Generolon

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT GENEOLON

Composition:

Active substance: minoxidil;

1 ml of solution contains minoxidil 20 mg or 50 mg;

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

Pharmaceutical form. Topical solution.

Main physicochemical properties:

Clear colorless or slightly yellowish aqueous-alcoholic solution with an alcoholic odor.

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

Pharmacological properties.

Pharmacodynamics.

The mechanism by which minoxidil stimulates hair growth is not fully understood. Possible mechanisms for halting hair loss include an increase in the diameter of the hair shaft, stimulation of the anagen (growth) phase of hair, prolongation of the anagen phase, and stimulation of the transition from the telogen phase back into anagen. Minoxidil is a peripheral vasodilator that improves microcirculation in the hair follicles. It stimulates vascular endothelial growth factor, promoting enhanced capillary development, which results in increased metabolic activity during the anagen phase of hair growth.

Pharmacokinetics.

Systemic absorption of minoxidil following topical application to intact, normal scalp skin amounts to 1–2% of the total applied dose. Skin absorption of minoxidil increases with higher dosage, increased frequency, or larger application surface area.

Absorbed minoxidil is metabolized in the liver, and excretion of minoxidil and its metabolites occurs primarily via the kidneys. After discontinuation of topical application, approximately 95% of absorbed minoxidil is eliminated from the body within 4 days.

Clinical characteristics.

Indications.

Generolon (20 mg/mL), topical solution, is indicated for the treatment of male-pattern alopecia in men and women aged 18 to 65 years.

Generolon (50 mg/mL), topical solution, is indicated for the treatment of male-pattern alopecia in men aged 18 to 65 years.

Not all individuals respond equally to minoxidil therapy. Although trends in data suggest that users who are younger, who have experienced hair loss over a short period of time, or who have a smaller area of baldness on the scalp are more likely to respond to minoxidil. Individual responses cannot be predicted.

Contraindications.

Hypersensitivity to the active substance or to any of the excipients of the medicinal product; pheochromocytoma; treated and untreated arterial hypertension; skin diseases of the scalp (including psoriasis and sunburn); shaved scalp; concurrent application on the scalp of occlusive dressings or other topical medicinal products. Generolon (50 mg/mL), topical solution, is contraindicated in women.

Interaction with other medicinal products and other forms of interaction.

Generolon should not be used concurrently with other topical medicinal products applied to the scalp (see section "Contraindications").

Concomitant use of Generolon and other topical medicinal products containing corticosteroids, tretinoin, dithranol, or vaseline, which alter skin permeability, may enhance the absorption of minoxidil.

An increased risk of orthostatic hypotension may theoretically occur due to systemic absorption of minoxidil in patients taking peripheral vasodilators, although this has not been clinically confirmed.

Guanothidine has been reported to interact with oral minoxidil preparations, resulting in rapid and pronounced reduction in blood pressure. There is a theoretical possibility of interaction between topically applied minoxidil and guanothidine.

Special precautions for use.

Before starting treatment with Generolon, ensure that the scalp skin is healthy and intact.

Generolon must not be used in case of inflammation, infection, irritation, or pain of the scalp skin.

Generolon 2% topical solution is indicated for the treatment of male-pattern alopecia in men and women. It should not be used for other causes of hair loss, such as absence of hair loss in family history, sudden and/or patchy hair loss, postpartum hair loss, or if the cause of hair loss is unknown.

Generolon 5% topical solution is indicated for the treatment of male-pattern alopecia in men. It should not be used for other causes of hair loss, such as absence of hair loss in family history, sudden and/or patchy hair loss, or if the cause of hair loss is unknown.

Patients should discontinue use of the medication and consult a physician if they experience low blood pressure, chest pain, rapid heartbeat, weakness, dizziness, unexpected weight gain, swelling of hands or feet, persistent redness or irritation of the scalp, or the appearance of any other unexpected new symptoms.

Patients with cardiovascular diseases or arrhythmia should consult a physician before starting treatment with Generolon.

Generolon topical solution is intended for external use only on the scalp. It should not be applied to other areas of the body.

Using doses higher than recommended or applying the medication more frequently than instructed will not improve results.

Unwanted hair growth may occur if the medication is applied 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 sites of minoxidil application in patients (or caregivers) using topical minoxidil. Hypertrichosis in infants was reversible within several months after discontinuation of minoxidil exposure. Therefore, contact between children and sites of minoxidil application should be avoided.

Hands must be thoroughly washed after each application. Inhalation of the solution vapors should be avoided.

Generolon topical solution contains ethanol.

Generolon 20 mg/mL topical solution contains 564 mg of alcohol (ethanol) per 1 mL of solution, equivalent to 18.8 mg/kg/day.

Generolon 50 mg/mL topical solution contains 243 mg of alcohol (ethanol) per 1 mL of solution, equivalent to 8.1 mg/kg/day.

This may cause a burning sensation on damaged skin and may irritate the eyes. If the medication comes into contact with mucous membranes, damaged skin, or eyes, these areas should be thoroughly rinsed with running water.

Generolon topical solution contains propylene glycol.

Generolon 20 mg/mL topical solution contains 104 mg of propylene glycol per 1 mL of solution, equivalent to 3.46 mg/kg/day.

Generolon 50 mg/mL topical solution contains 520 mg of propylene glycol per 1 mL of solution, equivalent to 17.33 mg/kg/day.

This may cause skin irritation.

In individual patients, changes in hair color and/or texture may occur during minoxidil use.

Some patients have reported increased hair loss after initiating therapy with topical minoxidil solution. This is most likely related to minoxidil's action of transitioning hair follicles from the resting phase (telogen phase) to the growth phase (anagen phase). As a result, old hair sheds and is replaced by new hair. This temporary increase in hair loss typically occurs 2–6 weeks after starting treatment and resolves within several weeks. If hair loss persists (>2 weeks), patients should discontinue use of topical minoxidil and consult a physician.

Patients should be aware that although widespread use of minoxidil has not demonstrated evidence of sufficient absorption to produce systemic effects, increased absorption due to improper use, individual variability, unusual sensitivity, or reduced integrity of the epidermal barrier caused by inflammatory processes or skin diseases (e.g., scalp skin damage or scalp psoriasis) may theoretically lead to systemic effects of minoxidil.

Accidental ingestion of the medication may result in serious cardiovascular adverse reactions. Therefore, this medication must be stored out of reach of children.

Use of a hair dryer during treatment is not recommended, as it may accelerate evaporation of the active substance.

The product is flammable. After opening the original packaging, the medication must be protected from open flames and high temperatures.

Do not use under occlusive dressings or immediately after shaving the scalp.

If no satisfactory results are observed after 4 months, a dermatologist consultation is required. Continuing or repeating treatment should be done only after consultation with a dermatologist.

Use during pregnancy or breastfeeding.

Pregnancy

Generolon 2% topical solution.

Use of this medication is contraindicated in pregnant women.

There are no adequate and well-controlled studies on the use of minoxidil in pregnant women. Animal studies have shown fetal risk at very high exposure levels compared to human exposure levels. There is a potential risk of fetal harm if used during pregnancy.

Generolon 5% topical solution is contraindicated for use in women.

Breastfeeding period

Generolon 2% topical solution.

Systemically absorbed minoxidil is excreted in breast milk. The effects of minoxidil on newborns and/or infants are unknown.

Use of this medication is contraindicated in women who are breastfeeding.

Breastfeeding should be discontinued during treatment with minoxidil.

Generolon 5% topical solution is contraindicated for use in women.

Ability to influence reaction rate when driving or operating machinery.

Based on pharmacodynamic data and the overall safety profile of minoxidil, minoxidil is not expected to affect the ability to drive or operate machinery.

Method of Administration and Dosage

Generolon 2%, topical solution, is intended for external use only in men and women aged 18 to 65 years.

Generolon 5%, topical solution, is intended for external use only in men aged 18 to 65 years.

Before applying the solution, the scalp and hair should be thoroughly dried. A dose of 1 mL (corresponding to 10 actuations of the spray pump) of minoxidil topical solution should be applied to the entire affected area of the scalp twice daily—morning and evening—starting from the center of the area to be treated. The daily dose should not exceed 2 mL. Hands must be washed after each application.

It may take four months or longer before signs of hair growth can be expected with the use of the 2% topical solution. It may take two months or longer before signs of hair growth can be expected with the use of the 5% topical solution.

If hair regrowth occurs, minoxidil topical solution should be applied twice daily to maintain hair growth. Reports indicate that hair loss may resume within 3–4 months after discontinuation of minoxidil, with progression of baldness.

Patients should discontinue treatment with the 2% topical solution if no improvement is observed within eight months.

Patients should discontinue treatment with the 5% topical solution if no improvement is observed within four months.

Elderly Patients

Use in elderly individuals is not recommended. The safety and efficacy of minoxidil in individuals aged 65 years and older have not been established.

Special Populations

There are no specific recommendations for the use of minoxidil in patients with renal or hepatic impairment.

Children

Do not administer this medication to children under 18 years of age.

Overdose

Accidental or intentional overdose of Generolon topical solution may lead to an increased intensity of adverse dermatological reactions, particularly itching, dryness, and irritation of the skin.

Systemic absorption of minoxidil may potentially increase if doses higher than recommended are applied to larger body surface areas or to areas other than the scalp.

Accidental ingestion of minoxidil may potentially cause systemic effects due to the pharmacological (vasodilatory) action of the drug (5 mL of Generolon 2% contains 100 mg of minoxidil, which is the maximum recommended dose for adults when minoxidil is administered orally for the treatment of arterial hypertension. 2 mL of Generolon 5% contains 100 mg of minoxidil, which is the maximum recommended dose for adults when minoxidil is administered orally for the treatment of arterial hypertension).

Signs and symptoms of minoxidil overdose primarily include cardiovascular disturbances associated with sodium and fluid retention. Tachycardia, arterial hypotension, dizziness, and somnolence may also occur.

Treatment

Treatment of minoxidil overdose should be symptomatic and supportive.

Beta-blockers should be administered for tachycardia. Diuretics should be used to manage fluid retention.

Adverse Reactions

In placebo-controlled studies, the overall frequency of adverse reactions by organ system classes was approximately five times higher in women than in men.

Clinical trials involving several thousand patients compared minoxidil topical solution with placebo topical solution (without active ingredient). Dermatological reactions such as irritation and itching occurred in patients after application of both solutions, which is attributable to the presence of propylene glycol in both formulations.

Data from 7 placebo-controlled studies involving 1197 men and women who used minoxidil topical solution (20 mg/mL and 50 mg/mL in combination) were used to evaluate adverse reactions. Additionally, adverse reactions reported during the post-marketing period are included.

The frequency of adverse reactions is categorized as follows: very common (≥10%); common (≥1% and <10%); uncommon (≥0.1% and <1%); rare (≥0.01% and <0.1%); very rare (<0.01%); frequency not known (cannot be estimated based on available data).

Immune system disorders

Common – hypersensitivity reactions (including facial swelling, generalized erythema, generalized pruritus, facial swelling, throat tightness).

Frequency not known – angioneurotic edema (including lip swelling, lip edema, oral cavity swelling, oropharyngeal swelling, pharyngeal swelling, tongue swelling, and tongue edema).

Psychiatric disorders

Frequency not known – depressed mood.

Nervous system disorders

Common – headache.

Uncommon – dizziness.

Eye disorders

Frequency not known – eye irritation.

Cardiovascular disorders

Rare – tachycardia, increased heart rate, chest pain.

Vascular disorders

Uncommon – arterial hypotension.

Respiratory, thoracic and mediastinal disorders

Uncommon – dyspnea.

Gastrointestinal disorders

Uncommon – nausea.

Frequency not known – vomiting.

Skin and subcutaneous tissue disorders

Common – hypertrichosis (unwanted hair growth in areas other than the scalp, including facial hair growth in women), pruritus (including pruritic rash, application site pruritus, generalized pruritus, and eye pruritus).

Uncommon – temporary hair loss (see section "Special Warnings and Precautions for Use"), changes in hair texture and color, skin desquamation (including at the application site, exfoliative rash, and exfoliative dermatitis), rash (including at the application site, pustular, papular, generalized, and macular rash), acne (acneiform rash), dermatitis (including contact dermatitis, application site dermatitis, allergic, atopic, and seborrheic dermatitis), and dry skin (including dryness at the application site).

General disorders and administration site conditions

Uncommon – peripheral edema, application site reactions (including skin irritation, which may sometimes spread to adjacent body areas, particularly ears and face), specifically pruritus, irritation, pain, swelling, erythema at the application site (including erythema and erythematous rash), which may occasionally be more severe and include desquamation, dermatitis, blistering, bleeding, and ulceration.

Investigations

Common – weight gain.

Patients should discontinue use of minoxidil and consult a physician if they experience chest pain, tachycardia, weakness, dizziness, sudden weight gain, or swelling of hands and feet, or persistent redness or irritation of the scalp.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after medicine authorization is important. It allows continued monitoring of the benefit-risk balance of the medicine. Healthcare professionals, pharmacists, patients, and 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

3 years (for 2% topical solution).

4 years (for 5% topical solution).

30 days after first opening of the bottle.

Storage conditions

Store at temperatures not exceeding 25 °C.

Keep out of reach and sight of children.

Packaging

60 mL in a bottle, 1 bottle with a measuring pump and spray nozzle in a cardboard box.

Prescription status

Over-the-counter (without prescription).

Manufacturer

Belupo, pharmaceuticals and cosmetics, Inc., Croatia.

Manufacturer's address and location of operations

Danica Street 5, 48000 Koprivnica, Croatia / Ulica Danica 5, 48 000 Koprivnica, Croatia.