PHENTOLAMINE MESYLATE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PHENTOLAMINE MESYLATE (PHENTOLAMINE MESYLATE).
Phentolamine mesylate is a non-selective competitive alpha-adrenergic antagonist (blocks alpha-1 and alpha-2 receptors), leading to vasodilation and decreased peripheral vascular resistance. It also antagonizes serotonin and produces direct vasodilation and positive inotropic and chronotropic effects.
| Metabolism | Hepatic metabolism via unknown pathways; no active metabolites identified. |
| Excretion | Renal (approximately 10% unchanged); remainder metabolized in liver with metabolites excreted renally and in feces via bile. |
| Half-life | Terminal elimination half-life is approximately 19 minutes; short half-life necessitates continuous or repeated dosing for sustained alpha-blockade. |
| Protein binding | Approximately 54% bound to plasma proteins. |
| Volume of Distribution | Approximately 0.6 L/kg; distributes into total body water, indicating extensive extravascular distribution. |
| Bioavailability | Intravenous: 100%; oral: limited and erratic (not clinically used); intramuscular/subcutaneous: well absorbed with complete bioavailability. |
| Onset of Action | Intravenous: immediate within 2 minutes; intramuscular: within 10–20 minutes; subcutaneous: within 15–20 minutes. |
| Duration of Action | Intravenous: 15–30 minutes; intramuscular/subcutaneous: 30–45 minutes; clinical effect is brief, requiring repeated administration for management of hypertensive emergencies or pheochromocytoma. |
5 mg intravenous or intramuscular, 1-2 hours before surgery for pheochromocytoma; for hypertensive crisis: 5-20 mg intravenous bolus, repeated as needed.
| Dosage form | INJECTABLE |
| Renal impairment | No specific dose adjustment recommended; use caution in severe renal impairment (GFR <30 mL/min) due to potential accumulation. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B: reduce dose by 50%; Child-Pugh Class C: avoid use or use with extreme caution. |
| Pediatric use | For hypertensive emergency: 0.05-0.1 mg/kg intravenous bolus, maximum 5 mg per dose; repeat every 5-15 minutes as needed. |
| Geriatric use | Start at low end of dosing range (e.g., 5 mg) due to increased sensitivity; monitor for hypotension and reflex tachycardia. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PHENTOLAMINE MESYLATE (PHENTOLAMINE MESYLATE).
| Breastfeeding | Excreted in breast milk in small amounts; M/P ratio not established. Due to potential for adverse effects in nursing infants (hypotension, tachycardia), caution is advised. Consider alternative agents or temporary discontinuation of breastfeeding. |
| Teratogenic Risk | FDA Pregnancy Category C. Animal studies have shown fetal harm (reduced fetal weight, increased resorptions) at doses 5 times the human dose. No adequate human studies in pregnant women. Risk cannot be ruled out; use only if potential benefit justifies potential risk to fetus. |
■ FDA Black Box Warning
No boxed warning
| Serious Effects |
["Hypersensitivity to phentolamine or any component of the formulation","Myocardial infarction or history of myocardial infarction","Coronary insufficiency or history of angina pectoris","Hypotension or uncorrected hypovolemia","Concurrent use with epinephrine or other vasoconstrictors (risk of severe hypotension and reflex tachycardia)"]
| Precautions | ["Myocardial infarction, cerebrovascular spasm, and cerebrovascular occlusion have been reported, especially in patients with existing cardiovascular disease.","Hypotension can occur; use with caution in patients with hypotension or hypovolemia.","Arrhythmias: exacerbate or provoke ventricular arrhythmias (due to positive inotropic/chronic effects).","Use caution in patients with coronary artery disease or angina.","Monitor blood pressure and heart rate frequently during administration."] |
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| Fetal Monitoring |
| Monitor maternal blood pressure and heart rate continuously during infusion. Assess fetal heart rate monitoring if used near term due to potential for maternal hypotension affecting placental perfusion. Observe for signs of maternal hypotension, reflex tachycardia, arrhythmias. |
| Fertility Effects | Impaired fertility observed in male rats at high doses (decreased spermatogenesis, reduced mating performance). Human data lacking; potential for reversible effects on male fertility due to alpha-adrenergic blockade affecting ejaculation. |