Calcium Channel Blocker
Highlights Of Prescribing Information
• Calcium channel blocker used most often for treating hypertension, especially in cats
• Slight negative inotrope; use with caution in patients with heart disease, hepatic dysfunction
• Potentially may cause anorexia & hypotension in cats early in therapy
• Hypertension may rapidly reoccur if dosages are missed
What Is Amlodipine Besylate Used For?
Oral amlodipine appears to be a useful agent in the treatment of hypertension in cats and many consider it the drug of choice for this indication. In pharmacokinetic studies, amlodipine has decreased blood pressure in dogs with chronic renal disease, but its efficacy in treating hypertensive dogs has been disappointing.
Hypertension in cats is usually secondary to other diseases (often renal failure or cardiac causes such as thyrotoxic cardiomyopathy or primary hypertrophic cardiomyopathy, etc.) and is most often seen in middle-aged or geriatric cats. These animals often present with acute clinical signs such as blindness, seizures, collapse or paresis. A cat is generally considered hypertensive if systolic blood pressure is > 160 mmHg. Early reports indicate that if antihypertensive therapy is begun acutely, some vision maybe restored in about 50% of cases of blindness secondary to hypertension.
Pharmacology / Actions
Amlodipine inhibits calcium influx across cell membranes in both cardiac and vascular smooth muscle. It has a greater effect on vascular smooth muscle, thereby acting as a peripheral arteriolar vasodilator and reducing afterload. Amlodipine also depresses impulse formation (automaticity) and conduction velocity in cardiac muscle.
No feline-specific data on the drug’s pharmacokinetics was located. In humans, amlodipine’s bioavailability does not appear to be altered by the presence of food in the gut. The drug is slowly but almost completely absorbed after oral administration. Peak plasma concentrations occur between 6-9 hours post-dose and effects on blood pressure are correspondingly delayed. The drug has very high plasma protein binding characteristics (approximately 93%). However, drug interactions associated with potential displacement from these sites have not been elucidated. Amlodipine is slowly, but extensively metabolized to inactive compounds in the liver. Terminal plasma half-life is approximately 35 hours in healthy humans, but is prolonged in the elderly and in those patients with hypertension or hepatic dysfunction.
Before you take Amlodipine Besylate
Contraindications / Precautions / Warnings
Because amlodipine may have slight negative inotropic effects, it should be used cautiously in patients with heart failure or cardiogenic shock. It should also be used cautiously in patients with hepatic disease or at risk for developing hypotension. A relative contraindication for amlodipine exists for humans with advanced aortic stenosis.
There is concern that using amlodipine alone for treating hypertension in cats with renal disease may expose glomeruli to higher pressures secondary to efferent arteriolar constriction. This is caused by localized increases in renin-angiotensin-aldosterone axis activity thereby allowing progressive damage to glomeruli. It is postulated that using an ACE inhibitor with amlodipine may help prevent this occurrence ().
Because of amlodipine’s relatively slow onset of action, hypotension and inappetence is usually absent in cats. Infrequently, cats may develop azotemia, lethargy, hypokalemia, reflex tachycardia and weight loss. In humans taking amlodipine, headache (7.3% incidence) is the most frequent problem reported.
Reproductive / Nursing Safety
While no evidence of impaired fertility was noted in rats given 8X overdoses, amlodipine has been shown to be fetotoxic (intrauterine death rates increased 5 fold) in laboratory animals (rats, rabbits) at very high dosages. No evidence of teratogenicity or mutagenicity was observed in lab animal studies. In rats, amlodipine prolonged labor. It is unknown whether amlodipine enters maternal milk. In humans, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans.)
Overdosage / Acute Toxicity
There were 69 exposures to amlodipine reported to the ASPCA Animal Poison Control Center (APCC; www.apcc.aspca.org) during 2005-2006. In these cases 59 were dogs with 7 showing clinical signs; the remaining 10 cases were cats with 2 showing clinical signs. Common findings in dogs, recorded in decreasing frequency included anorexia, lethargy, tachycardia, acidosis and bradycardia. Common findings in cats, recorded in decreasing frequency included lethargy and polydipsia.
Limited experience with other calcium channel blockers in humans has shown that profound hypotension and bradycardia may result. When possible, massive overdoses should be managed with gut emptying and supportive treatment. Beta-agonists and intravenous calcium maybe beneficial.
How to use Amlodipine Besylate
Amlodipine Besylate dosage for cats:
For treatment of systemic hypertension:
a) 0.625 mg (1/4 of a 2.5 mg tablet) PO once daily; some larger cats (>4 kg) or those with severe hypertension may require doses as high as 1.25 mg PO twice daily. Titrate dosage carefully, based upon BP determinations. ()
b) 0.625-1.25 mg (total dose) PO once daily. Amlodipine Besylate of choice; often successful as a single agent. Can be combined with an ACEI, beta-blocker or diuretic if needed. Maximum effect seen within 7 days of therapy. ()
Amlodipine Besylate dosage for dogs:
For adjunctive therapy for refractory heart failure:
a) For treatment of advanced mitral valve degeneration as an afterload reducer after ACE inhibitor maintenance therapy has been established: 0.2-0.4 mg/kg PO twice daily. Initiate therapy at 0.1 mg/kg PO twice daily and uptitrate weekly while monitoring blood pressure. ()
b) As an arterial vasodilator particularly in dogs moderately refractory, or recurrent CHF secondary to mitral regurgitation and maintained blood pressures: 0.1 mg/kg ql2-24h initially; titrate up as needed to 0.25 mg/kg PO ql2-24h; monitor blood pressure. ()
For treatment of systemic hypertension in dogs with chronic renal disease:
a) 0.05-0.25 mg/kg PO once daily. In many dogs, amlodipine appears to be less effective, even at high doses (1 mg/kg/day). ()
b) 0.1-0.2 mg/kg PO ql2-24h ()
■ May give with food
■ Missing dosages can cause rapid redevelopment of symptoms and damage secondary to hypertension
Chemistry / Synonyms
Amlodipine besylate, a dihydropyridine calcium channel-blocking agent, occurs as a white crystalline powder that is slightly soluble in water and sparingly soluble in alcohol.
Amlodipine Besylate may also as: amlodipini besilas, UK-48340-26, or UK-48340-11 (amlodipine maleate); many trade names are available.
Storage / Stability
Store amlodipine tablets at room temperature, in tight, light resistant containers.
Dosage Forms / Regulatory Status
Veterinary-Labeled Products: None
The ARCI (Racing Commissioners International) has designated this drug as a class 4 substance. See the appendix for more information.
Amlodipine Tablets: 2.5 mg, 5 mg, 10 mg; Norvasc (Pfizer); Amvaz (Reddy); (Rx)
Fixed-dose combination products with benazepril (Lotrel) or atorvastatin (Caduet) are available.