Minoxidil (minoxidil)

Dosage of minoxidil must be adjusted according to the patient's blood pressure response and tolerance.

The need for pretreatment with certain drugs (e.g., beta-blockers) and possible concomitant use of a diuretic should be considered in patients receiving minoxidil. (See Dosage and Administration: Administration.)

Although minoxidil has been used safely in usual doses for the management of hypertension in patients with renal failure, patients with renal failure or those receiving dialysis may require smaller doses of minoxidil (about one-third less than in patients who are not receiving dialysis). Since minoxidil is removed by dialysis, some clinicians recommend that on the day of dialysis the drug be administered immediately after dialysis if dialysis is at 9 a.m.; if dialysis is after 3 p.m., the daily dose is given at 7 a.m. (i.e., 8 hours before dialysis).

Minoxidil is administered orally. Minoxidil may be administered once or twice daily, depending on the patient's blood pressure response. The manufacturers recommend that the drug be administered once daily in patients whose supine diastolic pressure has been reduced by less than 30 mm Hg and twice daily in equally divided doses in those whose supine diastolic pressure has been reduced by more than 30 mm Hg during minoxidil therapy.

A beta-adrenergic blocking agent (beta-blocker) (e.g., equivalent to 80-160 mg of propranolol daily) must be given before minoxidil therapy is begun and should be continued during minoxidil therapy to minimize minoxidil-induced tachycardia and increased myocardial workload. If a beta-blocker is contraindicated, another sympathetic nervous system suppressant such as methyldopa (250-750 mg twice daily) should be used and must be started at least 24 hours before minoxidil because of the delayed onset of methyldopa's action. Limited clinical experience indicates that clonidine (0.1-0.2 mg twice daily) may be used as an alternative to methyldopa.

Minoxidil also must be used in conjunction with a thiazide (e.g., hydrochlorothiazide 50 mg twice daily, chlorthalidone 50-100 mg once daily) or loop diuretic (e.g., furosemide 40 mg twice daily) when initiating minoxidil therapy in patients dependent on renal function for maintenance of sodium and water balance. If excessive sodium and water retention results in weight gain exceeding 2.3 kg during minoxidil therapy, diuretic therapy should be changed to a loop diuretic or, in patients already receiving a loop diuretic, the dosage should be increased.

There is no enhanced messaging for this drug.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

Moderate Interaction: Assess the risk to the patient and take action as needed.

Minoxidil/Nsaids; Salicylates

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Oral minoxidil functions as a direct-acting peripheral vasodilator, lowering elevated systolic and diastolic blood pressure by reducing resistance in peripheral blood vessels. This triggers a compensatory increase in cardiac output and renin secretion and results in sodium and water retention. NSAIDs inhibit prostaglandin synthesis and also result in sodium and water retention.(1,2)

CLINICAL EFFECTS: The risk of heart failure may increase with oral minoxidil and NSAIDs due to their combined effects on blood vessel dilation, fluid retention, and altered sodium balance. Minoxidil efficacy may be compromised.(1,2)

PREDISPOSING FACTORS: Higher doses of oral minoxidil have been associated with serious adverse events, including hypotensive syncope, pericarditis, pericardial effusion, and myocardial infarction.(1-5)

PATIENT MANAGEMENT: Closely monitor body weight, fluid and electrolyte balance, and blood pressure when using oral minoxidil and NSAIDs concurrently. Minoxidil tablets should be co-administered with an appropriate diuretic to prevent fluid retention and potential congestive heart failure. A high-ceiling (loop) diuretic is often necessary alongside vigilant monitoring of body weight. Without concurrent diuretic use, minoxidil may lead to the retention of salt and water within a few days.(1,2)

DISCUSSION: While the manufacturer of minoxidil does not provide specific recommendations regarding NSAID co-administration, it emphasizes the necessity of combining minoxidil with a beta-blocker to prevent tachycardia and increased myocardial workload. Additionally, concurrent use with a diuretic is recommended to avert serious fluid accumulation and potential congestive heart failure. NSAID labeling warns about fluid retention, edema, an elevated risk of heart failure, and potential drug interactions with beta-blockers and diuretics which can result in a blunting of the antihypertensive and cardiovascular effects of these agents.(1-5)

Selected Antihypertensives And Vasodilators/Apomorphine

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Apomorphine causes dose-dependent decreases in blood pressure. Concurrent use with antihypertensive agents may result in additive effects on blood pressure.(1)

CLINICAL EFFECTS: Concurrent use of antihypertensives and apomorphine may result in orthostatic hypotension with or without dizziness, nausea, or syncope.(1)

PREDISPOSING FACTORS: The risk of orthostatic hypotension may be increased during dose escalation of apomorphine and in patients with renal or hepatic impairment.(1)

PATIENT MANAGEMENT: Patients receiving concurrent therapy should be monitored for hypotension. Counsel patients about the risk of orthostatic hypotension.(1)

DISCUSSION: Healthy volunteers who took sublingual nitroglycerin (0.4 mg) concomitantly with apomorphine experienced a mean largest decrease in supine systolic blood pressure (SBP) of 9.7 mm Hg and in supine diastolic blood pressure (DBP) of 9.3 mm Hg, and a mean largest decrease in standing SBP and DBP of 14.3 mm Hg and 13.5 mm Hg, respectively. The maximum decrease in SBP and DBP was 65 mm Hg and 43 mm Hg, respectively. When apomorphine was taken alone, the mean largest decrease in supine SBP and DBP was 6.1 mm Hg and 7.3 mm Hg, respectively, and in standing SBP and DBP was 6.7 mm Hg and 8.4 mm Hg, respectively.(1)

Selected Antihypertensives/Tizanidine

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Tizanidine is an alpha-2 agonist. Concurrent use with antihypertensive agents may result in additive effects on blood pressure.(1)

CLINICAL EFFECTS: Concurrent use of antihypertensives and tizanidine may result in hypotension.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Patients receiving concurrent therapy should be monitored for hypotension. The risk of hypotension may be decreased by careful titration of tizanidine dosages and monitoring for hypotension prior to dose advancement. Counsel patients about the risk of orthostatic hypotension.(1)

DISCUSSION: Severe hypotension has been reported following the addition of tizanidine to existing lisinopril therapy.(2-4)

There is no enhanced messaging for this drug.

• Pheochromocytoma

• 30 day risk period post-myocardial infarction
• Angina
• Chronic heart failure
• Pericardial effusion
• Pericardial tamponade
• Pericarditis

• Cerebrovascular disorder
• Kidney disease with reduction in glomerular filtration rate (GFr)

There is no enhanced messaging for this drug.

More Frequent

• Body fluid retention
• Cardiac arrhythmia
• Edema

Less Frequent

• Angina
• Chest pain
• Pericarditis

Rare or Very Rare

• Abnormal ECG
• Allergic dermatitis
• Bullous dermatitis
• Leukopenia
• Pericardial effusion
• Pericardial tamponade
• Pruritus of skin
• Pulmonary hypertension
• Stevens-johnson syndrome
• Thrombocytopenic disorder
• Toxic epidermal necrolysis

More Frequent

• Hirsutism

Rare or Very Rare

• Mastalgia
• Nausea
• Skin rash
• Vomiting

No enhanced messaging available.

No enhanced messaging available.

Pronounced hypertrichosis and multiple congenital anomalies, including dysmorphic facial features (e.g., depressed nasal bridge, low-set ears, micrognathia), bilateral clinodactyly, omphalocele, undescended testes, midphallic constriction, unusual fat distribution, and ventriculoseptal defect, occurred in a neonate born to a woman who received minoxidil, captopril, furosemide, and propranolol throughout pregnancy. Hypertrichosis (which appeared as a general increase in bristly hair that was longest in the sacral area) occurred in another infant born to a woman who had received minoxidil as well as metoprolol and prazosin throughout pregnancy. Cyanotic heart disease resulting in death occurred in a neonate born to a woman receiving minoxidil, furosemide, hydralazine, methyldopa, and phenobarbital therapy during the pregnancy; an autopsy revealed transposition of the great vessels and pulmonic bicuspid valvular stenosis. However, it is not known whether these effects resulted from minoxidil, concurrently administered drugs, the maternal condition, or other factors. There are no adequate and controlled studies to date using minoxidil in pregnant women, and the drug should be used during pregnancy only when the potential benefits justify the possible risks to the fetus. The effects of the drug on labor and delivery are not known.

Oral administration of minoxidil has been associated with evidence of increased fetal resorption in rabbits, but not rats, when administered at 5 times the maximum recommended oral human dosage. There has been no evidence of teratogenic effects in rats and rabbits. There was no evidence of teratogenic effects in rats receiving subcutaneous minoxidil dosages of 80 mg/kg daily (about 2000 times the maximal systemic human exposure achieved with daily administration of topical minoxidil); however, maternal toxicity was observed with this dosage. Evidence of developmental toxicity was observed in rats receiving subcutaneous dosages exceeding 80 mg/kg daily.

Minoxidil is distributed into milk. Because of the potential for adverse reactions from minoxidil in nursing infants, the drug should not be administered in nursing women.

No enhanced messaging available.