5-, and 10-mg tablets at a cost of about $0.63/2.5 mg.10 Because of the difficulty of splitting or quartering the tablets, it is often necessary to compound amlodipine into capsules containing either 0.3125 or 0.625 mg. Lactose has been found to be a suitable diluent. STORAGE AND HANDLING Amlodipine should be stored at a controlled room temperature of 59F to 86F (15C to 30C) and dispensed in tight, light-resistant containers.10 REFERENCES
1. Burges R, Moisey D: Unique pharmacological properties of amlodipine. Am J Cardiol 73:2A9A, 1994.

(continues on page 587)

Compendium June 2001

Equine 587

Amlodipine (continued from page 559)

2. Stopher DA, Beresford AP, Macrae PV, Humphrey MJ: The metabolism and pharmacokinetics of amlodipine in humans and animals. J Cardiovasc Pharmacol 12:S55S59, 1988. 3. Henik RA, Snyder PS, Volk LM: Treatment of systemic hypertension in cats with amlodipine besylate. JAAHA 33:226234, 1997. 4. Snyder PS: Evaluation of the antihypertensive agent amlodipine besylate in normotensive cats and a cat with systemic hypertension. J Vet Intern Med 53:11661169, 1994. 5. Snyder PS. Amlodipine: A randomized, blinded clinical trial in 9 cats with systemic hypertension. J Vet Intern Med 12:157162, 1998. 6. Henik RA: Diagnosis and treatment of feline systemic hypertension. Compend Contin Educ Pract Vet 19(2):163178, 1997. 7. Littman MP: Spontaneous systemic hypertension in 24 cats. J Vet Intern Med 8:986, 1994. 8. Zhang X, Hintze TH: Amlodipine releases nitric oxide from canine coronary microvessels: An unexpected mechanism of action of a calcium channel-blocking agent. Circulation 97:576580, 1998. 9. Jugdutt BI: Effects of amlodipine versus enalapril on left ventricular remodelling [abstract]. Can J Cardiol 13(10):945954, 1997. 10. Product information: Norvasc. New York, Pfizer, 2000. 11. Maggio F, DeFrancesco TC, Atkins CE, et al: Ocular lesions associated with systemic hypertension in cats: 69 cases (19851998). JAVMA 217(5):695702.