Amlodipine Besylate
Amlodipine Besylate Prescribing Information
Amlodipine besylate tablets, USP are indicated for the symptomatic treatment of chronic stable angina. Amlodipine besylate tablets may be used alone or in combination with other antianginal agents.
Amlodipine besylate tablets, USP are indicated for the treatment of confirmed or suspected vasospastic angina. Amlodipine besylate tablets may be used as monotherapy or in combination with other antianginal agents.
In patients with recently documented CAD by angiography and without heart failure or an ejection fraction <40%, amlodipine besylate is indicated to reduce the risk of hospitalization due to angina and to reduce the risk of a coronary revascularization procedure.
The effective antihypertensive oral dose in pediatric patients ages 6 to 17 years is 2.5 mg to 5 mg once daily. Doses in excess of 5 mg daily have not been studied in pediatric patients
The antihypertensive efficacy of amlodipine besylate has been demonstrated in a total of 15 double-blind, placebo-controlled, randomized studies involving 800 patients on amlodipine besylate and 538 on placebo. Once daily administration produced statistically significant placebo-corrected reductions in supine and standing blood pressures at 24 hours postdose, averaging about 12/6 mmHg in the standing position and 13/7 mmHg in the supine position in patients with mild to moderate hypertension. Maintenance of the blood pressure effect over the 24-hour dosing interval was observed, with little difference in peak and trough effect. Tolerance was not demonstrated in patients studied for up to 1 year. The 3 parallel, fixed dose, dose response studies showed that the reduction in supine and standing blood pressures was dose-related within the recommended dosing range. Effects on diastolic pressure were similar in young and older patients. The effect on systolic pressure was greater in older patients, perhaps because of greater baseline systolic pressure. Effects were similar in black patients and in white patients.
Two hundred sixty-eight hypertensive patients aged 6 to 17 years were randomized first to amlodipine besylate 2.5 or 5 mg once daily for 4 weeks and then randomized again to the same dose or to placebo for another 4 weeks. Patients receiving 2.5 mg or 5 mg at the end of 8 weeks had significantly lower systolic blood pressure than those secondarily randomized to placebo. The magnitude of the treatment effect is difficult to interpret, but it is probably less than 5 mmHg systolic on the 5 mg dose and 3.3 mmHg systolic on the 2.5 mg dose. Adverse events were similar to those seen in adults.
Tablets 5 mg: White to off-white, round unscored tablets, debossed with “C46” on one side and plain on other side
Tablets 10 mg: White to off-white, round unscored tablets, debossed with “C47” on one side and plain on other side
Amlodipine besylate tablets are contraindicated in patients with known sensitivity to amlodipine besylate.
Because amlodipine besylate is extensively metabolized by the liver and the plasma elimination half-life (t1/2) is 56 hours in patients with impaired hepatic function, titrate slowly when administering amlodipine besylate to patients with severe hepatic impairment.
Co-administration of simvastatin with amlodipine besylate increases the systemic exposure of simvastatin. Limit the dose of simvastatin in patients on amlodipine besylate to 20 mg daily
After oral administration of therapeutic doses of amlodipine besylate, absorption produces peak plasma concentrations between 6 and 12 hours. Absolute bioavailability has been estimated to be between 64% and 90%. The bioavailability of amlodipine besylate is not altered by the presence of food.
Amlodipine besylate is extensively (about 90%) converted to inactive metabolites via hepatic metabolism with 10% of the parent compound and 60% of the metabolites excreted in the urine. Ex vivo studies have shown that approximately 93% of the circulating drug is bound to plasma proteins in hypertensive patients. Elimination from the plasma is biphasic with a terminal elimination half-life of about 30 to 50 hours. Steady-state plasma levels of amlodipine besylate are reached after 7 to 8 days of consecutive daily dosing.
The pharmacokinetics of amlodipine besylate are not significantly influenced by renal impairment. Patients with renal failure may therefore receive the usual initial dose.
Elderly patients and patients with hepatic insufficiency have decreased clearance of amlodipine besylate with a resulting increase in AUC of approximately 40 to 60%, and a lower initial dose may be required. A similar increase in AUC was observed in patients with moderate to severe heart failure.
Co-administered cimetidine, magnesium-and aluminum hydroxide antacids, sildenafil, and grapefruit juice have no impact on the exposure to amlodipine besylate.
CYP3A inhibitors: Co-administration of a 180 mg daily dose of diltiazem with 5 mg amlodipine besylate in elderly hypertensive patients resulted in a 60% increase in amlodipine besylate systemic exposure. Erythromycin co-administration in healthy volunteers did not significantly change amlodipine besylate systemic exposure. However, strong inhibitors of CYP3A (e.g., itraconazole, clarithromycin) may increase the plasma concentrations of amlodipine besylate to a greater extent
Impact of amlodipine on other drugs
Amlodipine besylate is a weak inhibitor of CYP3A and may increase exposure to CYP3A substrates. Co-administered amlodipine besylate does not affect the exposure to atorvastatin, digoxin, ethanol and the warfarin prothrombin response time.
Amlodipine may increase the systemic exposure of cyclosporine or tacrolimus when coadministered. Frequent monitoring of trough blood levels of cyclosporine and tacrolimus is recommended and adjust the dose when appropriate
After oral administration of therapeutic doses of amlodipine besylate, absorption produces peak plasma concentrations between 6 and 12 hours. Absolute bioavailability has been estimated to be between 64% and 90%. The bioavailability of amlodipine besylate is not altered by the presence of food.
Amlodipine besylate is extensively (about 90%) converted to inactive metabolites via hepatic metabolism with 10% of the parent compound and 60% of the metabolites excreted in the urine. Ex vivo studies have shown that approximately 93% of the circulating drug is bound to plasma proteins in hypertensive patients. Elimination from the plasma is biphasic with a terminal elimination half-life of about 30 to 50 hours. Steady-state plasma levels of amlodipine besylate are reached after 7 to 8 days of consecutive daily dosing.
The pharmacokinetics of amlodipine besylate are not significantly influenced by renal impairment. Patients with renal failure may therefore receive the usual initial dose.
Elderly patients and patients with hepatic insufficiency have decreased clearance of amlodipine besylate with a resulting increase in AUC of approximately 40 to 60%, and a lower initial dose may be required. A similar increase in AUC was observed in patients with moderate to severe heart failure.
Co-administered cimetidine, magnesium-and aluminum hydroxide antacids, sildenafil, and grapefruit juice have no impact on the exposure to amlodipine besylate.
CYP3A inhibitors: Co-administration of a 180 mg daily dose of diltiazem with 5 mg amlodipine besylate in elderly hypertensive patients resulted in a 60% increase in amlodipine besylate systemic exposure. Erythromycin co-administration in healthy volunteers did not significantly change amlodipine besylate systemic exposure. However, strong inhibitors of CYP3A (e.g., itraconazole, clarithromycin) may increase the plasma concentrations of amlodipine besylate to a greater extent
Impact of amlodipine on other drugs
Amlodipine besylate is a weak inhibitor of CYP3A and may increase exposure to CYP3A substrates. Co-administered amlodipine besylate does not affect the exposure to atorvastatin, digoxin, ethanol and the warfarin prothrombin response time.