Minoksikutan® forte

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT MİNOXİDUTAN®FORTÉ

Composition:

Active substance: minoxidil;

1 ml of solution contains 50 mg of minoxidil;

Excipients: propylene glycol, ethanol 96%, purified water.

Pharmaceutical form. Topical spray solution.

Main physicochemical characteristics: clear solution, colorless to slightly yellowish.

Pharmacotherapeutic group. Medicinal products used in dermatology. Other dermatological preparations. ATC code D11AX01.

Pharmacological properties.

Pharmacodynamics.

Mechanism of action

The exact mechanism by which minoxidil stimulates hair growth is not fully understood. However, minoxidil may prevent hair loss in androgenetic alopecia in the following ways:

• increasing the diameter of the hair shaft;
• stimulating hair growth in the anagen phase;
• prolonging the anagen phase;
• shortening the telogen phase by more rapid transition to the anagen phase.

Pharmacodynamic effects

As a peripheral vasodilator, minoxidil enhances microcirculation in hair follicles. Minoxidil stimulates vascular endothelial growth factor (VEGF), which is likely responsible for increased capillary permeability and thus indicates high metabolic activity, which may be observed during the anagen phase.

The study data provided below refer to topical medicinal products containing minoxidil from the holder of the registration certificate for the original medicinal product: in clinical studies, the average serum concentration was found to be 1.6 ng/mL in patients using minoxidil. In pharmacological studies in hemodynamically sensitive patients with mild untreated hypertension, a minimal effect on heart rate was observed only at serum concentrations of 21.7 ng/mL or higher.

After discontinuation of treatment, scalp hair returns to its pretreatment state within 3–4 months.

Pharmacokinetics.

Absorption

When applied topically, 1–2% of the active substance is systemically absorbed from minoxidil solution, compared to 90–100% absorption following oral administration.

The study data provided below refer to topical medicinal products containing minoxidil from the holder of the registration certificate for the original medicinal product.

In a study in men, the mean serum concentration of minoxidil (AUC) for the 2% solution was 7.54 ng•h/mL, compared to a mean AUC of 35 ng•h/mL for the 2.5 mg oral dosage form. The mean plasma concentration (Cmax) for the topical solution was 1.25 ng/mL compared to 18.5 ng/mL after oral administration of 2.5 mg.

In another study in men, systemic absorption of the 50 mg/mL foam formulation was approximately half that of the 50 mg/mL solution. The mean AUC (0–12 hours) and Cmax for the 50 mg/mL foam, i.e., 8.81 ng•h/mL and 1.11 ng/mL respectively, were approximately 50% of the AUC (0–12 hours) and Cmax for the 5% solution, i.e., 18.71 ng•h/mL and 2.13 ng/mL, respectively.

For the 50 mg/mL foam, the time to peak plasma concentration (tmax) of 5.42 hours was comparable to that of the solution, i.e., 5.79 hours. Hemodynamic effects of minoxidil were not observed until serum concentrations reached 21.7 ng/mL.

Distribution

The volume of distribution after intravenous administration of 4.6 mg and 18.4 mg of minoxidil was 73.1 L and 69.2 L, respectively.

Biotransformation

Following topical application, approximately 60% of absorbed minoxidil is metabolized to glucuronides, primarily in the liver.

Elimination

The half-life of minoxidil after topical administration is 22 hours, compared to 1.49 hours for oral formulations. 97% of minoxidil is excreted in urine and 3% in feces.

Mean renal clearance of minoxidil and its glucuronides, based on data from oral formulations, is 261 mL/min and 290 mL/min, respectively.

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

Clinical characteristics.

Indications.

Minoxycutan® Forte is indicated for moderate hair loss (androgenetic alopecia) in men.

Contraindications.

Minoxycutan® Forte should not be used in the following cases:

• hypersensitivity to the active substance or to any of the excipients listed in the section "Composition";
• skin diseases of the scalp;
• intolerance to the 2% formulation, regardless of symptoms;
• this medication is contraindicated in women;
• individuals under 18 years of age or over 65 years of age.

Interaction with other medicinal products and other forms of interaction.

Minoxycutan® Forte should not be applied to the scalp together with other dermatological products or other agents that enhance skin absorption.

Interaction with vasodilating antihypertensive agents, such as guanethidine, has been reported when used concomitantly with oral forms of minoxidil, leading to rapid and pronounced reduction in blood pressure.

Special precautions for use

Before applying minoxidil topically, the patient should ensure that the scalp skin is normal and healthy.

It should not be applied if the scalp skin is inflamed, infected, irritated, or painful.

Increased transdermal absorption of minoxidil, which may lead to systemic effects, is possible in the following cases:

• dermatoses or lesions of the scalp skin;
• concomitant use of retinoic acid, anthralin, or any other topical irritant;
• increased dosage and/or increased frequency of application: it is essential to adhere strictly to the recommended dosage and method of administration.

Although widespread use of minoxidil solution has not revealed systemic effects, it cannot be excluded that greater absorption due to individual variability or unusual sensitivity may cause systemic effects. Patients should be warned about this possibility.

As a precaution, patients should be monitored for possible appearance of symptoms indicating systemic effects, such as decreased blood pressure, tachycardia, chest pain, loss of consciousness, dizziness, unexplained weight gain, signs of fluid retention, or swelling of hands or feet.

Monitoring should be initiated at the beginning of treatment and continued regularly. If systemic effects, severe dermatological reactions, or any other unexpected symptoms occur (see section "Adverse reactions"), treatment must be discontinued and the patient should consult a physician.

Patients with cardiovascular diseases or cardiac arrhythmia should consult a physician before using topical minoxidil. In such patients, the benefit-risk balance of treatment should be carefully considered. They should also be thoroughly informed about potential adverse reactions so that treatment can be stopped immediately upon their occurrence, and the physician should be notified.

If symptoms do not resolve or worsen, or if new symptoms appear, patients should discontinue treatment and consult a physician.

Minoxidil must not be used:

• in cases of localized and/or sudden hair loss, hair loss following illness or medication, or if the cause of alopecia is unknown;
• on other parts of the body;
• simultaneously with other topical medicines applied to the scalp.

In case of accidental contact with eyes, damaged skin, or mucous membranes, the solution may cause burning sensation and/or irritation. If contact occurs with sensitive areas (eyes, irritated skin, mucous membranes), they should be thoroughly rinsed with cold running water.

Accidental ingestion may cause serious adverse effects, including cardiovascular effects (see section "Adverse reactions"). Therefore, this medicinal product should be stored out of reach of children.

Exposure to sunlight should be avoided during minoxidil use.

Some patients have reported changes in hair color and/or texture.

Do not inhale.

Using a higher dose or increasing the frequency of application will not improve results.

Continuation of treatment is necessary to enhance and maintain hair regrowth. Otherwise, hair loss will resume.

During the first 2–6 weeks of treatment, temporary increased hair shedding may occur. If hair shedding persists, the patient should discontinue use of Minoxycutan® Forte and consult a physician.

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

Hypertrichosis in children after accidental topical exposure to minoxidil:

Cases of hypertrichosis in infants have been reported following skin contact with application sites of minoxidil in patients (caregivers) using topical minoxidil. Hypertrichosis in infants was reversible within several months after discontinuation of minoxidil exposure. Therefore, contact between children and minoxidil application sites should be avoided.

Minoxycutan® Forte contains 96% ethanol and may cause eye stinging and irritation. In case of accidental contact with sensitive skin areas (eyes, damaged skin, mucous membranes), the medicinal product should be washed off with large amounts of water.

This medicinal product contains 509 mg of propylene glycol (E 1520) per milliliter, which may cause skin irritation.

This medicinal product contains 248 mg of alcohol (ethanol) per milliliter. When applied to damaged skin, it may cause a burning sensation.

Use during pregnancy or breastfeeding.

Pregnancy

This medicinal product is contraindicated in women.

Breastfeeding period

After systemic absorption, minoxidil is excreted in human breast milk. This medicinal product is contraindicated in women.

Ability to affect reaction speed when driving vehicles or operating machinery.

This medicinal product may cause dizziness or arterial hypotension (see section "Adverse reactions"). Sensitive patients should not drive vehicles or operate machinery.

Method of Administration and Dosage

Dosage

Apply 1 mL of Minoxycutan® Forte twice daily (in the morning and evening) to the affected areas of the scalp.

The daily dosage should not exceed 2×1 mL of solution, regardless of the size of the affected scalp area.

Method of Administration

For topical use only.

Before applying Minoxycutan® Forte, ensure that the scalp is completely dry. Minoxycutan® Forte should not be applied to other parts of the body.

After applying the topical spray or solution of Minoxycutan® Forte, hands should be thoroughly washed to avoid accidental contact with mucous membranes and eyes.

After application of Minoxycutan® Forte, normal styling may be performed. However, the scalp should not be wetted for approximately 4 hours afterward to prevent washing off the medication.

Each package of Minoxycutan® Forte contains two different spray applicators:

• a pre-assembled applicator for application to larger areas,
• a separate applicator with an extended tip for smaller areas.

Both applicators can be interchanged by detaching one and replacing it with the other.

For a 1 mL dose, 6 actuations of the spray pump are required.

Instructions for Use/Application

The solution should be sprayed directly onto the scalp in the area of hair loss. Press the spray pump 6 times. After each actuation, spread the liquid evenly over the affected area with fingertips, avoiding inhalation of the spray.

Duration of Use

The onset and degree of hair growth vary among individual patients.

Generally, visible results require twice-daily application for 2 to 4 months. To maintain the effect, continuous twice-daily application is recommended. Applying Minoxycutan® Forte in higher amounts or more frequently does not enhance the therapeutic outcome. Adequate clinical experience supports treatment duration of up to 1 year.

If no effect is observed after 4 months of use, treatment should be discontinued.

Inadequate Dosing

If too little Minoxycutan® Forte has been applied or a dose has been missed, the patient should not apply an additional dose. Treatment should continue with the recommended dosage.

Children

Minoxycutan® Forte should not be used in children and adolescents under 18 years of age, as there are no controlled efficacy and safety data available for these age groups.

Overdose

Symptoms of Overdose

Application of Minoxycutan® Forte in doses exceeding the recommended amount or on abnormally large body surfaces (other than the scalp) may lead to increased systemic absorption of minoxidil.

Accidental ingestion may cause systemic effects due to the vasodilatory action of minoxidil. Signs and symptoms of possible overdose are of cardiovascular origin and may include arterial hypotension, tachycardia, lethargy, and fluid retention. Fluid retention can be managed with appropriate diuretic therapy. Tachycardia and angina are treated with a beta-blocker or another sympathoinhibitory agent. Symptomatic hypotension should be managed by intravenous administration of isotonic sodium chloride solution. The use of sympathomimetic agents such as noradrenaline and adrenaline should be avoided due to the risk of excessive cardiac stimulation.

Keep out of reach of children. In case of accidental ingestion, seek immediate medical attention or contact emergency services.

Adverse reactions

The adverse reactions listed below are classified according to the following frequency categories:

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)
Frequency not known (cannot be estimated based on available data)

The safety of topical minoxidil was evaluated based on data from seven placebo-controlled randomized clinical trials in adults investigating minoxidil solutions at 20 mg/mL or 50 mg/mL, and two placebo-controlled randomized clinical trials in adults investigating the 50 mg/mL minoxidil foam formulation.

The table below presents adverse reactions identified during clinical trials and post-marketing experience, organized by System Organ Class (SOC).

Reporting of suspected adverse reactions

Reporting of adverse reactions following the registration of a medicinal product is of great importance. It enables continuous monitoring of the benefit/risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life. 36 months.

After first opening – 6 weeks.

Storage conditions.

No special storage conditions required. Keep out of reach of children.

Do not freeze.

Contains flammable ethanol. Keep away from heaters and open flames.

Packaging.

60 ml of solution in a bottle with an integrated pump system and an adapter with an extended nozzle. One bottle with the instruction for medical use is placed in a carton.

Classification for supply. Over-the-counter (without prescription).

Manufacturer. mibe GmbH Arzneimittel.

Manufacturer's address and location of operations.

Muenchenstrasse 15, Breuna, Saxony-Anhalt, 06796, Germany.