Norvasc (Amlodipine Besylate) - Drug Interactions, Contraindications, Overdosage, etc

DRUG INTERACTIONS

Effect of other agents on NORVASC

CIMETIDINE: Co-administration of NORVASC with cimetidine did not alter the pharmacokinetics of NORVASC.

GRAPEFRUIT JUICE: Co-administration of 240 mL of grapefruit juice with a single oral dose of amlodipine 10 mg in 20 healthy volunteers had no significant effect on the pharmacokinetics of amlodipine.

MAALOX (antacid): Co-administration of the antacid Maalox with a single dose of NORVASC had no significant effect on the pharmacokinetics of NORVASC.

SILDENAFIL: A single 100 mg dose of sildenafil (Viagra®) in subjects with essential hypertension had no effect on the pharmacokinetic parameters of NORVASC. When NORVASC and sildenafil were used in combination, each agent independently exerted its own blood pressure lowering effect.

Effect of NORVASC on other agents

ATORVASTATIN: Co-administration of multiple 10 mg doses of NORVASC with 80 mg of atorvastatin resulted in no significant change in the steady-state pharmacokinetic parameters of atorvastatin.

DIGOXIN: Co-administration of NORVASC with digoxin did not change serum digoxin levels or digoxin renal clearance in normal volunteers.

ETHANOL (alcohol): Single and multiple 10 mg doses of NORVASC had no significant effect on the pharmacokinetics of ethanol.

WARFARIN: Co-administration of NORVASC with warfarin did not change the warfarin prothrombin response time.

In clinical trials, NORVASC has been safely administered with thiazide diuretics, beta-blockers, angiotensin-converting enzyme inhibitors, long-acting nitrates, sublingual nitroglycerin, digoxin, warfarin, non-steroidal anti-inflammatory drugs, antibiotics, and oral hypoglycemic drugs.

OVERDOSAGE

Single oral doses of amlodipine maleate equivalent to 40 mg amlodipine/kg and 100 mg amlodipine/kg in mice and rats, respectively, caused deaths. Single oral amlodipine maleate doses equivalent to 4 or more mg amlodipine/kg or higher in dogs (11 or more times the maximum recommended human dose on a mg/m² basis) caused a marked peripheral vasodilation and hypotension.

Overdosage might be expected to cause excessive peripheral vasodilation with marked hypotension and possibly a reflex tachycardia. In humans, experience with intentional overdosage of NORVASC is limited. Reports of intentional overdosage include a patient who ingested 250 mg and was asymptomatic and was not hospitalized; another (120 mg) was hospitalized, underwent gastric lavage and remained normotensive; the third (105 mg) was hospitalized and had hypotension (90/50 mmHg) which normalized following plasma expansion. A case of accidental drug overdose has been documented in a 19-month-old male who ingested 30 mg amlodipine (about 2 mg/kg). During the emergency room presentation, vital signs were stable with no evidence of hypotension, but a heart rate of 180 bpm. Ipecac was administered 3.5 hours after ingestion and on subsequent observation (overnight) no sequelae were noted.

If massive overdose should occur, active cardiac and respiratory monitoring should be instituted. Frequent blood pressure measurements are essential. Should hypotension occur, cardiovascular support including elevation of the extremities and the judicious administration of fluids should be initiated. If hypotension remains unresponsive to these conservative measures, administration of vasopressors (such as phenylephrine) should be considered with attention to circulating volume and urine output. Intravenous calcium gluconate may help to reverse the effects of calcium entry blockade. As NORVASC is highly protein bound, hemodialysis is not likely to be of benefit.

CONTRAINDICATIONS

NORVASC is contraindicated in patients with known sensitivity to amlodipine.