Minoxidil

Minoxidil is a potent direct arteriolar vasodilator. Oral tablets are kept for severe hypertension that has not responded to several other drugs, and the same molecule applied to the scalp treats male and female pattern hair loss. It always needs a beta blocker and a loop diuretic alongside it, because it causes reflex tachycardia and marked sodium and water retention.

Classification. Direct acting arteriolar vasodilator; potassium channel opener (through the active sulphate metabolite).

Mechanism. Minoxidil sulphate opens ATP sensitive potassium channels in arteriolar smooth muscle, causing hyperpolarisation and relaxation. Veins are barely affected. On the scalp it prolongs the growth phase of hair follicles.

Pharmacodynamics. Oral onset within 30 minutes, peak effect 2 to 8 hours, and a blood pressure effect that lasts up to 75 hours despite a short plasma half life. Diastolic pressure falls more than systolic. Hair growth takes 3 to 6 months of topical use.

Pharmacokinetics. Oral absorption about 90%. Plasma half life about 4 hours. Roughly 90% is metabolised in the liver (mainly by glucuronidation) and the rest is excreted in urine. Topical absorption through intact scalp is about 1 to 2%.

Severe resistant hypertension, adult (oral, specialist).

• Start 5 mg once daily (2.5 mg in older adults or kidney impairment).

• Increase by 5 to 10 mg at intervals of at least 3 days (faster only under close observation).

• Usual maintenance 10 to 40 mg daily as a single dose or in 2 divided doses; maximum 100 mg daily.

• Give with a beta blocker (for example atenolol 50 to 100 mg daily or an equivalent) and a loop diuretic (furosemide 40 mg twice daily at the start, adjusted as needed).

Hypertension, children under 12 years (specialist). Start 0.2 mg/kg once daily; increase by 0.1 to 0.2 mg/kg every 3 days; usual maintenance 0.25 to 1 mg/kg daily; maximum 50 mg daily. Over 12 years: adult dosing.

Pattern hair loss, adult (topical).

• Men: 5% solution or foam, 1 mL (solution) or half a capful (foam) applied to the dry scalp twice daily; maximum 2 mL daily.

• Women: 2% solution 1 mL twice daily, or 5% foam half a capful once or twice daily.

• Wash hands after use. Review at 4 to 6 months and stop if there is no response.

Contraindications. Phaeochromocytoma; acute myocardial infarction (within the first weeks); dissecting aortic aneurysm; pulmonary hypertension due to mitral stenosis; pericardial effusion unless treated; porphyria; hypersensitivity. Topical use: broken or inflamed scalp skin.

Warnings. Pericardial effusion and tamponade (check clinically and by echocardiogram when dyspnoea or chest pain appears); salt and water retention and heart failure; worsening angina from reflex tachycardia; hypertrichosis in nearly all patients on oral treatment (counsel women and children early). Do not start as an outpatient without monitoring: first doses can cause a rapid fall in blood pressure.

Adverse effects. Fluid retention, oedema, tachycardia, hypertrichosis, ECG T wave changes, pericardial effusion, headache, breast tenderness. Topical: scalp irritation, unwanted facial hair, dizziness if absorbed.

Interactions. Guanethidine: severe postural hypotension (avoid). Other antihypertensives and anaesthetics: additive hypotension. Non steroidal anti-inflammatory drugs: block the antihypertensive effect and worsen retention. Sympathomimetics: reduce effect. Topical tretinoin or irritants raise absorption.

Special groups.

• Pregnancy: oral use only if essential, with specialist care; hypertrichosis has been reported in the newborn. Topical use: avoid.

• Breastfeeding: excreted in milk; avoid oral use. Topical: avoid.

• Patients of African ancestry: good response to vasodilators, but the same need for a diuretic and a beta blocker applies.

• Older adults: start at 2.5 mg once daily.

• Kidney impairment: start 2.5 mg; the active metabolite accumulates; large fluid shifts on dialysis, so give the dose after dialysis.

• Liver impairment: use with care and lower doses.

Formulations. Tablets 2.5 and 10 mg; topical solution 2% and 5%; topical foam 5%.

Administration. Oral tablets with or without food, at the same time each day. Never use as a single antihypertensive.

Baseline. Blood pressure (lying and standing), heart rate, ECG, weight, creatinine, electrolytes, clinical examination for heart failure and pericardial rub.

Monitoring. Blood pressure and heart rate at each dose change. Daily weight and oedema; target a weight gain of less than 1 kg a week. Sodium, potassium and creatinine 1 to 2 weeks after any dose change, then every 3 to 6 months. Repeat ECG at 1 to 2 months, and echocardiogram if any symptom of effusion.

Stopping. Withdraw slowly over weeks while blood pressure is watched; if stopped abruptly, a rebound rise in blood pressure is possible. Stop at once if pericardial effusion or tamponade develops.

Common prescribing errors. Giving without a loop diuretic or a beta blocker; starting at 10 mg or more; not warning women about hair growth; using the 5% preparation on the scalp of women at the wrong frequency; letting a child take adult tablets.