What is Minoxidil?

Minoxidil is an anti-hypertensive peripheral vasodilator drug being primarily used for different patterns of baldness and hair loss in men & women. It belongs to the drug class of pyrimidine derivatives (Arteriolar smooth muscle). It is commonly known by the trade name as “Rogaine”outside of India and Mintop, Tugain, Regaine, etc. in India.

How Minoxidil was discovered and what were the earlier forms of Minoxidil?

Earlier, Minoxidil was used to treat the hypertension in the form of pills named as “Loniten.” But researchers noticed that it also helps in the hair growth. So, its use as medicine for hair growth was started. Since it led to hair growth all over the body, it could not be used in the same form. The researchers then opted for a new formulation in the form of lotion that could be directly applied to the scalp without affecting other body parts.

How minoxidil transformed from an anti-hypertensive drug to hair fall drug?

Minoxidil emanated from a research program which was held in 1960 by Upjohn chemists. They were evaluating the gastric acid effects of a compound named “DAM” (N, N- diallymelamine) from a chemical catalogue. On analyzing,

  • They panned out that DAM reduced blood pressure in dogs but not in humans.
  • They opted for DAM metabolites named DAMN-O which went into several clinical trials in patients suffering from hypertension in 1961. It resulted in the lowered blood pressure but caused some side effects including salt and water retention, even heart failure. So DAMN-O was withdrawn from the study.

Further Upjohn researchers amalgamated several DAMN-O analogues including Minoxidil keeping the factors of side effects in mind and avoiding it. Along with minoxidil, several diuretics and beta blockers were added in the study to reverse the water and salt retention. Minoxidil showed reduction in blood pressure levels with minimal side effects during clinical trials. As word from people got out that minoxidil resulted in hair re-growth, Upjohn researchers in Kalamazoo headquarters, Michigan, inundated with the volunteers for hair loss trials with a topical formulation. This trial was performed on macaques (a species prone to hair thinning) and re-growth of hair was observed. After that, Upjohn launched minoxidil as “Regaine” topical solution of 2% in UK in 1988. Minoxidil was the first drug approved by the US Food and Drug Administration in August 1988 for the treatment of male patterned hair loss (Androgenetic alopecia).

How Does Minoxidil works and how it reduces the hair fall?

  • Minoxidil is known as a potent vasodilator which helps to stimulate the growth of hair. Minoxidil when applied on the scalp:
    1. Is converted into an active form Minoxidil sulphite with the help of the enzyme sulfonyl transferase.
    2. It works by opening the potassium channels which facilitates the cell membrane hyper-polarization and expansion of blood vessels.
    3. Thus, oxygen becomes readily available to the hair follicles in the scalp which results in hair growth by conversion of Telogen (resting) hair into anagen (growing) hair.
    Activation of Minoxidil
  • Minoxidil also directly stimulates the hair growth through the activation of prostaglandin endoperoxide synthase-1 (PGHS-1, main isoform present in the dermal papilla cells).
  • It also produces an increase in number of dermal papilla cells by activating ß-catenin activity.
    How Topical Minoxidil Works

How does Minoxidil promote hair re-growth?

Minoxidil is best known for treatment in men and women with hair loss or thinning at the top of the scalp. It promotes hair growth by:

  • Increasing the follicular size and hair shaft diameter of hair
  • Reversing hair follicle miniaturization
    How Minoxidil Causes Hair Growth

What are the different formulations of Minoxidil?

Common customized and most commonly used formulations of minoxidil are 2% and 5%. Apart from this, 10% and 15% formulations of minoxidil, with added active ingredients are also available but no scientific data is available for these formulations. The various formulations are as follows:

  • Loniten: Oral antihypertensive drug. It is not prescribed for long term treatment of hair loss.
  • 2% Topical Solution: Commonly known as Rogaine (first liquid formulation). It is no longer recommended for men but still in use by women to reverse hair loss.
  • 5% Topical Solution (Minoxidil Solution and Minoxidil Lotion): Recommended for men, newly formulated. Higher success rate than 2% solution of minoxidil.
  • 5% Aerosol Foam (Minoxidil Foam): More advanced formulation specially introduced for men suffering from contact dermatitis due to the use of minoxidil formulations. Shows success rate of approximately 85% in men.
  • Higher than 5% Formulations: Shows significantly less hair re-growth than 5% formulations, also produces more side effects.

Minoxidil 2% helps to stop hair loss and promotes hair re-growth in 30% of men, whereas 5% solution of minoxidil gives the success rate of approximately 65%.

What are the differences between formulations of Minoxidil?

  • The main difference between the various types of minoxidil formulation (2%, 5%, 10% & 15%) is the type and the volume of the solvent being used.
  • Generally, 5% formulation is considered as a standard formulation.
  • Higher concentrations include high amount of glycerin along with propylene glycol. They both act as humectants (preserves moisture) which make the product viscous, sticky and it takes more time to dry.
Brand name Company Name Formulation Composition M.R.P(Range b/w)
Rogaine Rogaine Sol. 5% & Foam 5% Minoxidil 5% ,Alcohol, 30% v/v, propylene glycol, 50% v/v $40.39 – $606.84
MINTOP Dr. Reddy’s Lab Sol. 2% & Lotion 2% Minoxidil 2% = 20 mg Rs.256
MINTOP Dr. Reddy’s Lab Sol. 10% & Foam 10% Minoxidil 10% = 100mg Rs760- Rs.886
TUGAIN Cipla Sol. 5% , Foam 5% & Gel 5% Minoxidil + Abs. Alcohol
5% + 30%
Rs.598.50 – Rs. 805
TUGAIN Cipla Sol. 10% Foam 10% Minoxidil + Abs. Alcohol
10% + 40%- 50.63%
Rs. 841- Rs. 917.50
Amexidil-5 Sun Pharmaceutical Sol. 5% Aminexil (1.5% w/v) + Minoxidil Topical (5% w/v) Rs. 510
Regaine Jannsen Pharmaceutical Sol. 2% , 5% Minoxidil 2% +Propylene glycol 208 mg/ml &
Minoxidil 5%,
Rs. 357 – Rs. 735
         
Disclaimer: The above indicated prices are not fixed. They may vary with respect to time.

Drug Interactions

Minoxidil is a relatively safe drug but you must tell you doctor all the drugs (and also herbal supplements, caffeine, nicotine, alcohol) which you are using as it may lead to some of the interactions as shown below.:

Drug Interactions of minoxidil
  • Amifostine: Using minoxidil within 24 hours of receiving amifostine could lower your blood pressure to unsafe levels.
  • Guanethidine: It may cause profound orthostatic hypotensive effects (It is a form of low blood pressure that happens when you stand up from sitting or lying down. Orthostatic hypotension can make you feel dizzy or lightheaded, and maybe even faint).
  • Rituximab: It may increases the hypotensive effect of minoxidil.
  • Tretinoin: The risk or severity of adverse effects can be increased when Minoxidil is combined with Tretinoin.
  • Others: May induce profound hypotensive state.

Contraindications

  • Hypersensitivity to minoxidil or any other ingredient in the formulation
  • Other topical medications

Medical uses of Minoxidil:

Men and women have different patterns of baldness. For women, 2% minoxidil is effective while for men, 5% minoxidil is recommended.

  • Women: Minoxidil 2% is the only drug which is FDA-approved to treat female pattern baldness. Doctors refer to the Ludwig classification for the description of female pattern of hair baldness. In women, it is used to treat hair loss due to:
    1. Androgenic alopecia
    2. Post menopause
    3. Hereditary hair loss aged 18-65 years
  • Men: Minoxidil 5% is FDA-approved for men with male pattern hair loss.
    1. Androgenic alopecia
    2. Hereditary hair loss
  • Other uses: Minoxidil 5% is FDA-approved for men with male pattern hair loss.
    1. Hair transplant
    2. Chemotherapy induced alopecia
    3. Alopecia Areata
    4. Alopecia Areata Incognita
    5. Scarring alopecia
    6. Hereditary Hypotrichosis
    7. Monilethrix
    8. Retards the ageing of human keratinocytes

How to use Minoxidil?

Minoxidil is applied to the scalp to stimulate the hair growth. The patient should follow the necessary instructions before the application of minoxidil.

Liquid/ Lotion:

How to apply Minoxidil Lotion

Foam:

How to apply Minoxidil Foam

If you are using spray, spray evenly on the bald area. Make sure that the hair are dry before application of the medicine.

Recommended Dosage of Minoxidil for Hair loss:

  • Men:
    1. 1ml of 2% or 5% solution to affected area, twice daily
    2. Half capful of 5% foam to affected area, twice daily
  • Men: Minoxidil 5% is FDA-approved for men with male pattern hair loss.
    1. 1ml of 2% solution to affected area, twice daily.
  • If a dose is missed:
    1. Skip the dose missed and use only the prescribed next dose. Do not use a double dose to make up for the missed doses.

Possible Side effects of Minoxidil

The most common side effects of minoxidil are:

  • Minoxidil induced hair fall or Telogen Effluvium: Sometimes, when the hair start getting stimulated from the telogen to the anagen phase, they fall off. This is a positive sign and the patient should not stop the medication for the fear of hair fall.
  • Contact Dermatitis
  • Scaling
  • Exacerbation of Seborrheic dermatitis
  • Skin irritation or itching
  • Yellowish discoloration of hair
  • Tachycardia or irregular heartbeats (Rare)

Precautions:

  • Before Using;
    1. Non-hereditary Factors: Hormonal factors like Thyroid can also lead to hair fall. Overactive or underactive thyroid gland may cause hair to fall out. So, you must take the treatment of that from your doctor.
    2. Scalp Disorders: If you are suffering from skin disorders like scalp psoriasis, avoid using minoxidil. Scalp psoriasis can cause dry and itchy scalp along with inflammation.
    3. Shaved scalp: If you have recently shaved your scalp, avoid using minoxidil immediately. This may lead to redness or itchy scalp.
    4. Wound: If you have any open wound or cut on the scalp, avoid using minoxidil. It can cause burning sensation on the skin.
  • While Using:
    1. Do not apply on the other parts of the body.
    2. Avoid contact with the eyes.
  • After Using:
    1. Wash your hands properly.
    2. Do not apply more than the recommended dosage.
    3. Do not use any hair color after the application.
    4. Avoid going to bed immediately after the application. Use at least before 1 hour.
    5. Do not use hair dryers or do not perm your hair after the application.
    6. Avoid direct contact to sun rays.

Duration and Results of the treatment:

Duration

As hair won’t re-grow overnight, procedure will take time. It can take up to 4-6 months while in some cases; it can take more than 8-9 months. It varies from patient to patient.

Regrowth

Re-growing hair and taking care of them is just like the same as we take care of our other body parts. The more you stick to the instructed routine, better the Minoxidil results will be.

Caution

  • If pregnant or breast-feeding, ask a health professional before use. Keep out of reach of children.
  • If swallowed, get medical help or contact a Poison Control Center right away.
  • Do not use on children or babies.

Physiology Pharmacology
White to off-white, odorless, crystalline solid Peripheral vasodilator
Soluble in water to the extent of approximately 2 mg/mL 90% absorbed from the GI tract
Insoluble in acetone, chloroform or ethyl acetate Average plasma half-life in man is 4.2 hours.
Inactive ingredients include colloidal silicon dioxide, corn starch, lactose anhydrous, magnesium stearate and microcrystalline cellulose. Minoxidil does not bind to plasma proteins and does not cross the blood brain barrier
Chemically, Minoxidil is 6-(Piperidin-1-yl) pyrimidine-2, 4-diamine 3-oxide used as hair growth stimulator. In US pharmacopeia, Minoxidil is used officially under the labeled amount i.e. not less than 90% and not more than 110%.

For its determination in pharmaceutical formulations and biological samples, different methods have been proposed. Following techniques are used for the determination of dosage forms and quantitative analysis of the minoxidil with the added benefits of cost savings.

  • HPLC (high performance liquid chromatography) with UV detection
  • Electrochemical detection
  • Gas chromatography (GC)
  • Radioimmunoassay (RIA)

Many scientific research or clinical studies have been conducted on minoxidil and various physical or chemical data have been collected which is as follows:

Clinical Data:

  • Common Trade name: Rogaine
  • Pregnancy category: C
  • Routes of Administration: Oral/ Topical
  • ATC code: C02DC01 & D11AX01

Legal Status:

  • UK:P (Pharmacy medicines) (for topical use, otherwise POM. Cannot be prescribed on the NHS)
  • US:OTC Rx only for by mouth form

Pharmacokinetic Data:

  • Metabolism:Primarily hepatic
  • Biological half life: 4.2 h
  • Excretion:Renal

Clinical & Physical Data:

  • Formula: C9H15N5O
  • Melting point:Melting point: 248 °C (478 °F)
  • Molar Mass: 209.251 g/mol
  • Solubility in water: <1 mg/mL(20 °C)

*POM= Prescription only medicine, OTC= Over the counter, ATC= Anatomical Therapeutic Chemical Classification system

Quick Facts

  • Did you know that approximately 35 million men and 21 million women suffer from hair loss?
  • A year- long test of the minoxidil (Rogaine) on 1833 men had actually convinced doctors regarding Rogaine’s safety and in some cases patients administered with the drug actually grew hair.

Frequently Asked Questions about Minoxidil

Women who are pregnant or breastfeeding, are advised to stop using minoxidil. Minoxidil can get absorbed into the skin and can cause birth defects. When women are pregnant, there is an increase in the hormone levels which makes hair look thicker. After the delivery, shedding of hair known as post partum hair loss usually occurs. Once you have finished breastfeeding, you can use minoxidil.

No, it won’t work faster. Hair will grow according to the hair growth cycle. Always use the recommended dosage of minoxidil as frequent application of it can cause side effects.

No. it is not necessary to wash your hair before the application. Make sure your hair are completely dry because there are chances that minoxidil gets evaporated or diluted on the wet hair.

Yes, you can continue but be careful while using products. Choose mild or gentle shampoo or conditioner. Do not use hair styling tools like dryers, straighteners or curlers after the application of minoxidil.

If the treatment is stopped, you will not lose your hair that grew but they can revert to their previous pattern of hair loss. So consult doctor before you stop using minoxidil.

Taking a break of one week will cause no problem. It becomes crucial after one month.

After stopping minoxidil application, you can face hair fall again after one month. It may vary from patient to patient. So consult with your doctor before stopping minoxidil.

Sources

1. Rossi A, Cantisani C, Melis L, Iorio A, Scali E, Calvieri S. Minoxidil use in dermatology, side effects and recent patents. Recent patents on inflammation & allergy drug discovery [Internet]. 2012 [cited 6 May 2002]; 2012(22409453):130-6. Available from: https://www.ncbi.nlm.nih.gov/pubmed/22409453.

2. Bryan J. How minoxidil was transformed from an antihypertensive to hair-loss drug [Internet]. Pharmaceutical Journal. 2017 [cited 20 July 2011]. Available from: http://www.pharmaceutical-journal.com/news-and-analysis/news/how-minoxidil-was-transformed-from-an-antihypertensive-to-hair-loss-drug/11080942.article

3. M. Parsley W. Minoxidil results: is Minoxidil a viable hair loss treatment for women? [Internet]. ishrs.org. 2015 [cited 30 April 2015]. Available from: http://www.ishrs.org/female-hair-loss/non-surgical-hair-restoration/options-rogaine.htm

4. Rumsfield J, West D, Fiedler-Weiss V. Topical minoxidil therapy for hair regrowth. Clinical pharmacy [Internet]. 1987 [cited 6 May 1987];6(5):386-92. Available from: https://www.ncbi.nlm.nih.gov/pubmed/3311578

5. Mysore V, Dua K. Hair transplantation.11:71 1st ed. New Delhi: Jaypee Hights Medical Pub; 2016.

6. Hasanzadeh H, Nasrollahi S, Halavati N, Saberi M, Firooz A. Efficacy and safety of 5% minoxidil topical foam in male pattern hair loss treatment and patient satisfaction. Acta dermatovenerologica Alpina, Pannonica, et Adriatica [Internet]. 2016 [cited September 2016];3(25):41-44. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27695865.

7. Katz H. Topical minoxidil: review of efficacy and safety. Cutis [Internet]. 1989 [cited 10 August 2017]; 43(1):94-8. Available from: https://www.ncbi.nlm.nih.gov/pubmed/2644080

8. Kwack M, Kang B, Kim M, Kim J, Sung Y. Minoxidil activates β-catenin pathway in human dermal papilla cells: a possible explanation for its anagen prolongation effect. Journal of dermatological science [Internet]. 2011 [cited 10 August 2017]; 62(3):154-9. Available from: https://www.ncbi.nlm.nih.gov/pubmed/21524889

9. Quan Q D, Rodney S. Female pattern hair loss: Current treatment concepts. Clinical interventions in aging [Internet]. 2007 [cited 10 August 2017];2(2):189–199. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2684510/

10. Rizwana I, Prakash K. V, Mohan G. K. Simultaneous Estimation of Minoxidil and Aminexil in Bulk and Pharmaceutical Formulations by Rp-Hplc Method. Orient J Chem 2015;31(1). Available from: http://www.orientjchem.org/?p=7630

11. Sánchez-Regaña M, Llambí-Mateos F, Salleras-Redonnet M, Iglesias Sancho M, Collgros Totosaus H, Umbert-Millet P. Simultaneous Estimation of Minoxidil and Aminexil in Bulk and Pharmaceutical Formulations by Rp-Hplc Method. Actas dermo-sifiliográficas [Internet]. 2017 [cited 10 August 2017]; 104(9):738-56. Available from: https://www.ncbi.nlm.nih.gov/pubmed/22818830

12. Michelet J, Commo S, Billoni N, Mahé Y, Bernard B. Activation of cytoprotective prostaglandin synthase-1 by minoxidil as a possible explanation for its hair growth-stimulating effect. The Journal of investigative dermatology [Internet]. 1997 [cited 10 August 2017];108(2):205-9. Available from: https://www.ncbi.nlm.nih.gov/pubmed/9008235

13. Desi Reddy R, Reddy.K L, Sowjanya. T. Recent Applications of Analytical Techniques for Quantitative Pharmaceutical Analysis: A Review. International Journal of Universal Pharmacy and Bio Sciences [Internet]. 2017 [cited 10 August 2017];2(4). Available from: http://www.ijupbs.com/Uploads/26.%20RPA1300148.pdf

14. Minoxidil [Internet]. En.wikipedia.org. 2017 [cited 10 August 2017]. Available from: https://en.wikipedia.org/wiki/Minoxidil

15. Minoxidil [Internet]. PubChem. 2017 [cited 10 August 2017]. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/minoxidil

16. Minoxidil (On the skin) – National Library of Medicine – PubMed Health [Internet]. PubMed Health. 2017 [cited 10 August 2017]. Available from: https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0011238/?report=details

17. Drug Facts [Internet]. FDA. 2017 [cited 10 August 2017]. Available from: https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm078877.pd

18. Post Hair Transplant usage of Minoxidil Increases Hair Growth [Internet]. Hair Loss Resources, Articles, Products & Forums. 2017 [cited 10 August 2017]. Available from: http://hairloss.org/hair-loss-products/minoxidil-treatment-for-post-hair-transplant/

19. Minoxidil [Internet]. Regaine UK HCP. 2017 [cited 10 August 2017]. Available from: https://www.regaineprofessional.co.uk/minoxidil

20. TUGAIN Foam [Internet]. CiplaMed. 2017 [cited 10 August 2017]. Available from: https://ciplamed.com/content/tugain-foam


Wwhatsapp Share This