MINOXIDIL BAILLEUL 5 % Cutaneous Application Solution 3Bottle/60ml

Minoxidil ...............................................................................................................................................................5 g

For 100 ml.

Excipient(s) with known effect: propylene glycol, ethanol at 96%

This medicine is indicated for moderate hair loss (androgenetic alopecia) in male subjects.

Dosage

Reserved for adult males.

Cutaneous use.

Apply 2 times per day a dose of 1 ml to the scalp, starting from the centre of the area to be treated. This dose must be respected regardless of the extent of the area concerned..

The total daily dose must not exceed 2 ml.

Spread the product with the fingertips so as to cover the entire area to be treated.

After applying the solution, wash your hands thoroughly.

Do not apply the product to any other part of the body.

Apply to perfectly dry hair and scalp.

Duration of use

Results may not be visible until at least 2 to 4 months of treatment applied twice a day. The onset and degree of response vary from subject to subject.

Do not stop applications, as there is a risk of reverting to the previous state after a period of 3 or 4 months.

Stop using minoxidil if there is no improvement after 4 months of application.

Paediatric population

Not applicable

Method of administration

The mode of application varies depending on the delivery system used with the bottle

Spray pump : This system is suitable for application over large surfaces.

1. Remove the cap from the bottle.

2. Direct the pump toward the center of the surface to be treated, actuate it once and spread the product with the fingertips so as to cover the entire area to be treated. Repeat the operation 6 times to apply a dose of 1 ml (i.e. 7 sprays in total).

Avoid inhaling the product.

3. Rinse the sprayer with hot water and replace the cap on the bottle after each use.

Sprayer fitted with an applicator: This system is suitable for application to small areas or under the hair.

1. Remove the cap from the bottle.

2. Remove the upper element of the pump. Fit the applicator and press firmly.

3. Direct the pump toward the center of the surface to be treated, actuate it once and spread the product with the fingertips so as to cover the entire area to be treated.

Repeat the operation 6 times to apply a dose of 1 ml (i.e. 7 sprays in total).

Avoid inhaling the product.

4. Rinse the applicator with hot water and replace the cap on the bottle after each use.

•  Hypersensitivity to the active substance or to any of the excipients listed in section Composition.
•  Scalp diseases.
•  Poor tolerance to the form at 2%, regardless of the symptoms.
•  This medicine is contraindicated in women.
•  In subjects under 18 years of age or over 65 years of age.

Special warnings

Topical minoxidil must be used on normal, healthy scalp and must not be administered if the scalp skin is inflamed, infected, irritated or painful.

Increased percutaneous absorption of minoxidil, which may cause systemic effects, is possible (see section Contraindications).

• dermatosis or lesion of the scalp,
• concomitant application of retinoic acid, anthralin or any other irritating topical product,
• increase in the applied dose and/or increase in the frequency of applications: it is imperative to observe the dosage and the method of administration.

Likewise, although extensive use of minoxidil solution has not revealed any systemic effects, it cannot be excluded that greater absorption linked to individual variability or unusual sensitivity could cause systemic effects. Patients should be warned of this.

As a precaution, it is advisable to regularly monitor for the possible appearance of symptoms suggestive of systemic effects, such as decreased blood pressure, tachycardia, chest pain, loss of consciousness, dizziness, unexplained weight gain or signs of fluid and sodium retention (swelling of the hands or feet).

Monitoring should be carried out at the start of treatment and then regularly. If systemic effects or severe dermatological reactions or any other unexpected symptom occur (see section Adverse effects), treatment must be discontinued and the patient must consult a doctor.

Patients with cardiovascular disease or cardiac arrhythmia must consult a doctor before using topical minoxidil. In these subjects, the benefit of treatment must be weighed. They should be especially warned of potential undesirable effects so that treatment is interrupted as soon as any of them occurs and a doctor is informed.

If symptoms persist or worsen, or if new symptoms appear, patients must discontinue treatment and consult a doctor.

Do not apply minoxidil:

• in case of hair loss occurring in patches and/or abruptly, hair loss following an illness or drug treatment, or if the cause of the alopecia is unknown.
• on another part of the body.
• at the same time as other medicines on the scalp.

Hypertrichosis in children following accidental topical exposure to minoxidil:

Cases of hypertrichosis have been reported in infants after skin contact at the minoxidil application sites of patients (caregivers) using topical minoxidil. The hypertrichosis was reversible within a few months when the infants were no longer exposed to minoxidil. Contact between children and minoxidil application sites must therefore be avoided.

This medicine contains:

• 200 mg of propylene glycol per dose of 1 ml. Propylene glycol may cause skin irritation.
• 586 mg of alcohol (ethanol at 96%) per dose of 1 ml. This may cause a burning sensation on damaged skin. Keep away from any flame, lit cigarette or source of intense heat.

Precautions for use

In case of accidental contact with the eye, irritated skin or a mucous membrane, the solution may cause a burning sensation and/or irritation. In case of contact with sensitive surfaces (eye, irritated skin, mucous membranes), rinse thoroughly with cold running water.

Accidental ingestion is likely to result in severe undesirable effects, including cardiac effects (see section Adverse effects). This product must therefore be kept out of the reach of children.

Sun exposure is not recommended when applying this product

Some patients have noticed a change in the colour and/or texture of their hair.

Do not inhale.

Using a higher dose or frequency will not result in improved results.

Continued treatment is necessary to increase and maintain hair regrowth. Otherwise, hair loss will resume.

A temporary increase in hair loss may occur during the first 2 to 6 weeks of treatment. If hair loss persists, the patient should stop using Minoxidil Bailleul and consult their doctor.

Unwanted hair growth may occur due to transfer of the product to areas other than the scalp.

Topical minoxidil must not be used at the same time as other medicines (in particular, corticosteroids, tretinoin, anthralin) on the scalp, as these topical medicines may alter the permeability of the skin and lead to a change in the absorption of minoxidil.

An interaction with vasodilator antihypertensives such as guanethidine has been reported with oral formulations of minoxidil, leading to a rapid and marked drop in blood pressure.

Pregnancy

In animals, studies carried out on minoxidil have not shown any teratogenic effect.

This medicine is contraindicated in women.

Breast-feeding

When administered systemically, minoxidil passes into breast milk.

This medicine is contraindicated in women.

Fertility

No adequate or well-controlled studies have been conducted regarding fertility in women.

Studies conducted in animals have shown toxicity to fertility, a decrease in conception and implantation rates and a reduction in the number of live births at exposure levels far exceeding those anticipated in humans (see section Preclinical safety). The potential risk for humans is not known.

Minoxidil may cause dizziness or hypotension (see section Adverse effects). If patients experience such disorders, they should not drive or use machines.

 The safety of topical minoxidil is based on 7 randomised, placebo-controlled clinical studies in adults evaluating minoxidil in solution at 2% or 5%, and two randomised, placebo-controlled clinical studies in adults evaluating the foam formulation at 5%.

The undesirable effects identified during clinical studies and after marketing authorisation are presented in the table below. In this table, frequencies are presented according to the following convention:

Very common ≥ 1/10

Frequent ≥ 1/100 and < 1/10

Uncommon ≥ 1/1 000 and < 1/100

Rare ≥ 1/10 000 and < 1/1 000

Very rare < 1/10 000

Not known (frequency cannot be estimated from the available data)

Adverse reactions are presented by frequency category based on 1) the incidence in clinical trials or epidemiological studies, if available, or 2) when the incidence cannot be estimated, the frequency category is listed as "not known"

* this adverse event was observed during clinical studies of minoxidil foam.

Reporting of suspected adverse effects:

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reaction via the national reporting system: National Agency for the Safety of Medicines and Health Products (ANSM) and the network of Regional Centres of Pharmacovigilance - Website: https://signalement.social-sante.gouv.fr.

An increase in systemic absorption of minoxidil that may lead to adverse events may occur if doses higher than the recommended dosage are applied to larger body areas or areas other than the scalp.

Accidental ingestion may cause systemic effects due to the vasodilatory action of minoxidil. Signs and symptoms of a possible overdose would be cardiovascular in nature, with hypotension, tachycardia, lethargy and fluid and sodium retention. Fluid and sodium retention may be treated with appropriate diuretic therapy; tachycardia and angina with a beta-blocker or another inhibitor of the sympathetic nervous system. Symptomatic hypotension could be treated by intravenous administration of isotonic sodium chloride solution. The use of sympathomimetics, such as noradrenaline and adrenaline, should be avoided due to excessive cardiac stimulation.

Keep out of the reach of children. In case of ingestion, contact a doctor or an emergency service immediately.

Pharmacotherapeutic class: OTHER DERMATOLOGICAL MEDICINES, ATC code: D11AX01.

Mechanism of action

The precise mechanism of action is not known, but certain effects of minoxidil include stimulation and prolongation of the anagen growth phase, and stimulation of the transition of hair follicles from the resting (telogen) phase to the growth (anagen) phase.

Preclinical efficacy and safety

Applied topically, minoxidil stimulates keratinocyte growth in vitro and in vivo and hair regrowth in certain subjects with androgenetic alopecia. This effect appears after approximately 2 to 4 months of product use and varies between subjects. Upon discontinuation of treatment, regrowth ceases and a return to the initial state is expected within 3 or 4 months.

Topical application of minoxidil in controlled clinical trials in normotensive or untreated hypertensive patients did not give rise to the observation of systemic manifestations related to absorption of minoxidil.

Absorption

When applied topically, minoxidil is only poorly absorbed: an average amount of 1,7% (for values ranging from 0,3 to 4,5%) of the applied dose reaches the systemic circulation.

By comparison, when administered orally in tablet form (in the treatment of certain hypertensions), minoxidil is almost completely absorbed from the gastrointestinal tract. A dose of 1 ml of solution corresponding to an application to the skin of 50 mg of minoxidil would therefore result in an absorption of approximately 0,85 mg of minoxidil.

In one study, the area under the curve (AUC) of minoxidil as a 2% solution was on average 7,54 ng·h/ml, compared with a mean AUC of 35,1 ng·h/ml for the 2,5 mg oral formulation. The mean maximum serum concentration (Cmax) for the topical solution was 1,25 ng/ml, compared with 18,5 ng/ml following administration of an oral dose of 2,5 mg.

In another study, the systemic absorption of a 5% foam formulation was approximately half that of a 5% topical solution. The mean AUC (0-12 h) and Cmax for the 5% foam were 8,81 ng·h/ml and 1,11 ng/ml, respectively, corresponding to approximately 50% of the AUC (0-12 h) and Cmax of the 5% solution (18,71 ng•h/ml and 2,13 ng/ml, respectively).

The AUC of the 5% minoxidil foam used once daily was similar to that of a 2% minoxidil solution used twice daily in female subjects.

The Tmax for the 5% foam (5,42 h) was similar to the Tmax for the 5% solution (5,79 h). The haemodynamic effects of minoxidil are not visible until mean serum minoxidil concentrations reach 21,7 ng/ml.

Distribution

The volume of distribution of minoxidil after intravenous administration was estimated at 70 litres.

Biotransformation The biotransformation of minoxidil absorbed after topical application is not fully known.

Approximately 60% of the minoxidil absorbed after topical application is metabolised to minoxidil glucuronide, mainly in the liver.

Elimination

The mean half-life of topical minoxidil averages 22 hours. Minoxidil and its metabolites are excreted 97% in the urine and 3% in the faeces.

After discontinuation of topical application, approximately 95% of the absorbed minoxidil is eliminated within 4 days.

Preclinical data from conventional safety pharmacology, repeated-dose toxicity, genotoxicity and carcinogenicity studies did not reveal any particular risk for humans.

Specific cardiac effects in dogs were observed at low doses, leading to significant haemodynamic effects associated with cardiac changes in repeated-dose toxicity studies. The available data did not show similar effects in humans treated with minoxidil, orally or cutaneously.

Mutagenic potential

Minoxidil showed no signs of mutagenic or genotoxic potential in a number of in vitro and in vivo assays.

Carcinogenicity

A high incidence of hormone-dependent tumours was observed in mice and rats. These tumours are due to secondary hormonal effects (hyperprolactinaemia) observed only in rodents at extremely high doses, occurring through a mechanism similar to that observed with reserpine.

Topical application of minoxidil did not cause effects on hormonal status in women. Consequently, the tendency of minoxidil to promote hormone-mediated tumours does not constitute a carcinogenic risk in humans.

Teratogenicity

Animal reproductive toxicity studies (rat and rabbit) showed signs of maternal toxicity and a risk to the foetus at exposure levels very high compared with those expected in humans.

Fertility

Doses of minoxidil greater than 9 mg/kg (at least 25 times the human exposure) administered subcutaneously to rats were associated with a reduction in fertilisation and implantation rates, as well as a reduction in the number of live offspring.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

3 years.

Flammable product.

No special requirements.