Label: PAPAVERINE HYDROCHLORIDE injection, solution

Papaverine Hydrochloride, USP, is the hydrochloride of an alkaloid obtained from opium or prepared synthetically. It belongs to the benzylisoquinoline group of alkaloids. It does not contain a phenanthrene group as do morphine and codeine.

Papaverine Hydrochloride, USP, is 6,7-dimethoxy-1- veratrylisoquinoline hydrochloride and contains, on the dried basis, not less than 98.5% of C 20H 21NO 4 •HCl. The molecular weight is 375.85. The structural formula is as shown.

Papaverine Hydrochloride occurs as white crystals or white crystalline powder. One gram dissolves in about 30 mL of water and in 120 mL of alcohol. It is soluble in chloroform and practically insoluble in ether.

Papaverine Hydrochloride Injection, USP, is a clear, colorless to pale-yellow solution.

Papaverine Hydrochloride, for parenteral administration, is a smooth-muscle relaxant that is available in vials containing 30 mg/mL. Each vial also contains edetate disodium 0.005%. pH may be adjusted with sodium citrate and/or citric acid.

The most characteristic effect of papaverine is relaxation of the tonus of all smooth muscle, especially when it has been spasmodically contracted. Papaverine Hydrochloride apparently acts directly on the muscle itself. This relaxation is noted in the vascular system and bronchial musculature and in the gastrointestinal, biliary and urinary tracts.

The main actions of papaverine are exerted on cardiac and smooth muscle. Papaverine relaxes various smooth muscles, especially those of larger arteries; this relaxation may be prominent if spasm exists. The antispasmodic effect is a direct one and unrelated to muscle innervation, and the muscle still responds to drugs and other stimuli causing contraction. Papaverine has minimal actions on the central nervous system, although very large doses tend to produce some sedation and sleepiness in some patients. In certain circumstances, mild respiratory stimulation can be observed, but this is therapeutically inconsequential. Papaverine stimulates respiration by acting on carotid and aortic body chemoreceptors.

Papaverine relaxes the smooth musculature of the larger blood vessels, including the coronary, cerebral, peripheral, and pulmonary arteries. This action is particularly evident when such vessels are in spasm, induced reflexly or by drugs, and it provides the basis for the clinical use of papaverine in peripheral or pulmonary arterial embolism.

Experimentally in dogs, the alkaloid has been shown to cause fairly marked and long-lasting coronary vasodilatation and an increase in coronary blood flow. However, it also appears to have a direct inotropic effect and, when increased mechanical activity coincides with decreased systemic pressure, increases in coronary blood flow may not be sufficient to prevent brief periods of hypoxic myocardial depression.

Papaverine is effective by all routes of administration. A considerable fraction of the drug localizes in fat deposits and in the liver, with the remainder being distributed throughout the body. It is metabolized in the liver. About 90% of the drug is bound to plasma protein. Although estimates of its biologic half-life vary widely, reasonably constant plasma levels can be maintained with oral administration at 6 hour intervals. The drug is excreted in the urine in an inactive form.

Papaverine is recommended in various conditions accompanied by spasm of smooth muscle, such as vascular spasm associated with acute myocardial infarction (coronary occlusion), angina pectoris, peripheral and pulmonary embolism, peripheral vascular disease in which there is a vasospastic element, or certain cerebral angiospastic states, and visceral spasm, as in ureteral, biliary, or gastrointestinal colic.

Intravenous injection of papaverine is contraindicated in the presence of complete atrioventricular heart block. When conduction is depressed, the drug may produce transient ectopic rhythms of ventricular origin, either premature beats or paroxysmal tachycardia.

Papaverine Hydrochloride is not indicated for the treatment of impotence by intracorporeal injection. The intracorporeal injection of papaverine hydrochloride has been reported to have resulted in persistent priapism requiring medical and surgical intervention.

The following side effects have been reported: general discomfort, nausea, abdominal discomfort, anorexia, constipation or diarrhea, skin rash, malaise, vertigo, headache, intensive flushing of the face, perspiration, increase in the depth of respiration, increase in heart rate, a slight rise in blood pressure, and excessive sedation.

Hepatitis, probably related to an immune mechanism, has been reported infrequently. Rarely, this has progressed to cirrhosis.

To report SUSPECTED ADVERSE REACTIONS, contact BPI Labs, LLC at (727) 471-0850 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

Drug dependence resulting from the abuse of many of the selective depressants, including papaverine hydrochloride, has been reported.

Papaverine Hydrochloride may be administered intravenously or intramuscularly. The intravenous route is recommended when an immediate effect is desired, but the drug must be injected slowly over the course of 1 or 2 minutes to avoid uncomfortable or alarming side effects.

Parenteral administration of papaverine hydrochloride in doses of 1 to 4 mL is repeated every 3 hours as indicated. In the treatment of cardiac extrasystoles, 2 doses may be given 10 minutes apart.

Papaverine Hydrochloride Injection, USP, 30 mg/mL is available as 

54288-142-10                                2mL Vial                                                  packaged in boxes of 10.

54288-142-25                                2mL Vial                                                  packaged in boxes of 25.

Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) (See USP Controlled Room Temperature).
PROTECT FROM LIGHT. RETAIN IN CARTON UNTIL TIME OF USE.

Manufactured by:

BPI Labs, LLC

12393 Belcher Rd S, Suite 450

Largo, FL USA 33773

LI33I

R-2303