Norvasc

NORVASC®
(amlodipine besylate) Tablets for oral administration


INDICATIONS
Hypertension
NORVASC® is indicated for the treatment of hypertension. It may be used alone or in combination with other antihypertensive agents.
Coronary Artery Disease (CAD)
Chronic Stable Angina
NORVASC is indicated for the symptomatic treatment of chronic stable angina. NORVASC may be used alone or in combination with other antianginal agents.
Vasospastic Angina (Prinzmetal's or Variant Angina)
NORVASC is indicated for the treatment of confirmed or suspected vasospastic angina. NORVASC may be used as monotherapy or in combination with other antianginal agents.
Angiographically Documented CAD
In patients with recently documented CAD by angiography and without heart failure or an ejection fraction < 40%, NORVASC is indicated to reduce the risk of hospitalization due to angina and to reduce the risk of a coronary revascularization procedure.

DRUG INTERACTIONS
In Vitro Data
In vitro data indicate that NORVASC has no effect on the human plasma protein binding of digoxin, phenytoin, warfarin, and indomethacin.
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.
Magnesium and Aluminum Hydroxide Antacid
Co-administration of a magnesium and aluminum hydroxide antacid with a single dose of NORVASC had no significant effect on the pharmacokinetics of NORVASC.
Sildenafil
A single 100 mg dose of sildenafil 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.
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.
Simvastatin
Co-administration of multiple doses of 10 mg of amlodipine with 80 mg simvastatin resulted in a 77% increase in exposure to simvastatin compared to simvastatin alone. Limit the dose of simvastatin in patients on amlodipine to 20 mg daily.
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.
CYP3A4 Inhibitors
Co-administration of a 180 mg daily dose of diltiazem with 5 mg amlodipine in elderly hypertensive patients resulted in a 60% increase in amlodipine systemic exposure. Erythromycin co-administration in healthy volunteers did not significantly change amlodipine systemic exposure. However, strong inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, ritonavir) may increase the plasma concentrations of amlodipine to a greater extent. Monitor for symptoms of hypotension and edema when amlodipine is co-administered with CYP3A4 inhibitors.
CYP3A4 Inducers
No information is available on the quantitative effects of CYP3A4 inducers on amlodipine. Blood pressure should be closely monitored when amlodipine is co-administered with CYP3A4 inducers.
Drug/Laboratory Test Interactions
None known.