Phentolamine Mesylate

INDICATIONS AND USAGE 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.

DOSAGE AND ADMINISTRATION The reconstituted solution should be used upon preparation and should not be stored. 1. Prevention or control of hypertensive episodes in the patient with pheochromo-cytoma. 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.) 2. 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. 3. 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. a. Intravenous Preparation The CONTRAINDICATIONS , WARNINGS , and PRECAUTIONS sections should be reviewed. Sedatives, analgesics, and all other medications except those that might be deemed essential (such as digitalis and insulin) are withheld for at least 24 hours, and preferably 48 to 72 hours, prior to the test. Antihypertensive drugs are withheld until blood pressure returns to the untreated, hypertensive level. This test is not preformed on a patient who is normotensive. Procedure The patient is kept at rest in a supine position throughout the test, preferably in a quiet, darkened room. Injection of phentolamine is delayed until blood pressure is stabilized, as evidenced by blood pressure readings taken every 10 minutes for at least 30 minutes. Five milligrams of phentolamine mesylate is dissolved in 1 mL of Sterile Water for Injection. The dose for adults is 5 mg; for children, 1 mg. The syringe needle is inserted into the vein, and injection is delayed until pressor response to venipuncture has subsided. Phentolamine is injected rapidly. Blood pressure is recorded immediately after injection, at 30-second intervals for the first 3 minutes, and at 60-second intervals for the next 7 minutes. Interpretation A positive response, suggestive of pheochromocytoma, is indicated when the blood pressure is reduced more than 35 mm Hg systolic and 25 mm Hg diastolic. A typical positive response is a reduction in pressure of 60 mm Hg systolic and 25 mm Hg diastolic. Usually, maximal effect is evident within 2 minutes after injection. A return to preinjection pressure commonly occurs within 15 to 30 minutes but may occur more rapidly. If blood pressure decreases to a dangerous level, the patient should be treated as outlined under OVERDOSAGE . A positive response should always be confirmed by other diagnostic procedures, preferably by measurement of urinary catecholamines or their metabolites. A negative response is indicated when the blood pressure is elevated, unchanged, or reduced less than 35 mm Hg systolic and 25 mm Hg diastolic after injection of phentolamine. A negative response to this test does not exclude the diagnosis of pheo-chromocytoma, especially in patients with paroxysmal hypertension in whom the incidence of false-negative responses is high. b. Intramuscular If the intramuscular test for pheochromocytoma is preferred, preparation is the same as for the intravenous test. Five milligrams of phentolamine me …

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

ADVERSE REACTIONS 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.

Drug Interactions See DOSAGE AND ADMINISTRATION . Diagnosis of pheochromocytoma , Preparation .

DESCRIPTION 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 C 17 H 19 N 3 O•CH 4 O 3 S 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. structural formula

OVERDOSAGE Acute Toxicity No deaths due to acute poisoning with phentolamine have been reported. Oral LD 50 ’s (mg/kg): mice, 1000; rats, 1250. Signs and Symptoms 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. Treatment 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 norepi-nephrine, 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.

HOW SUPPLIED Phentolamine Mesylate for Injection, USP, 5 mg, for intramuscular or intravenous use, is supplied as follows: NDC 0143-9564-01 - 2 mL vials packaged individually. NDC 0143-9564-10 - 2 mL vials packaged in cartons of 10 vials. The reconstituted solution should be used upon preparation and should not be stored. Store at 20° to 25° C (68° to 77° F) [See USP Controlled Room Temperature]. To report SUSPECTED ADVERSE REACTIONS, contact Hikma Pharmaceuticals USA Inc. at 1-877-845-0689, or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . For Product Inquiry call 1-877-845-0689. Manufactured by: HIKMA FARMACÊUTICA (PORTUGAL), S.A. Estrada do Rio da Mó, 8, 8A e 8B – Fervença – 2705-906 Terrugem SNT, PORTUGAL Distributed by: Hikma Pharmaceuticals USA Inc. Berkeley Heights, NJ 07922 Revised May 2022 PIN385-WES/5