DESCRIPTION. Each Phenoxybenzamine Hydrochloride Capsule, USP contains 10 mg of phenoxybenzamine hydrochloride, USP. Inactive ingredients consist of anhydrous lactose, black monogramming ink, colloidal silicon dioxide and sodium lauryl sulfate. The black monogramming ink contains ammonium hydroxide, iron oxide black, isopropyl alcohol, N-butyl alcohol, propylene glycol, and shellac. The capsule shells also contain FD&C Red No. 40, gelatin, purified water and titanium dioxide.Phenoxybenzamine is N-(2-Chloroethyl)-N-(1-methyl-2-phenoxyethyl)benzylamine hydrochloride:Phenoxybenzamine hydrochloride is white to almost white powder with molecular weight of 340.3, which melts between 136 and 141C. It is soluble in alcohol and chloroform; insoluble in ether and water. chem.
ADVERSE REACTIONS SECTION.
ADVERSE REACTIONS. The following adverse reactions have been observed, but there are insufficient data to support an estimate of their frequency. Autonomic Nervous System: Postural hypotension, tachycardia, inhibition of ejaculation, nasal congestion, miosis. These so-called side effects are actually evidence of adrenergic blockade and vary according to the degree of blockade. Miscellaneous: Gastrointestinal irritation, drowsiness, fatigue.
CLINICAL PHARMACOLOGY SECTION.
CLINICAL PHARMACOLOGY. Phenoxybenzamine hydrochloride is long-acting, adrenergic, alpha-receptor blocking agent, which can produce and maintain chemical sympathectomy by oral administration. It increases blood flow to the skin, mucosa and abdominal viscera, and lowers both supine and erect blood pressures. It has no effect on the parasympathetic system. Twenty to 30 percent of orally administered phenoxybenzamine appears to be absorbed in the active form.1 The half-life of orally administered phenoxybenzamine hydrochloride is not known; however, the half-life of intravenously administered drug is approximately 24 hours. Demonstrable effects with intravenous administration persist for at least to days, and the effects of daily administration are cumulative for nearly week.1.
CONTRAINDICATIONS. Conditions where fall in blood pressure may be undesirable; hypersensitivity to the drug or any of its components.
DOSAGE & ADMINISTRATION SECTION.
DOSAGE AND ADMINISTRATION. The dosage should be adjusted to fit the needs of each patient. Small initial doses should be slowly increased until the desired effect is obtained or the side effects from blockade become troublesome. After each increase, the patient should be observed on that level before instituting another increase. The dosage should be carried to point where symptomatic relief and/or objective improvement are obtained, but not so high that the side effects from blockade become troublesome. Initially, 10 mg of phenoxybenzamine hydrochloride twice day. Dosage should be increased every other day, usually to 20 to 40 mg or times day, until an optimal dosage is obtained, as judged by blood pressure control. Long-term use of phenoxybenzamine is not recommended (see PRECAUTIONS: Carcinogenesis and Mutagenesis).
GENERAL PRECAUTIONS SECTION.
General Administer with caution in patients with marked cerebral or coronary arteriosclerosis or renal damage. Adrenergic blocking effect may aggravate symptoms of respiratory infections.
HOW SUPPLIED SECTION.
HOW SUPPLIED. Phenoxybenzamine Hydrochloride Capsules, USP 10 mg capsule is supplied as red opaque/red opaque capsule with 54 036 printed in black on the cap and 54 036 printed in black ink on the capsule body, containing white to off-white powder.NDC 0054-0349-25: Bottle of 100 Capsules. Storage Store at 20 to 25C (68 to 77F). [See USP Controlled Room Temperature.].
INDICATIONS & USAGE SECTION.
INDICATIONS AND USAGE. Phenoxybenzamine hydrochloride capsules are indicated in the treatment of pheochromocytoma, to control episodes of hypertension and sweating. If tachycardia is excessive, it may be necessary to use beta-blocking agent concomitantly.
NURSING MOTHERS SECTION.
Nursing Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions from phenoxybenzamine hydrochloride, decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
OVERDOSAGE. SYMPTOMS These are largely the result of blocking of the sympathetic nervous system and of the circulating epinephrine. They may include postural hypotension, resulting in dizziness or fainting; tachycardia, particularly postural; vomiting; lethargy; shock.
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.
Package/Label Display Panel . bottle1.
PEDIATRIC USE SECTION.
PRECAUTIONS. General Administer with caution in patients with marked cerebral or coronary arteriosclerosis or renal damage. Adrenergic blocking effect may aggravate symptoms of respiratory infections. Drug Interactions2 Phenoxybenzamine hydrochloride may interact with compounds that stimulate both alpha-and beta-adrenergic receptors (i.e., epinephrine) to produce an exaggerated hypotensive response and tachycardia. (See WARNINGS.) Phenoxybenzamine blocks hyperthermia production by levarterenol, and blocks hypothermia production by reserpine. Carcinogenesis and Mutagenesis Case reports of carcinoma in humans after long-term treatment with phenoxybenzamine have been reported. Hence long-term use of phenoxybenzamine is not recommended.3, Carefully weigh the benefits and risks before prescribing this drug. Phenoxybenzamine hydrochloride showed in vitro mutagenic activity in the Ames test and mouse lymphoma assay; it did not show mutagenic activity in vivo in the micronucleus test in mice. In rats and mice, repeated intraperitoneal administration of phenoxybenzamine hydrochloride (three times per week for up to 52 weeks) resulted in peritoneal sarcomas. Chronic oral dosing in rats (for up to years) produced malignant tumors of the small intestine and non-glandular stomach, as well as ulcerative and/or erosive gastritis of the glandular stomach. Whereas squamous cell carcinomas of the non-glandular stomach were observed at all tested doses of phenoxybenzamine hydrochloride, there was no-observed-effect-level of 10 mg/kg for tumors (carcinomas and sarcomas) of the small intestine. This dose is, on body surface area basis, about twice the maximum recommended human dosage of 20 mg b.i.d. Pregnancy Teratogenic Effects:Pregnancy Category C:Adequate reproductive studies in animals have not been performed with phenoxybenzamine hydrochloride. It is also not known whether phenoxybenzamine can cause fetal harm when administered to pregnant woman. Phenoxybenzamine should be given to pregnant woman only if clearly needed.. Nursing Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions from phenoxybenzamine hydrochloride, decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Pediatric Use.
Pregnancy Teratogenic Effects:Pregnancy Category C:Adequate reproductive studies in animals have not been performed with phenoxybenzamine hydrochloride. It is also not known whether phenoxybenzamine can cause fetal harm when administered to pregnant woman. Phenoxybenzamine should be given to pregnant woman only if clearly needed.
WARNINGS. Phenoxybenzamine-induced alpha-adrenergic blockade leaves beta-adrenergic receptors unopposed. Compounds that stimulate both types of receptors may, therefore, produce an exaggerated hypotensive response and tachycardia.