PHENTOLAMINE MESYLATE
FOR INJECTION, USP

Rx ONLY.

Phentolamine Mesylate for Injection USP, is an antihypertensive, available in vials for intravenous and intramuscular administration. Each vial contains phentolamine mesylate USP, 5 mg and mannitol USP, 25 mg in sterile, lyophilized form.

Phentolamine mesylate is m-[N-(2-Imidazolin-2-ylmethyl)-p-toluidino]phenol monomethanesulfonate (salt), and its structural formula is:

Molecular Formula - C₁₇H₁₉N₃O•CH₄O₃S                                  M.W. - 377.47

Phentolamine mesylate USP is a white or off-white, odorless crystalline powder. Its solutions are acid to litmus. It is freely soluble in water and in alcohol, and slightly soluble in chloroform. It melts at about 178°C.

Phentolamine mesylate produces an alpha-adrenergic block of relatively short duration. It also has direct, but less marked, positive inotropic and chronotropic effects on cardiac muscle and vasodilator effects on vascular smooth muscle.

Phentolamine has a half-life in the blood of 19 minutes following intravenous administration. Approximately 13% of a single intravenous dose appears in the urine as unchanged drug.

Phentolamine Mesylate for Injection is indicated for the prevention or control of hypertensive episodes that may occur in a patient with pheochromocytoma as a result of stress or manipulation during preoperative preparation and surgical excision.

Phentolamine Mesylate for Injection is indicated for the prevention or treatment of dermal necrosis and sloughing following intravenous administration or extravasation of norepinephrine.

Phentolamine Mesylate for Injection is also indicated for the diagnosis of pheochromocytoma by the phentolamine blocking test.

Myocardial infarction, history of myocardial infarction, coronary insufficiency, angina, or other evidence suggestive of coronary artery disease; hypersensitivity to phentolamine or related compounds.

Myocardial infarction, cerebrovascular spasm, and cerebrovascular occlusion have been reported to occur following the administration of phentolamine, usually in association with marked hypotensive episodes.

For screening tests in patients with hypertension, the generally available urinary assay of catecholamines or other biochemical assays have largely replaced the phentolamine and other pharmacological tests for reasons of accuracy and safety. None of the chemical or pharmacological tests is infallible in the diagnosis of pheochromocytoma. The phentolamine blocking test is not the procedure of choice and should be reserved for cases in which additional confirmatory evidence is necessary and the relative risks involved in conducting the test have been considered.

Tachycardia and cardiac arrhythmias may occur with the use of phentolamine or other alpha-adrenergic blocking agents. When possible, administration of cardiac glycosides should be deferred until cardiac rhythm returns to normal.

See DOSAGE AND ADMINISTRATION. Diagnosis of pheochromocytoma, Preparation.

Long-term carcinogenicity studies, mutagenicity studies, and fertility studies have not been conducted with phentolamine.

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 in nursing infants from phentolamine, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

See DOSAGE AND ADMINISTRATION.

Acute and prolonged hypotensive episodes, tachycardia, and cardiac arrhythmias have been reported. In addition, weakness, dizziness, flushing, orthostatic hypotension, nasal stuffiness, nausea, vomiting, and diarrhea may occur.

No deaths due to acute poisoning with phentolamine have been reported.

Oral LD₅₀’s (mg/kg): mice, 1000; rats, 1250.

Overdosage with phentolamine is characterized chiefly by cardiovascular disturbances, such as arrhythmias, tachycardia, hypotension, and possibly shock. In addition, the following might occur: excitation, headache, sweating, pupillary contraction, visual disturbances; nausea, vomiting, diarrhea; hypoglycemia.

There is no specific antidote.

A decrease in blood pressure to dangerous levels or other evidence of shocklike conditions should be treated vigorously and promptly. The patient’s legs should be kept raised and a plasma expander should be administered. If necessary, intravenous infusion or norepinephrine, titrated to maintain blood pressure at the normotensive level, and all available supportive measures should be included. Epinephrine should not be used, since it may cause a paradoxical reduction in blood pressure.

The reconstituted solution should be used upon preparation and should not be stored.

• Prevention or control of hypertensive episodes in the patient with pheochromocytoma. For preoperative reduction of elevated blood pressure, 5 mg of phentolamine mesylate (1 mg for children) is injected intravenously or intramuscularly 1 or 2 hours before surgery, and repeated if necessary.
  During surgery, phentolamine mesylate (5 mg for adults, 1 mg for children) is administered intravenously as indicated, to help prevent or control paroxysms of hypertension, tachycardia, respiratory depression, convulsions, or other effects of epinephrine intoxication. (Postoperatively, norepinephrine may be given to control the hypotension that commonly follows complete removal of a pheochromocytoma.)
• Prevention or treatment of dermal necrosis and sloughing following intravenous administration or extravasation of norepinephrine.
  For Prevention: 10 mg of phentolamine mesylate is added to each liter of solution containing norepinephrine. The pressor effect of norepinephrine is not affected.
  For Treatment: 5 to 10 mg of phentolamine mesylate in 10 mL of saline is injected into the area of extravasation within 12 hours.
• Diagnosis of pheochromocytoma - phentolamine blocking test.
  The test is most reliable in detecting pheochromocytoma in patients with sustained hypertension and least reliable in those with paroxysmal hypertension. False-positive tests may occur in patients with hypertension without pheochromocytoma.

If the intramuscular test for pheochromocytoma is preferred, preparation is the same as for the intravenous test. Five milligrams of phentolamine mesylate is then dissolved in 1 mL of Sterile Water for Injection. The dose for adults is 5 mg intramuscularly; for children, 3 mg. Blood pressure is recorded every 5 minutes for 30 to 45 minutes following injection. A positive response is indicated when the blood pressure is reduced 35 mm Hg systolic and 25 mm Hg diastolic, or more, within 20 minutes following injection.

Note: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Phentolamine Mesylate for Injection USP, 5 mg, for intramuscular or intravenous use, is supplied in a 2 mL vial and individually boxed. NDC 55390-113-01.

The reconstituted solution should be used upon preparation and should not be stored.

Store at controlled room temperature, 15° to 30°C (59° to 86°F).

Manufactured for:                                               Manufactured by:

Bedford Laboratories™                                       Ben Venue Laboratories™

Bedford, OH 44146                                             Bedford, OH 44146

May 1999                                                           PHT-P01