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Amlodipine, a dihydropyridinecalcium-channel blocker, is

commonly used to treat hy-pertension. The drug is long acting,vasoselective, and structurally relatedto nifedipine. Unlike other calciumantagonists, amlodipine has a highvolume of distribution, low elimina-tion rate, and prolonged half-life.

PHARMACOLOGYAmlodipine inhibits the movement

of calcium ions across the cell mem-brane. The drug decreases heart rate

and has negative inotropic effects onthe cardiovascular system. The overalleffect is peripheral vasodilation, whichresults in reduced blood pressure. Themajor mechanism of action of calci-um antagonists is a reduction in vas-cular smooth muscle tone. This isachieved by interfering with the exci-tationcontraction coupling process,

which is dependent on intracellularcalcium transport.1

In contrast to other dihydropy-

ridines, amlodipine has a long plasmahalf-life (35 hours in humans; 30hours in dogs) and high oral bioavail-ability (63% in humans; 88% indogs) and can be given as once-dailytreatment because of the slow onset ofpeak concentrations (3 to 8 hours af-

ter dosing).2 Pharmacokinetic studieshave not been reported in cats, butoral administration in healthy catsdoes not result in hypotension, tachy-cardia, or any other adverse effects.3,4

In a recent study,5 average daily sys-tolic blood pressure measurementssuggested that the duration of action

in cats is at least 24 hours.Amlodipine is slowly and almostcompletely absorbed from the gas-trointestinal tract without regard tofood. The drug undergoes extensivehepatic metabolism in humans; there-fore, it is not recommended in cats

with liver dysfunction.3

INDICATIONSAmlodipine is used to treat sys -

temic hypertension in cats (defined as

systolic pressure greater than 160 mmHg and diastolic pressure greater than100 mm Hg).6,7 Systemic hyperten-sion in cats is usually secondary to hy-perthyroidism or chronic renal failure.In patients with hyperthyroidism,treatment and maintenance of the hy-perthyroid state are essential in themanagement of the hypertension.

Amlodipine has been shown to causethe release of nitric oxide from bloodvessels, consequently resulting in va-

sodilation.8

The drug also preservesleft ventricular volume and functionduring healing after reperfused my-ocardial infarction in dogs.9

CAUTIONSThe most common adverse effects

in humans treated with amlodipineare edema, dizziness, fatigue, andheart palpitations.10 No adverse ef-fects, including hypotension, tachy-cardia, weight loss, or fatigue, were re-ported in cats3,5; some owners evenreported improvement in their petsattitudes, appetites, and activity levels

during treatment.

3

Use in PregnancyAmlodipine is considered a preg-

nancy category C drug: Insignificantdata exist to determine whether it canbe safely administered to pregnant an-imals. No teratogenicity occurred

when pregnant rats and rabbits weretreated with up to 10 mg/kg PO ofamlodipine during their respective pe-riods of organogenesis. This is rough-

ly 8 to 23 times the maximum rec-ommended human dose based onmg/m2. Pregnant patients should onlybe treated when the benefit of treat-ment outweighs the risk.10

Acute ToxicitySingle doses of 40 mg/kg in mice

and 100 mg/kg in rats caused deaths.In dogs, a single dose of 4 mg/kg orhigher caused marked peripheral va-sodilation and hypotension. In cases

of overdose, breathing and bloodpressure should be monitored fre-quently. If hypotension is unresolved,vasopressors and intravenous calciumgluconate can be administered to re-verse the effects of calcium entryblockade.10

Rebecca Montgomery Arnold, PharmDCampbell University

Buies Creek, North Carolina

P H A R M P R O F I L E

AMLODIPINE

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DRUG INTERACTIONSAdministration 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 nodrugdrug interactions.10

DOSAGE AND ADMINISTRATIONThe 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

PO should be administered. The drug can be given withoutregard to meals.

Blood pressure must be checked periodically to ensure thecat is not hypotensive. Cats given amlodipine must undergoroutine ophthalmic examinations to check for retinal le-

sions. Usually referred to as hypertensive retinopathy, theselesions can be characterized by hemorrhage, detachment,and retinal edema.11

PREPARATIONSAmlodipine besylate, which is not labeled for veterinary

use, is available as Norvasc (Pfizer, New York) in strengthsof 2.5-, 5-, and 10-mg tablets at a cost of about $0.63/2.5mg.10 Because of the difficulty of splitting or quartering thetablets, it is often necessary to compound amlodipine intocapsules containing either 0.3125 or 0.625 mg. Lactose hasbeen found to be a suitable diluent.

STORAGE AND HANDLINGAmlodipine should be stored at a controlled room tem-

perature of 59F to 86F (15C to 30C) and dispensed intight, light-resistant containers.10

REFERENCES1. Burges R, Moisey D: Unique pharmacological properties of amlodip-

ine.Am J Cardiol73:2A9A, 1994.

Compendium June 2001 Small Animal/Exotics 559

Client Counseling Information

I Amlodipine is a safe, effective medication forreducing blood pressure in cats and dogs but mustbe administered exactly as prescribed.

I

This medication can be given once daily withoutregard 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 theveterinarian immediately.

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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 ani-mals.J Cardiovasc Pharmacol12:S55S59, 1988.

3. Henik RA, Snyder PS, Volk LM: Treatment of systemic hyperten-sion in cats with amlodipine besylate.JAAHA33:226234, 1997.

4. Snyder PS: Evaluation of the antihypertensive agent amlodipine be-sylate in normotensive cats and a cat with systemic hypertension. JVet Intern Med53:11661169, 1994.

5. Snyder PS. Amlodipine: A randomized, blinded clinical trial in 9 cats

with systemic hypertension.J Vet Intern Med12:157162, 1998.6. Henik RA: Diagnosis and treatment of feline systemic hypertension.

Compend Contin Educ Pract Vet19(2):163178, 1997.7. Littman MP: Spontaneous systemic hypertension in 24 cats. J Vet

Intern Med8:986, 1994.8. Zhang X, Hintze TH: Amlodipine releases nitric oxide from canine

coronary microvessels: An unexpected mechanism of action of a cal-cium channel-blocking agent. Circulation97:576580, 1998.

9. Jugdutt BI: Effects of amlodipine versus enalapril on left ventricular

remodelling [abstract]. Can J Cardiol13(10):945954, 1997.10. Product information: Norvasc. New York, Pfizer, 2000.11. Maggio F, DeFrancesco TC, Atkins CE, et al: Ocular lesions associ-

ated with systemic hypertension in cats: 69 cases (19851998). JAVMA

217(5):695702.