Phenoxybenzamine (Monograph)

Brand name: Dibenzyline
Drug class: Non-selective alpha-Adrenergic Blocking Agents
VA class: AU200
CAS number: 63-92-3

Medically reviewed by Drugs.com on Mar 22, 2024. Written by ASHP.

Introduction

α-Adrenergic blocking agent; a haloalkylamine.^{a b}

Uses for Phenoxybenzamine

Pheochromocytoma

Prevention or treatment of paroxysmal hypertension and sweating in patients with pheochromocytoma.^{a b}

Considered drug of choice for medical management of pheochromocytoma until surgery is performed and for prolonged treatment of hypertension caused by pheochromocytoma notamenable to surgery.^a

Used in conjunction with a β-adrenergic blocking agent (propranolol) to control symptoms from excessive β-receptor stimulation in patients with inoperable or metastatic pheochromocytoma or to control tachycardia prior to or during pheochromocytomectomy.^{a b} (See General under Dosage and Administration.)

Peripheral Vascular Diseases

Has been used as adjunctive therapy in the treatment of peripheral vasospastic disorders associated with increased α-adrenergic activity^{† [off-label]} (e.g., Raynaud’s syndrome, acrocyanosis, and frostbite sequelae) but efficacy in the treatment of peripheral vascular disease is not established.^a

Phenoxybenzamine should not be used in diseases affecting large blood vessels.^a

Micturition Disorders and Urinary Retention

Has been used in the treatment of micturition disorders^{† [off-label]} resulting from neurogenic bladder,¹⁰⁰ functional outlet obstruction,¹⁰⁰ or partial prostatic obstruction.^{100 101 102 103}

Has been used for the prevention and treatment of acute postoperative urinary retention^{† [off-label]},^{105 106 107 108} including that associated with the use of epidural morphine.^{107 108}

Phenoxybenzamine Dosage and Administration

General

• Adjust dosage carefully according to individual requirements and response.^{a b}

• Minimize adverse effects by starting with small doses and gradually increasing the dosage until the desired effect is obtained or adverse effects occur.^{a b}

• If concomitant propranolol therapy is required, initiate phenoxybenzamine prior to use of propranolol and continue during propranolol therapy in order to prevent severe hypertension due to unopposed α-adrenergic stimulation.^a

Administration

Oral Administration

Administer orally in divided doses.^a If GI irritation occurs, administer with milk.^a

Dosage

Available as phenoxybenzamine hydrochloride; dosage expressed in terms of the salt.^a

Pediatric Patients

Pheochromocytoma

Oral

Initially, 0.2 mg/kg or 6 mg/m² once daily; do not exceed 10 mg. ^a

Increase dosage gradually until an adequate response is achieved (e.g., BP is controlled). ^a

Usual maintenance dosage: 0.4–1.2 mg/kg or 12–36 mg/m² daily.^a

Adults

Pheochromocytoma

Oral

Initially, 10 mg twice daily.^{a b}

Increase dosage gradually every other day until an adequate response is achieved (e.g., BP is controlled).^{a b}

Usual maintenance dosage: 20–40 mg 2 or 3 times daily; higher dosages may be required.^a

Peripheral Vascular Diseases† [off-label]

Oral

Initially, 10 mg twice daily. ^a

Increase dosage gradually every other day until an adequate response is achieved.^a

Usual maintenance dosage: 20–40 mg 2 or 3 times daily; higher dosages may be required.^a

Prescribing Limits

Pediatric Patients

Pheochromocytoma

Oral

Initially, maximum 10 mg daily.^a

Special Populations

No special population dosage recommendations at this time.^b

Cautions for Phenoxybenzamine

Contraindications

• Conditions where a decrease in BP is undesirable.^{a b}

• Known hypersensitivity to phenoxybenzamine or any ingredient in the formulation.^b

Warnings/Precautions

Warnings

Cardiovascular Effects

Phenoxybenzamine’s α-adrenergic blocking effect leaves β-receptors unopposed; concomitant use with drugs that stimulate α- and β-adrenergic receptors (i.e., epinephrine) may cause an exaggerated hypotensive response and tachycardia.^b (See Specific Drugs under Interactions.)

Phenoxybenzamine-induced tachycardia may precipitate CHF and angina in patients with compensated CHF or CAD.^a

General Precautions

Respiratory Effects

May aggravate symptoms of respiratory infections.^b

Arteriosclerosis

Use with caution in patients with marked cerebral or coronary arteriosclerosis.^b

Specific Populations

Pregnancy

Category C.^b

Lactation

Not known whether phenoxybenzamine is distributed into milk.^{a b} Caution if used in nursing women.^{a b}

Pediatric Use

Safety and efficacy not established.^b

Renal Impairment

Use with caution in patients with renal damage.^b

Common Adverse Effects

Nasal congestion,^{a b} miosis,^{a b} postural hypotension,^a dizziness,^a tachycardia.^{a b}

Drug Interactions

Specific Drugs

Phenoxybenzamine Pharmacokinetics

Absorption

Bioavailability

Variably absorbed from the GI tract;^a 20–30% of an oral dose is absorbed.^b

Onset

Following oral administration, onset of action is gradual over a period of several hours. ^a

Duration

α-Adrenergic blockade persists for 3–4 days following oral administration of a single dose; after administration of fixed daily doses, α-adrenergic blocking effects are cumulative for about 7 days.^a

Distribution

Extent

Highly lipid soluble; may accumulate in fat following administration of large doses.^a

Not known whether phenoxybenzamine crosses the placenta or is distributed into milk.^{a b}

Elimination

Metabolism

Dealkylated to form N-phenoxyisopropyl-benzylamine.^a

Elimination Route

Excreted in urine and bile.^a

Half-life

Approximately 24 hours.^{a b}

Stability

Storage

Oral

Capsules

25°C (may be exposed to 15–30°C).^b

Actions

• Long-acting, α-adrenergic blocking agent that produces and maintains chemical sympathectomy.^b

• Inhibits responses (primarily excitatory responses of smooth muscle and exocrine glands) to adrenergic stimuli by noncompetitively blocking α-adrenergic receptors; however, does not affect β-adrenergic receptors^a or the parasympathetic system.^b

• Exact mechanism of action not fully elucidated; appears to form a reactive ethylenimonium intermediate and a highly reactive carbonium ion that forms stable covalent bonds with sulfhydryl, phosphate, amino, and carboxyl groups of α-adrenergic receptors.^a

• Blocks α-adrenergic responses to circulating epinephrine and/or norepinephrine and to norepinephrine released at the adrenergic nerve ending.^a

• Acts on vascular smooth muscle to block epinephrine- and norepinephrine-induced vasoconstriction and causes peripheral vasodilation and reflex tachycardia.^a Reverses the pressor effect of epinephrine (“epinephrine reversal”) and blocks, but does not reverse, the vasoconstrictor effects of norepinephrine.^a

• Increases blood flow to the skin, mucosa, and abdominal viscera; lowers BP;^b blocks pupillary dilation, lid retraction, and adrenergically mediated sweating; and decreases uterine motility.^a

Advice to Patients

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

• Importance of taking only as prescribed; do not increase dosage or duration of therapy unless otherwise instructed by a clinician.^a

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^a

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

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.

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