Minoxidil, sold under the brand namesLoniten andRogaine among others, is amedication used for the treatment ofhigh blood pressure andpattern hair loss.[7][8][9] It is anantihypertensive and avasodilator.[17] It is available as ageneric medication by prescription inoraltablet form andover-the-counter as atopical liquid or foam.[10][11][18][19]
Minoxidil, when used forhypertension, is generally reserved for use in severe hypertension patients who do not respond to at least two agents and adiuretic.[20] Minoxidil is also generally administered with aloop diuretic to preventsodium retention andpotassium retention.[20] It may also cause areflex tachycardia and thus is prescribed with abeta blocker.[20]
Minoxidil, when applied topically, is used for the treatment of hair loss.[21] It is effective in helping promote hair growth in people withandrogenic alopecia regardless of sex.[21] Minoxidil must be used indefinitely for continued support of existing hair follicles and the maintenance of any experienced hair regrowth.[8][9]
Low-dose oral minoxidil (LDOM) is usedoff-label against hair loss and to promote hair regrowth.[22] Oral minoxidil is an effective and well-tolerated treatment alternative for patients having difficulty with topical formulations.[23][24][25]
Minoxidil requires at least 2 to 4 months before the first benefits on hair growth can be observed.[2] Maximal effectiveness occurs after 12 months.[2]
Minoxidil is available in the form oforaltablets,topicalsolution, topicalfoam, and topicalspray.[4] The tablets include 2.5 and 10 mg forms, the solutions include 2% and 5% forms, and the foam and spray are both 5% concentration.[2][4] The topical solutions are formulated withpolyethylene glycol (PEG) to enhanceabsorption of minoxidil.[4] The topical solution is often referred to asminoxidil topical solution (MTS) and the topical foam is known asminoxidil topical foam (MTF).[2]
Side effects of oral minoxidil may include swelling of the face and extremities, rapid heartbeat, or lightheadedness. Cardiac lesions, such as focalnecrosis of thepapillary muscle and subendocardial areas of the left ventricle, have been observed in laboratory animals treated with minoxidil.[10]Pseudoacromegaly is an extremely rare side effect reported with large doses of oral minoxidil.[27]
Topically applied minoxidil is generally well tolerated, but common side effects include itching of the eyes, general itching, irritation at the treated area, and unwanted hair growth elsewhere on the body.[28]Alcohol andpropylene glycol present in some topical preparations may dry the scalp, resulting indandruff andcontact dermatitis.[29]
Sublingual minoxidil may have reduced side effects with retained effectiveness compared to oral minoxidil.[16][30][15] This is due to lessminoxidil sulfate being formed duringfirst-pass metabolism and due to local activation of minoxidil into minoxidil sulfate withinhair follicles.[16][30][15] In a preliminaryclinical trial, no adverse effects or changes inblood pressure occurred with low-dose sublingual minoxidil.[30][15]
Minoxidil has been implicated in causingpericardial effusions[31] including life-threatening cases ofcardiac tamponade.[32] There have beencase reports dating back to the 1980s describing this phenomenon, including topical[32] and oral formulations.[33] The frequency of these occurrences has previously been reported at 3%, but the true frequency is difficult to determine as a large proportion of patients in this cohort also hadrenal insufficiency and may have had an effusion preceding the use of minoxidil.[34]
In 2013 or 2014, a seven-year-old girl was admitted to a children's hospital inToulouse in France after accidentally ingesting a teaspoon of Alopexy (a brand name for minoxidil in France). The child vomited constantly after ingestion and showedhypotension andtachycardia for 40 hours.[35] The authors of the report on the incident stressed that the product should be kept out of reach of children, and urged manufacturers to consider more secure child-resistant packaging.[36]
Combination oforal minoxidil withguanethidine can result in profoundorthostatic hypotension.[12]
Low-dose dailyaspirin can reduce the effectiveness of topical minoxidil for hair loss.[37][3][38] This is thought to be because aspirin inhibitssulfotransferase activity and hence prevents conversion of aspirin into its active formminoxidil sulfate.[37][3][38]Salicylic acid is also a sulfotransferase inhibitor and could likewise affect the effectiveness of topical minoxidil.[37][38] In addition,paracetamol (acetaminophen) is asulfatescavenger and may inhibit minoxidil activation into minoxidil sulfate and effectiveness.[3][39]
Themechanism by which minoxidil promotes hair growth is not fully understood. Minoxidil is anadenosine 5'-triphosphate-sensitivepotassium channel opener,[40] causinghyperpolarization of cell membranes. Theoretically, by widening blood vessels and opening potassium channels, it allows more oxygen, blood, and nutrients to thefollicles. Moreover, minoxidil contains anitric oxide moiety and may act as a nitric oxide agonist. This may cause follicles in thetelogen phase to shed, which are then replaced by thicker hairs in a newanagen phase. Minoxidil is aprodrug that is converted bysulfation via thesulfotransferaseenzymeSULT1A1 to its active form,minoxidil sulfate. The effect of minoxidil is mediated byadenosine, which triggers intracellular signal transduction via bothadenosine A1 receptors and two sub-types of adenosine A2 receptors (A2A andA2B receptors).[41] Minoxidil acts as an activator of theKir6/SUR2 channel upon selective binding to SUR2.[42] The expression ofSUR2B in dermal papilla cells might play a role in the production of adenosine.[41] Minoxidil induces cell growth factors such as VEGF, HGF, IGF-1 and potentiates HGF and IGF-1 actions by the activation of uncoupledsulfonylurea receptor on the plasma membrane of dermal papilla cells.[43]
A number ofin vitro effects of minoxidil have been described in monocultures of various skin and hair follicle cell types including stimulation of cellproliferation, inhibition of collagen synthesis, and stimulation ofvascular endothelial growth factor,prostaglandin synthesis andleukotriene B4 expression.[44]
Minoxidil causes a redistribution of cellular iron through its apparent capacity to bind this metal ion. By binding iron in a Fenton-reactive form, intracellularhydroxyl radical production would ensue, but hydroxyl would be immediately trapped and scavenged by the minoxidil to generate a nitroxyl radical. It is presumed that this nitroxyl radical will be capable of reduction byglutathione to reform minoxidil. Such a process would cycle until the minoxidil is otherwise metabolized and would result in rapid glutathione depletion with glutathione disulphide formation and therefore with concomitant consumption ofNADPH/NADH and other reducing equivalents.[45] Minoxidil inhibitedPHD by interfering with the normal function ofascorbate, acofactor of the enzyme, leading to a stabilization ofHIF-1α protein and a subsequent activation ofHIF-1. In an in vivo angiogenesis assay, millimolar minoxidil increased blood vessel formation in a VEGF-dependent manner. Minoxidil inhibition of PHD occurs via interruptingascorbate binding to iron.[46] The structural feature of positioning amines adjacent to nitric oxide may confer the ability of millimolar minoxidil to chelate iron, thereby inhibiting PHD. Minoxidil is capable oftetrahydrobiopterin inhibition as a cofactor for nitric oxide synthase.[47]
Minoxidil stimulatesprostaglandin E2 production by activatingCOX-1[48] andprostaglandin endoperoxide synthase-1 but inhibitsprostacyclin production. Additionally, expression of theprostaglandin E2 receptor, the most upregulated target gene in theβ-catenin pathway of DP cells, was enhanced by minoxidil, which may enable hair follicles to grow continuously and maintain the anagen phase.[49]
Due to the anti-fibrotic activity of minoxidil inhibition of enzymelysyl hydroxylase present infibroblast may result in the synthesis of ahydroxylysine-deficient collagen. Minoxidil can also potentially stimulateelastogenesis in aortic smooth muscle cells, and in skin fibroblasts in a dose-dependent manner. In hypertensive rats, minoxidil increases elastin levels in the mesenteric, abdominal, and renal arteries by a decrease inelastase enzyme activity in these tissues. In rats, potassium channel openers decrease calcium influx which inhibits elastin gene transcription throughextracellular signal-regulated kinase 1/2 (ERK 1/2)-activator protein 1 signaling pathway. ERK 1/2 increases, through elastin gene transcription, adequately cross-linked elastic fiber content synthesized by smooth muscle cells, and decreases the number of cells in the aorta.[50]
Minoxidil possessesα2-adrenergic receptoragonist activity,[51] stimulates the peripheralsympathetic nervous system (SNS) by way of carotid and aorticbaroreceptor reflexes. Minoxidil administration also brings an increase in plasmarenin activity, largely due to the aforementioned activation of the SNS. This activation of therenin-angiotensin axis further prompts increased biosynthesis ofaldosterone; whereas plasma and urinary aldosterone levels are increased early in the course of treatment with minoxidil, over time these values tend to normalize presumably because of accelerated metabolic clearance of aldosterone in association with hepatic vasodilation.[20]
Minoxidil may be involved in the inhibition ofserotonin5-HT2 receptors.[52]
Minoxidil might increase blood-tumor barrier permeability in a time-dependent manner by down-regulatingtight junction protein expression and this effect could be related toROS/RhoA/PI3K/PKB signal pathway.[53] Minoxidil significantly increasesROS concentration when compared to untreated cells.[medical citation needed]
Minoxidil treatment resulted in a 0.22 fold change for5α-R2 (p < 0.0001)in vitro. This antiandrogenic effect of minoxidil, shown by significant downregulation of 5α-R2 gene expression in HaCaT cells, may be one of its mechanisms of action in alopecia.[54]
Minoxidil is less effective when the area of hair loss is large. In addition, its effectiveness has largely been demonstrated in younger men who have experienced hair loss for less than 5 years. Minoxidil use is indicated for central (vertex) hair loss only.[55] Two clinical studies are being conducted in the US for a medical device that may allow patients to determine if they are likely to benefit from minoxidil therapy.[56]
Conditions such asCantú syndrome have been shown to mimic the pharmacological properties of minoxidil.[57][58]
Minoxidil is readilyabsorbed from thegastrointestinal tract withoral administration.[4] Its absorption from the gut is around 90% or more.[4][12][13] The drug reachespeak levels after about 30 to 60 minutes hour.[4][12][13][59] Following attainment of peak levels, concentrations of minoxidil rapidly decline.[12]Sublingual minoxidil is expected to have higherbioavailability than topical minoxidil.[16][60] Peak levels with sublingual administration occurred after 30 minutes.[15] The bioavailability of oral minoxidil is not affected by food and it can be taken in either a fasted or fed state.[14]
In the case oftopical administration to thescalp, the absorption of minoxidil is only about 1.2 to 1.4%.[4] With thisroute, serum levels of minoxidil are usually less than 5 ng/mL and are frequently undetectable.[4] It has been predicted that application of 5% topical minoxidil twice to the entire scalp might be equivalent to a single 5.4 mg oral dose of minoxidil in terms ofsystemic exposure.[4][61] Thestratum corneum of the scalp is saturated by minoxidil and acts as a reservoir for the drug.[2] This results in a continuous flow of minoxidil in the scalp, with absorption being completed after about 10 to 12 hours.[2] Based on these findings, topical minoxidil is generally applied twice daily.[2] A wet scalp has been found to increase the absorption of topical minoxidil.[2]
Peak levels of minoxidil with oral minoxidil were 16.8 ng/mL with 2.5 mg, 37.2 ng/mL with 5 mg, and 74.7 ng/mL with 10 mg doses.[14][59] Mean peak minoxidil levels with a single 0.45 mg dose of sublingual minoxidil were 1.62 ng/mL (range 0.3–5.3 ng/mL).[15] Circulating levels of 0.6 ng/mL with 2% solution and 1.6 ng/mL with 5% solution occur with topical minoxidil.[2] However, levels vary between individuals, with a range of undetectable to 7.5 ng/mL with 3% solution in 12 individuals in one study.[4][62] Significant cardiological and hemodynamic effects are said to occur with minoxidil when serum minoxidil levels exceed 20 ng/mL.[2][63]
Thevolume of distribution of oral minoxidil is greater than 200 L.[14] Minoxidil does not cross theblood–brain barrier and hence isperipherally selective.[4][14][12] It shows minimal or negligibleplasma protein binding.[4][14][12]
Minoxidil is aprodrug ofminoxidil sulfate, which can be formed both systemically and locally withinhair follicles.[4][2][39] Thisactive metabolite is 14-fold morepotent than minoxidil in stimulatingcysteine incorporation incultured rodent hair folliclesex vivo.[2][39] Similarly to minoxidil, it also stimulates hair follicle growth.[2][39] Minoxidil issulfated into minoxidil sulfate by at least fourcytosolicsulfotransferaseenzymes found inskin,scalp,smooth muscle,liver, andfibroblasts.[2] The primary sulfotransferase involved in sulfation of minoxidil in hair follicles isSULT1A1, whereas in the liver, it isSULT2A1.[4][16]Expression of this enzyme has been found to predict the effectiveness of topical minoxidil.[4]
Oral minoxidil is subject tofirst-pass metabolism, including rapid and extensive metabolism in theliver.[2] A majority of orally administered minoxidil, about 90%, is metabolized in the liver viaglucuronidation,hydroxylation, and sulfation, with glucuronidation being the primarymetabolic pathway and minoxidil glucuronide being the predominantmetabolite of minoxidil.[4][14][12][13] Conversely, topical minoxidil bypasses the first pass through the liver and is not subject to first-pass metabolism.[2] Similarly,sublingual minoxidil also bypasses first-pass metabolism.[16][30][60]
Minoxidil isexcreted almost exclusively (>97%) inurine.[2] About 10 to 15% is excreted in urine unchanged.[3] Theelimination half-life of oral minoxidil is about 3 to 4 hours.[4][12][13] Conversely, the half-life of topical minoxidil is 22 hours on average.[2] Oral minoxidil is excreted within 12 to 20 hours in urine.[4] Despite this however, the hypotensive effect of oral minoxidil lasts approximately 72 hours following a single dose.[14] With discontinuation of topical minoxidil, about 95% of systemically absorbed minoxidil is excreted within 4 days.[4] The renalclearance of oral minoxidil is 352 mL/minute.[14]
Minoxidil is an odorless, white to off-white, crystalline powder (crystals from methanol-acetonitrile). When heated to decomposition it emits toxic fumes of nitrogen oxides. It decomposes at 259-261 °C.[64] Itssolubility (mg/ml) ispropylene glycol 75,methanol 44,ethanol 29,2-propanol 6.7,dimethylsulfoxide 6.5, water 2.2,chloroform 0.5,acetone <0.5,ethyl acetate <0.5,diethyl ether <0.5,benzene <0.5,acetonitrile <0.5. The pKa of minoxidil is 4.61.
Minoxidil, 6-amino-1,2-dihydro-1-hydroxy-2-imino-4-piperidinopyrimidine, is synthesized frombarbituric acid, the reaction of which withphosphorus oxychloride gives 2,4,6-trichloropyrimidine. Upon reaction with ammonium, this turns into 2,4-diamino-6-chloropyrimidine. Next, the resulting 2,4-diamino-6-chloropyrimidine undergoes a reaction with 2,4-dichlorophenol in the presence of potassium hydroxide, giving 2,4-diamino-6-(2,4-dichlorophenoxy)-pyrimidine. Oxidation of this product with 3-chloroperbenzoic acid gives 2,4-diamino-6-(2,4-dichlorophenoxy)pyrimidine-3-oxide, the 2,4-dichlorophenoxyl group of which is replaced with a piperidine group at high temperature, giving minoxidil.[66]
Minoxidil was developed in the late 1950s by theUpjohn Company (later became part ofPfizer) to treatulcers. In trials using dogs, the compound did not cure ulcers but proved to be a powerful vasodilator. Upjohn synthesized over 200 variations of the compound, including the one it developed in 1963 and named minoxidil.[67] These studies resulted in the U.S.Food and Drug Administration (FDA) approving minoxidil (with the brand name Loniten) in the form of oraltablets to treathigh blood pressure in 1979.[68][69]
When Upjohn received permission from the U.S.Food and Drug Administration (FDA) to test the new drug as medicine for hypertension they approached Charles A. Chidsey, at theUniversity of Colorado School of Medicine.[67] He conducted two studies,[70][71] the second study showing unexpected hair growth. Puzzled by this side-effect, Chidsey consulted Guinter Kahn (who while a dermatology resident at the University of Miami had been the first to observe and report hair development on patients using the minoxidil patch) and discussed the possibility of using minoxidil for treatinghair loss.[citation needed]
Kahn, along with his colleague Paul J. Grant, had obtained a certain amount of minoxidil and conducted their own research, since they were first to make the side effect observation. Neither Upjohn or Chidsey at the time were aware of the side effect of hair growth.[72] The two doctors had been experimenting with a 1% solution of minoxidil mixed with several alcohol-based liquids.[73] Both parties filed patents to use minoxidil for hair loss prevention, which resulted in a decade-long trial between Kahn and Upjohn, which ended with Kahn's name included in a consolidated patent (U.S. #4,596,812 Charles A Chidsey, III and Guinter Kahn) in 1986 and royalties from the company to both Kahn and Grant.[72]
Meanwhile, the effect of minoxidil on hair loss prevention was so clear that in the 1980s physicians were prescribing Lonitenoff-label to their balding patients.[69]
In August 1988, the FDA approved minoxidil for treating baldness in men[69][73] under the brand name "Rogaine" (FDA rejected Upjohn's first choice, Regain, as misleading[74]). The agency concluded that although "the product will not work for everyone", 39% of the men studied had "moderate to dense hair growth on the crown of the head".[74] "Men's Rogaine", marketed by Johnson & Johnson went off-patent on January 20, 2006.[75]
In 1991, Upjohn made the product available for women.[73] "Women's Rogaine", marketed by Johnson & Johnson, went off-patent in February 2014.[75]
In February 1996, the FDA approved both theover-the-counter sale and the production ofgeneric formulations of minoxidil.[69] Upjohn replied to that by lowering prices to half the price of the prescription drug[73] and by releasing a prescription 5% formula of Rogaine in 1997.[69][76] In 1998, a 5% formulation of minoxidil was approved for nonprescription sale by the FDA.[77] The 5% aerosol foam formula was approved for medical use in the US in 2006.[78][79] The generic versions of the 5% aerosol foam formula were approved in 2017.[80][81]
In 2017, a study of pharmacy prices in four states for 41 over-the-counter minoxidil products which were "gender-specified" found that the mean price for minoxidil solutions was the same for women and men even though the women's formulations were 2% and the men's were 5%, while the mean price for minoxidil foams, which were all 5%, was 40% higher for women. The authors noted this was the first timegender-based pricing had been shown for a medication.[82]
As of June 2017[update], Minoxidil is sold under many brand names worldwide, including but not limited to: Alomax, Alopek, Alopexy, Alorexyl, Alostil, Aloxid, Aloxidil, Anagen, Apo-Gain, Axelan, Belohair, Boots Hair Loss Treatment, Botafex, Capillus, Carexidil, Coverit, Da Fei Xin, Dilaine, Dinaxcinco, Dinaxil, Ebersedin, Eminox, Folcare, Follixil, Guayaten, Hair Grow, Hair-Treat, Hairgain, Hairgaine, Hairgrow, Hairway, Headway, Inoxi, Ivix, Keranique, Lacovin, Locemix, Loniten, Lonnoten, Lonolox, Lonoten, Loxon, M E Medic, Maev-Medic, Mandi, Manoxidil, Mantai, Men's Rogaine, Minodil, Minodril, Minostyl, Minovital, Minox, Minoxi, Minoxidil, Minoxidilum, Minoximen, Minoxiten, Minscalp, Mintop, Modil, Morr, Moxidil, Neo-Pruristam, Neocapil, Neoxidil, Nherea, Nioxin, Noxidil, Oxofenil, Pilfud, Pilogro, Pilomin, Piloxidil, Re-Stim, Re-Stim+, Recrea, Regain, Regaine, Regaxidil, Regro, Regroe, Regrou, Regrowth, Relive, Renobell Locion, Reten, Rexidil, Rogaine, Rogan, Scalpmed, Si Bi Shen, Splendora, Superminox, Trefostil, Tricolocion, Tricoplus, Tricovivax, Tricoxane, Trugain, Tugain, Unipexil, Vaxdil, Vius, Women's Regaine, Xenogrow, Xtreme Boost, Xtreme Boost+, Xue Rui, Ylox, and Zeldilon.[83] It is also sold as acombination medication withamifampridine under the brand names Gainehair and Hair 4 U; and as a combination withtretinoin andclobetasol under the brand name Sistema GB.[83]
Anextended-release formulation of low-doseoral minoxidil is under development for treatment ofhair loss.[84][85][86][87] It is being developed by Veradermics under the developmental code nameVDPHL01.[84][85][86][87] As of September 2025, it is inphase 3clinical trials for this indication.[84][86][87]
A low-dosesublingual formulation of minoxidil is under development for treatment of hair loss.[88][89][90] It is being developed by Samson Clinical.[88][89][90] As of September 2025, it is in phase 3 clinical trials for this indication.[88][89][90]
Finasteride/latanoprost/minoxidil (developmental code name TH-07 or TH07; Triple Hair) is atopicalcombination drug including minoxidil,finasteride, andlatanoprost which is under development for the treatment of hair loss.[91][92] As of December 2023, it is inphase 2 clinical trials for this indication.[91]
AB-103 is a minoxidilsulfotransferase stimulant which enhances minoxidil conversion into its active formminoxidil sulfate inhair follicles and is under development as a topical medication for the treatment of hair loss.[93] Sulfotransferase activity inhair follicles has been associated with minoxidil's clinical effectiveness.[94][2] As of February 2024, AB-103 is in phase 3 clinical trials for this indication, although there have been no new updates since 2019.[93]
Minoxidil has been studied for enhancement offacial hair or beard growth intransgender men.[95][96][97]
Minoxidil has been studied in the treatment ofonychodystrophy (nail problems).[98] A 2025systematic review found that it has been assessed in at least 6 clinical studies for this purpose and that the employed formulations included 2 to 5%topical minoxidil and 1.25 to 2.5 mg/dayoral minoxidil.[98] The drug has been found to increase the rate of nail growth, improve nail appearance, increase nail strength, and resolveyellow nail discoloration.[98]
Minoxidil is being investigated as a potential treatment forovarian cancer.[99]
Minoxidil is highlytoxic todogs andcats, even in doses as small as a drop or lick.[100] There are reported cases of cats dying shortly after coming in contact with minimal amounts of the substance.[101]
There is no specificantidote, butlipid rescue has been used successfully.[102][103]
Sublingual doses of 0.45 and 0.90 mg minoxidil were evaluated by Sinclair et al.31 as sublingual route bypasses hepatic first-pass metabolism, sublingual minoxidil could be used to increase follicular minoxidil sulfate bioavailability and thus hair growth. As hepatic sulphation of minoxidil enhances the hemodynamic effect, sublingual minoxidil would decrease the hemodynamic adverse effects and consequently improve safety profile.
Sublingual minoxidil has been proposed as an alternative route of administration to obtain the same improvement in hair density with lower doses. Moreover, a sublingual dose would avoid hepatic first-pass metabolism and may reduce the AEs. The results of the first phase 1B clinical trial have recently been published [34]. Patients receiving sublingual minoxidil 0.45 mg daily had a significant improvement in hair density after 6 months. Higher doses (1.35 and 4.05 mg) were also effective. None of the patients reported AEs and investigators did not find significant changes in blood pressure.
Salicylate and aspirin can inhibit sulfotransferase. A recent study showed that the follicular enzymatic activity decreased following 14 days of low-dose aspirin use. Thus, prior or concomitant use of aspirin decreases the clinical response to topical minoxidil.11
The expression of sulfonylurea receptor 2B and of the adenosine A1, A2A, and A2B receptors was detected in dermal papilla cells by means of reverse transcription polymerase chain reaction analysis.
As mentioned earlier, the hair-growth-promoting properties of minoxidil were clear from initial development. [...] Of concern, if excessive doses are used, even topically, there is the potential for minoxidil to have systemic effects—precipitating a possible "drug-induced Cantú syndrome." Indeed [pulmonary hypertension (PH)], edema, coarsening of facial features, and even reopening of the ductus arteriosus are associated with the Kir6.1/SUR2B active [potassium channel openers (KCOs)] minoxidil and diazoxide (156–158). Multiple KCOs induce and prolong anagen, the rapidly dividing stage of hair, in cultured follicles to promote growth, which can be reversed by the KATP inhibitor tolbutamide (86–88, 159). It is possible that CS-associated mutations have the same hair growth cycle effects, though this requires clarification. Thinking more broadly about the electrical consequences, KATP activation versus voltage-gated calcium channel (VGCC) activation would be expected to have opposing electrophysiological effects, and interestingly Timothy syndrome, caused by gain-of-function mutations in the VGCC, CaV1.2 is associated with baldness at birth (160), potentially the reverse mechanistic phenomenon.
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