Side effects of low-dose oral minoxidil for treating alopecia

To the Editor: We appreciate the analysis of minoxidil-related information of adverse events by Ortega-Quijano and colleagues, particularly the information highlighting 8 patients prescribed oral minoxidil (Loniten; Pfizer). Our case series included a diverse sample of healthy dermatology patients with both scarring and nonscarring alopecias (n = 51). The patients were seen at 2 community dermatology clinics in a large and ethnically heterogenous metropolis—Toronto, Canada—and the mean patient age was 42 years.1Beach R.A. McDonald K.A. Barrett B.M. Low dose oral minoxidil for treating alopecia: a 3-year North American retrospective case series.J Am Acad Dermatol. 2021; 84: 761-763Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar The patients were screened for a history of cardiac, liver, and renal disease. Treatment was deferred if they screened positive. This finding contrasts with the data extracted from the US Food and Drug Administration Adverse Event Reporting System (FAERS), in which 4 of the 8 adverse reactions were experienced by patients greater than 70 years of age, 3 of whom required hospitalization, and the youngest stated patient age was 46. It is important that prescribing dermatologists are aware of contraindications to prescription of low-dose oral minoxidil (LDOM) including drug hypersensitivity, pheochromocytoma, pulmonary hypertension with mitral stenosis, and severe hepatic impairment.2Pfizer Canada Inc LONITEN (minoxidil tablets USP) Product Monograph. Kirland, Quebec2013Google Scholar From a cardiovascular perspective, minoxidil acts a systemic vasodilator, which leads to reflex tachycardia that can provoke myocardial ischemia.3Markham Jr., R.V. Gilmore A. Pettinger W.A. Brater D.C. Corbett J.R. Firth B.G. Central and regional hemodynamic effects and neurohumoral consequences of minoxidil in severe congestive heart failure and comparison to hydralazine and nitroprusside.Am J Cardiol. 1983; 52: 774-781Abstract Full Text PDF PubMed Scopus (11) Google Scholar Accordingly, minoxidil should be avoided in patients who have angina or recent myocardial infarction. Minoxidil can also promote substantial fluid retention by modulating renal hemodynamics, tubular action, and systemic neurohormonal activation.3Markham Jr., R.V. Gilmore A. Pettinger W.A. Brater D.C. Corbett J.R. Firth B.G. Central and regional hemodynamic effects and neurohumoral consequences of minoxidil in severe congestive heart failure and comparison to hydralazine and nitroprusside.Am J Cardiol. 1983; 52: 774-781Abstract Full Text PDF PubMed Scopus (11) Google Scholar Thus, it should be avoided in patients with heart failure or those at high risk for it. Because it can promote ischemia and fluid retention, minoxidil is best avoided in patients with left ventricular hypertrophy. Pericardial effusions are another important adverse effect whose mechanism remains undetermined to our knowledge.4Houston M.C. McChesney J.A. Chatterjee K. Pericardial effusion associated with minoxidil therapy.Arch Intern Med. 1981; 141: 69-71Crossref PubMed Scopus (18) Google Scholar Consequently, minoxidil is at least a fourth-line agent in contemporary hypertension management. When used as an antihypertensive agent, the American Society of Hypertension and the International Society of Hypertension suggest that the dosage of minoxidil range from 5 to 10 mg, which can be split to 1 to 3 times daily.5Weber M.A. Schiffrin E.L. White W.B. et al.Clinical practice guidelines for the management of hypertension in the community: a statement by the American Society of Hypertension and the International Society of Hypertension.J Clin Hypertens (Greenwich). 2014; 16: 14-26Crossref PubMed Scopus (591) Google Scholar When used for alopecia conditions, the recommended 1.25 mg dose is considerably lower and can be increased to 2.5 mg if tolerated.1Beach R.A. McDonald K.A. Barrett B.M. Low dose oral minoxidil for treating alopecia: a 3-year North American retrospective case series.J Am Acad Dermatol. 2021; 84: 761-763Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar Intake of LDOM before sleeping is recommended to minimize the perception and potential impact of hypotensive symptoms. In the FAERS database of adverse event reports, the dose of minoxidil was not stated. Most historic reports on the adverse effects of minoxidil involved patients with longstanding uncontrolled hypertension, resulting in left ventricular hypertrophy, myocardial infarction, heart failure, or advanced kidney disease.3Markham Jr., R.V. Gilmore A. Pettinger W.A. Brater D.C. Corbett J.R. Firth B.G. Central and regional hemodynamic effects and neurohumoral consequences of minoxidil in severe congestive heart failure and comparison to hydralazine and nitroprusside.Am J Cardiol. 1983; 52: 774-781Abstract Full Text PDF PubMed Scopus (11) Google Scholar,4Houston M.C. McChesney J.A. Chatterjee K. Pericardial effusion associated with minoxidil therapy.Arch Intern Med. 1981; 141: 69-71Crossref PubMed Scopus (18) Google Scholar Moreover, the doses used were generally 10 mg/d or more. Although vasodilation and fluid retention are predictably dose-dependent effects of minoxidil,3Markham Jr., R.V. Gilmore A. Pettinger W.A. Brater D.C. Corbett J.R. Firth B.G. Central and regional hemodynamic effects and neurohumoral consequences of minoxidil in severe congestive heart failure and comparison to hydralazine and nitroprusside.Am J Cardiol. 1983; 52: 774-781Abstract Full Text PDF PubMed Scopus (11) Google Scholar the dose dependence of pericardial effusions is unclear.4Houston M.C. McChesney J.A. Chatterjee K. Pericardial effusion associated with minoxidil therapy.Arch Intern Med. 1981; 141: 69-71Crossref PubMed Scopus (18) Google Scholar However, most reports of minoxidil-attributed pericardial effusions involved doses 10 mg/d or more or end-stage renal disease.4Houston M.C. McChesney J.A. Chatterjee K. Pericardial effusion associated with minoxidil therapy.Arch Intern Med. 1981; 141: 69-71Crossref PubMed Scopus (18) Google Scholar Accordingly, we expect lower rates of these adverse effects with LDOM in healthy individuals. Nonetheless, subsequent symptoms of chest pain, dyspnea, or persistent edema in patients taking LDOM for alopecia should prompt appropriate investigations. The investigation of adverse effects by Ortega-Quijano and colleagues serves as further context in determination of suitable candidates for prescription of LDOM for alopecia. None disclosed. Comment on "Low dose oral minoxidil for treating alopecia: A 3-year North American retrospective case series": Adding further evidence about side effectsJournal of the American Academy of DermatologyVol. 84Issue 5PreviewTo the Editor: We read with interest the article by Beach et al1 addressing the tolerability and effectiveness of low-dose oral minoxidil (LDOM) for treating androgenetic alopecia. With regard to tolerability, a recent review found that, except for hypertrichosis, side effects were infrequent.2,3 Those results are consistent with the ones of the referred study. Full-Text PDF