Phentolamine (Monograph)

Drug class: Non-selective alpha-Adrenergic Blocking Agents
VA class: AU200
CAS number: 65-28-1

Medically reviewed by Drugs.com on Jan 17, 2024. Written by ASHP.

Introduction

α-Adrenergic blocking agent, an imidazoline.^{177 a}

Uses for Phentolamine

Diagnosis of Pheochromocytoma

Used as an aid in the diagnosis of pheochromocytoma.^{a 177}

Determination of blood catecholamine concentrations, urinary assay of catecholamines, or other biochemical assays are the safest and most reliable diagnostic methods and they have largely replaced phentolamine and other pharmaceutical tests.^{177 a} No test, however, is completely reliable.^{177 a}

May be used when additional confirmatory evidence of pheochromocytoma is required and potential benefits outweigh the possible risks.^{177 a}

Test is more reliable with sustained than with paroxysmal hypertension; no diagnostic value in absence of hypertension at the time of the test.^{177 a}

Sudden and marked reduction in BP following parenteral administration of phentolamine suggests pheochromocytoma;^a however, false-negative and false-positive responses are frequent.^{177 a}

Hypertension in Pheochromocytoma

May be administered immediately prior to or during pheochromocytomectomy to prevent or control paroxysmal hypertension resulting from anesthesia, stress, or operative manipulation of the tumor.^a

Has been used to manage pheochromocytoma until surgery is performed and for prolonged treatment of hypertension when the tumor is not operable; however, phenoxybenzamine is considered the drug of choice because it has a longer duration of action.^a

Hypertensive Crises

Has been used in the treatment of hypertensive emergencies (severe elevations in BP >180/120 mm Hg accompanied by new or worsening target organ dysfunction) induced by catecholamine excess (e.g., pheochromocytoma, drug interactions with an MAO inhibitor, amphetamine overdosage, cocaine toxicity, clonidine withdrawal)^{† [off-label]}.¹²⁰⁰

Extravasation of Catecholamines

Used to prevent dermal necrosis and sloughing following IV administration or extravasation of norepinephrine.^{177 200}

Has been used to prevent necrosis after extravasation of dopamine^{† [off-label]}.^a

MI

Has been used to decrease impedance to left ventricular ejection and the infarct size in patients with MI associated with left ventricular failure^{† [off-label]}.^a

However, contraindicated in patients with MI,^{177 a} and investigators do not recommend for routine use, since left ventricular function and the ECG must be monitored continuously.^a

Erectile Dysfunction

Self-injection of small doses combined with papaverine hydrochloride into the corpus cavernosum has been effective for the treatment of erectile dysfunction^{† [off-label]} (ED, impotence).^{103 105 106 107 108 110 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127}

Combination has been effective in patients with neurogenic^{103 105 106 108 110 112 113 115 116 118 119 120 122 123 124 127} and/or limited vasculogenic impotence^{103 105 106 108 110 112 113 115 116 120 122 123 124 127} or with psychogenic impotence,^{105 106 108 123 124 127} but efficacy in those with a vasculogenic component of their impotence may be variable depending on the extent and type of vascular dysfunction.^{103 108 110 115 120 123 124}

Erection, which can be potentiated by sexual arousal, usually occurs within 10 minutes after injection of the drugs and may persist for 1 to several hours;^{105 106 108 113 114 116 118 119 124} tolerance to the drugs may occur during long-term use;^{105 114 124} priapism may occur.^{103 105 106 107 108 110 113 115 116 124 125 126 127}

Cocaine-induced Acute Coronary Syndrome

Has been used as an adjunct in the management of cocaine overdose^{† [off-label]} to reverse coronary vasoconstriction.¹⁹⁶

Phentolamine Dosage and Administration

General

Diagnosis of Pheochromocytoma

• Withhold sedatives, analgesics (e.g., opiates), and all other medications except essential drugs (e.g., digitalis, insulin) for at least 24 hours (preferably 48-72 hours) prior to the test.¹⁷⁷

• Withhold antihypertensive drugs until BP returns to untreated hypertensive levels.¹⁷⁷

• Before injection, the patient should rest in a supine position (preferably in a quiet, darkened room) until the BP is stabilized; read BP every 10 minutes for at least 30 minutes to establish basal BP.^{177 a}

• After insertion of needle, delay IV injection until venipuncture effect on blood pressure has passed; then inject rapidly.^{177 a}

• After IV injection, record BP immediately (at 30-second intervals for the first 3 minutes, then 1-minute intervals for the next 7 minutes).^{177 a}

• After IM administration, determine BP at 5-minute intervals for 30-45 minutes.^a

• Typical BP response in patients with pheochromocytoma is a decrease of 60 mm Hg systolic and 25 mm Hg diastolic within 2 minutes after IV administration or 20 minutes after IM administration.^{177 a} BP usually returns to pretest levels within 15–30 minutes or 3–4 hours, following IV¹⁷⁷ or IM administration, respectively.^a

• Positive response/test is a BP decrease ≥35 mm Hg systolic and 25 mm Hg diastolic;^a negative response is when BP is unchanged, elevated, or lowered <35 mm Hg systolic and 25 mm Hg diastolic.^{177 a}

• Confirm positive response by other diagnostic procedures, preferably by measurement of urinary catecholamines or their metabolites.¹⁷⁷

Hypertensive Crisis Secondary to Catecholamine Excess

• Adults with a compelling indication—severe preeclampsia or eclampsia, pheochromocytoma crisis: Reduce SBP to <140 mm Hg during the first hour.¹²⁰⁰

• Adults with a compelling indication—acute aortic dissection: Reduce SBP to <120 mm Hg within the first 20 minutes.¹²⁰⁰

• Initial goal of IV therapy in adults with a hypertensive emergency without a compelling indication is to reduce SBP by ≤25% within the first hour, followed by further BP reduction if stable to 160/110 or 160/100 mm Hg within the next 2–6 hours, avoiding excessive declines in BP that could precipitate renal, cerebral, or coronary ischemia.¹²⁰⁰ If this BP is well tolerated and the patient is clinically stable, may implement further gradual reductions toward normal BP in the next 24–48 hours.¹²⁰⁰

Administration

Administer usually by IV or IM injection; also may be administered by IV infusion.^{177 a} Has been administered by intracavernous injection^† for the treatment of impotence.^{103 105 106 107 108 110 112 113 114 115}

IV Administration

Reconstitution

Reconstitute vial containing 5 mg of lyophilized drug with 1 mL of sterile water to provide solution containing 5 mg of phentolamine mesylate per mL.^{177 a}

Dilution

IV infusion: for prevention of tissue necrosis and sloughing following extravasation or IV administration of norepinephrine, may add reconstituted phentolamine mesylate to each L of solution containing norepinephrine.^{177 a}

Rate of Administration

IV injection for pheochromocytoma test: inject rapidly.^{177 a}

IM Administration

Reconstitution

Reconstitute vial containing 5 mg of lyophilized drug with 1 mL of sterile water to provide solution containing 5 mg of phentolamine mesylate per mL.^{177 a}

Local Infiltration

Reconstitution

Reconstitute vial containing 5 mg of lyophilized drug with 1 mL of sterile water to provide solution containing 5 mg of phentolamine mesylate per mL.^{177 a}

Dilution

For treatment or prevention of tissue necrosis and sloughing following extravasation of catecholamines, dilute the appropriate amount of reconstituted phentolamine mesylate in 10–15 mL of 0.9% sodium chloride injection.^{177 a}

Dosage

Available as phentolamine mesylate; dosage expressed in terms of phentolamine mesylate.^{177 a}

Pediatric Patients

Diagnosis of Pheochromocytoma

IV (Preferred Route)

1 mg,^{177 a} 0.1 mg/kg, or 3 mg/m².^a

IM

3 mg.^{177 a}

Hypertension in Pheochromocytoma

Pheochromocytomectomy

IV

Preoperatively: 1 mg,^{177 a} 0.1 mg/kg, or 3 mg/m², 1–2 hours before surgery; may repeat if necessary.^a

During surgery: 1 mg,^{177 a} 0.1 mg/kg, or 3 mg/m².^a

Postoperatively: may administer norepinephrine to control hypotension (usually following complete pheochromocytoma removal);¹⁷⁷ however, hypotension is more often prevented by administration of blood, plasma, or 5% albumin in 0.9% sodium chloride injection to correct the reduced blood volume.^a

IM

Preoperatively: 1 mg,^{177 a} 0.1 mg/kg, or 3 mg/m², 1–2 hours before surgery; may repeat if necessary.^a

Extravasation of Catecholamines

Dopamine Extravasation

Local Infiltration

Prevention of tissue necrosis and sloughing: 0.1–0.2 mg/kg (maximum 10 mg per dose).^a

Immediate and conspicuous local hyperemic changes occur if the area is infiltrated within 12 hours.^a

Adults

Diagnosis of Pheochromocytoma

IV (Preferred Route) or IM

5 mg.^{177 a}

Hypertension in Pheochromocytoma

Pheochromocytomectomy

IV

Preoperatively: 5 mg, 1–2 hours before surgery; repeat if necessary.^{177 a}

During surgery, to prevent or control paroxysms of hypertension, tachycardia, respiratory depression, seizures, or other effects of excessive epinephrine secretion due to manipulation of the tumor: 5 mg as needed.^{177 a}

IM

Preoperatively: 5 mg, 1-2 hours before surgery; repeat if necessary.^{177 a}

Hypertensive Crises Secondary to Catecholamine Excess†

IV

5 mg as a rapid IV injection (“bolus”); some experts recommend repeating dose every 10 minutes as necessary to achieve desired BP target.¹²⁰⁰

Extravasation of Catecholamines

Extravasation of Norepinephrine

Local Infiltration

Treatment of tissue necrosis and sloughing: 5–10 mg (diluted in 10 mL of 0.9% sodium chloride) injected into affected area within 12 hours.^{177 200}

Immediate and conspicuous local hyperemic changes occur if the area is infiltrated within 12 hours; ineffective if used >12 hours after extravasation.¹⁷⁷

IV Infusion

Prevention of tissue necrosis and sloughing: Add 10 mg to each liter of IV fluid containing norepinephrine; pressor effect of norepinephrine is unaffected.^{177 200}

Extravasation of Dopamine†

Local Infiltration

Prevention of tissue necrosis and sloughing: 5–10 mg (in 10–15 mL of 0.9% sodium chloride) infiltrated (using a syringe with a fine hypodermic needle) liberally throughout the affected area.^a

Immediate and conspicuous local hyperemic changes occur if the area is infiltrated within 12 hours.^a

MI†

IV Infusion

For treatment of left ventricular failure secondary to acute MI^†, dosages of 0.17–0.4 mg/minute have been used.^a

Erectile Dysfunction†

Intracavernosal Self-injection

Usually 0.5–1 mg (range: 0.08–1.25 mg) combined with papaverine hydrochloride 2.5–37.5 mg has been effective.^a

Tolerance with long-term use may require dosage increase.^{105 114 124}

Prescribing Limits

Pediatric Patients

Extravasation of Catecholamines

Dopamine Extravasation

Local Infiltration

Maximum 10 mg per dose.^a

Cautions for Phentolamine

Contraindications

• MI or history of MI.^{177 a} However, results of some studies indicate that the drug may have a beneficial effect in patients with MI.^a

• Coronary insufficiency, angina, or other evidence suggestive of CAD.^{177 a}

• Known hypersensitivity to phentolamine, related compounds, or any ingredient in the formulation.^{177 a}

Warnings/Precautions

Warnings

Cardiovascular Effects

Risk of MI, cerebrovascular spasm or occlusion, usually in association with marked hypotension.^{177 a}

Risk of tachycardia, cardiac arrhythmias; defer cardiac glycoside administration until cardiac rhythm returns to normal.¹⁷⁷

Risk of severe hypotension or other signs and symptoms of shock; treat with prompt supportive measures and norepinephrine (if necessary).^a Do not administer epinephrine for hypotension since it may cause a paradoxical fall in BP.^a

Diagnostic Tests for Pheochromocytoma

Phentolamine and other pharmaceutical tests no longer procedures of choice for diagnosis of pheochromocytoma; may be used when additional confirmatory evidence of pheochromocytoma is required and the potential benefits of the tests outweigh the possible risks.^{177 a} Urinary assay of catecholamines or other biochemical assays are the safest and most reliable methods.^{177 a} Consider that no test is completely reliable.^{177 a}

Possible false-negative responses to phentolamine test (e.g., in patients with paroxysmal hypertension or with a pheochromocytoma not secreting enough epinephrine or norepinephrine to elevate BP or sustain an elevation).^a

False-positive reactions (occurring more commonly than false-negative) reported in patients with essential hypertension, uremia, or in those who received sedatives, opiates, or antihypertensive drugs.^a (See Specific Drugs under Interactions.)

Do not perform test on normotensive patients.^a

Major Toxicities

Intracavernosal Therapy

Intracavernosal therapy for impotence could result in persistent priapism (a medical emergency) which requires immediate medical and/or surgical intervention.^{103 105 106 107 108 110 113 115 116 120 124 125 126 127 128} If not treated immediately, penile tissue damage and permanent loss of potency may occur.^{142 152 161 162 163}

Intracavernosal therapy (administered by self-injection) may be problematic in patients receiving anticoagulants, those who cannot tolerate transient hypotension, and those with poor manual dexterity, poor vision, or severe psychiatric disease.¹²⁵

General Precautions

GI Conditions

Use with caution in patients with gastritis or peptic ulcer.^a

MI

Monitor left ventricular function and ECG continuously during IV infusion of the drug.^a

Specific Populations

Pregnancy

Category C.¹⁷⁷

Lactation

Not known whether phentolamine is distributed into milk.¹⁷⁷ Discontinue nursing or the drug.¹⁷⁷

Common Adverse Effects

Abdominal pain, nausea, vomiting, diarrhea, exacerbation of peptic ulcer, weakness, dizziness, flushing, orthostatic hypotension, and nasal congestion.^{177 a}

Drug Interactions

Specific Drugs

Phentolamine Pharmacokinetics

Absorption

Onset

IV injection: maximum effect (in positive pheochromocytoma test) within 2 minutes.^{177 a}

IM injection: maximum effect usually within 20 minutes.^{177 a}

Intracavernous injection: (penile erection) within 10 minutes.^{105 106 108 113 114 116 118 119 124}

Duration

IV injection: return to pretest BP usually within 15–30 minutes or less.^a

IM injection: return to pretest BP within 3–4 hours.^a

Intracavernous injection: penile erection may persist for 1 to several hours.^{105 106 108 113 114 116 118 119 124}

Distribution

Extent

Not known whether phentolamine is distributed into milk.^{177 a}

Elimination

Elimination Route

Excreted in urine (10–13%) as unchanged drug; the fate of the remainder is not known.^{177 a}

Half-life

19 minutes following IV administration.¹⁷⁷

Stability

Storage

Parenteral

Powder for Injection

15–30°C.^{177 a}

Use reconstituted solution at time of preparation; do not store.^{177 a}

Compatibility

Drug Compatibility

Actions

• Competitively blocks α-adrenergic receptors (primarily excitatory responses of smooth muscle and exocrine glands), but action is transient and incomplete.^a

• More effective in antagonizing responses to circulating epinephrine and/or norepinephrine than in antagonizing responses to mediator released at the adrenergic nerve ending.^a

• Causes peripheral vasodilation and decreases peripheral resistance, primarily by direct relaxation of vascular smooth muscle, but α-adrenergic blockade also contributes to vasodilation.^a

• Stimulates β-adrenergic receptors and produces a positive inotropic and chronotropic effect on the cardiac muscle (increasing cardiac output)^a and vascular effects on vascular smooth muscle.¹⁷⁷

• Usual doses lower BP maintained by circulating epinephrine or norepinephrine, but have little effect on the BP of healthy individuals or patients with essential hypertension.^a

• In patients with acute MI associated with hypertension and/or left ventricular failure, administration of IV phentolamine results in improvement in left ventricular performance; cardiac output, stroke index, heart rate, and cardiac index are increased and left ventricular filling pressure is decreased.^a

• Advise patients (using intracavernosal therapy for impotence) to contact their clinician if they develop a persistent (e.g., longer than 4 hours) erection during such therapy.^{132 133}

• Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.

• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.^{177 a}

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Medical Disclaimer