minoxidil (Rx)

>10%

Hypertrichosis (80%)

Abnormal ECG (60%)

1-10%

Pericardial effusion (3%)

Frequency Not Defined

Angina

Cardiac tamponade

Fluid and sodium retention

Hypotension

Pericarditis

Tachyarrhythmia

Stevens-Johnson syndrome (rare )

Hirsutism

Leukopenia (rare)

Thrombocytopenia (rare)

Toxic epidermal necrolysis

Contraindications

Hypersensitivity to minoxidil

Pheochromocytoma

Cautions

Reserve for severe hypertension refractory to other drugs

In patients with severe blood pressure elevation, too rapid control of blood pressure, especially with intravenous agents, can precipitate syncope, cerebrovascular accidents, myocardial infarction and ischemia of special sense organs with resulting decrease or loss of vision or hearing; patients with compromised circulation or cryoglobulinemia may also suffer ischemic episodes of affected organs

Patients with malignant hypertension should have initial treatment with minoxidil carried out in a hospital setting, both to assure that blood pressure is falling and to assure that it is not falling more rapidly than intended

Neonatal hypertrichosis reported following exposure to minoxidil during pregnancy

Although minoxidil does not itself cause orthostatic hypotension, administration to patients already receiving guanethidine can result in profound orthostatic effects; if at all possible, discontinue guanethidine well before minoxidil is begun; if this is not possible, therapy should be started in hospital and patient should remain institutionalized until severe orthostatic effects are no longer present or patient has learned to avoid activities that provoke them

Therapy not used in patients who have had a myocardial infarction within preceding month; it is possible that reduction of arterial pressure with drug might further limit blood flow to myocardium, although this might be compensated by decreased oxygen demand because of lower blood pressure

Patients with renal failure or on dialysis, may require smaller doses and should have close medical supervision to prevent exacerbation of renal failure or precipitation of cardiac failure

Pericarditis and pericardial effusion

• There have been reports of pericarditis occurring in association with therapy; the relationship of this association to renal status is uncertain; pericardial effusion, occasionally with tamponade, has been observed in about 3% of treated patients not on dialysis, especially those with inadequate or compromised renal function
• Although in many cases, pericardial effusion associated with a connective tissue disease, uremic syndrome, congestive heart failure, or marked fluid retention, there have been instances in which these potential causes of effusion were not present; observe patients closely for any suggestion of a pericardial disorder, and perform echocardiographic studies if suspicion arises
• More vigorous diuretic therapy, dialysis, pericardiocentesis, or surgery may be required; if effusion persists, withdrawal of drug should be considered in light of other means of controlling hypertension and patient’s clinical status

Concomitant treatment for prevention of tachycardia

• Therapy increases heart rate; angina may worsen or appear for first time during treatment, probably because of increased oxygen demands associated with increased heart rate and cardiac output
• Increase in rate and occurrence of angina generally can be prevented by concomitant administration of a beta-adrenergic blocking drug or other sympathetic nervous system suppressant
• Ability of beta-adrenergic blocking agents to minimize papillary muscle lesions in animals further supports using agent concomitantly; round-the-clock effectiveness of sympathetic suppressant should be ensured

Water retention

• Congestive heart failure—concomitant use of adequate diuretic required; drug must usually be administered concomitantly with diuretic adequate to prevent fluid retention and possible congestive heart failure; high ceiling (loop) diuretic is almost always required
• Monitor body weight if drug is used without a diuretic; retention of several hundred milli-equivalents of salt and corresponding volumes of water can occur within a few days, leading to increased plasma and interstitial fluid volume and local or generalized edema
• Diuretic treatment alone, or in combination with restricted salt intake, will usually minimize fluid retention, although reversible edema did develop in approximately 10% of nondialysis patients so treated
• Ascites reported; diuretic effectiveness limited mostly by disease-related impaired renal function; condition of patients with preexisting congestive heart failure occasionally deteriorated in association with fluid retention although because of fall in blood pressure (reduction of afterload), more than twice as many improved than worsened
• Rarely, refractory fluid retention may require discontinuation of therapy; provided that patient is under close medical supervision, it may be possible to resolve refractory salt retention by discontinuing therapy for 1 or 2 days and then resuming treatment in conjunction with vigorous diuretic therapy

Pregnancy Category: C

Lactation: controversial; excreted in breast milk, not recommended for long term use if breastfeeding

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Direct vasodilator; dilate arterioles with little effect on vein, decreases systemic resistance, which subsequently decreases blood pressure.

Pharmacokinetics

Half-Life: 4 hr

Excretion: Urine (12% as unchanged drug)

Duration: 2-5 Days

Peak Plasma Time: PO (HTN): 1 hr

Bioavailability: PO (HTN): 90%

Protein Bound: Negligible

Metabolism: liver, 88% via glucuronidation

Metabolite: minoxidil-0-glucuronide (active)

Onset

• Initial effect: PO (HTN): 30-60 min
• Max effect: PO (HTN): 4-8 hr