30 mg Extended-Release Tablet
CALCIUM CHANNEL BLOCKER

 

FORMULATION:
Each Extended-Release tablet contains:
Nifedipine, USP ...............................…………………………………. 30 mg

PRODUCT DESCRIPTION:
Nifedipine is dihydropyridine calcium channel blocker. Its main uses are as an antianginal (especially in Prinzmetal’s angina) and antihypertensive, although a large number of other indications have recently been found for this agent, such as Raynaud’s phenomenon, premature labor, and painful spasms of pulmonary hypertension, patients whose symptoms respond to calcium channel blocker.

PHARMACOKINETICS:
General characteristics:
Nifedipine Extended-Release Tablets are formulated to provide nifedipine at an approximately constant rate over 24 hours. Nifedipine is released from the tablet at a zero-order rate. The pharmacokinetic profile of this formulation is characterized by low peak-trough fluctuation. 0-24 hour plasma concentration versus time profiles at steady state are plateau-like, rendering the Nifedipine Extended-Release Tablet appropriate for once-a-day administration. The delivery rate is independent of gastrointestinal pH or motility. Upon swallowing, the biologically inert components of the tablet remain intact during gastrointestinal transit and are eliminated in the faeces as an insoluble form.

Absorption
Orally administered Nifedipine is almost completely absorbed in the gastrointestinal tract. The systemic availability of orally administered Nifedipine immediate release formulations (nifedipine capsules) is 45-56% owing to a first pass effect. At steady-state, the bioavailability of Nifedipine-Extended-Release Tablets ranges from 68-86% relative to
Nifedipine capsules. Administration in the presence of food slightly alters the early rate of absorption but does not influence the extent of drug availability.

Distribution
Nifedipine is about 95% bound to plasma protein (albumin). The distribution half-life after intravenous administration has been determined to be 5 to 6 minutes.

Biotransformation
After oral administration, nifedipine is metabolized in the GUT wall and in the liver, primarily by oxidative processes. These metabolites show no pharmacodynamic activity. Nifedipine is eliminated in the form of its metabolites, predominantly via the kidneys, with approximately 5-15% being excreted via the bile in the faeces. Non-metabolized nifedipine can be detected only in traces (below 1.0%) in the urine.

Elimination
The terminal elimination half-life is 1.7 to 3.4 hours in conventional formulations (nifedipine capsules). The terminal half-life following Nifedipine-Extended-Release Tablets administration does represent a meaningful parameter as a plateau–like plasma concentration is maintained during release from the tablets and absorption. After release and absorption of the last dose the plasma concentration finally declines with an elimination half-life as seen in conventional formulations.

Characteristics in patients:
There are no significant differences in the pharmacokinetics of nifedipine between healthy subjects and subjects with renal impairment. Therefore, dosage adjustment is not needed in these patients. In patients with hepatic impairment, the elimination half-life is distinctly prolonged and the total clearance is reduced. Owing to the duration of action of the formulation, Nifedipine Extended-Release Tablets should not be administered in these patients.

INDICATIONS:
For the treatment of all grades of hypertension.
For the prophylaxis of chronic stable angina pectoris either as mono therapy or in combination with a beta-blocker.