Minoxidil


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Talel Badri


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Updated:
10/9/2019 2:53:36 PM

Indications

Minoxidil (also called 2,4-pyrimidinediamine, 6-(1-piperidinyl)-, 3-oxide) is used since 1987 as a topical agent for the treatment of androgenic alopecia. Minoxidil was first designed, in the 1970s, as a potent peripheral vasodilator agent for the treatment of severe refractory hypertension. Regarding its serious side effects, oral minoxidil has been reserved only for cases of severe hypertension which are reluctant to maximum doses of three antihypertensive agents, including a diuretic.

Since about one-fifth of patients under oral minoxidil treatment developed hypertrichosis, a topical form was developed for the treatment of androgenic alopecia, initially for males and subsequently also for females. This topic will deal only with topical minoxidil since it is the most commonly used form of the molecule.[1][2][3][4]

Two forms of topical minoxidil are available: a solution (liquid form) and a foam. The solution contains alcohol and propylene glycol which are two molecules necessary to solve minoxidil and increase its uptake in the tissues. Formulations containing 2% and 5% minoxidil are generally used in scalp alopecia in patients who are over age 18 (the use of minoxidil in children is off-label). Long-term use of minoxidil is recommended to maintain the clinical results, as these effects regress with the drug discontinuation.[5][6][5]

Current uses of topical minoxidil include:

  • Androgenic alopecia (the only FDA-approved indication)
  • Alopecia areata (including alopecia areata incognita): Minoxidil may induce a good clinical response, either used alone or combined with other drugs such as corticosteroids.
  • Alopecia induced by chemotherapy: Minoxidil may minimize hair loss and accelerate regrowth.
  • Hair transplant: A frequent telogen effluvium is observed after the intervention. Minoxidil, before and after hair transplant, minimizes hair loss. The treatment should be temporarily suspended three days before intervention to avoid excessive bleeding.
  • Scarring alopecia: Since minoxidil has a probable antifibrotic action, it may be efficient in the early course of some dermatoses leading to scarring alopecia, such as scalp burning disease.
  • Monilethrix: Minoxidil leads to synchronization of entry of hair follicles into anagen phase.
  • Hereditary alopecia/hypotrichosis: The use of minoxidil may be beneficial in this indication, mainly by inducing a thickening in hair shafts.

Mechanism of Action

Topical minoxidil (empirical formula C9H15N5O) is a hair growth stimulator. Its mechanism of action is not exactly established. Scalp sulfotransferase changes minoxidil into minoxidil sulfate, which is thought to be the active form of the molecule. Variations between individuals in sulfotransferase activity may be an explanation of interindividual variations in minoxidil efficiency.[7]

Minoxidil acts by shortening telogen phase and thus causing the quiescent hair follicles to enter prematurely into anagen phase. The shortening of telogen phase may induce an important telogen effluvium after the initiation of minoxidil therapy. In the other hand, minoxidil induces an extension of the duration of anagen phase. Increased hair length and diameter is a clinical effect of minoxidil.

The effect of minoxidil occurs after approximately 8 weeks of treatment, and it is maximal after 4 months.

Minoxidil is thought to intervene on the potassium channels of the vascular smooth muscles and hair follicles, which may induce the following effects:

  • Stimulation of the microcirculation near the hair follicles by inducing arteriolar vasodilation, which may cause hair growth. Minoxidil induces the expression of vascular endothelial growth factor (VEGF) which increases vascularization around the hair follicles, thus contributing to hair growth
  • Activation of the prostaglandin-endoperoxide synthase one which stimulates hair growth   
  •  Inhibition of the effects of androgens on the androgen-sensitive hair follicles
  • Direct stimulating action on the hair follicles: Minoxidil may act as an ‘epidermal growth factor’ on matrix cells delaying their aging, thus prolonging the duration of anagen phase, probably via the activation of the beta-catenin pathway  

Minoxidil may have antifibrotic properties since it can affect collagen synthesis.

Administration

Minoxidil is available in the United States as an over-the-counter topical agent. It is used twice daily (1 ml dosage each). No scalp massage is needed after use. Minoxidil uptake is about 50% after an hour and 75% after 4 hours. Some practitioners associate microneedling with topical minoxidil to enhance its efficiency, but more studies are needed to assess the value of such an association.[8][9][10]

Oral minoxidil is not FDA-approved for hair loss even though some clinical trials have used it at various doses (0.25 to 2.5 mg daily).

Studies have shown that 5% minoxidil was more effective than 2% minoxidil in the treatment of alopecia. Clinical response to minoxidil is more pronounced if alopecia evolves since less than 5 years (mainly in young adults), and the hair follicles are not deeply miniaturized.

Adverse Effects

Minoxidil is well tolerated. However, propylene glycol contained in the liquid form (solution) of minoxidil may be the cause of some adverse effects reported by patients:

  • Minoxidil-induced telogen effluvium: the shortening of telogen phase by minoxidil causes marked shedding
  • Skin irritation: with erythema, discomfort and burn sensation
  • Scaly changes of the scalp: due to irritation or exacerbation of seborrheic dermatitis
  • Isolated itching
  • Allergic contact dermatitis: with erythema, eczematous skin reaction, and itching.

Minoxidil and propylene glycol are the major allergens in allergic contact dermatitis. Patch testing may be helpful to reveal the causative agent. In case of allergic contact dermatitis to propylene glycol, minoxidil foam (i.e., not containing propylene glycol) may be used.

  •  Localized or generalized hypertrichosis: this effect seen during oral minoxidil treatment may also be observed with topical form. It is probably related to the prolongation of anagen phase. This effect seems to be more commonly encountered with 5% minoxidil than 2% minoxidil.

Contraindications

Minoxidil is contraindicated in patients who have a history of hypersensitivity to the drug or its components (such as propylene glycol).

The use of minoxidil is not advised in pregnant and breastfeeding women. Even though minoxidil is not known to be teratogenic, rare cases of congenital disabilities have been reported.

Monitoring

Patients using topical minoxidil should be regularly monitored for scalp changes and localized/generalized hypertrichosis. Hypotension is exceptionally reported in patients using topical minoxidil.

Toxicity

Percutaneous toxicity is exceptional after a conventional use of minoxidil. There is no known antidote for minoxidil massive oral ingestion. Accidental oral ingestion of minoxidil results usually in mild effects, mainly vomiting and does rarely require hospitalization. However, cases of hypotension, tachycardia, and/or electrocardiographic changes after accidental ingestion have been reported. Refractory hypotension may be managed by intravenous fluids and vasopressor agents. Gastric wash and activated charcoal may be indicated to prevent systemic toxicity in massive accidental ingestion of minoxidil.

Enhancing Healthcare Team Outcomes

Male pattern baldness has no cure and the drug industry often hypes up new drugs. Minoxidil has been around for 3 decades and is widely prescribed by nurse practitioners, primary care providers and dermatologists. Unfortunately, minoxidil is not an effective drug for hair growth; it is not reliable or consistent in its effectiveness. Most men see no difference compared to a placebo. Healthcare workers should educate patients that there is no good agent for hair growth and most products on the market are shams and scams- minoxidil falls somewhere in the middle. It is a porhibitively expensive drug which does not work for hair growth.[7]


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Minoxidil - References

References

Jimenez-Cauhe J,Saceda-Corralo D,Rodrigues-Barata R,Hermosa-Gelbard A,Moreno-Arrones OM,Fernandez-Nieto D,Vaño-Galvan S, Effectiveness and safety of low-dose oral minoxidil in male androgenetic alopecia. Journal of the American Academy of Dermatology. 2019 May 2;     [PubMed]
Hunter N,Sayed K,Hay RA,Allam R,Hussein N, Comparing the Efficacy of Mesotherapy to Topical Minoxidil in the Treatment of Female Pattern Hair Loss Using Ultrasound Biomicroscopy: A Randomized Controlled Trial. Acta dermatovenerologica Croatica : ADC. 2019 Mar;     [PubMed]
Ahluwalia J,Fabi SG, The psychological and aesthetic impact of age-related hair changes in females. Journal of cosmetic dermatology. 2019 Apr 23;     [PubMed]
Anouar I,Hjira N,Boui M, Loose Anagen Syndrome: A Little Response to Minoxidil. International journal of trichology. 2019 Mar-Apr;     [PubMed]
Verma K,Tegta GR,Verma G,Gupta M,Negi A,Sharma R, A Study to Compare the Efficacy of Platelet-rich Plasma and Minoxidil Therapy for the Treatment of Androgenetic Alopecia. International journal of trichology. 2019 Mar-Apr;     [PubMed]
Gajjar PC,Mehta HH,Barvaliya M,Sonagra B, Comparative Study between Mesotherapy and Topical 5% Minoxidil by Dermoscopic Evaluation for Androgenic Alopecia in Male: A Randomized Controlled Trial. International journal of trichology. 2019 Mar-Apr;     [PubMed]
Freire PCB,Petri V,Atallah AN, Minoxidil for Patchy Alopecia Areata: Systematic Review and Meta-Analysis. Journal of the European Academy of Dermatology and Venereology : JEADV. 2019 Mar 5;     [PubMed]
Sharma A,Goren A,Dhurat R,Agrawal S,Sinclair R,Trüeb RM,Vañó-Galván S,Chen G,Tan Y,Kovacevic M,Situm M,McCoy J, Tretinoin enhances minoxidil response in androgenetic alopecia patients by upregulating follicular sulfotransferase enzymes. Dermatologic therapy. 2019 Apr 11;     [PubMed]
Sung CT,Juhasz ML,Choi FD,Mesinkovska NA, The Efficacy of Topical Minoxidil for Non-Scarring Alopecia: A Systematic Review Journal of drugs in dermatology : JDD. 2019 Feb 1;     [PubMed]
Fabbrocini G,Cantelli M,Masarà A,Annunziata MC,Marasca C,Cacciapuoti S, Female pattern hair loss: A clinical, pathophysiologic, and therapeutic review. International journal of women's dermatology. 2018 Dec;     [PubMed]

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