Minoxidil (Topical)


VA CLASSIFICATION
Primary: DE900

Commonly used brand name(s): Apo-Gain; Gen-Minoxidil; Minoxigaine; Rogaine; Rogaine Extra Strength For Men; Rogaine For Men; Rogaine For Women.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Hair growth stimulant, alopecia androgenetica, topical—

Indications

Accepted

Alopecia androgenetica (treatment)—Minoxidil topical solution is indicated for treatment of alopecia androgenetica (also called male pattern baldness in men) in both adult males and females for the 2% strength {01} {17} {30} {31} and in adult males only for the 5% strength {29}. Alopecia androgenetica is expressed in males as baldness of the vertex of the scalp and/or as frontal hair recession {06} {12}. In females, it is expressed as diffuse hair loss or thinning in the frontoparietal areas {06} {12} {14} {17}. Topical minoxidil is less likely to be effective in men with predominantly frontal hair loss than in patients with the other forms of alopecia androgenetica {11}.

Acceptance not established
There are insufficient data to show that 2% minoxidil is effective in the treatment of alopecia areata {12} {16} {18} {21}.


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    209.25 {13}

pKa—
    4.6

Mechanism of action/Effect:

Topical minoxidil stimulates hair growth in some persons with alopecia androgenetica. The mechanism by which minoxidil stimulates hair growth is not established {20}, but possible mechanisms include increased cutaneous blood flow as a result of vasodilation, {01} {02} {09} {10} {11} {16} stimulation of resting hair follicles (telogen phase) into active growth (anagen phase), {01} {02} {09} {10} and stimulation of hair follicle cells. {11} {15} {16} {18}


Other actions/effects:

Most studies have not found changes in blood pressure {09}. In one report of 30 patients using 3% topical minoxidil for 15 months, seven normotensive patients absorbed a sufficient amount of minoxidil to decrease their systolic blood pressure by 60 mm of mercury and their diastolic blood pressure by 24 mm of mercury. The patients were asymptomatic and tachycardia did not occur {04}. Systemically absorbed oral minoxidil may cause peripheral arterial vasodilation, reduced peripheral resistance, a reflex increase in heart rate and cardiac output, and fluid retention {02}.

Absorption:

Low percutaneous absorption; 1.6 to 3.9% of the total applied topical dose is absorbed systemically {01} {03}; however, absorption may increase if medication is applied to inflamed skin. Applying a 5-microliter-per-squared-centimeter dose to the entire scalp is expected to yield a systemic dose of 1.2 mg for the 1% topical solution of minoxidil and 2.7 mg for the 5% solution of minoxidil. Applying a 1 or 2% topical concentration of minoxidil to up to 50% of the scalp is unlikely to cause systemic side effects, since the average absorbed dose is less than 1.2 mg of minoxidil. {03}

Onset of action:

At least 4 months {01} {02} with twice-daily applications for the 2% strength, and 2 months for the 5% strength (although in some patients effect still takes 4 months) {29}.

Duration of action:

In one study with continuous treatment using topical minoxidil for alopecia androgenetica, hair regrowth tended to peak at one year, with a slow decline in regrowth over subsequent years. Even so, after 41/2 to 5 years of treatment, there were still more nonvellus hairs than there were at the beginning of the treatment. {02} {26} {19}

New hair growth achieved during therapy may be expected to be lost 3 to 4 months after withdrawal of minoxidil, and progressive hair loss will resume. {01} {29}

Elimination:
    Renal—Approximately 95% of systemically absorbed minoxidil is eliminated within 4 days {03} {08}.


Precautions to Consider

Carcinogenicity

A 1-year study of minoxidil applied topically in rats and rabbits showed no evidence of carcinogenicity {27}.

Mutagenicity

Minoxidil was not found to be mutagenic in the Salmonella (Ames) test, the DNA damage/alkaline elution assay, or the rat micronucleus test {27}.

Pregnancy/Reproduction
Fertility—
There was a dose-dependent decreased conception rate in male and female rats given 1 or 5 times the maximum recommended oral antihypertensive human dose {27}.

Pregnancy—
Adequate and well-controlled studies in humans have not been done {27}.

With oral administration of minoxidil, no teratogenic effects occurred in rats or rabbits, but there was evidence of increased fetal resorption in rabbits (but not rats) at 5 times the maximum recommended antihypertensive human dose {27}.


Labor and delivery—

The effects of minoxidil on labor or delivery are unknown {27}.

Breast-feeding

Orally administered minoxidil is distributed into breast milk. It is not known whether topical minoxidil is distributed into breast milk. However, because of the potential for adverse effects, topical minoxidil should not be administered to women who are breast-feeding. {27}

Pediatrics

No information is available on the relationship of age to the effects of topical minoxidil in pediatric patients. Safety and efficacy have not been established for pediatric patients up to 18 years of age. Use in infants is not recommended. {27}


Geriatrics


No information is available on the relationship of age to the effects of this medication in geriatric patients. Safety and efficacy have not been established in patients older than 65 years of age. {27}

Older patients up to 65 years of age have not demonstrated geriatric-specific problems that would limit the usefulness of topical minoxidil; however, the best results are shown in younger patients with a short history of hair loss {11}.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

» Corticosteroids, topical or{27}
» Petrolatum, topical or{27}
» Retinoids, topical{21}{23}    (concurrent use on the same area may enhance cutaneous absorption of topical minoxidil because of increased stratum corneum permeability and is not recommended; in one patient, concurrent use of a topical retinoid on the same area as topical minoxidil caused a lesion consisting of granulation tissue similar to pyogenic granuloma {23})


Guanethidine    (concurrent use may increase the chance of orthostatic hypotension {27})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
Allergy to minoxidil or propylene glycol{27}
Cardiovascular disease or{06}
Hypertension{04}{06}    (patients with these conditions were excluded from the clinical trials of topical minoxidil because of the potential that adverse systemic effects could occur for the rare patient who might receive significant systemic absorption from its use; although their deaths were not attributable to topical minoxidil treatment, unexplained sudden death occurred in two patients with underlying undetected, untreated cardiovascular conditions who used topical minoxidil {05} {06})


Skin irritation or abrasion, including scalp psoriasis or severe sunburn    (systemic absorption may be increased {01} {26})



Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Blood pressure{02}{04}{09} and
Heart rate{02}{09} and
Weight{02}{09}    (if a patient's history indicates a potential problem, determinations are recommended prior to initiation of therapy and at periodic intervals during therapy to check for possible systemic effects; if systemic effects occur, it is recommended that minoxidil be discontinued; minimal effects on blood pressure are expected in normotensive patients {07} {09})




Side/Adverse Effects

Note: Although their deaths were not attributed to topical minoxidil therapy, sudden death has been reported in two patients treated with topical minoxidil who had underlying cardiovascular conditions—one patient had undetected Wolff-Parkinson-White syndrome and the other patient had untreated hypertension and cardiosclerotic cardiovascular disease {05} {06}.

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence less frequent
    
Contact dermatitis {01}{05}{22}(itching or skin rash)

Incidence rare
    
Allergic reaction{01} (reddened skin; skin rash; swelling of face)
    
alopecia, increased (increased hair loss)
    
burning of scalp{01}
    
folliculitis {10}(acne; inflammation or soreness at root of hair)—at site of application

Signs and symptoms of systemic absorption
—Rare    
Chest pain
    
fast or irregular heartbeat{10}
    
headache {27}
    
hypotension —usually not symptomatic
    
lightheadedness {27}
    
neuritis (numbness or tingling of hands, feet, or face)
    
reflex hypertension {10}
    
sexual dysfunction {27}(decrease of sexual ability or desire)
    
sodium and water retention (swelling of face, hands, feet, or lower legs; rapid weight gain)
    
vasodilation (flushing; headache)
    
visual disturbances, including decreased visual acuity (blurred vision or other changes in vision{27})

Note: Signs and symptoms of toxicity resulting from systemic absorption are unlikely unless a patient applies minoxidil too frequently to a large surface area (such as that occurring in a woman who had alopecia totalis {10}) or unless the product is ingested orally (as was the case of one man attempting suicide by consuming topical minoxidil) {24} {26}.






Overdose
For specific information on the agents used in the management of oral ingestion of topical minoxidil overdose, see:
   • Phenylephrine or Dopamine in Sympathomimetic Agents—Cardiovascular Use (Parenteral-Systemic) monograph; and/or
   • Vasopressin (Systemic) monograph.
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).

Clinical effects of overdose
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
    
Chest pain
    
fast or irregular heartbeat{10}
    
hypotension —usually not symptomatic
    
neuritis (numbness or tingling of hands, feet, or face)
    
reflex hypertension
    
sodium and water retention (swelling of face, hands, feet, or lower legs; rapid weight gain)
    
vasodilation (flushing; headache)


Treatment of overdose
If systemic toxicity occurs as a result of overdose by oral ingestion of topical minoxidil, treatment may include the following {01} {24}:

To enhance elimination—Hemodialysis. Minoxidil and its metabolites are hemodialyzable.

Specific treatment—Hypotension may be treated with phenylephrine, angiotensin II, vasopressin, or dopamine, but these medications are recommended only if lack of perfusion of a vital organ occurs. Sympathomimetic medications, such as norepinephrine or epinephrine, should be avoided because of the risk of excessive cardiac stimulation.

Supportive care—Administration of intravenous sodium chloride injection is recommended to maintain blood pressure and facilitate urine formation. Patients in whom intentional overdose is known or suspected should be referred for psychiatric consultation.


Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Minoxidil (Topical) .
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Allergy to minoxidil or propylene glycol (an inactive component of the preparation)

Pregnancy—Animal studies using oral minoxidil have shown problems during pregnancy, but not birth defects





Breast-feeding—Not recommended, since medication may cause problems in nursing babies
Other medications, especially topical corticosteroids, petrolatum, or retinoids

Proper use of this medication
Reading patient instructions carefully

» Not using more medication or more frequently than prescribed; not applying to other parts of body; risk of adverse systemic effects with excessive use

» Not using other skin products on treated skin; hair colorings, hair permanents, and hair relaxers may be used during the course of minoxidil therapy, but minoxidil should be washed from scalp before their use; avoid using minoxidil 24 hours before and after hair products are applied, and do not double doses to make up for these missed minoxidil doses

Proper administration techniqueApplying to affected area of dry scalp, beginning at the center of the balding area; not shampooing hair for 4 hours after minoxidil application

Method of application depends on applicator used (spray, extended spray tip, dropper, and/or rub-on assembly)

Washing hands immediately after application to remove any medication that may be on them

Allowing full drying for 2 to 4 hours; minoxidil can stain clothing, hats, or bed linens if not allowed to fully dry; however, not using hairdryer to speed drying, since this could decrease efficacy of the medication by removing product from the hair or scalp

Avoiding transfer of medication to other parts of body or onto bed linens by allowing complete drying of medication before retiring

Checking with physician before applying to abraded, irritated, or sunburned scalp

» Avoiding contact with eyes, nose, or mouth; flushing area with large amounts of cool tap water if accidental contact occurs; avoiding inhalation of pump spray

» Proper dosing
Missed dose: Using as soon as remembered if within a few hours; not using if almost time for next dose; not doubling amount used

» Proper storage

Precautions while using this medication
Regular visits to physician to check progress

Telling physician if itching, burning, or redness occurs after application; if reaction is severe, washing minoxidil off and checking with physician before using again

Hair loss may continue for 2 weeks after initiating minoxidil therapy, but if it continues, patient should discuss continuation of medication with physician. If hair growth does not increase in 4 months, patient should discuss continuation of medication with physician


Side/adverse effects
Signs of potential side effects, especially contact dermatitis, allergic reaction, burning of scalp, folliculitis, increased alopecia, and systemic absorption (chest pain, fast or irregular heartbeat, hypotension, lightheadedness, neuritis, reflex hypertension, sexual dysfunction, sodium and water retention, vasodilation, and visual disturbances, including decreased visual acuity)


General Dosing Information
If systemic effects occur, topical minoxidil should be discontinued and the patient should be seen by a physician {27}.

Females are advised not to use the 5% solution because it does not work any better in females than the 2% solution and has caused excessive or unusual facial hair growth in females {29}. Minoxidil will not work in males or females who experience hair loss caused by endocrine or nutritional problems or caused by skin damage that can occur from scarring, burns, or severe hair grooming methods, such as hair loss from ponytails or cornrowing {29}. Minoxidil will not work for sudden or patchy hair loss {29}.

If dermatologic reactions occur, it is recommended that discontinuation of topical minoxidil therapy be considered. {01} Patients should not apply minoxidil if skin is red, infected, irritated, or painful {29}.

Hair loss may continue for 2 weeks after initiation of minoxidil therapy, but if it continues past 2 weeks, patient should notify physician. If hair growth has not improved in 4 months of therapy, patient should reconsider continuing the use of topical minoxidil {29}.

Patient should be instructed about proper administration of topical minoxidil, including the avoidance of inhaling the spray mist {27}. In the event of accidental contact with sensitive areas (eye, abraded skin, mucous membranes), the sensitive area that is burning or irritated should be washed with copious amounts of cool water {27}. Application should be restricted to the thinning or balding area of the scalp, and hands should be washed afterwards to avoid inadvertent translocation of minoxidil to inappropriate areas of the body {27}. Waiting 2 to 4 hours for the minoxidil to dry before retiring is also recommended to avoid translocation of medication and to avoid rubbing it off inadvertently onto bed linens {27}. Minoxidil may stain bed linens, hats, or clothing if it has not fully dried {29}.

Topical minoxidil should be applied to the dry skin of the scalp. A hairdryer should not be used after application, as it might interfere with the efficacy of minoxidil {27}. At least 4 hours should be allowed after minoxidil application before shampooing {29}.

Hair colorings, hair permanents, and hair relaxers may be used with topical minoxidil; however, to avoid skin irritation, patient should wash minoxidil from scalp first before having hair treatments, avoid using minoxidil 24 hours before and 24 hours after having chemical treatments, and avoid making up missed doses by using more minoxidil when treatment is reinitiated {29}.


Topical Dosage Forms

MINOXIDIL TOPICAL SOLUTION

Usual adult dose
Hair growth stimulant
Adults up to 65 years of age: Topical, to the scalp, 1 mL two times a day. {01}

Adults 65 years of age and older: Use and dose have not been established {27}.

Note: The same dose is used regardless of the size of the area being treated. {01}



Usual pediatric dose
Hair growth stimulant
Infants: Use is not recommended {27}.

Children up to 18 years of age: Use and dose have not been established {27}.


Strength(s) usually available
U.S.—


2% (20 mg per mL) (OTC) [Rogaine For Men (alcohol 60% v/v) (propylene glycol) (water){31}] [Rogaine For Women (alcohol 60% v/v) (propylene glycol) (water){30}][Generic]{32}


5% (50 mg per mL) (OTC) [Rogaine Extra Strength For Men (alcohol 30% v/v) (propylene glycol 50% v/v) (water){29}]

Canada—


2% (20 mg per mL) (Rx) [Apo-Gain (alcohol 63%) (propylene glycol) (water){08}] [Gen-Minoxidil (alcohol) (propylene glycol) (water){27}] [Minoxigaine (alcohol 63%) (propylene glycol) (water){28}] [Rogaine (alcohol 63%){01}]

Note: Packaging may include spray, extended spray, dropper, and/or rub-on tips for application. {08} {27} {28} {30} {31} {32}


Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container. Protect from light. Protect from freezing. {29} {30}

Auxiliary labeling:
   • For external use only.



Revised: 07/20/1998



References
  1. Rogaine (Pharmacia & Upjohn). In: Gillis MC, editor. CPS Compendium of pharmaceuticals and specialties. 32nd ed. Ottawa: Canadian Pharmaceutical Association; 1997. p. 1399-1400.
  1. De Villez RL. Topical minoxidil therapy in hereditary androgenetic alopecia. Arch Dermatol 1985 Feb; 121: 197-202.
  1. Franz TJ. Percutaneous absorption of minoxidil in man. Arch Dermatol 1985 Feb; 121: 203-6.
  1. Ranchoff RE, Bergeld WF. Topical minoxidil reduces blood pressure [letter]. J Am Acad Dermatol 1985 Mar; 12: 586-7.
  1. Olsen EA, Weiner MS, Delong ER, et al. Topical minoxidil in early male pattern baldness. J Am Acad Dermatol 1985 Aug; 13: 185-92.
  1. Baral J. Minoxidil and sudden death [letter]. J Am Acad Dermatol 1985 Aug; 13(2 Pt 1): 297-9.
  1. Feinstein RP. The effect of topical minoxidil on blood pressure [letter]. J Am Acad Dermatol 1985 Oct; 13(4): 673-4.
  1. Apo-Gain product monograph (Apotex—Canada), Rev 7/7/94, Rec 1/28/98.
  1. Rumsfield JA, West DP, Fiedler-Weiss VC, et al. Topical minoxidil therapy for hair regrowth. Clin Pharm 1987 May; 6(5): 386-92.
  1. Clissold SP, Heel RC. Topical minoxidil. A preliminary review of its pharmacodynamic properties and therapeutic efficacy in alopecia areata and alopecia androgenetica [review]. Drugs 1987 Feb; 33(2): 107-22.
  1. Kvedar JC, Baden HP. Topical minoxidil in the treatment of male pattern alopecia [review]. Pharmacotherapy 1987; 7(6): 191-7.
  1. Olsen EA. Alopecia. Evaluation and management [review]. Primary Care 1989 Sep; 16(3): 765-87.
  1. Canada JR, editor. USP dictionary of USAN and international drug names 1998. Rockville, MD: The United States Pharmacopeial Convention, Inc.; 1997. p. 478.
  1. Olsen EA. Topical minoxidil in the treatment of androgenetic alopecia in women. Cutis 1991 Sep; 48(3): 243-8.
  1. Baden HP, Kubilus J. Effect of minoxidil on cultured keratinocytes. J Invest Dermatol 1983 Dec; 81(6): 558-60.
  1. Fiedler-Weiss VC. Potential mechanisms of minoxidil-induced hair growth in alopecia areata. J Am Acad Dermatol 1987 Mar; 16(3 Pt 2): 653-6.
  1. Whiting DA, Jacobson C. Treatment of female androgenetic alopecia with minoxidil 2%. Int J Dermatol 1992 Nov; 31(11): 800-4.
  1. Fiedler-Weiss VC, Buys CM. Response to minoxidil in severe alopecia areata correlates with T lymphocyte stimulation. Br J Dermatol 1987 Dec; 117(6): 759-63.
  1. Olsen EA, Weiner MS, Amara IA, et al. Five-year follow-up of men with androgenetic alopecia treated with topical minoxidil. J Am Acad Dermatol 1990 Apr; 22(4): 643-6.
  1. Cohen RL, Alves ME, Weiss VC, et al. Direct effects of minoxidil on epidermal cells in culture. J Invest Dermatol 1984 Jan; 82(1): 90-3.
  1. DeVillez RL. The therapeutic use of topical minoxidil [review]. Dermatol Clin 1990 Apr; 8(2): 367-75.
  1. Wilson C, Walkden V, Powell S, et al. Contact dermatitis in reaction to 2% topical minoxidil solution. J Am Acad Dermatol 1991 Apr; 24(4): 661-2.
  1. Barran R. Explosive eruption of pyogenic granuloma on the scalp due to topical combination therapy of minoxidil and retinoic acid. Dermatologica 1989; 179(2): 76-8.
  1. McCormick MA, Forman MH, Manoguerra AS. Severe toxicity from ingestion of a topical minoxidil preparation. Am J Emerg Med 1989 Jul; 7(4): 419-21.
  1. Trattner A, Ingber A. Topical treatment with minoxidil 2% and smoking intolerance. Ann Pharmacother 1992; 26(2): 198-9.
  1. Koperski JA, Orenberg EK, Wilkinson DI. Topical minoxidil therapy for androgenetic alopecia. A 30-month study. Arch Dermatol 1987 Nov; 123(11): 1483-7.
  1. Gen-Minoxidil product monograph (Genpharm—Canada), Rev 1/94, Rec 5/96.
  1. Minoxigaine (Altimed [Kenral]). In: Gillis MC, editor. CPS Compendium of pharmaceuticals and specialties. 32nd ed. Ottawa: Canadian Pharmaceutical Association; 1997. p. 948.
  1. Rogaine Extra Strength For Men package insert (Pharmacia & Upjohn Consumer Healthcare—US), Rec 2/98.
  1. Rogaine For Women packaging (Pharmacia & Upjohn Consumer Healthcare—US), Rec 2/98.
  1. Rogaine For Men packaging (Pharmacia & Upjohn Consumer Healthcare—US), Rec 2/96.
  1. Minoxidil package insert (Lemmon—US), Rev 3/96, Rec 5/96.
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