Minoxidil: An Underused Vasodilator for Resistant or Severe Hypertension

Domenic A. Sica, MD

Disclosures
In This Article

Dosing Considerations

The beginning dose of minoxidil can be as low as 2.5 mg/d with a maintenance dose generally falling in the range of 10-40 mg/d. Minoxidil can be given from once to three times daily with the most common frequency of administration being twice daily. The twice-daily, or occasionally the thrice-daily, dosing regimen is preferred in patients receiving high doses of minoxidil to avoid an excessive peak hypotensive effect as may come to pass with one large daily dose. Occasionally, doses of minoxidil in excess of 40 mg/d are required to normalize BP. Although the manufacturer's maximum recommended dose is 100 mg/d it is unusual for patients to require more than 20 mg in a single dose and 40 mg as a total daily dose. A starting dose of minoxidil can be safely titrated upward fairly quickly, with dose escalation every 3-4 days. If vasodilator side effects occur with a particular dose of minoxidil, dose escalation should occur at a slowed pace.

The rapid titration of minoxidil over a several-day time span may be followed by a gradual loss of BP control over the ensuing days as sodium retention and tachycardia evolve. These counterregulatory adjustments should be anticipated even as therapy starts with minoxidil. The weight gain with minoxidil can be sudden and extreme, in part because patients are seldom advised to limit sodium intake as it is begun. Once significant edema is present a sensible step is to temporarily discontinue minoxidil (or significantly reduce the dose) and allow the edema to resolve of its own accord. This maneuver obviates the need for a high-dose loop diuretic regimen and allows an earlier restart of minoxidil with a more reasonable diuretic regimen.

An accelerated dosing schedule can be used with minoxidil to achieve rapid BP control in patients with severe diastolic hypertension (>120 mm Hg).[2,7,27] For example, 2 hours after having received a combination of both furosemide (40 mg) and propranolol (40 mg), a 20-mg loading dose of oral minoxidil was given to nine symptomatic patients whose diastolic BP exceeded 120 mm Hg.[2] A booster dose of 5-20 mg, calculated on the basis of each patient's response to the loading dose of minoxidil, was given 4 hours hence if diastolic BP still exceeded 100 mm Hg. With this therapeutic line of attack, systolic and diastolic BPs fell progressively over the ensuing several hours.

This approach shows that an orally administered regimen of propranolol, furosemide, and minoxidil produces prompt and sustained BP reduction in patients with severe hypertension who require immediate BP reduction. These early studies with minoxidil occurred at a time when the treatment of accelerated symptomatic hypertension was constrained by the absence of intravenous therapies; thus, this approach outlined is not a substitute for the treatment of symptomatic hypertension with parenteral therapies but rather a matching strategy to ease the transition from intravenous to oral medications.

Also, minoxidil loading should always be preceded by ß-blocker or combined -ß therapy because high-dose minoxidil can be expected to significantly increase pulse rate and thereby increase the likelihood of (and risk from) myocardial ischemia.[2,7,27] Finally, this course of action is recommended only under strict supervision because prolonged hypotension has been occasionally seen after an initial 10-mg minoxidil dose.[28]

Minoxidil topically applied for male-pattern baldness can be transdermally absorbed. To this end, it has been observed over a several-month period of treatment with topical minoxidil that left ventricular end-diastolic volume, cardiac output, and left ventricular mass all can increase.[29] To this end, the manufacturer of topical minoxidil in their instructions to patients provides a specific warning to stop its use and consult a physician if a patient experiences chest pain, rapid heartbeat, swelling, or a significant weight gain.[30] These are self-evident manifestations of minoxidil effect that are easily identified by a patient. The more significant cardiac structural effects that have been described with topically administered minoxidil must be identified by physicians.

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