Description
Nisoldipine is a yellow crystalline substance, practically insoluble in water but soluble in ethanol. It has a molecular weight of 388.4. Nisalanorm® tablets comprise three layers: a top barrier layer, a middle layer containing nisoldipine, and a bottom barrier layer. The erodible barrier layers and the hydrogel middle layer provide for the controlled release of the drug. Nisalanorm® tablets contain either 8.5, 17, or 34 mg of nisoldipine for once-a-day oral administration. Inactive ingredients in the formulation include: Hypromellose, hypromellose phthalate, lactose, glyceryl behenate, povidone, magnesium stearate, silicon dioxide, methacrylic acid copolymer, and sodium lauryl sulfate. Inactive ingredients in the film coating include: polydextrose, titanium dioxide, hypromellose, polyethylene glycol, iron oxide, and carnauba wax. Additionally, the 17 mg formulation contains FD&C Yellow #5. Mechanism of Action: Nisoldipine is a member of the dihydropyridine class of calcium channel antagonists (calcium ion antagonists or slow channel blockers) that inhibit the transmembrane influx of calcium into vascular smooth muscle and cardiac muscle. It reversibly competes with other dihydropyridines for binding to the calcium channel. Because the contractile process of vascular smooth muscle is dependent upon the movement of extracellular calcium into the muscle through specific ion channels, inhibition of the calcium channel results in dilation of the arterioles. In vitro studies show that the effects of nisoldipine on contractile processes are selective, with greater potency on vascular smooth muscle than on cardiac muscle. Although, like other dihydropyridine calcium channel blockers, nisoldipine has negative inotropic effects in vitro, studies conducted in intact anesthetized animals have shown that the vasodilating effect occurs at doses lower than those that affect cardiac contractility. he effect of nisoldipine on blood pressure is principally a consequence of a dose-related decrease of peripheral vascular resistance. While nisoldipine, like other dihydropyridines, exhibits a mild diuretic effect, most of the antihypertensive activity is attributed to its effect on peripheral vascular resistance. INDICATIONS AND USAGE: Nisalanorm® is indicated for the treatment of hypertension. It may be used alone or in combination with other antihyper-tensive agents. CONTRAINDICATIONS: Nisalanorm® is contraindicated in patients with known hypersensitivity to dihydropyridine calcium channel blockers. WARNINGS: Increased angina and/or myocardial infarction in patients with coronary artery disease: Rarely, patients, particularly those with severe obstructive coronary artery disease, have developed increased frequency, duration and/or severity of angina, or acute myocardial infarction on starting calcium channel blocker therapy or at the time of dosage increase. The mechanism of this effect has not been established. In controlled studies of Nisalanorm® in patients with angina this was seen about 1.5% of the time in patients given nisoldipine, compared with 0.9% in patients given placebo. PRECAUTIONS: General Hypotension: Because nisoldipine, like other vasodilators, decreases peripheral vascular resistance, careful monitoring of blood pressure during the initial administration and titration of Nisalanorm® is recommended. Close observation is especially important for patients already taking medications that are known to lower blood pressure. Although in most patients the hypotensive effect of Nisalanorm® is modest and well tolerated, occasional patients have had excessive and poorly tolerated hypotension. These responses have usually occurred during initial titration or at the time of subsequent upward dosage adjustment. Congestive Heart Failure: Although acute hemodynamic studies of nisoldipine in patients with NYHA Class II-IV heart failure have not demonstrated negative inotropic effects, safety of Nisalanorm® in patients with heart failure has not been established. Caution therefore should be exercised when using Nisalanorm® in patients with heart failure or compromised ventricular function, particularly in combination with a beta-blocker. Patients with Hepatic Impairment: Because nisoldipine is extensively metabolized by the liver and, in patients with cirrhosis, it reaches blood concentrations about 5 times those in normals, Nisalanorm® should be administered cautiously in patients with severe hepatic dysfunction (See DOSAGE AND ADMINISTRATION).
