Phenoxybenzamine is a medication primarily used to manage symptoms associated with pheochromocytoma, a rare tumor of the adrenal glands that can cause high blood pressure and other symptoms due to excessive catecholamine secretion. It belongs to a class of drugs known as alpha blockers, which work by relaxing certain muscles and blood vessels to improve blood flow and lower blood pressure.

Phenoxybenzamine works by blocking alpha-adrenergic receptors, specifically the alpha-1 receptors. By doing so, it prevents the action of adrenaline and noradrenaline (epinephrine and norepinephrine), leading to relaxation of smooth muscle in blood vessels and other parts of the body. This relaxation results in vasodilation (widening of blood vessels), which reduces blood pressure and improves blood flow to various organs.

Phenoxybenzamine is a non-selective alpha-adrenergic receptor blocker that acts on the post-ganglionic smooth muscles present in the blood vessels and urinary bladder. It is thus used to treat hypertension associated with pheochromocytoma and urination problems.

Phenoxybenzamine Uses:

• Pheochromocytoma:
  • It is indicated for the treatment of sweating and hypertension associated with pheochromocytoma.
• Off Label Use of Phenoxybenzamine in Adults:
  • It is used in the treatment of hypertensive crisis caused by sympathomimetic amines;
  • It is used for problems of micturition associated with neurogenic bladder, functional outlet obstruction, and partial prostate obstruction.

Other alpha-adrenergic receptor blockers include:

• Tamsulosin (Flomax)
• Alfuzosin (Uroxatral)
• Doxazosin (cardura)

Phenoxybenzamine Dose in Adults

Phenoxybenzamine Dose in the treatment of Pheochromocytoma:

• Phenoxybenzamine is a medicine used to treat a rare tumor called pheochromocytoma, which can cause high blood pressure.
• When taken by mouth, the typical starting dose is 10 mg twice a day.
• Doctors may increase the dose slowly every other day until the blood pressure gets better.
• The usual range is 20 to 40 mg taken 2 to 3 times a day.
• Some people may need higher doses, up to 240 mg daily, but this is less common.

Phenoxybenzamine Dose in the treatment of Micturition disorders (off-label):

• When phenoxybenzamine is used off-label to treat micturition disorders (problems with urination), the typical oral dose is 10 to 20 mg taken 1 to 2 times a day.
• This dosage may vary depending on individual factors, so it's essential to follow your doctor's instructions carefully.

Phenoxybenzamine Dose in Childrens

Phenoxybenzamine Dose in the preoperative management of Pheochromocytoma:

• In children and adolescents being treated for pheochromocytoma before surgery, the initial oral dose of phenoxybenzamine is typically 0.2 to 0.25 mg per kilogram of body weight, given once or twice a day.
• The maximum dose for a single administration is 10 mg.
• Doctors may gradually increase the dose every 4 days until the desired effect is achieved.
• Reported maintenance doses range from 0.4 to 3 mg per kilogram of body weight per day, divided into doses every 6 to 8 hours.
• The maximum single maintenance dose is 40 mg, and the maximum daily dose is 4 mg per kilogram of body weight per day.

Pregnancy Risk Factor C

• Phenoxybenzamine has a pregnancy risk factor of C, meaning there haven't been enough studies in animals to know its effects on pregnancy.
• It's uncertain if taking phenoxybenzamine during pregnancy can harm the baby or affect the ability to have children.
• If you're pregnant or planning to become pregnant, it's essential to talk to your doctor about the potential risks and benefits of using phenoxybenzamine.

Use during breastfeeding:

• It's uncertain if phenoxybenzamine passes into breast milk.
• Since serious side effects could occur in the nursing baby, the manufacturer advises either stopping breastfeeding or discontinuing the drug, considering how important the treatment is for the mother's health.

Dose in Kidney Disease:

• The manufacturer's labeling does not specify any dosage adjustments for phenoxybenzamine in individuals with renal impairment.
• However, it's advised to use the medication with caution in such cases.
• If you have kidney problems and need to take phenoxybenzamine, your doctor will monitor you closely and may adjust the dosage if necessary to ensure your safety and effectiveness of the treatment.

Dose in Liver Disease:

• The manufacturer's labeling does not mention any specific dosage adjustments for phenoxybenzamine in individuals with hepatic (liver) impairment.
• However, it's important to use caution when administering the medication to patients with liver problems.

Side effects of phenoxybenzamine:

• Cardiovascular:
  • Orthostatic Hypotension
  • Tachycardia
• Central Nervous System:
  • Drowsiness
  • Fatigue
  • Inhibited Ejaculation
• Gastrointestinal:
  • Gastrointestinal Irritation
• Ophthalmic:
  • Miosis
• Respiratory:
  • Nasal Congestion

Contraindications to Phenoxybenzamine:

• Phenoxybenzamine should not be used in individuals who have a hypersensitivity (allergic reaction) to the drug itself or any component of its formulation.
• Additionally, it should be avoided in conditions where a decrease in blood pressure could be harmful or undesirable.

Warnings and precautions

Cardiovascular effects

• When taken with medications that stimulate both alpha- and beta-adrenergic receptors, phenoxybenzamine may lead to an exaggerated drop in blood pressure and faster heart rate

Cardiovascular disease

• People with significant blockages in blood vessels of the brain or heart should use phenoxybenzamine cautiously.

Renal impairment

• If you have kidney problems, be cautious when using phenoxybenzamine.

Respiratory infection

• Phenoxybenzamine could worsen symptoms of respiratory infections.

Phenoxybenzamine: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring Parameters:

Phenoxybenzamine can affect your blood pressure, pulse rate, and orthostatic measurements.

• Blood Pressure: It can lower your blood pressure, helping to manage conditions like high blood pressure or pheochromocytoma.
• Pulse: It may cause your pulse rate to increase, especially if you're also taking medications that stimulate both alpha- and beta-adrenergic receptors.
• Orthostatics: When you change positions (like going from lying down to standing up), phenoxybenzamine might affect how your body adjusts, possibly leading to dizziness or lightheadedness.

How to administer Phenoxybenzamine?

• When taking phenoxybenzamine orally, you can take it with or without food.
• If you experience stomach upset, taking it with milk may help to reduce this discomfort.

Mechanism of action of Phenoxybenzamine:

• Phenoxybenzamine works by creating a prolonged and noncompetitive blockage of alpha-adrenergic receptors in the nerves after they leave the spinal cord.
• This action occurs in both the glands that release fluids and the smooth muscles of the body.
• Specifically, it helps to relax the muscles around the urethra and increases the opening of the bladder.

Onset of Action:

• Phenoxybenzamine typically starts working within 2 hours of administration, with its maximum effect occurring within 4 to 6 hours.

Duration:

• When given intravenously (IV), its effects can last for at least 3 to 4 days.

Distribution:

• It spreads throughout the body, potentially building up in fatty tissues.

Bioavailability:

• Around 20% to 30% of the drug is absorbed into the bloodstream when taken orally.

Half-life Elimination:

• The half-life of phenoxybenzamine when given intravenously is approximately 24 hours.

Excretion:

• The drug is primarily eliminated from the body through urine and bile.

International Brand Names of Phenoxybenzamine:

• Dibenzyline
• Dibenzyran
• Fenoxene
• Lition
• Seton

Phenoxybenzamine Brand Names in Pakistan:

No Brands Available in Pakistan.