Minoxidil - Drug Monograph

Introduction

Minoxidil is a vasodilator medication initially developed as an oral antihypertensive agent but now primarily used topically for the treatment of androgenetic alopecia (pattern hair loss). It represents one of the first FDA-approved medications for hair loss and remains a cornerstone of pharmacological management for this condition.

Mechanism of Action

Minoxidil's exact mechanism in promoting hair growth is not fully understood but appears to involve multiple pathways:

• Direct stimulation of hair follicles by prolonging the anagen (growth) phase
• Vasodilation of cutaneous blood vessels, improving follicular blood supply
• Opening of potassium channels in vascular smooth muscle
• Possible effects on cellular proliferation and differentiation
• Potential modulation of androgen effects on hair follicles

The oral formulation acts as a potent peripheral arteriolar vasodilator by hyperpolarizing vascular smooth muscle cells through potassium channel activation.

Indications

• Topical: Androgenetic alopecia (male and female pattern hair loss) in adults
• Oral: Severe hypertension (resistant to maximum doses of a diuretic plus two other antihypertensives)

• Alopecia areata
• Chemotherapy-induced alopecia
• Eyebrow and eyelash enhancement
• Telogen effluvium

Dosage and Administration

• 2% solution: Apply 1 mL twice daily to affected areas
• 5% solution: Apply 1 mL twice daily (men) or once daily (women)
• Foam formulations: Half-capful twice daily

• Initial dose: 5 mg once daily
• Maintenance dose: 10-40 mg daily in single or divided doses
• Maximum dose: 100 mg daily

• Renal impairment: Dose reduction required
• Hepatic impairment: Use with caution
• Elderly: Start with lower doses
• Pediatrics: Not recommended for hair loss treatment

Pharmacokinetics

• Topical: Approximately 1.4% systemic absorption through intact skin
• Oral: Rapid and nearly complete (90%)

• Protein binding: Minimal
• Volume of distribution: Approximately 2-3 L/kg
• Crosses placenta and enters breast milk

• Extensive hepatic metabolism primarily via glucuronidation
• Sulfotransferase enzymes in hair follicles may activate minoxidil

• Half-life: 3-4 hours (parent drug)
• Primary excretion: Renal (90%), mainly as metabolites
• Dialyzable: Yes

Contraindications

• Hypersensitivity to minoxidil or any formulation components
• Pheochromocytoma
• Acute myocardial infarction
• Dissecting aortic aneurysm
• Oral formulation in pregnancy (Category C)

Warnings and Precautions

• Oral: May cause pericardial effusion, tamponade, tachycardia, angina
• Topical: Systemic absorption can cause cardiovascular effects in susceptible individuals
• Monitor for fluid retention and edema

• Irritant and allergic contact dermatitis
• Hypertrichosis (excessive hair growth) in areas beyond application site
• Exacerbation of underlying scalp conditions

• Pregnancy and breastfeeding: Use only if potential benefit justifies risk
• Patients with history of cardiovascular disease: Use with caution
• Avoid use on irritated or broken skin

Drug Interactions

• Guanethidine: Enhanced hypotensive effects
• Other antihypertensives: Additive hypotensive effects
• Topical corticosteroids: Increased systemic absorption
• Topical retinoids: May increase irritation
• Alcohol-containing products: Increased skin irritation

Adverse Effects

• Scalp irritation (7% of users)
• Pruritus (5%)
• Dryness/scaling (5%)
• Hypertrichosis (3-5%)
• Contact dermatitis (2%)

• Pericardial effusion (3%)
• Tamponade (rare)
• Tachycardia (10%)
• Fluid retention/edema (7%)
• Angina pectoris (5%)
• Electrolyte imbalances

• Temporary increased hair loss (2-8 weeks after initiation)

Monitoring Parameters

• Scalp examination for irritation
• Assessment of treatment efficacy (photographs recommended)
• Blood pressure (in susceptible patients)
• Signs of hypertrichosis

• Regular blood pressure monitoring
• ECG monitoring for tachycardia
• Body weight for fluid retention
• Echocardiogram if symptoms suggest pericardial effusion
• Renal function tests
• Electrolyte levels

Patient Education

• Apply to completely dry scalp
• Wash hands thoroughly after application
• Allow solution to dry before going to bed
• Avoid other hair products for at least 1 hour after application

• Results require 4-6 months of continuous use
• Initial shedding is normal and indicates medication activity
• Treatment must continue indefinitely to maintain results
• Effectiveness varies among individuals

• Discontinue if chest pain, dizziness, or rapid heartbeat occurs
• Report significant scalp irritation
• Avoid contact with eyes, mucous membranes, and broken skin
• Keep away from children and pets (toxic if ingested)

• Store at room temperature
• Keep away from heat and open flame
• Do not freeze

References

1. FDA Prescribing Information: Rogaine (minoxidil) topical solution 2. Messenger AG, Rundegren J. Minoxidil: mechanisms of action on hair growth. Br J Dermatol. 2004;150(2):186-194. 3. Olsen EA, Whiting D, Bergfeld W, et al. A multicenter, randomized, placebo-controlled, double-blind clinical trial of a novel formulation of 5% minoxidil topical foam versus placebo in the treatment of androgenetic alopecia in men. J Am Acad Dermatol. 2007;57(5):767-774. 4. Zins GR. The mechanism of action of minoxidil sulfate on vascular smooth muscle. J Cardiovasc Pharmacol. 1988;12 Suppl 2:S30-S36. 5. Lucky AW, Piacquadio DJ, Ditre CM, et al. A randomized, placebo-controlled trial of 5% and 2% topical minoxidil solutions in the treatment of female pattern hair loss. J Am Acad Dermatol. 2004;50(4):541-553. 6. Physician's Desk Reference, 2023 Edition 7. UpToDate: Minoxidil drug information 8. Lexicomp Online: Minoxidil monograph