Phenoxybenzamine
Medicine Type :
Allopathy
Allopathy
Prescription Type:
Prescription Required
Prescription Required
Approval :
DCGI (Drugs Controller General of India)
DCGI (Drugs Controller General of India)
Schedule
Schedule H
Schedule H
Pharmacological Class:
Alpha Adrenergic blockers, Therapy Class:
Antihypertensive, Phenoxybenzamine is an Antihypertensive agent belonging to Alpha Adrenergic blockers.
Phenoxybenzamine is used to treat Pheochromocytoma and episodes of hypertension and sweating. It is also used to treat Hypertensive crises caused by sympathomimetic amines, Micturition problems associated with neurogenic bladder, functional outlet obstruction, and partial prostate obstruction.
Phenoxybenzamine is Incompletely and variably absorbed from the gastrointestinal tract with a bioavailability of 20-30% and gets distributed and accumulates in the adipose tissues.
It gets metabolized in the liver via dealkylation into N-phenoxyisopropyl-benzylamine and gets excreted mainly via urine and bile with an elimination half-life of approx 24 hours.
The onset of Action of Phenoxybenzamine is within 2 hr
The Duration of action of Phenoxybenzamine is ≥3-4 days.
The common side effects are dizziness, drowsiness, headache, weakness, Nausea, strong irregular heartbeat, swelling, and dizziness upon standing.
Phenoxybenzamine is available in the form of a dosage form, such as a capsule.
Phenoxybenzamine is available in the USA, UK, Canada, Australia, and India.
Phenoxybenzamine produces its therapeutic actions by blocking alpha receptors, leading to muscle relaxation and a widening of the blood vessels. This widening of the blood vessels results in a lowering of blood pressure.
Phenoxybenzamine is available in the form of a dosage form, such as a capsule.
Phenoxybenzamine comes as a capsule to take by mouth. It usually is taken two or three times a day.
Phenoxybenzamine is used to treat Pheochromocytoma and episodes of hypertension and sweating. It is also used to treat Hypertensive crises caused by sympathomimetic amines; Micturition problems associated with neurogenic bladder, functional outlet obstruction, and partial prostate obstruction.
Phenoxybenzamine covalently binds to α-receptors causing long-lasting noncompetitive inhibition of postganglionic synapses, thus blocking the effects of epinephrine and norepinephrine at α1 and α2 receptors, causing arterial and venous vasodilation and reflex tachycardia.
Phenoxybenzamine is approved for its use in the following clinical indications:-
- Pheochromocytoma: Treatment of sweating and hypertension associated with Pheochromocytoma.
Although not approved, there have been certain label use documented for Phenoxybenzamine which include:
- The hypertensive crisis caused by sympathomimetic amines; Micturition problems associated with neurogenic bladder, functional outlet obstruction, and partial prostate obstruction
Phenoxybenzamine is available in various dosage strengths: 10 mg.
Phenoxybenzamine is available in the form of a dosage form such as a capsule.
- Dose Adjustment in Pediatric Patients.
Pheochromocytoma, preoperative management:
Children and Adolescents:
Oral: Initial: 0.2 to 0.25 mg/kg/dose once or twice daily; maximum dose: 10 mg/dose; slowly titrate (eg, every 4 days) to effect; increments of 0.2 mg/kg/day have been reported; reported maintenance dose range: 0.4 to 3 mg/kg/day in divided doses every 6 to 8 hours; maximum single maintenance dose: 40 mg/dose; maximum daily dose: 4 mg/kg/day.
- Dosage adjustment for concomitant therapy:
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Phenoxybenzamine is approved for the treatment of Pheochromocytoma.
Foods high in tyramine, a substance that affects blood pressure, also can make symptoms worse. Tyramine is common in foods that are fermented, aged, pickled, cured, overripe or spoiled
Phenoxybenzamine may be in the following
- Hypersensitivity to drug or any component of the formulation; conditions in which a fall in blood pressure may be undesirable.
- CVA, recovery period (usually 3-4 weeks) after acute MI, conditions where a decrease in blood pressure may be undesirable (e.g. coronary artery disease, stroke)
The treating physician must closely monitor the patient and keep pharmacovigilance as follows.
Concerns related to adverse effects:
• Cardiovascular effects: An exaggerated hypotensive response and tachycardia may occur when administered concurrently with compounds that stimulate both alpha- and beta-adrenergic receptors.
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with marked cerebral or coronary atherosclerosis.
• Renal impairment: Use with caution in patients with renal impairment.
• Respiratory infection: May aggravate symptoms of respiratory infections.
Dosage form specific issues:
• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity ("gasping syndrome") in neonates; the "gasping syndrome" consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse.
Other warnings/precautions:
• Long-term use: Not recommended for long-term use due to case reports of cancer in humans; carefully weigh the risk and benefits before use.
Alcohol Warning
Avoid taking alcohol with Phenoxybenzamine as it may result in side effects like headache, dizziness and faintness.
Pregnancy Warning
Pregnancy - Teratogenic Effects
Pregnancy Category C
Adequate reproductive studies in animals have not been performed with phenoxybenzamine hydrochloride. It is also not known whether Phenoxybenzamine can cause fetal harm when administered to a pregnant woman. Phenoxybenzamine should be given to a pregnant woman only if clearly needed.
Food Warning
Salt Substitutes: Those who are taking Phenoxybenzamine should avoid sodium, calcium and magnesium-rich foods. The salts may reduce the blood-pressure lowering effect of Phentolamine.
The adverse reactions related to molecule Phenoxybenzamine can be categorized as
- Common Adverse effect:
Cough ,headache, dizziness, drowsiness
- Less Common adverse effects:
Swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower, hoarseness, difficulty breathing or swallowing, lightheadedness, fainting, rash, yellowing of the skin or eyes, fever, sore throat, chills, and other signs of infection.
- Rare Adverse effect:
Postural hypotension with dizziness, compensatory tachycardia.
The clinically relevant drug interactions of Phenoxybenzamine is briefly summarized here.
Lidocaine and Epinephrine
- Alpha-/Beta-Agonists: Alpha1-Blockers may diminish the vasoconstricting effect of Alpha-/Beta-Agonists. Similarly, Alpha-/Beta-Agonists may antagonize Alpha1-Blocker vasodilation. Monitor therapy
- Alpha1-Agonists: Alpha1-Blockers may diminish the vasoconstricting effect of Alpha1-Agonists. Similarly, Alpha1-Agonists may antagonize Alpha1-Blocker vasodilation. Monitor therapy
- Alpha1-Blockers: May enhance the antihypertensive effect of other Alpha1-Blockers. Avoid combination
- Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification
- Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy
- Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy
- Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
- Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
- Beta-Blockers: May enhance the orthostatic hypotensive effect of Alpha1-Blockers. The risk associated with ophthalmic products is probably less than systemic products.
- Symptoms: Profound hypotension leading to dizziness or fainting, tachycardia, collapse, vomiting, lethargy, shock.
- Management: Symptomatic and supportive treatment. Induce vomiting and/or gastric lavage. Treat hypotension with plasma expanders and by postural measures.
Pharmacodynamics:
Phenoxybenzamine covalently binds to α-receptors causing long lasting noncompetitive inhibition of postganglionic synapses thus blocking the effects of epinephrine and norepinephrine at α1 and α2 receptors causing arterial and venous vasodilation and reflex tachycardia.
It produces long-lasting noncompetitive alpha-adrenergic blockade of postganglionic synapses in exocrine glands and smooth muscle; relaxes urethra and increases opening of the bladder
Pharmacokinetics:
- Absorption: Incompletely and variably absorbed from the gastrointestinal tract. Bioavailability: 20-30%.
- Distribution: Distributed and accumulates in the adipose tissues.
- Metabolism: Metabolized in the liver via dealkylation into N-phenoxyisopropyl-benzylamine.
- Excretion: Mainly via urine and bile. Elimination half-life: Approx. 24 hour.
There are some clinical studies of the drug Phenoxybenzamine mentioned below:
- https://druginfo.nlm.nih.gov/m.drugportal/rn/75659-07-3
- https://clinicaltrials.gov/ct2/show/NCT03960866
- https://pubmed.ncbi.nlm.nih.gov/18573982/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076863/
- https://www.mims.com/india/drug/info/Phenoxybenzamine ?type=full&mtype=generic
- https://www.uptodate.com/contents/Phenoxybenzamine-drug-information?search=Phenoxybenzamine -drug-in&usage_type=panel&kp_tab=drug_general&source=search_result&selectedTitle=1~37&display_rank=1#F162889
- https://go.drugbank.com/drugs/DB00590
- https://www.rxlist.com/consumer_Phenoxybenzamine _cardura/drugs-condition.htm
- https://reference.medscape.com/drug/cardura-xl-Phenoxybenzamine -342343
Published on: 25 Oct 2022 10:37 AM GMT
