Prescription Drugs

CLINICAL PHARMACOLOGY The main actions of papaverine are exerted on cardiac and smooth muscle. Like quinidine, papaverine acts directly on the heart muscle to depress conduction and prolong the refractory period. Papaverine relaxes various smooth muscles. This relaxation may be prominent if spasm exists. The muscle cell is not paralyzed by papaverine and still responds to drugs and other stimuli causing contraction. The antispasmodic effect is a direct one and unrelated to muscle innervation. Papaverine is practically devoid of effects on the central nervous system. Papaverine relaxes the smooth musculature of the large blood vessels, especially coronary, systemic peripheral and pulmonary arteries. Perhaps by its direct vasodilating action on cerebral blood vessels, papaverine increases cerebral blood flow and decreases cerebral vascular resistance in normal subjects; oxygen consumption is unaltered. These effects may explain the benefit reported from the drug in cerebral vascular encephalopathy. The direct actions of papaverine on the heart to depress conduction and irritability and to prolong the refractory period of the myocardium provide the basis for its clinical trial in abrogating atrial and ventricular premature systoles and ominous ventricular arrhythmias. The coronary vasodilator action could be an additional factor of therapeutic value when such rhythms are secondary to insufficiency or occlusion of the coronary arteries. In patients with acute coronary thrombosis, the occurrence of ventricular cardiac arrhythmias is serious and requires measures designed to decrease myocardial irritability. Papaverine may have advantages over quinidine used for a similar purpose, in that it may be given in an emergency by the intravenous route, does not depress myocardial contraction or cause cinchonism and produces coronary vasodilation.

Papaverine Hydrochloride Sustained Release Capsules, 150 mg DESCRIPTION Papaverine hydrochloride, C20H21NO4•HCl, is a white, crystalline powder, odorless, with a slight bitter taste and is soluble in water. Each capsule contains: papaverine hydrochloride USP 150 mg. Chemically, it is Isoquinoline,1-[(3,4-dimethoxyphenyl)methyl]-6,7-dimethoxy-, hydrochloride. It has a molecular weight of 375.85. It has the following structural formula: Manufactured in a special base which is designed for prolonged release. Each capsule also contains the following inactive ingredients: FD&C blue No. 1, FD&C red No. 40, gelatin, pharmaceutical glaze, povidone, silicon dioxide, sodium lauryl sulfate, corn starch, sucrose and talc.

INDICATIONS For the relief of cerebral and peripheral ischemia associated with arterial spasm and myocardial ischemia complicated by arrhythmias. DOSAGE AND ADMINISTRATION One capsule every 12 hours. In difficult cases administration may be increased to one capsule every 8 hours or two capsules every 12 hours. HOW SUPPLIED Papaverine Hydrochloride Sustained Release Capsules are supplied as: 150 mg brown and clear capsules, imprinted E 5156 and are available in bottles of 100, 500 and 1000. Storage Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Protect from moisture. To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc. at 1-800-525-8747 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Manufactured for: Sandoz Inc. Princeton, NJ 08540. Manufactured by: Epic Pharma, LLC. Laurelton, NY 11413. Rev. 11/08.

PATIENT INFORMATION No information provided. Please refer to the PRECAUTIONS sections.

OVERDOSE No information provided. CONTRAINDICATIONS Large doses can depress atrioventricular and intraventricular conduction and thereby produce serious arrhythmias.

SIDE EFFECTS Although occurring rarely, the reported side effects of papaverine include nausea, abdominal distress, anorexia, constipation, malaise, drowsiness, vertigo, sweating, headache, diarrhea, skin rash, flushing of face, increase in heart rate and depth of respiration and slight increase in blood pressure. DRUG INTERACTIONS No information provided.

WARNINGS No information provided. PRECAUTIONS Use with caution in patients with glaucoma. Hepatic hypersensitivity has been reported with gastrointestinal symptoms, jaundice, eosinophilia and altered liver function tests. Discontinue drug if these occur.