Because hepatic biotransformation is the predominant route for the disposition of nifedipine, its pharmacokinetics may be altered in patients with chronic liver disease. ADALAT CC has not been studied in patients with hepatic disease; however, in patients with hepatic impairment (liver cirrhosis) nifedipine has a longer elimination half-life and higher bioavailability than in healthy volunteers.

The degree of protein binding of nifedipine is high (92%-98%). Protein binding may be greatly reduced in patients with renal or hepatic impairment.

After administration of ADALAT CC to healthy elderly men and women (age > 60 years), the mean Cmax is 36% higher and the average plasma concentration is 70% greater than in younger patients.

In healthy subjects, the elimination half-life of a different sustained release nifedipine formulation was longer in elderly subjects (6.7 h) compared to young subjects (3.8 h) following oral administration. A decreased clearance was also observed in the elderly (348 mL/min) compared to young subjects (519 mL/min) following intravenous administration.

Co-administration of nifedipine with grapefruit juice results in up to a 2-fold increase in AUC and Cmax, due to inhibition of CYP3A4 related first-pass metabolism.

Clinical Studies: ADALAT CC produced dose-related decreases in systolic and diastolic blood pressure as demonstrated in two double-blind, randomized, placebo-controlled trials in which over 350 patients were treated with ADALAT CC 30, 60 or 90 mg once daily for 6 weeks. In the first study, ADALAT CC was given as monotherapy and in the second study, ADALAT CC was added to a beta-blocker in patients not controlled on a beta-blocker alone. The mean trough (24 hours post-dose) blood pressure results from these studies are shown below:

MEAN REDUCTIONS IN TROUGH SUPINE BLOOD PRESSURE (mmHg) SYSTOLIC/DIASTOLIC

The trough/peak ratios estimated from 24 hour blood pressure monitoring ranged from 41%-78% for diastolic and 46%-91% for systolic blood pressure.

Hemodynamics: Like other slow-channel blockers, nifedipine exerts a negative inotropic effect on isolated myocardial tissue. This is rarely, if ever, seen in intact animals or man, probably because of reflex responses to its vasodilating effects. In man, nifedipine decreases peripheral vascular resistance which leads to a fall in systolic and diastolic pressures, usually minimal in normotensive volunteers (less than 5-10 mm Hg systolic), but sometimes larger. With ADALAT CC, these decreases in blood pressure are not accompanied by any significant change in heart rate. Hemodynamic studies of the immediate release nifedipine formulation in patients with normal ventricular function have generally found a small increase in cardiac index without major effects on ejection fraction, left ventricular end-diastolic pressure (LVEDP) or volume (LVEDV). In patients with impaired ventricular function, most acute studies have shown some increase in ejection fraction and reduction in left ventricular filling pressure.

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