Minoxidil is a piperidinopyrimidine-derivative vasodilator5, 19, 20, 37, 43, 44, 73 that possesses hair growth stimulant properties.4, 9, 14, 15, 20, 40, 43, 44, 56
Minoxidil is used topically to stimulate regrowth of hair in balding areas of individuals with androgenetic alopecia (male-pattern alopecia, hereditary alopecia, common male baldness).1, 5, 6, 7, 8, 9, 15, 16, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 39, 40, 59, 83, 85 Androgenetic alopecia in men is expressed as baldness of the vertex (crown) of the scalp.1, 115, 116, 117 Topical minoxidil therapy is effective in promoting hair regrowth on the vertex of the scalp1, 5, 7, 15, 16, 30, 115, 116 but appears to have little or no effect on temporal recession;101 the efficacy of topical minoxidil therapy for frontal alopecia in men has not been evaluated objectively to date.5, 7, 15, 30, 35, 40, 100, 101, 115, 116 There is evidence to suggest that men most likely to respond to topical minoxidil therapy are those younger115, 116 than 40 years of age,5, 100, 101 those in whom treatment is initiated relatively early (less than 10 years' duration of hair loss),6, 20, 23, 39, 100, 101, 115, 116 those with a small diameter of baldness (less than 10 cm),5, 6, 23, 39, 100, 101, 115, 116 and those who have a large number of terminal or indeterminate (intermediate) hairs before initiation of treatment.5, 23, 39, 100, 101 At least 2 or at least 4 months of continuous therapy with minoxidil 5 or 2% topical solution, respectively, usually is required for evidence of response;1, 23, 25, 27, 30, 34, 36, 59, 115, 116, 121, 122, 123, 126 however, treatment for 4 months or up to a year with minoxidil 5 or 2% topical solution, respectively, may be warranted before deciding that the alopecia is unresponsive.1, 5, 6, 7, 23, 39, 121, 122, 123, 126 While the ultimate benefit of topical minoxidil therapy depends on the subjective perceptions of the treated individual,5, 7, 30 cosmetically acceptable hair regrowth as determined by study investigators has been reported in approximately one-third of men after 6-12 months of twice-daily therapy in most clinical studies,5, 6, 7, 8, 9, 16, 22, 23, 26, 27, 28, 31, 37, 108, 115 and complete coverage of the balding areas of the scalp occurs rarely.5, 7, 33, 100, 101, 115 Current evidence suggests that such therapy must be continued indefinitely for maintenance of hair growth.1, 6, 7, 9, 24, 40, 67, 83, 100, 101, 109, 115, 116, 121, 122, 123, 126
Limited evidence from long-term studies in men indicates that continuous therapy with minoxidil topical solution can maintain an increased level of hair growth in most responders with androgenetic alopecia for at least up to 5 years,5, 31, 108, 109 although twice-daily application appears to be necessary for maintenance of response.5, 7, 32, 109 However, a controlled assessment of the efficacy of topical minoxidil therapy for extended periods of continuous treatment (e.g., beyond 4-6 months) in men has not been performed.1, 8, 22, 23, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37 It has been suggested that a principal benefit of topical minoxidil therapy may be slowing of the progression of androgenetic alopecia rather than stimulation of hair regrowth, since hair loss appears to be halted or reduced in most individuals receiving therapy even if they do not achieve cosmetically acceptable hair regrowth.5, 7, 8, 15, 25, 27, 29, 31, 32, 39, 40 In some studies, the rate of hair regrowth reached a plateau or decreased after 8-12 months or longer22, 32, 36, 40, 83, 109 and/or hair loss in nonvertex balding areas resumed during continued therapy with topical minoxidil;32, 40 however, limited data indicate that terminal hair counts may continue to increase in patients who are maintained on therapy for several years.108 When topical minoxidil therapy is discontinued, most new hair usually is lost within a few (e.g., 3-4) months,1, 6, 7, 67, 101, 115, 121, 122, 123, 126 and resumption of genetically determined hair loss appears to occur.6, 100 Further long-term studies are needed to determine the influence of topical minoxidil therapy on the natural course of androgenetic alopecia.9, 15, 30, 33
Evaluation of the efficacy of topical minoxidil therapy in androgenetic alopecia is complicated by variability in study design and criteria, both subjective and objective, used for evaluation of cosmetic benefit.5, 9, 16, 39, 40, 41, 42, 56 In addition, some clinical studies used extemporaneous formulations prepared from minoxidil oral tablets;24, 56 such formulations reportedly demonstrate marked variability in minoxidil concentration.5, 7, 9, 15, 16, 39 Most randomized, controlled studies in men with androgenetic alopecia have used a minoxidil 2 or 3% solution supplied by the manufacturer (Pharmacia & Upjohn).8, 22, 23, 25, 26, 27, 28, 29, 30, 31, 32, 34, 35, 36, 115 In these studies, healthy individuals with hair loss at the vertex of the scalp were treated twice daily with a minoxidil 2 or 3% solution or placebo (vehicle only); after 4 months, the placebo group received the minoxidil 3% solution for the remainder of the 12-month studies.22, 23, 25, 27, 28, 29, 30, 31, 32, 34, 35, 36, 115 Efficacy of topical minoxidil therapy was evaluated objectively using hair counts and measurement of the diameter of the bald area on the vertex of the scalp and subjectively by investigators' and treated individuals' assessments of cosmetic benefit.22, 23, 25, 26, 27, 28, 29, 30, 31, 32, 34, 35, 36, 115
The extent of baldness in most studies of topical minoxidil therapy in individuals with androgenetic alopecia has been categorized using the Hamilton hair loss classification54 or various modifications of this classification.55 Most studies conducted to date in men with androgenetic alopecia have included individuals with at least Hamilton type III vertex hair loss.8, 22, 23, 24, 25, 26, 29, 30, 31, 32, 33, 34, 35, 36 The Hamilton type III vertex classification is used to describe hair loss principally on the vertex of the scalp, with frontal recession not exceeding that of type III hair loss.23, 55
In evaluating hair regrowth in androgenetic alopecia, most studies classified hair type as vellus, terminal, or indeterminate.8 Vellus hair is soft, unmedullated, usually unpigmented, and less than 2 cm long, while terminal hair is longer, coarser, and generally medullated and pigmented;60 hairs with intermediate lengths and shaft diameters are classified as indeterminate.8 It is principally the terminal and indeterminate hair (collectively referred to as “nonvellus” hair for the purposes of hair counting)5, 7, 15, 22, 25, 26, 27, 28, 29, 30, 32, 33, 34, 35, 36 that contributes to cosmetic appearance in subjective evaluations of efficacy.15, 28, 29 In several studies, regrowth of nonvellus hair as assessed by hair counts at 4-6 months was substantially greater in individuals receiving topical minoxidil than in those receiving placebo.1, 22, 26, 28, 30, 31, 33, 34, 115 However, some individuals receiving the placebo vehicle also had growth of nonvellus hair, suggesting either increased accuracy of the individual performing hair counts or actual stimulation of hair growth by ingredients in the vehicle or scalp massage during drug application.22, 26, 29, 33, 34, 36 In addition, although 4 months of topical minoxidil therapy produced substantially greater increases in nonvellus hairs compared with placebo in several studies,1, 22, 28, 30, 31, 34 the manufacturer states that investigator evaluation of terminal (cosmetically acceptable) hair regrowth in clinical studies showed no difference between drug and placebo at this time.1, 115 This latter finding may have resulted from a delayed effect of therapy on such regrowth,1, 100 but the lack of a placebo group after 4-6 months in most studies1, 8, 22, 23, 25, 26, 27, 28, 29, 30, 31, 32, 34, 36, 37 precludes an objective evaluation of the long-term response to therapy.5, 7
Objective evidence of hair regrowth (i.e., increase in hair counts) in individuals with androgenetic alopecia treated with minoxidil topical solution frequently does not correlate well with perceived cosmetic results;8, 22, 25, 30, 42 even a substantial (e.g., twofold to threefold) increase in the number of hairs in a balding area of the scalp may not be perceived as an appreciable cosmetic benefit.9, 31, 42 Cosmetically acceptable hair regrowth, when defined, has been described using such phrases as “improvement sufficient to allow reclassification into a less severe pattern of baldness,”25 hair “long enough to be cut or combed,”27 or regrowth of a “modest or moderate amount of hair that was visible and cosmetically pleasing.”30 Cosmetically acceptable hair regrowth as assessed by study investigators was achieved in only about 25-30% or less of treated individuals in most clinical studies after 6-12 months of therapy,5, 6, 7, 8, 9, 16, 22, 23, 26, 27, 28, 31, 37 although up to 60% of individuals in a few studies were judged to have moderate cosmetic benefits.30, 32, 33, 35
Several clinicians have stated that few (e.g., 5-10%) individuals with androgenetic alopecia using minoxidil topical solution have a subjective perception of dense hair regrowth.5, 7, 31, 40 In general, subjective assessments of treated individuals regarding hair regrowth were more favorable than those of the study investigators,30, 31 even in cases where the investigator noted little or no cosmetic benefit;30, 31, 32 however, optimism about hair regrowth tends to diminish with time,32, 40 even though vertex hair loss usually ceases with continued therapy.5, 7, 8, 15, 25, 27, 29, 31, 32, 39, 40
Androgenetic alopecia in women is expressed as diffuse hair loss or thinning of hair in the frontoparietal areas.115, 117, 119, 124 Data from a limited number of controlled trials in women with androgenetic alopecia indicate that therapy with topical minoxidil is effective in producing discernible regrowth of nonvellus hair as evaluated by objective and subjective criteria.115, 118, 119, 124, 125 In evaluating females in whom androgenetic alopecia is suspected, the possibility of an underlying endocrine abnormality such as polycystic ovary (Stein-Leventhal) syndrome, Cushing's syndrome, androgen-secreting tumors, or hypothyroidism should be considered.9, 84, 100, 101
In two 8-month controlled trials in women (18-45 years old, 90% were white) with androgenetic alopecia and Ludwig grade I or II diffuse frontoparietal hair thinning, topical minoxidil was more effective than placebo in producing hair regrowth as determined by hair counts and investigator and patient evaluations of hair regrowth.115 The Ludwig system for classifying androgenetic alopecia in women is as follows: grade I, perceptible thinning of the hair on the crown, limited in the front by a line situated 1-3 cm behind the frontal hair line; grade II, pronounced rarefaction of the hair on the crown within the area seen in grade I; and grade III, full baldness within the area seen in grades I and II.118, 119, 120 Women receiving topical minoxidil in these 2 trials had mean increases from baseline of 22.7 or 33.2 nonvellus hairs, respectively, compared with mean increases of 11 or 19.1 nonvellus hairs, respectively, with placebo.115, 118 Growth of new hair was evaluated by study investigators in these 2 trials according to the following criteria: no visible new growth; minimal growth, defined as definite growth but no substantial covering of thinning areas; moderate growth, defined as new growth partially covering thinning areas but less dense than in nonthinning areas (readily discernible); or dense growth, defined as full covering of thinning areas and similar in density to nonthinning areas.115, 118 According to study investigators, discernible (moderate or minimal) regrowth of nonvellus hair occurred in 63% (13% moderate and 50% minimal) or 44% (12% moderate and 32% minimal) of women who received topical minoxidil therapy in these 2 respective studies compared with 39% (6% moderate and 33% minimal) or 29% (5% moderate and 24% minimal), respectively, of those receiving placebo (vehicle).115, 118 Growth of new hair was assessed by patients as no visible new growth, minimal growth (barely discernible), moderate growth (readily discernible), or dense growth.115 According to patients' self-evaluations, hair regrowth occurred in 59% (19% moderate and 40% minimal) or 55% (1% dense, 24% moderate, and 30% minimal) of women in the 2 studies who received topical minoxidil therapy compared with 40% (7% moderate and 33% minimal) or 41% (12% moderate and 29% minimal), respectively, of those who received placebo.115, 118
Self-medication 116, 121, 122, 123, 126 with topical minoxidil 2 or 5% solution may be considered by men who have general thinning of hair at the vertex of the scalp.115, 116, 121, 122, 123, 126 Self-medication 117 with topical minoxidil 2% solution may be considered by women who have general thinning of hair in frontoparietal areas.115, 117 The topical minoxidil 5% solution should not be used by women.126 (See Cautions: Precautions and Contraindications.) The drug may be ineffective in men or women with more extensive hair loss.116, 117, 121, 122, 123, 126 Self-medication 116, 117, 121, 122, 123, 126 with topical minoxidil is not recommended for patchy hair loss (alopecia areata) or if hair loss was sudden.116, 117, 121, 122, 123, 126 In addition, the manufacturer states that self-medication with topical minoxidil is not recommended for patients without a family history of hair loss or for those with hair loss associated with childbirth, nor should it be used by those who have hair loss that occurs suddenly or for unknown reasons.116, 117, 121, 122, 123, 126
Topically applied minoxidil has been used as a 1, 3, or 5% solution, ointment, or cream to promote hair regrowth in males and females with alopecia areata†, including those with the most severe forms, alopecia totalis (complete loss of scalp hair) or alopecia universalis (complete loss of body hair).9, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53 Overnight petrolatum occlusion of the treated area, which has been reported to enhance efficacy,52, 53 has been used in some studies.45, 46, 49, 52, 53 A cosmetically acceptable response to topical minoxidil therapy appears most likely to occur in patients with patchy alopecia areata;16, 53, 114 patients with total loss of scalp or body hair at baseline (i.e., those with alopecia totalis or universalis) usually have the poorest and most delayed response.9, 46, 49, 50, 52, 53, 83 Efficacy of any therapy in patients with alopecia areata is difficult to evaluate because of the spontaneous hair regrowth and hair loss characteristic of the disease.46, 51 As in androgenetic alopecia, some patients with alopecia areata receiving treatment with the vehicle alone in controlled studies have had regrowth of terminal hair,48, 49, 100 and hair loss has resumed in other patients during continued topical minoxidil therapy.51, 52, 53, 83
In controlled studies, cosmetically acceptable hair regrowth (usually defined as hair regrowth sufficient to cover the scalp and conceal areas of residual hair loss or elimination of the need to wear a wig or cap)10, 15, 45, 49, 52, 100 has been observed in approximately 44-54% of patients with severe alopecia areata† after approximately 2 months to 2 years of continuous therapy with minoxidil 1, 3, or 5% topical solution or ointment;44, 45, 46, 49, 51, 52, 53 most patients respond within 2-4 months44, 45, 49, 52, 53 and have maximum responses within 1 year,53 although some clinicians suggest that an even longer period may be required for maximum benefit.100 Topical minoxidil also has promoted minimal regrowth of eyebrows and beard when applied to these areas in a few patients with alopecia universalis.51, 52 Some evidence of a dose-response relationship in terms of extent of hair growth and cosmetic benefit has been reported in patients with alopecia areata receiving topical minoxidil therapy, with a 5% concentration producing better hair regrowth than lower concentrations.15, 49, 51, 53 Topical minoxidil therapy does not appear to alter the underlying course of the disease; discontinuance of the drug usually results in substantial loss of new hair within 2-4 weeks in patients with alopecia areata.15, 51, 52, 53, 101, 114
In general, patient age, gender, duration of disease, or family history of autoimmune disease, atopy, or alopecia areata do not correlate with response to topical minoxidil therapy in patients with alopecia areata†;44, 49, 52, 53 however, limited evidence suggests that alopecia areata in patients with increased pretreatment peripheral lymphocyte blastogenesis following mitogen stimulation may exhibit an enhanced response to topical minoxidil therapy.10, 13 Additional study is needed to further define the rate of cosmetically acceptable response to topical minoxidil therapy in patients with alopecia areata who have varying degrees of hair loss severity.15
Topical minoxidil therapy has been used as an adjunct to hair transplantation†.64, 65 Limited evidence suggests that the drug may promote better evolution of hair grafts by reducing postoperative shedding of hair and hastening the onset of postshedding hair regrowth.64, 65 Further study is required to determine the role of topical minoxidil therapy for this and other conditions in which stimulation of hair regrowth may be beneficial.101
Minoxidil solution is applied topically to the scalp.1, 116, 117, 121, 122, 123, 126 Twice-daily application appears to be necessary for optimum results.1, 5, 7, 32, 85, 116, 117, 121, 122, 123, 126 Individuals receiving topical minoxidil therapy should be carefully instructed regarding proper use of the solution.116, 117, 121, 122, 123, 126 To obtain optimum results, these individuals should be given a copy of the instructions provided by the manufacturers.116, 117, 121, 122, 123, 126
Topical minoxidil solution is applied to the total affected areas of the scalp using one of the applicators provided by the manufacturers (i.e., metered-spray applicator, extender spray applicator, dropper applicator).85 The manufacturers' patient information should be consulted for specific methods of application.116, 117, 121, 122, 123, 126 Individuals being treated for androgenetic alopecia should be advised that because of the risk of adverse systemic effects, the topical preparation is intended for application to the scalp only and should not be applied to other areas of the body.116, 117, 121, 122, 123, 126
Prior to application of minoxidil topical solution, the hair and scalp should be dry.1, 116, 117, 121, 122, 123, 126 Individuals applying minoxidil topical solution with their fingertips should be instructed to wash their hands thoroughly afterward.1, 116, 117, 121, 122, 123, 126 When the metered-spray or extender-spray applicator is used, inhalation of the spray mist should be avoided.1, 116, 117, 121, 122, 123, 126
When the dropper applicator is used as directed, the applicator delivers 1 mL of minoxidil topical solution (20 or 50 mg of minoxidil in the 2 or 5% solution, respectively).116, 121, 122, 123, 126 When the metered-spray or extender-spray applicator is used, delivery of a 1-mL dose requires pumping the spray attachment 6 times (i.e., with approximately 3.3 or 8.3 mg of drug per metered spray with the 2 or 5% solution, respectively).116, 117, 126 When used as directed, each bottle of minoxidil topical solution should last 25-30 days provided substantial amounts of solution are not lost during applicator changes.101, 116, 117, 121, 122, 123, 126
For self-medication or supervised therapy to stimulate hair regrowth in men with androgenetic alopecia, the usual dosage of topical minoxidil is 1 mL of a 2 or a 5% solution applied to the total affected (balding and anticipated balding) areas of the scalp twice daily, usually in the morning and evening.1, 5, 6, 7, 8, 9, 15, 16, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 39, 40, 59, 83, 101, 116, 117, 121, 122, 123, 126 In women with androgenetic alopecia, the usual dosage of topical minoxidil is 1 mL of a 2% solution applied to the total affected areas twice daily, usually in the morning and evening;117 the 5% topical minoxidil solution should not be used in women. (See Cautions: Precautions and Contraindications.) Each 1-mL dose should provide adequate coverage of the affected areas; more frequent application or use of doses exceeding 1 mL should not be employed in an attempt to speed results since such dosages have not been shown to accelerate the rate of hair regrowth but may increase the risk of systemic adverse effects.116, 117, 121, 122, 123, 126 A total daily dosage of 2 mL should not be exceeded.1, 116, 117, 121, 122, 123, 126 In addition, individuals receiving topical minoxidil therapy should be advised not to attempt to make up for missed doses of the drug; instead, they simply should restart twice-daily application and return to their usual schedule.116, 117, 121, 122, 123, 126
The onset and degree of hair regrowth with topical minoxidil therapy is variable, but continuous twice-daily therapy for 4 months or longer with the 2% topical solution usually is necessary before evidence of regrowth is observed;1, 23, 25, 27, 30, 34, 36, 59, 101, 116, 117, 121, 122, 123 hair regrowth may be apparent at 2 months with the 5% topical solution.126 Continued therapy for 4 months or up to a year in individuals using minoxidil 5 or 2% topical solution, respectively, may be warranted before deciding that the alopecia is unresponsive.1, 5, 6, 7, 23, 39, 116, 117, 121, 122, 123, 126 Self-medication 116, 117, 121, 122, 123 with topical minoxidil should be stopped and a clinician consulted if hair regrowth is not detected within 8 months in women117 or 12 months in men using minoxidil 2% topical solution,116, 121, 122, 123, 126 or within 4 months in men using minoxidil 5% topical solution.126 Because subjective perceptions of the treated individual may contribute substantially to response,5, 7 it is important that the individual have realistic expectations about the usual time course and degree of hair regrowth that can be achieved with topical minoxidil therapy and understand that such therapy must be continued indefinitely for maintenance of hair regrowth.1, 6, 7, 67, 100, 101, 116, 117, 121, 122, 123, 126 The manufacturers' patient information can be consulted for such information.116, 117, 121, 122, 123, 126
The optimum dosage of topical minoxidil therapy for alopecia areata† remains to be established.38, 39, 40, 51, 53 In controlled studies in a limited number of patients with alopecia areata (including those with alopecia totalis or universalis), 1 mL of a 1 or 5% hydroalcoholic, propylene glycol-containing topical minoxidil solution (1% solution not currently commercially available) has been applied twice daily (in the morning and at bedtime) to affected areas on the scalp.45, 46, 49, 52, 53, 100, 101 The drug also has been applied topically at a concentration of 3% and as creams and ointments.46, 47, 48, 50, 51, 52 Overnight petrolatum occlusion of the treated areas has been used in some patients with alopecia areata,45, 46, 49, 53, 101 although the manufacturer cautions that the risk of adverse systemic effects may be increased with such therapy.1 There is some evidence that the use of occlusion52, 53, 101, 114 and relatively high dosages (e.g., using a 5% solution)15, 49, 51, 53, 101, 114 may enhance response as determined by terminal hair regrowth; however, response as determined by cosmetically acceptable regrowth may not be affected substantially by these factors,101, 114 and additional study is necessary.15
Topically applied minoxidil generally is well tolerated.1, 2, 5, 15, 16, 22, 23, 25, 26, 27, 28, 29, 30, 31, 32, 33, 36, 37, 38, 39, 40, 44, 45, 46, 47, 49, 51, 52, 53, 56, 59, 61, 83 Except for adverse dermatologic reactions, which were more common in minoxidil-treated individuals, the incidences of adverse effects in individuals treated with topical minoxidil solution in controlled studies have not differed substantially from those in individuals receiving placebo.1, 85
Although the manufacturer states that the typical systemic effects of orally administered minoxidil (weight gain, edema, tachycardia, hypotension) have not been directly attributed to therapy with the commercially available topical minoxidil preparation to date,1, 85 such effects occasionally have been reported in individuals receiving the drug topically.1, 9, 22, 32, 40, 86, 93, 100, 110, 111 Therefore, the potential for adverse systemic effects following topical application of the drug exists, especially when larger than recommended doses are applied to inflamed or abraded skin, the drug is used in individuals with propensity for greater percutaneous absorption of the drug or with increased sensitivity to the drug's effects, or the drug is misused.1, 9, 93, 101 (See Cautions: Precautions and Contraindications.) At least 8 deaths have been reported in patients receiving topical minoxidil solution in Upjohn-sponsored studies, and at least 2 other patients reportedly have died while receiving extemporaneous topical formulations of the drug.22, 100, 110, 111 However, analysis of these cases suggest that the deaths were not caused by topical minoxidil therapy.110, 112
Most studies of topical minoxidil therapy for androgenetic alopecia did not include individuals with cardiovascular, renal, hepatic, endocrine, or scalp disease,1, 5, 7, 8, 9, 15, 16, 22, 23, 24, 27, 29, 30, 31, 32, 33, 39, 56, 86 and individuals receiving corticosteroids, cytotoxic agents, peripheral vasodilators, bronchodilators, or anticonvulsants also were excluded.5, 15, 23, 56 The possibility that such balding individuals may be at increased risk of adverse systemic effects of minoxidil compared with healthy balding individuals with normal scalps should be considered.1, 5, 85
Dermatologic and Sensitivity Reactions
The most common adverse effects of minoxidil topical solution are local dermatologic reactions such as pruritus,1, 5, 8, 9, 15, 16, 22, 23, 26, 27, 29, 30, 32, 40, 46, 56, 83, 85, 96 dryness,5, 22, 40, 83 and scaling/flaking.1, 5, 9, 26, 46, 83 Local irritation or burning, including irritant dermatitis, also has been reported commonly and is usually mild;1, 5, 9, 15, 16, 26, 29, 38, 39, 46, 51, 53, 56, 83, 85, 96 however, in rare cases, it may be severe enough to require discontinuance of the drug.46, 51, 56 Local irritation of the scalp reportedly occurs more frequently with the 5% than with the 2% topical minoxidil solution.126 Local irritation may result in part from alcohol contained in the commercially available formulation.1, 85 In addition, the wearing of a wig or hairpiece may have contributed to local irritation in some cases.53 Alcohol contained in the preparation also can cause a burning sensation and irritation of the eyes, mucous membranes, or sensitive or abraded skin areas.1, 40, 85, 101 If the topical solution comes in contact with any of these areas, the area should be flushed with large amounts of cool water; a physician should be contacted if burning or irritation persists.1, 85, 116, 117, 121, 122, 123 Eczema,1 seborrhea,26 papular rash,28 folliculitis,9, 28, 83, 88 local erythema1, 26, 46 or flushing,5 exacerbation of hair loss,1 alopecia,1, 32, 40 and hypertrichosis1 also have been reported. Scalp comedones have been reported in a few patients receiving topical minoxidil therapy,9, 40, 87 but a causal relationship to the drug appears unlikely.40, 88
Increased hair growth outside the area of drug application (e.g., face and/or beard, eyebrows, ear, arm) has been reported,1, 5, 22, 32, 46, 50, 51, 52, 83 possibly resulting from inadvertent transfer of the drug solution.5 Severe, diffuse hypertrichosis involving the face and limbs has been reported in women after 2-3 months of therapy with topical minoxidil 5% solution for the treatment of androgenetic alopecia.132 The hypertrichosis resolved within 4-5 months following discontinuance of therapy with the drug.132
Allergic contact dermatitis,1, 9, 15, 16, 24, 27, 28, 30, 38, 39, 40, 45, 49, 56, 83, 89, 90, 92, 96 usually attributed to minoxidil27, 38, 45, 49, 56, 89, 90, 96 but in some cases to propylene glycol in the vehicle,27, 30, 89, 91, 92 has been reported occasionally in individuals receiving topical minoxidil therapy. Although at least 1 case of photoallergic contact dermatitis (after exposure to sunlight) has been reported during topical minoxidil therapy,9, 15, 16, 83, 90 several patients have received concurrent therapy with topical minoxidil solution and UV light (with or without topical psoralen treatment) without evidence of photoallergic reactions.96, 100 Nonspecific allergic reactions, hives, allergic rhinitis, facial swelling, and other sensitivity reactions also have been reported in individuals receiving topical minoxidil therapy, but these effects have not been attributed directly to the drug.1
Adverse cardiovascular effects reported in individuals receiving topical minoxidil therapy have included edema,1 chest pain (usually transient or intermittent),1, 9, 26, 31, 32, 40, 83, 93 palpitations,1, 9, 40, 93 and increases or decreases in blood pressure1, 9, 26, 39, 40, 83, 94, 95 and/or pulse rate;1, 26 these effects generally have not been directly attributed to therapy with the commercially available topical minoxidil formulation.1, 26, 101 ECG changes, most frequently early repolarization, unusual P-wave axis, nonspecific T-wave changes, and intraventricular conduction delay, have been reported in patients receiving topical minoxidil therapy, but a causal relationship has not been established.22, 32, 100
The manufacturer states that no clinically important systemic effects were observed in healthy males receiving therapy with 1 mL of minoxidil 3% topical solution 8 times daily to the scalp or chest during a 2-week, placebo-controlled study in which vital signs, ECG, and echocardiographic monitoring was used.1, 101 Although small but statistically significant increases in left ventricular mass, left ventricular end-diastolic volume, cardiac output, and pulse rate (standing) reportedly were detected via echocardiographic monitoring during 6 months of therapy in a placebo-controlled study of healthy men with androgenetic alopecia receiving 1 mL of minoxidil 2% solution topically twice daily,86 the manufacturer and some experts have questioned these findings.101 In addition, there was no echocardiographic evidence of cardiac volume overload associated with chronic minoxidil therapy in a larger placebo-controlled study in healthy males with androgenetic alopecia receiving 1 mL of 2-3% topical solutions of the drug twice daily for up to 12 months.101 During therapy with an extemporaneously prepared47 minoxidil 3% solution, a woman with extensive alopecia areata (alopecia totalis) experienced intermittent chest pain and palpitations,9, 40, 93 which resolved after substitution of a minoxidil 1% topical solution.40, 93 The adverse effects in this woman, who had a normal baseline ECG and no history of cardiovascular disease, may have been related to increased systemic absorption of the drug secondary to application of excessive amounts of the solution, the extensive nature of the alopecia, and/or occlusion resulting from wearing a wig.9, 93 The possibility that these or other adverse cardiovascular effects associated with systemic minoxidil therapy (see Cautions in Minoxidil 24:08.20) may result from percutaneous absorption of topically applied drug should be considered.1, 85, 86
Orally administered minoxidil has produced several types of cardiac abnormalities, including papillary muscle and subendocardial necrosis, hemorrhagic lesions, epicarditis, and hypertrophy and dilation, in certain species of animals (e.g., dog, minipig, rat).1, 73 However, the relevance of these animal findings to humans is not clear, and autopsy findings have not revealed the presence of these characteristic lesions (especially atrial lesions) to date in humans receiving the drug orally.1, 73
Nervous System and Musculoskeletal Effects
Adverse nervous system effects reported occasionally in individuals receiving topical minoxidil therapy have included headache1, 24, 31, 40, 56, 83 (including exacerbation of preexisting migraine),24 dizziness,1, 28, 56, 83 weakness,28, 83 taste alterations,28, 83 faintness,1 lightheadedness,1, 56 and vertigo.1 Anxiety, mental depression, and fatigue have been reported rarely.1 Adverse musculoskeletal effects reported occasionally in individuals receiving topical minoxidil therapy have included fractures,1 back pain,1 retrosternal chest pain of muscular origin,1, 28 and tendinitis.1 However, none of these nervous system or musculoskeletal effects has been attributed directly to the drug.1
Adverse genitourinary effects, including urinary tract infections, renal calculi, urethritis, prostatitis, epididymitis, and sexual dysfunction (impotence),27, 28, 83 have been reported rarely in individuals receiving topical minoxidil therapy, but a causal relationship to the drug has not been established.1, 27
Other adverse effects reported in individuals receiving topical minoxidil therapy but not attributed directly to the drug have included bronchitis,1 upper respiratory infection,1 transient dyspnea,31 sinusitis,1 diarrhea,1 nausea,1 vomiting,1 weight gain,1 lymphadenopathy,1 thrombocytopenia,1 ear infection,1 endocrine effects (e.g., breast enlargement),1, 56 conjunctivitis,1 and visual disturbances such as decreased visual acuity.1
Precautions and Contraindications
In weighing the potential benefits and risks of topical minoxidil therapy, individuals being considered for such therapy should have a medical history and physical examination performed, including assessment of the condition of the scalp, and be advised of the potential risks.1 The manufacturer warns that individuals being considered as candidates for topical therapy with the drug should have a healthy, normal scalp since local abrasion or inflammation can increase percutaneous absorption of minoxidil and the risk of adverse systemic effects.1 Topical application of minoxidil solution to stimulate hair growth in areas of the body other than the scalp is not recommended.116, 117, 121, 122, 123 It is particularly important that the risks versus benefits of topical minoxidil therapy be assessed carefully in individuals older than 50 years of a those with cardiac, renal, or hepatic disease or scalp abnormalities; and those receiving potentially interacting drugs concomitantly (e.g., hypotensive agents such as guanethidine); such individuals should be closely monitored if a decision is made to initiate therapy.1, 5 In addition, individuals with underlying cardiac disease, including coronary artery disease or congestive heart failure, should be informed that adverse systemic effects of topical minoxidil therapy may be particularly serious should they occur.1
Individuals receiving topical minoxidil therapy and their clinician should be aware of the manifestations of common and otherwise potentially serious adverse effects associated with systemic minoxidil therapy, particularly sodium and water retention, weight gain, local or generalized edema, pericardial effusion, pericarditis, tamponade, tachycardia, and increased frequency or development of angina.1, 85 The manufacturer's labeling for oral minoxidil and the minoxidil monograph in 24:08.20 can be consulted for additional information on adverse effects associated with systemic therapy. While such effects generally appear to be unlikely during topical minoxidil therapy,1, 5, 15, 16, 23, 26, 28, 29, 36, 40, 44, 45, 46, 47, 49, 51, 52, 53, 56, 61, 85, 101 certain individuals may be at increased risk of their development because of underlying disease, sensitivity to the drug, or achievement of higher than usual systemic concentrations (e.g., secondary to misuse or enhanced percutaneous penetration of topical drug).1, 85 Individuals receiving topical minoxidil therapy should be advised to watch for and report the occurrence of increased heart rate,1, 116, 117, 121, 122, 123 sudden unexplained weight gain,1, 116, 117, 121, 122, 123 difficulty in breathing (especially when lying down),1 worsening or development of angina pectoris (chest pain),1, 116, 117, 121, 122, 123 edema (swelling) of the face, hands, ankles, or abdomen, or other systemic effects1, 116, 117, 121, 122, 123 and should be monitored 1 month after initiating therapy and at least every 6 months thereafter for the possible development of such effects.1 If systemic effects occur, topical minoxidil therapy should be discontinued.1, 116, 117, 121, 122, 123
Minoxidil topical solution should not be used for self-medication if the scalp is inflamed, erythematous, infected, irritated, or painful.116, 117, 121, 122, 123 As with other topically applied drugs, inflammation or disease processes associated with decreased integrity of the epidermal barrier (e.g., excoriations of the scalp, severe sunburn, scalp psoriasis) may increase percutaneous absorption of minoxidil and potentially increase the likelihood of systemic adverse effects.1, 101 Individuals receiving topical minoxidil therapy should be advised to temporarily discontinue therapy with the drug if their scalp becomes irritated101 or severely sunburned.85 Mild erythema resulting from exposure to UV light does not appear to enhance substantially percutaneous absorption of the drug.101 Systemic absorption of minoxidil may be increased if minoxidil topical solution is used more frequently or in larger doses than recommended or if the solution is applied to areas of the body other than the scalp; therefore, individuals should be advised to use the drug only as directed.1 (See Dosage and Administration: Dosage.) Percutaneous absorption of the drug is not altered by use of a hot-air hair dryer.101
In evaluating females in whom androgenetic alopecia is suspected, the possibility of an underlying endocrine abnormality such as Cushing's disease, polycystic ovary (Stein-Leventhal) syndrome, hypothyroidism, or an androgen-secreting tumor should be considered.9, 84, 100, 101 The manufacturer states that topical minoxidil 5% solution should not be used by women since it has not been shown to improve hair regrowth better than the 2% topical solution and may be harmful if used during pregnancy or breastfeeding.126
The type of vehicle and other characteristics of the formulation of topically applied minoxidil potentially may affect systemic absorption of the drug.57, 58, 63, 128 The US Food and Drug Administration (FDA) has requested that oral minoxidil tablets not be used for extemporaneous compounding of minoxidil solutions for topical use; if prepared, such extemporaneous formulations should be considered to share the toxic potentials of systemically administered minoxidil.58
Minoxidil topical solution is contraindicated in individuals with a history of hypersensitivity to any ingredient in the commercially available formulation.1
Safety and efficacy of minoxidil 2% topical solution in children younger than 18 years of age have not been established.1 The manufacturers state that minoxidil topical solutions should not be used for self-medication in individuals younger than 18 years of age.116, 117, 121, 122, 123, 126
Mutagenicity and Carcinogenicity
In vitro studies using minoxidil in a microbial system (i.e., Ames test), the DNA damage/alkaline elution assay, unscheduled DNA synthesis assay, or mouse or rat micronucleus tests have not shown the drug to be mutagenic.1, 74, 115 An equivocal result was observed in an in vitro cytogenetic assay using Chinese hamster cells at long exposure times, but results of a similar assay using human lymphocytes were negative.115
In a 2-year carcinogenicity study in mice, an increased incidence of mammary adenomas and adenocarcinomas was observed in females receiving topical minoxidil dosages of 8, 25, or 80 mg/kg daily.115 This effect was attributed to increased prolactin activity.115 Hyperprolactinemia is known to enhance mammary neoplasms in mice but has not been associated with mammary tumorigenesis in women, and topical administration of minoxidil has not been shown to cause hyperprolactinemia in women in clinical studies.115 In addition, percutaneous absorption of minoxidil is greater in rodents than in humans receiving topical minoxidil to stimulate hair regrowth.115 In a 2-year carcinogenicity study in rats, topical minoxidil was associated with an increased incidence of pheochromocytomas in males and females and an increased incidence of preputial gland adenomas in males.115 However, increases in the incidence of neoplasms observed in carcinogenicity studies involving topical administration of minoxidil in mice or rats were typical of those expected in rodents receiving other hypotensive agents (e.g., adrenal pheochromocytomas in rats) or experiencing treatment-related hormonal alterations (e.g., mammary carcinomas in female mice, preputial gland adenomas in male rats).115 None of the observed changes in incidence of neoplasms in mice or rats was considered relevant to the safety of humans receiving topical minoxidil to stimulate hair regrowth, since these rodent species differ from humans with respect to percutaneous absorption of minoxidil and mechanisms of tumorigenesis.115
There was no evidence of epithelial hyperplasia or tumorigenesis at sites of minoxidil application in rats or mice in 2-year carcinogenicity studies.115 There was no evidence of carcinogenicity in rats or rabbits receiving topical minoxidil for 1 year.115 In a 12-month photocarcinogenicity study, topical minoxidil (2 and 5%) did not substantially reduce the latency period of UV light-initiated skin tumors in hairless mice compared with controls.115
For information on carcinogenicity of orally administered minoxidil, see Mutagenicity and Carcinogenicity in Minoxidil 24:08.20.
Pregnancy, Fertility, and Lactation
Although there are no adequate and controlled studies to date in humans receiving oral or topical minoxidil, orally administered minoxidil has been associated with evidence of increased fetal resorption in rabbits, but not rats, when given at dosages 5 times the maximum recommended human oral antihypertensive dosage.115 There was no evidence of teratogenic effects of orally administered minoxidil in rats or rabbits.115 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.115 Evidence of developmental toxicity was observed in rats receiving subcutaneous dosages exceeding 80 mg/kg daily.115 For additional information on the potential risks of oral minoxidil therapy during pregnancy, see Cautions: Pregnancy, Fertility, and Lactation, in Minoxidil 24:08.20. The effects of the drug on labor and delivery are not known.115
Minoxidil produced a dose-dependent reduction in conception rate when administered orally to male and female rats in dosages 1 or 5 times the maximum recommended human oral antihypertensive dosage (based on a 50-kg patient).115
Minoxidil is distributed into milk after oral administration.72, 115 Because of the potential for serious adverse effects in nursing infants if topically applied drug were absorbed percutaneously and distributed into breast milk, the manufacturer recommends that minoxidil topical solution not be administered to nursing women.115
Topical minoxidil has been used concomitantly with topical tretinoin or in a tretinoin-containing vehicle in a limited number of individuals for potential additive or synergistic effects on hair regrowth.113, 129 In one study in a limited number of individuals with androgenetic alopecia, combined topical therapy with tretinoin and low-dose minoxidil (a 0.5% solution) appeared to be more effective than tretinoin alone in stimulating hair regrowth.113 In addition, marked hair regrowth was reported in a healthy man with androgenetic alopecia who was treated for 8 months with an extemporaneously prepared hydroalcoholic solution of minoxidil 3% and tretinoin 0.01% (1 mL twice daily) in conjunction with oral finasteride 5 mg daily.129 However, a threefold increase in the percutaneous absorption of minoxidil has been reported with concomitant topical tretinoin administration,101, 129, 130 and the safety and efficacy of combined therapy with topical minoxidil and tretinoin and/or other drugs require further elucidation.131
Exposure to UV light does not appear to potentiate substantially minoxidil-induced hair regrowth or adverse effects.96, 101 Although limited evidence suggests that mild erythema resulting from exposure to middle wavelength UV light (UVB) does not enhance substantially percutaneous absorption of minoxidil,101 the possibility that more severe UV light-induced skin injury (e.g., severe sunburn) could enhance percutaneous absorption of the drug should be considered.1, 101 (See Cautions: Precautions and Contraindications.)
The manufacturer states that no drug interactions have been reported in patients receiving minoxidil topical solution concurrently with other drugs.1 However, the possibility exists theoretically that following topical application, systemically absorbed minoxidil could interact with other concomitantly administered drugs (e.g., potentiation of orthostatic hypotension in patients receiving concomitant guanethidine therapy).1
There are no known cases to date of overdosage resulting from topical application of the commercially available minoxidil topical solution.1 Systemic absorption and the risk of topical overdosage may be increased if the usual dose and frequency of topical administration are exceeded, or the drug is applied to large surface areas, areas other than the scalp, or damaged or inflamed areas.1 In addition, ingestion of the topical preparation can be expected to potentially produce effects associated with overdosage of minoxidil oral tablets (e.g., cardiovascular effects resulting from fluid retention, tachycardia, hypotension).1 Although no apparent adverse effects or sequelae were observed in a 3-year-old boy who reportedly ingested 1-2 mL of a topical minoxidil 3% solution and vomited but had a blood concentration of total (unchanged and glucuronidated) minoxidil of approximately 320 ng/mL,1 the potential for toxic effects resulting from the relatively high drug concentration in commercially available minoxidil topical solution (i.e., 20 mg/mL, with just 5 mL providing the maximum recommended adult dosage for hypertension) exists with inadvertent ingestion of this or other similar topical preparations of the drug.1
For additional information on acute minoxidil overdosage, see Acute Toxicity in Minoxidil 24:08.16.
Topically applied minoxidil is a hair growth stimulant.1, 4, 9, 15, 20, 40, 43, 44, 56 The mechanism(s) by which topically applied minoxidil and/or a metabolite of the drug stimulate vertex hair regrowth in androgenetic (male-pattern) alopecia or other forms of alopecia has not been fully elucidated.1, 4, 15, 16, 17, 31 However, because minoxidil has stimulated hair regrowth in several forms of alopecia, it appears that the drug acts at the level of the hair follicle,4, 5, 6, 7, 9, 10, 14, 15, 16, 17, 18, 19, 20, 62, 81 possibly involving direct stimulation of hair follicle epithelial growth.4, 6, 9, 10, 14, 15, 17, 18, 19, 20, 81, 100 Limited evidence suggests that the drug induces changes such as hypertrophy and a return to more normal hair follicle diameter and depth in existing small follicles (i.e., regrowth) rather than stimulation of new hair follicle formation.4, 5, 6, 7, 9, 17, 19, 20, 59 While increased scalp blood flow resulting from local vasodilation often has been proposed as a principal mechanism of minoxidil's effect on hair growth,1, 9, 62 this mechanism has not been substantiated consistently11, 12 and not all vasodilators produce hypertrichosis.15, 16 The contribution, if any, of the propylene glycol vehicle to the drug's effects on hair growth has not been fully elucidated.9, 22, 26, 29, 33, 34, 36, 92
Androgenetic alopecia (male-pattern alopecia, hereditary alopecia, common male baldness) is a condition characterized by progressive miniaturization of the hair follicles,3, 4, 6, 20, 22, 100 a shortened anagen (growth) phase of the hair cycle,4 and a decrease in the diameter and length of the hair shaft;4, 19 circulating androgens and a genetic predisposition are necessary for development of this condition.3, 4, 9, 22, 100 Minoxidil-induced stimulation of hair growth does not appear to depend on interference with the action of androgens on the hair follicle epithelium6, 9, 22, 99 since patients receiving the drug do not develop abnormal serum androgen concentrations or abnormal urinary excretion of 17-hydroxysteroids and 17-ketosteroids.20, 22, 45 In addition, the drug can induce hair regrowth in androgen-independent forms of alopecia (e.g., alopecia areata).15, 44, 45, 46, 48, 49, 52, 53, 114
The possible role of vasodilation of the scalp vessels in promoting hair regrowth in patients treated with topical minoxidil remains to be fully elucidated.10, 11, 12, 15, 16, 17, 19, 20 Preliminary evidence suggests that the activity of minoxidil sulfotransferase (the enzyme that converts the drug to its sulfate) is higher in the hair follicle than in epidermis or dermis.17 Minoxidil sulfate, which may be formed preferentially in the hair follicle following topical application of the drug, exhibits more potent vasodilatory activity than the parent drug.17 However, while some evidence indicates that topical application of minoxidil produces dose-dependent increases in scalp blood flow,62 this finding has not been substantiated consistently.11, 12, 107 In addition, limited data suggest that the activity of minoxidil sulfotransferase may not correlate with response to the drug in patients with alopecia areata.15, 80
Current evidence suggests that minoxidil-induced effects on hair follicle epithelium may be principally involved in hair regrowth stimulated by the drug.4, 6, 9, 10, 14, 15, 17, 18, 19, 20, 81 Studies in animal cell cultures indicate that minoxidil directly induces proliferation of hair epithelial cells near the base of the hair follicle and increases incorporation of cysteine and glycine into the follicle;14 cysteine residues cross-link to form cystine, which provides strength to the hair shaft.59 The drug also appears to induce hypertrophy of existing small follicles, prolong the anagen phase of the hair follicle, and accelerate the cyclic turnover of vellus hair follicles, enabling these follicles to produce thick, terminal hair;4, 6, 9, 19, 20, 106 these effects result in a decrease in vellus hair follicles, an increase in terminal hair follicles, and an increase in the diameter of the hair shaft.6, 106 Biopsy specimens obtained after topical treatment with minoxidil demonstrate enlargement of preexisting hair follicles but no evidence of new hair follicle formation.4, 5, 7, 19
It has been suggested that local irritation or stimulation by ingredients in the topical minoxidil vehicle (i.e., alcohol or propylene glycol)9, 26, 33, 34, 36, 92, 98 or by scalp massage29, 33, 97 may promote hair growth. However, the contribution of these effects to the efficacy of topical minoxidil therapy appears to be minimal since orally administered minoxidil also causes hypertrichosis.102, 103, 104
In vitro studies demonstrate different effects of minoxidil on epithelial cells and lymphocytes,10, 81 which may lead to synergistic effects on hair growth in patients with alopecia areata.6, 10, 18 In cultures of murine epithelial cells, minoxidil increased cell proliferation, prolonged cell passage time (delayed senescence), and altered cell morphology;10, 18, 81 the latter 2 effects also have been observed in cultures of human keratinocytes.100, 105 Human lymphocytes exposed to minoxidil in cell culture demonstrated a modest suppression of mitogen-induced blast formation.6, 10, 82 Despite such in vitro changes in lymphocytes, topical minoxidil treatment does not appear to alter the underlying disease process in patients with alopecia areata; discontinuance of the drug after effective therapy usually results in recurrence of alopecia.44, 51, 52, 100, 101, 114
Information on the pharmacokinetics of minoxidil after topical application is limited;9, 38 most such information is derived from studies in which hydroalcoholic solutions with varying proportions of propylene glycol, alcohol, and water were used as vehicles.21, 61
Percutaneous absorption of minoxidil appears to be minimal following topical application of minoxidil solution to intact scalp.1, 15, 16, 43, 61 However, systemic absorption of topically applied minoxidil is variable and depends on several factors, including the vehicle used in the formulation, the area of application, condition of the skin (e.g., being increased with local abrasion or inflammation), and interindividual variation in the extent of percutaneous absorption.1, 39, 61 Percutaneous absorption of the drug does not appear to be altered by use of a hot-air hair dryer.101 Although limited in vitro evidence has demonstrated comparable release of minoxidil from solutions with different proportions of propylene glycol, alcohol, and water,57 other in vitro data from a study using a vehicle consisting only of alcohol and propylene glycol indicate that skin penetration increases with increasing alcohol concentrations.128 Release of topically applied minoxidil from a cream base differs substantially from that from solution formulations,57 and water-in-oil creams appear to differ markedly from oil-in-water creams or ointments in terms of the rate and concentration dependency of drug permeation through human skin.63 Absorption of minoxidil from extemporaneously prepared solutions, ointments, creams, or other such topical formulations may not be comparable to that from the commercially available topical minoxidil solution.5, 7, 9, 16, 39, 57
Percutaneous absorption of minoxidil following topical application of 2% hydroalcoholic, propylene glycol-containing solutions of the drug generally has been reported to average 0.3-4.5% of the applied dose.1, 43, 61, 70, 101 In a preliminary study in healthy balding men, the systemic bioavailability of minoxidil 2 or 3% topical solution (20- or 30-mg doses, respectively) at steady state relative to that of a 2.5-mg oral tablet averaged 1.4 or 1.2%, respectively.70 Based on urinary excretion of radiolabeled drug administered to healthy men in another study, percutaneous absorption of minoxidil after application of 1 or 5% minoxidil solutions to the scalp generally averaged 1.6-3.9% of the applied dose, based on urinary recovery of radiolabeled drug.61 In studies in animals, 5-36% of topically applied doses was absorbed systemically.9, 43 Serum concentrations achieved after topical application of minoxidil solutions are variable,27, 31 and clinical studies of topical minoxidil therapy have found no correlation between serum minoxidil concentrations and hair growth.22, 25, 27 In controlled studies in individuals with androgenetic alopecia or alopecia areata, serum concentrations of minoxidil after topical application of 1, 2, 3, or 5% solution formulations (with or without nightly petrolatum occlusion) generally averaged 2 ng/mL or less.1, 15, 16, 25, 27, 28, 31, 45, 49, 52 However, about 1% of individuals receiving a 2% topical solution achieved peak serum concentrations of 5 ng/mL or greater, and a few patients achieved concentrations approaching 30 ng/mL.1 In part, increased percutaneous absorption of the drug in some individuals may have resulted from alterations in the stratum corneum (e.g., secondary to irritation and inflammation from shaving of the scalp).1, 66 In addition, some individuals may have a propensity for enhanced percutaneous absorption of the drug.1, 61 (See Cautions: Precautions and Contraindications.) Data from healthy balding men indicate that peak serum concentrations of unchanged minoxidil after oral doses of 5 mg daily generally are 20-30 times higher than mean serum concentrations achieved after twice-daily topical application of approximately 20 mg (1 mL) of minoxidil as a 2% solution.1, 68, 101
Absorption of minoxidil after topical application of the solution appears to be slower and more prolonged than that after oral administration.15, 16, 68, 70 In monkeys, serum minoxidil concentrations obtained 2, 4, 6, 15, and 24 hours after topical application of a minoxidil 5% solution were relatively constant, averaging about 15 ng/mL.17 In patients with alopecia areata, the serum concentration profiles after topical application of minoxidil 1 or 5% solutions also suggests that absorption occurs over a period of at least 24 hours.15, 16 Evidence from individuals receiving 2-8 applications daily of minoxidil topical solutions in concentrations of 0.01-3% suggests that increasing the concentration or frequency of application of minoxidil does not produce proportionate increases in absorption;21, 61 these findings suggest that saturation of the stratum corneum with drug may occur after the initial dose.21, 69
A dose-response relationship with regard to increases in hair counts reportedly has been observed in several studies of topical minoxidil therapy,5, 7, 8, 16, 33, 44, 49, 51, 53 but only limited evidence of a correlation between drug concentration (i.e., applied dose) and cosmetic benefit has been reported.25, 49, 51, 53 Solution concentrations of minoxidil as low as 0.1% have been associated with measurable increases in hair counts compared with those observed with the propylene glycol vehicle alone, but clinically evident hair growth generally has been noted only with minoxidil solution concentrations of 1% or higher.8 Dose-response studies suggest that a 2% concentration of minoxidil in the topical solution is more effective in promoting hair growth than lower concentrations, although differences in hair counts in these studies often have not been statistically significant.5, 7, 8, 33 In multicenter studies, the minoxidil 2% solution appeared to be as effective as the 3% solution in producing cosmetically acceptable hair regrowth, with less potential for systemic absorption.5, 7, 22, 23, 27, 30, 31
The distribution of topically applied minoxidil has not been fully determined.100, 101 Limited evidence suggests that intact stratum corneum serves as a barrier that inhibits substantial diffusion of topically applied minoxidil into systemic circulation,68, 71, 101 but additional study is needed.100 Skin biopsy specimens obtained after topical application of a radiolabeled minoxidil 1 or 5% solution to the scalp of healthy balding men indicate an average retention in the skin of 2.6% or less of the applied dose after 24 hours, with twice as much radioactivity in the dermis as in the epidermis.61 The remainder of the dose remained on the skin or presumably was lost to the environment.9, 43, 61
The distribution of minoxidil into milk following topical application of the drug is not known, but the drug has been shown to distribute into milk following oral administration in lactating women.1, 72 (See Cautions: Pregnancy, Fertility, and Lactation.)
The metabolic fate and elimination characteristics of topically applied minoxidil have not been fully determined.1 A study in healthy men receiving radiolabeled drug indicates that following topical application, systemically absorbed minoxidil is excreted principally in urine; no fecal radioactivity was detected in this study.61 Following cessation of topical minoxidil dosing, approximately 95% of systemically absorbed drug is eliminated within 4 days.1 An appreciable portion of a topically applied dose appears to be removed from the surface of the scalp via inadvertent contact with hands or clothing, volatilization, displacement by air currents, or other nonsystemic means.9, 43, 61
Minoxidil is a piperidinopyrimidine-derivative vasodilator5, 19, 20, 37, 43, 44, 73 that possesses hair growth stimulant properties.4, 9, 14, 15, 20, 40, 43, 44, 56 Minoxidil occurs as a white to off-white, odorless, crystalline powder, which is slightly soluble (approximately 2 mg/mL) in water, soluble in alcohol (approximately 15-30 mg/mL) or propylene glycol (approximately 90 mg/mL), and practically insoluble in acetone, chloroform, or ethyl acetate at a room temperature of 20°C.1, 43, 76, 101 For topical use, minoxidil is commercially available as a 2% and a 5% solution in a vehicle of alcohol, propylene glycol, and water.116, 117, 121, 122, 123, 126 The 2 and 5% solutions contain alcohol 60 and 30%, respectively.121, 122, 123, 126
Commercially available minoxidil topical solutions should be stored at a temperature of 20-25°C.126, 132
Extemporaneous formulations of minoxidil have been reported to have variable stability, depending on the vehicle and method of preparation,15, 16, 39 and the FDA requests that physicians and pharmacists refrain from preparing extemporaneous topical formulations using commercially available minoxidil tablets.58 (See Cautions: Precautions and Contraindications.)
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Topical | Solution | 2%* | ||
Rogaine® Hair Regrowth Treatment for Men | ||||
Rogaine® Hair Regrowth Treatment for Women | Pfizer | |||
5%* | Rogaine® for Men Extra Strength | Pfizer | ||
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
1. The Upjohn Company. Rogaine® (minoxidil topical solution) prescribing information. Kalamazoo, MI; 1990 Feb.
2. The Upjohn Company. Rogaine® (minoxidil topical solution) product information. Kalamazoo, MI; 1988 Aug.
3. Dawber RPR. Aetiology and pathophysiology of hair loss. Dermatologica . 1987; 175(Suppl 2):23-8.
4. Headington JT. Hair follicle biology and topical minoxidil: possible mechanisms of action. Dermatologica . 1987; 175(Suppl 2):19-22. [PubMed 3319729]
5. Katz HI. Topical minoxidil: review of efficacy and safety. Cutis . 1989; 43:94-8. [PubMed 2644080]
6. Voorhees JJ. Editor's summary. Dermatologica . 1987; 175(Suppl 2):54-6.
7. Katz HI. Topical minoxidil: review of efficacy. Clin Dermatol . 1988; 6:195-9. [PubMed 3063371]
8. Shupack JL, Kassimir JJ, Thirumoorthy T et al. Dose-response study of topical minoxidil in male pattern alopecia. J Am Acad Dermatol . 1987; 16:673-6. [PubMed 3549801]
9. Clissold SP, Heel RC. Topical minoxidil: preliminary review of its pharmacodynamic properties and therapeutic efficacy in alopecia areata and alopecia androgenetica. Drugs . 1987; 33:107-22. [PubMed 3552591]
10. Fiedler-Weiss VC. Potential mechanisms of minoxidil-induced hair growth in alopecia areata. J Am Acad Dermatol . 1987; 16:653-6. [PubMed 3558910]
11. Bunker CB, Dowd PM. Topical minoxidil, scalp hair, and vasodilatation. Lancet . 1987; 1:1266.
12. Bunker CB, Dowd PM. Alterations in scalp blood flow after the epicutaneous application of 3% minoxidil and 0.1% hexyl nicotinate in alopecia. Br J Dermatol . 1987; 117:668-9. [PubMed 3689690]
13. Fiedler-Weiss VC, Buys CM. Response to minoxidil in severe alopecia areata correlates with T lymphocyte stimulation. Br J Dermatol . 1987; 117:759- 63. [PubMed 3501310]
14. Buhl AE, Waldon DJ, Kawabe TT et al. Minoxidil stimulates mouse vibrissae follicles in organ culture. J Invest Dermatol . 1989; 92:315-20. [PubMed 2465357]
15. Fiedler VC. Minoxidil: clinical and basic research in perspective. Semin Dermatol . 1987; 6:101- 7.
16. Fiedler-Weiss VC. Minoxidil. Dermatol Clin . 1987; 5:627-35. [PubMed 3301118]
17. Uno H, Cappas A, Brigham P. Action of topical minoxidil in the bald stump-tailed macaque. J Am Acad Dermatol . 1987; 16:657-68. [PubMed 3558911]
18. Fiedler VC, Buys CM. Immunohistochemical characterization of the cellular infiltrate in severe alopecia areata before and after minoxidil treatment. Dermatologica . 1987; 175(Suppl 2):29-35. [PubMed 2961630]
19. Headington JT, Novak E. Clinical and histologic studies of male pattern baldness treated with topical minoxidil. Curr Ther Res Clin Exp . 1984; 36:1098-106.
20. Uno H, Cappas A, Schlagel C. Cyclic dynamics of hair follicles and the effect of minoxidil on the bald scalps of stumptailed macaques. Am J Dermatopathol . 1985; 7:283-97. [PubMed 4051135]
21. Eller MG, Szpunar GJ, Della-Coletta AA. Absorption of minoxidil after topical application: effect of frequency and site of application. Clin Pharmacol Ther . 1989; 45:396-402. [PubMed 2702797]
22. Olsen EA, Weiner MS, Delong ER et al. Topical minoxidil in early male pattern baldness. J Am Acad Dermatol . 1985; 13:185-92. [PubMed 3900155]
23. De Villez RL. Topical minoxidil therapy in hereditary androgenetic alopecia. Arch Dermatol . 1985; 121:197-202. [PubMed 3883902]
24. Tosti A. Topical minoxidil useful in 18% of patients with androgenetic alopecia: a study of 430 cases. Dermatologica . 1986; 173:136-8. [PubMed 3770260]
25. Storer JS, Brzuskiewicz J, Floyd H et al. Review: topical minoxidil for male pattern baldness. Am J Med Sci . 1986; 291:328-33. [PubMed 3518451]
26. Civatte J, Laux B, Simpson NB et al. 2% topical minoxidil solution in androgenetic baldness: preliminary European results. Dermatologica . 1987; 175(Suppl 2):42-9. [PubMed 3319731]
27. Rietschel RL, Duncan SH. Safety and efficacy of topical minoxidil in the management of androgenetic alopecia. J Am Acad Dermatol . 1987; 16:677-85. [PubMed 3549802]
28. Kreindler TG. Topical minoxidil in early androgenetic alopecia. J Am Acad Dermatol . 1987; 16:718-24. [PubMed 3549807]
29. Roberts JL. Androgenetic alopecia: treatment results with topical minoxidil. J Am Acad Dermatol . 1987; 16:705-10. [PubMed 3549805]
30. Savin RC. Use of topical minoxidil in the treatment of male pattern baldness. J Am Acad Dermatol . 1987; 16:696-704. [PubMed 3549804]
31. Katz HI, Hien NT, Prawer SE et al. Long-term efficacy of topical minoxidil in male pattern baldness. J Am Acad Dermatol . 1987; 16:711-8. [PubMed 3549806]
32. Olsen EA, DeLong ER, Weiner MS. Long-term follow-up of men with male pattern baldness treated with topical minoxidil. J Am Acad Dermatol . 1987; 16:688-95. [PubMed 3549803]
33. Olsen EA, DeLong ER, Weiner MS. Dose-response study of topical minoxidil in male pattern baldness. J Am Acad Dermatol . 1986; 15:30-7. [PubMed 3722507]
34. De Villez RL. Androgenetic alopecia treated with topical minoxidil. J Am Acad Dermatol . 1987; 16:669-72. [PubMed 3549800]
35. De Villez RL. Topical minoxidil for androgenetic alopecia: optimizing the chance for success by appropriate patient selection. Dermatologica . 1987; 175(Suppl 2):50-3.
36. Koperski JA, Orenberg EK, Wilkinson DI. Topical minoxidil therapy for androgenetic alopecia. Arch Dermatol . 1987; 123:1483-7. [PubMed 3314717]
37. Vanderveen EE, Ellis CN, Kang S et al. Topical minoxidil for hair regrowth. J Am Acad Dermatol . 1984; 11:416-21. [PubMed 6384289]
38. Weiss VC, West DP. Topical minoxidil therapy and hair regrowth. Arch Dermatol . 1985; 121:191-2. [PubMed 3977331]
39. Rumsfield JA, West DP, Fiedler-Weiss VC. Topical minoxidil therapy for hair regrowth. Clin Pharm . 1987; 6:386-92. [PubMed 3311578]
40. de Groot AC, Nater JP, Herxheimer A. Minoxidil: hope for the bald? Lancet . 1987; 1:1019-21. Editorial.
41. Mitchell AD, De Villez R. Minoxidil for male- pattern baldness. Lancet . 1987; 1:1436. [PubMed 2884528]
42. de Groot AC, Nater JP, Herxheimer A. Minoxidil for male-pattern baldness. Lancet . 1987; 2:563. [PubMed 2887848]
43. Novak E, Franz TJ, Headington JT et al. Topically applied minoxidil in baldness. Int J Dermatol . 1985; 24:82-7. [PubMed 3886571]
44. Fenton DA, Wilkinson JD. Topical minoxidil in the treatment of alopecia areata. BMJ . 1983; 287:1015-7. [PubMed 6412929][PubMedCentral]
45. Weiss VC, West DP, Fu TS et al. Alopecia areata treated with topical minoxidil. Arch Dermatol . 1984; 120:457-63. [PubMed 6703751]
46. Price VH. Double-blind, placebo-controlled evaluation of topical minoxidil in extensive alopecia areata. J Am Acad Dermatol . 1987; 16:730-6. [PubMed 3549809]
47. King CM, Harrop B, Dave VK. Topical minoxidil in the treatment of alopecia areata. BMJ . 1983; 287:1380. [PubMed 6416428][PubMedCentral]
48. Maitland JM, Aldridge RD, Main RA et al. Topical minoxidil in the treatment of alopecia areata. BMJ . 1984; 288:794. [PubMed 6423083][PubMedCentral]
49. Fiedler-Weiss VC, West DP, Buys CM et al. Topical minoxidil dose-response effect in alopecia areata. Arch Dermatol . 1986; 122:180-2. [PubMed 3947124]
50. White SI, Friedmann PS. Topical minoxidil lacks efficacy in alopecia areata. Arch Dermatol . 1985; 121:591. [PubMed 3994404]
51. Price VH. Topical minoxidil in extensive alopecia areata, including 3-year follow-up. Dermatologica . 1987; 175(Suppl 2):36-41. [PubMed 3691913]
52. Price VH. Topical minoxidil (3%) in extensive alopecia areata, including long-term efficacy. J Am Acad Dermatol . 1987; 16:737-44. [PubMed 3549810]
53. Fiedler-Weiss VC. Topical minoxidil solution (1% and 5%) in the treatment of alopecia areata. J Am Acad Dermatol . 1987; 16:745-8. [PubMed 3549811]
54. Hamilton JB. Patterned loss of hair in man: types and incidence. Ann NY Acad Sci . 1951; 53:708- 28. [PubMed 14819896]
55. Norwood OT. Male pattern baldness: classification and incidence. South Med J . 1975; 68:1359-65. [PubMed 1188424]
56. Roenigk HH Jr, Pepper E, Kuruvilla S. Topical minoxidil therapy for hereditary male pattern alopecia. Cutis . 1987; 39:337-42. [PubMed 3556042]
57. Paraskevas D, Rekkas D, Choulis N et al. In vitro release of minoxidil from topical formulations. Arch Dermatol . 1987; 123:1433-4. [PubMed 3674904]
58. Anon. Unapproved use of minoxidil. FDA Drug Bull . 1985; 15:38.
59. Kvedar JC, Baden HP. Topical minoxidil in the treatment of male pattern alopecia. Pharmacotherapy . 1987; 7:191-7. [PubMed 3328164]
60. Ebling FJ. Biology of hair follicles. In: Fitzpatrick TB, Eisen AZ, Wolff K et al, eds. Dermatology in general medicine. 3rd ed. New York: McGraw-Hill Book Company; 1987:213-9.
61. Franz TJ. Percutaneous absorption of minoxidil in man. Arch Dermatol . 1985; 121:203-6. [PubMed 3977334]
62. Wester RC, Maibach HI, Guy RH et al. Minoxidil stimulates cutaneous blood flow in human balding scalps: pharmacodynamics measured by laser Doppler velocimetry and photopulse plethysmography. J Invest Dermatol . 1984; 82:515-7. [PubMed 6239893]
63. Chiang CM, Flynn GL, Weiner ND et al. Bioavailability assessment of topical delivery systems: in vitro delivery of minoxidil from prototypical semi- solid formulations. Int J Pharm . 1989; 49:109-14.
64. Bouhanna P. Topical minoxidil used before and after hair transplantation. J Dermatol Surg Oncol . 1989; 15:50-3. [PubMed 2910964]
65. Kassimir JJ. Use of topical minoxidil as a possible adjunct to hair transplant surgery. J Am Acad Dermatol . 1987; 16:685-7. [PubMed 3558912]
66. Szpunar GJ, Dalm EP, Albert KS. The effect of using shaved versus bald scalps on the bioavailability of topically applied minoxidil 2% solution. Pharm Res . 1986; 3(Suppl):114S.
67. Olsen EA, Weiner MS. Topical minoxidil in male pattern baldness: effects of discontinuation of treatment. J Am Acad Dermatol . 1987; 17:97-101. [PubMed 3301926]
68. Fiedler-Weiss VC, Rumsfield J, Buys CM et al. Evaluation of oral minoxidil in the treatment of alopecia areata. Arch Dermatol . 1987; 123:1488-90. [PubMed 3674909]
69. Eller MG, Szpunar GJ, Della-Coletta AA et al. Systemic absorption of minoxidil after topical application: effect of minoxidil concentration. Clin Pharmacol Ther . 1988; 43:137.
70. Szpunar GJ, Dalm EP, Albert KS. The bioavailability of 2% and 3% minoxidil topical solutions relative to a 2.5 mg oral minoxidil tablet (Loniten-Upjohn). Pharm Res . 1986; 3(Suppl):114S.
71. Stehle RG, Ho NFH, Grady RK et al. In vitro percutaneous absorption of minoxidil and characterization of metabolic properties of hairless mouse skin. Pharm Res . 1986; 3(Suppl):72S.
72. Valdivieso A, Valdes G, Spiro TE et al. Minoxidil in breast milk. Ann Intern Med . 1985; 102:135. [PubMed 3966734]
73. The Upjohn Company. Loniten® (minoxidil oral tablets) prescribing information. Kalamazoo, MI; 1986 Mar.
74. Schop RN, Goldberg MT. Nongenotoxicity of minoxidil in murine hair follicles as determined by the nuclear aberration assay. Toxicol Appl Pharmacol . 1988; 92:150-4. [PubMed 3341023]
75. Kubilus J, Kvedar JC, Baden HP. Effect of minoxidil on pre- and postconfluent keratinocytes. J Am Acad Dermatol . 1987; 16:648-52. [PubMed 2435772]
76. The United States Pharmacopeia, 21st rev. and The national formulary, 16th ed. Suppl 7. Rockville, MD: The United States Pharmacopeial Convention, Inc; 1988:2902.
77. Muller SA. Alopecia: syndromes of genetic significance. J Invest Dermatol . 1973; 60:475-92. [PubMed 4581946]
78. Tromovitch TA, Glogau RG, Stegman SJ. Medical treatment of male pattern alopecia (androgenic alopecia). Head Neck Surg . 1985; 7:336-9. [PubMed 3988537]
79. Adachi K. The metabolism and control mechanism of human hair follicles. Curr Probl Dermatol . 1973; 5:37-78. [PubMed 4362370]
80. Fiedler-Weiss VC, Johnson GA, Buys CM et al. Minoxidil sulfate and sulfotransferase activity in alopecia areata. Clin Res . 1987; 35:682A.
81. Cohen RL, Alves MEAF, Weiss VC et al. Direct effects of minoxidil on epidermal cells in culture. J Invest Dermatol . 1984; 82:90-3. [PubMed 6197493]
82. Fiedler-Weiss VC, Buys CM. Alopecia areata and control lymphocyte blastogenesis suppressed by in vitro minoxidil. J Invest Dermatol . 1986; 87:139.
83. Anon. Topical minoxidil for baldness. Med Lett Drugs Ther . 1987; 29:87-8. [PubMed 3306300]
84. Dawber RPR. Alopecia and hirsutism. Clin Exp Dermatol . 1982; 7:177-82. [PubMed 7083623]
85. The Upjohn Company. Minoxidil topical solution (Rogaine®): information for the patient. Kalamazoo, MI; 1988 Aug.
86. Leenen FHH, Smith DL, Unger WP. Topical minoxidil: cardiac effects in bald man. Br J Clin Pharmacol . 1988; 26:481-5. [PubMed 3191000][PubMedCentral]
87. Baral J. Scalp comedones after topical minoxidil. J Am Acad Dermatol . 1985; 13:1051. [PubMed 2934443]
88. Olsen EA. Scalp comedones after topical minoxidil. J Am Acad Dermatol . 1985 13:1051-2. Reply.
89. van der Willigen AH, Dutree-Meulenberg RO, Stolz E et al. Topical minoxidil sensitization in androgenic alopecia. Contact Dermatitis . 1987; 17:44- 5. [PubMed 2958212]
90. Tosti A, Bardazzi F, De Padova MP et al. Contact dermatitis to minoxidil. Contact Dermatitis . 1985; 13:275-6. [PubMed 4085233]
91. Degreef H, Hendrickx I, Dooms-Goossens A. Allergic contact dermatitis to minoxidil. Contact Dermatitis . 1985; 13:194-5. [PubMed 2932293]
92. Castillo G, Moshell AN, Jorgensen H et al. Contact sensitization to topically applied minoxidil solution: possible mechanism of action. Clin Res . 1985; 33:629A.
93. Yates VM, King CM, Harrop B. Topical minoxidil in the treatment of alopecia areata. BMJ . 1984; 288:1087. [PubMed 6423205][PubMedCentral]
94. Ranchoff RE, Bergfeld WF. Topical minoxidil reduces blood pressure. J Am Acad Dermatol . 1985; 12:586-7. [PubMed 3989020]
95. Feinstein RP. The effect of topical minoxidil on blood pressure. J Am Acad Dermatol . 1985; 13:673- 4. [PubMed 3908507]
96. Pestana A, Olsen EA, Delong ER et al. Effect of ultraviolet light on topical minoxidil-induced hair growth in advanced male pattern baldness. J Am Acad Dermatol . 1987; 16(5 Pt 1):971-6. [PubMed 3294945]
97. Herring BD. Unravelling the pathophysiology of male pattern baldness. J Natl Med Assoc . 1985; 77:142,145. [PubMed 3981649][PubMedCentral]
98. Mitchell AJ, Krull EA. Alopecia areata: pathogenesis and treatment. J Am Acad Dermatol . 1984; 11:763-75. [PubMed 6210311]
99. Parker LN, Lifrak ET, Odell WD. Lack of a gonadal or adrenal androgenic mechanism for the hypertrichosis produced by diazoxide, phenytoin and minoxidil. Biochem Pharmacol . 1982; 31:90-3.
100. Reviewers' comments (personal observations); 1989 Jul.
101. Cohon MS (The Upjohn Company, Kalamazoo, MI): Personal communication; 1989 July 13.
102. Linas SL, Nies AS. Minoxidil. Ann Intern Med . 1981; 94:61-5. [PubMed 6108737]
103. Burton JL, Marshall A. Hypertrichosis due to minoxidil. Br J Dermatol . 1979; 101:593-5. [PubMed 518830]
104. Mehta PK, Mamdani B, Shansky RM et al. Severe hypertension: treatment with minoxidil. JAMA . 1975; 233:249-52. [PubMed 1173832]
105. Baden HP, Kubilus J. Effect of minoxidil on cultured keratinocytes. J Invest Dermatol . 1983; 81:558-60. [PubMed 6196423]
106. Abell E, Cary MM. The pathologic effect of minoxidil in male pattern alopecia. J Invest Dermatol . 1986; 86:459.
107. De Boer EM, Bezemer PD, Bruynzeel DP et al. Does topical minoxidil increase skin blood flow? Acta Derm Venereol (Stockh) . 1988; 68:271-4.
108. Rietschel RL, Robertson DB. Duration of minoxidil therapy to yield maximum benefit. Arch Dermatol . 1988; 124:1569. [PubMed 3421734]
109. Olsen EA, Weiner MS, Amara IA et al. Five year follow-up of men with androgenetic alopecia treated with topical minoxidil. (unpublished observations) J Am Acad Dermatol . 1990; 22:643-6.
110. Spindler JR. Deaths occurring during clinical studies of topical minoxidil. J Am Acad Dermatol . 1987; 16:725-9. [PubMed 3549808]
111. Baral J. Minoxidil and sudden death. J Am Acad Dermatol . 1985; 13:297-8. [PubMed 4044954]
112. Vanderveen EE. Minoxidil and sudden death. J Am Acad Dermatol . 1985; 13:298-9.
113. Bazzano GS, Terezakis N, Galen W. Topical tretinoin for hair growth promotion. J Am Acad Dermatol . 1986; 15(4 Part 2):880-3,890-3. [PubMed 3771854]
114. Whiting DA. The treatment of alopecia areata. Cutis . 1987; 40:247-50. [PubMed 3308336]
115. Pharmacia & Upjohn. Rogaine® (minoxidil) topical solution prescribing information. In: Physicians' desk reference. 50th ed. Montvale, NJ: Medical Economics Company. 1996; 2637- 41.
116. Pharmacia & Upjohn. Rogaine® Hair Regrowth Treatment for Men (minoxidil) topical solution patient information. Kalamazoo, MI; undated (816-693-000).
117. Pharmacia & Upjohn. Rogaine® Hair Regrowth Treatment for Women (minoxidil) topical solution patient information. Kalamazoo, MI; undated (816-701-000).
118. DeVillez RL, Jacobs JP, Szpunar CA et al. Androgenetic alopecia in the female. Treatment with 2% topical minoxidil solution. Arch Dermatol . 1994; 130:303-7. [PubMed 8129407]
119. Jacobs JP, Szpunar CA, Warner ML. Use of topical minoxidil therapy for androgenetic alopecia in women. Int J Dermatol . 1993; 32:758-62. [PubMed 8225725]
120. Ludwig E. Classification of the types of androgenetic alopecia (common baldness) occurring in the female sex. Br J Dermatol . 1977; 97:247-54. [PubMed 921894]
121. Copley Pharmaceutical Inc. Minoxidil topical solution 2% patient information. Canton, MA; undated (LEA500702).
122. Bausch & Lomb Pharmaceuticals, Inc. Minoxidil topical solution 2% patient information. Tampa, FL; 1996 May.
123. Barre-National Inc. Minoxidil topical solution 2% patient information. Baltimore, MD; 1996 Mar.
124. Whiting DA, Jacobson C. Treatment of female androgenetic alopecia with minoxidil 2%. Int J Dermatol . 1992; 31:800-4. [PubMed 1428436]
125. Olsen EA. Topical minoxidil in the treatment of androgenetic alopecia in women. Cutis . 1991; 48:243-8. [PubMed 1935254]
126. Pharmacia & Upjohn Consumer Healthcare. Rogaine® Extra Strength for Men Hair Regrowth Treatment (minoxidil) topical solution patient information. Kalamazoo, MI; undated (817-069-000).
127. Pharmacia & Upjohn consumer Healthcare, Kalamazoo, MI: Personal communication.
128. Tata S, Flynn GL, Weiner ND. Penetration of minoxidil from ethanol/propylene glycol solutions: effect of application volume and occlusion. J Pharm Sci . 1995; 84:688-91. [PubMed 7562405]
129. Walsh DS, Dunn CL, James WD et al. Improvement in androgenetic alopecia (stage V) using topical minoxidil in a retinoid vehicle and oral finasteride. Arch Dermatol . 1995; 131:1373-5. [PubMed 7492124]
130. Ferry JJ, Forbes KK, Vanderlugt JT et al. Influence of tretinoin on the percutaneous absorption of minoxidil from an aqueous topical solution. Clin Pharmacol Ther . 1990; 47:439-46. [PubMed 2328551]
131. Rand S. Hair growth therapy(ies) for androgenetic alopecia. Arch Dermatol . 1996; 132:714-5. [PubMed 8651731]
132. Pharmacia & Upjohn. Rogaine® For Women Hair Regrowth Treatment (minoxidil 2%) Topical Solution product information. In: Physician's desk reference for nonprescription drugs. 21st ed. Montvale, NJ; Medical Economics Company Inc; 2000:711-2.