DIBENZYLINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DIBENZYLINE (DIBENZYLINE).
Phenoxybenzamine is an irreversible, non-selective alpha-adrenergic antagonist that binds covalently to alpha-1 and alpha-2 receptors, blocking the effects of catecholamines. It also has antihistaminic and antiserotonergic activity.
| Metabolism | Metabolized in the liver via unknown pathways; produces an active metabolite (N-desmethyl phenoxybenzamine). Undergoes enterohepatic recirculation. |
| Excretion | Primarily renal elimination of metabolites; <1% excreted unchanged in urine. Biliary/fecal excretion accounts for a minor fraction. |
| Half-life | Approximately 24 hours. Due to irreversible alpha-adrenergic receptor blockade, the clinical duration of action significantly exceeds the plasma half-life. |
| Protein binding | ~99% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Approximately 10-20 L/kg. Large Vd indicates extensive tissue distribution and high receptor binding. |
| Bioavailability | Oral: 20-30% due to extensive first-pass metabolism. No intravenous bioavailability data (administered IV). |
| Onset of Action | Oral: 2-4 hours. Intravenous: 15-30 minutes. |
| Duration of Action | 3-4 days after single dose; cumulative effect with repeated dosing due to irreversible receptor binding. |
Initial dose: 10 mg orally once daily. Increase by 10 mg at 4-day intervals as tolerated. Usual maintenance dose: 20-40 mg orally once daily. Maximum: 60 mg daily.
| Dosage form | CAPSULE |
| Renal impairment | No specific dose adjustment guidelines available. Use with caution in severe renal impairment due to potential for accumulation. |
| Liver impairment | No specific dose adjustment guidelines available. Use with caution in severe hepatic impairment. |
| Pediatric use | Initial: 0.2 mg/kg orally once daily. Increase gradually. Maximum: 10 mg daily. Safety and efficacy not established in children under 12 years. |
| Geriatric use | Initiate at lower dose (10 mg orally once daily) and titrate cautiously due to increased sensitivity, risk of orthostatic hypotension, and potential anticholinergic effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DIBENZYLINE (DIBENZYLINE).
| Breastfeeding | No data on excretion in human milk. M/P ratio unknown. Because of the potential for serious adverse reactions (e.g., hypotension, tachycardia) in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. |
| Teratogenic Risk | Pregnancy Category C. Animal studies have shown adverse effects (e.g., fetal resorption, skeletal anomalies) at doses 2-3 times the human dose. No adequate human studies. Risk cannot be ruled out; use only if potential benefit justifies potential risk. First trimester: possible teratogenic effects based on animal data. Second and third trimesters: risk of fetal hypoxia due to maternal hypotension and reduced uterine blood flow. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to phenoxybenzamine or any component of the formulation","Conditions where a fall in blood pressure is undesirable (e.g., hypotension, recent myocardial infarction, stroke)","Concurrent use with specific alpha-2 agonists (may antagonize effects)","Severe renal impairment (relative contraindication)","Pregnancy and lactation (risk vs. benefit assessment required)"]
| Precautions | ["May cause severe hypotension, especially when rising from a supine position (orthostatic hypotension)","May cause reflex tachycardia","Use with caution in patients with cerebrovascular or cardiovascular disease","May cause nasal congestion, miosis, and ejaculatory failure","Potential for drug interactions with other antihypertensives and alpha agonists","Should be avoided in patients with a history of severe allergic reaction to the drug"] |
| Food/Dietary | No specific food restrictions, but avoid alcohol as it may exacerbate orthostatic hypotension. Take with food or milk to minimize gastrointestinal irritation. Avoid tyramine-rich foods (e.g., aged cheeses, cured meats) if also taking MAOIs, though this is not a direct interaction with phenoxybenzamine. |
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| Fetal Monitoring | Monitor maternal blood pressure and heart rate closely, especially during dose titration and in the perioperative period. Fetal heart rate monitoring recommended during labor and delivery to detect signs of fetal distress. Assess uterine tone and activity due to potential effects on uterine smooth muscle. |
| Fertility Effects | No adequate studies on fertility effects in humans. In animal studies, phenoxybenzamine caused reversible inhibition of ejaculation in males and may impair fertility (e.g., decreased sperm motility). In females, no significant effects on fertility observed in animal studies. |
| Clinical Pearls | Dibenzyline (phenoxybenzamine) is a non-selective, irreversible alpha-adrenergic blocker used primarily for the management of pheochromocytoma. Its long duration of action (3-4 days) stems from covalent binding to alpha receptors. Always initiate therapy in a hospital setting due to risk of profound hypotension and reflex tachycardia. Dose titration is essential to control hypertension while minimizing orthostatic hypotension. Preoperative use for pheochromocytoma requires alpha blockade for at least 10-14 days before surgery. Stools and urine may turn pink or red due to metabolite excretion; educate patient to avoid alarm. Avoid use in patients with shock or heart failure. Concurrent beta-blockers should be used cautiously to prevent unopposed alpha-mediated vasoconstriction. |
| Patient Advice | Take this medication exactly as prescribed, usually twice daily with meals to reduce stomach upset. · Rise slowly from sitting or lying down to prevent dizziness and fainting due to low blood pressure on standing. · This drug may cause nasal congestion, drowsiness, or blurred vision; avoid driving if affected. · Your urine or stool may turn pink or reddish; this is harmless and due to the medication. · Avoid alcohol and other medications that lower blood pressure without consulting your doctor. · Do not stop taking this medicine suddenly unless directed by your doctor. · Keep all appointments for blood pressure monitoring and dose adjustments. |