ALOPEXY 2 % Cutaneous application 3Spray bottle/60ml

Minoxidil ........................................................................................................................................................ 20 mg

For 1 ml of solution

Excipient with known effect: propylene glycol (E1520) 50 mg, ethanol at 96% 443,9 mg.

This medicine is indicated for moderate hair loss (androgenetic alopecia) in adults, men or women. It promotes hair growth and stabilises hair loss.

RESERVED FOR ADULTS.

Dosage

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 daily dose must not exceed 2 ml.

Special population

Elderly

ALOPEXY is not recommended in patients over 65 years of age due to the lack of data on safety and efficacy.

Paediatric population

There is no relevant use of minoxidil in the paediatric population for the indication of moderate androgenetic alopecia. Therefore, the safety and efficacy of ALOPEXY in children under 18 years of age have not been established. No data are available. Thus, ALOPEXY is not recommended in children under 18 years of age.

Method of administration

Cutaneous use.

Do not swallow.

Use one of the administration systems (see below) to apply ALOPEXY.

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

Before and after applying the solution, wash hands thoroughly.

Apply to perfectly dry hair and scalp.

Method of application

The child-resistant cap must be removed by pressing down on the cap while turning it counterclockwise (to the left). Only the tamper-evident seal should remain on the bottle.

Depending on the dispensing system used:

Use of the dropper:

The dropper allows precise withdrawal of 1 ml of solution to be spread over the entire area to be treated.

Use of the metered-dose pump with applicator:

6 sprays are necessary in order to apply a dose of 1 ml.

This system is suitable for application to small areas or under the hair.

Screw the metered-dose pump onto the bottle.

For application: direct the pump towards the centre of the area to be treated, press once and spread the product with the fingertips so as to cover the entire area to be treated.

Hypersensitivity to the active substance or to any of the excipients listed in section Composition.

Warnings

Increased percutaneous absorption of minoxidil, which may cause systemic effects, is possible in the case of:

• dermatosis or lesion of the scalp,

• increase in the applied dose and/or increase in the frequency of application: it is imperative to respect the posology 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.

Patients with proven cardiovascular disease or cardiac arrhythmias must consult a doctor before using minoxidil.

In subjects with a cardiac history, the benefit of the treatment must be evaluated. They should be warned in particular of potential adverse effects so that treatment is stopped as soon as any of them appears and a doctor is informed.

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

Minoxidil is not indicated in the absence of a family history of alopecia, in cases of sudden and/or patchy hair loss, hair loss following childbirth, or hair loss due to an unknown cause.

The patient must stop using this medicine and consult a doctor if hypotension is detected, in the case of chest pain, rapid heartbeat, fainting or dizziness, unexplained sudden weight gain, oedema of the hands or feet, or persistent redness or irritation of the scalp.

Hypertrichosis in children following unintentional 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.

Precautions for use

Minoxidil should only be used on a normal, healthy scalp. It must not be used if the scalp shows redness, inflammation, infection or irritation, or is painful, or if other treatments are being applied to the scalp.

In case of accidental contact with sensitive surfaces (eye, wound, damaged skin, mucous membrane), the excipients contained in the solution may cause a burning sensation and irritation: rinse abundantly with cold running water.

Inhalation of the spray mist must be avoided.

Accidental ingestion may lead to serious adverse cardiac effects (see section Overdose). Therefore, this medicine must be kept out of the reach of children.

This medicine contains 443,9 mg of alcohol (ethanol) per ml. This may cause a burning sensation on damaged skin.

Sun exposure is not recommended during application of minoxidil.

Pharmacokinetic interaction studies in humans have shown that percutaneous absorption of minoxidil is increased by tretinoin and anthralin due to increased permeability of the stratum corneum; betamethasone dipropionate increases local tissue concentrations of minoxidil and decreases its systemic absorption.

Although not clinically proven, the risk of orthostatic hypotension in patients also treated with peripheral vasodilators cannot be excluded.

Topically, the absorption of minoxidil is controlled and limited by the Stratum corneum. Concomitant use of topical medicinal products that affect the barrier formed by the Stratum corneum may lead to an increase in the absorption of minoxidil. Therefore, concomitant use of ALOPEXY and other topical medicinal products is not recommended.

Pregnancy

No adequate controlled studies have been conducted in pregnant women. Studies in animals have shown a risk to the foetus at exposure levels sufficiently high relative to those expected for human exposure. There is a low, although unlikely, risk of adverse effects on the foetus in humans (see section Preclinical safety).

ALOPEXY is not recommended during pregnancy and in women of childbearing potential not using contraception.

Breast-feeding

Systemically absorbed minoxidil is excreted in human milk. A risk to newborns/infants cannot be excluded.

ALOPEXY must not be used during breast-feeding.

Fertility

In a fertility study in male and female rats, a dose-dependent decrease in conception rate was observed (see section Preclinical safety). The potential risk in humans is unknown.

ALOPEXY has no or negligible influence on the ability to drive and use machines.

Patients who experience dizziness or hypotension should not drive or use machines (see section Adverse effects).

The following adverse reactions have been reported after use of the minoxidil 2% and 5% solution in men and women with an incidence greater than 1% and greater than the placebo group in 7 placebo-controlled clinical studies.

In addition, adverse reactions reported post-marketing are reported with an unknown frequency.

The adverse reactions and their frequencies are listed below by System Organ Class according to the MedDRA database and by frequency. Frequencies are defined using the following classification: Very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1 000 to < 1/100); rare (≥ 1/10 000 to < 1/1 000), very rare (< 1/10 000), not known (cannot be estimated from the available data).

The most frequently observed reactions consist of minor skin reactions.

Frequent topical application may cause irritation and dryness of the skin, due to the presence of ethanol.

Reporting of suspected adverse reactions

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/.

Signs and symptoms

There is no data indicating that topically applied minoxidil is absorbed in sufficient quantity to cause systemic effects. Overdose is unlikely when the medicinal product is used in accordance with the instructions.

If this medicinal product is applied to an area where the integrity of the skin barrier is reduced due to trauma, inflammation or a skin condition, systemic effects of overdose are possible.

The undesirable effects below, which are very rare, may occur due to the systemic effects of minoxidil:

Accidental ingestion may cause systemic effects due to the vasodilator action of minoxidil (5 mL of solution contain 100 mg of minoxidil, i.e. the maximum dose used for oral administration in adults treated for arterial hypertension).

Treatment

In case of minoxidil overdose, symptomatic treatment as well as supportive measures should be instituted.

Fluid and sodium retention may be treated with appropriate diuretic therapy, tachycardia and angina with a beta-blocking agent 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.

Pharmacotherapeutic class: OTHER DERMATOLOGICALS

ATC code: D11AX01.

Mechanism of action

Applied topically, minoxidil stimulates keratinocyte growth in vitro and in vivo and hair growth in certain subjects with androgenetic alopecia.

This effect occurs after approximately 4 months (or longer) of use of the product and varies from subject to subject.

When treatment is stopped, hair regrowth ceases and a return to the initial state is predictable within 3 or 4 months.

The precise mechanism of action is not known.

Clinical efficacy and safety

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

Absorption

When applied locally, absorption of minoxidil through the skin is limited: percutaneous absorption of minoxidil after topical application of a 2% hydroalcoholic solution containing propylene glycol has generally been reported to be between 0,3 and 4,5% of the applied dose. The systemic bioavailability, at steady state, of minoxidil 20 mg/ml topical solution (20 mg) compared with that of an oral tablet of 2,5 mg was on average 1,4%. Following twice-daily application of 1 ml of ALOPEXY 20 mg/ml solution for cutaneous application for seven days on an area of 100 cm2 of the scalp of 24 healthy volunteers with androgenetic alopecia, the Cmax of minoxidil was found to be less than 2 ng/ml.

By comparison, the lowest intravenous dose of minoxidil producing a clinically significant haemodynamic effect in patients with mild to moderate hypertension is 6,86 mg, corresponding to a minoxidil concentration of 21,7 ng/ml. When administered orally (in the treatment of certain forms of hypertension), minoxidil is almost completely absorbed by the gastrointestinal tract. Systemic concentrations of minoxidil after topical administration depend on the applied dose, the frequency of application and the barrier function of the stratum corneum.

Absorption of minoxidil after topical application is not influenced by sex, exposure to ultraviolet rays, simultaneous application of moisturiser, occlusion (wearing headwear or a hair prosthesis), evaporation of the solvent (hair dryer) or by the size of the application area.

Biotransformation

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

Elimination

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

Non-clinical data from conventional studies of safety pharmacology, repeated-dose toxicity, genotoxicity or carcinogenic potential did not reveal any particular risk for humans.

Cardiac effects in dogs were observed at low doses, resulting in 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.

In a fertility study conducted in rats by the oral route, a dose-dependent reduction in conception rate was reported from the dose of 3 mg/kg/day (at least 12 times human exposure). In a subcutaneous study, minoxidil doses above 9 mg/kg/day (at least 36 times human exposure) were associated with a reduction in conception and implantation rates as well as a decrease in the number of live pups.

Minoxidil did not show teratogenic potential in rats and rabbits at oral doses up to 10 mg/kg/day, and in rats at subcutaneous doses up to 11 mg/kg/day (at least 40 times human exposure). Nevertheless, developmental toxicity (including an increase in foetal resorptions in both species, and in rats, skeletal abnormalities, stillbirths and reduced pup survival) was observed only at exposures considered sufficiently higher than the maximum human exposure, indicating low relevance for clinical use.

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

Before opening : 30 months.

After opening : 1 month.

This medicine does not require any particular storage precautions.

Flammable product.

Keep away from heat, hot surfaces, sparks, open flames and any other source of ignition. Do not smoke.

No special requirements.