Generolon

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT GENEOLON

Composition:

active substance: minoxidil;

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

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

Pharmaceutical form. Topical solution.

Main physicochemical characteristics:

a 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 (resting) phase back into the anagen phase. Minoxidil is a peripheral vasodilator that improves microcirculation in hair follicles. It stimulates vascular endothelial growth factor, promoting enhanced capillary development, which results in significantly 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 surface area of solution application.

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.

Contraindications.

Hypersensitivity to the components of the drug; pheochromocytoma, treated and untreated hypertension; skin diseases of the scalp (including psoriasis and sunburn); shaved scalp; simultaneous use of occlusive dressings or other topical agents on the scalp. Generolon (50 mg/mL), topical solution, is contraindicated for use in women.

Interaction with other medicinal products and other forms of interaction.

Generolon should not be used simultaneously with other topical agents applied to the scalp.

Concomitant use of Generolon and other topical agents containing corticosteroids, tretinoin, dithranol, or white soft paraffin, which alter the skin's protective functions, may enhance the absorption of minoxidil.

Orthostatic hypotension may potentially be intensified due to systemic absorption of minoxidil in patients taking peripheral vasodilators, although this has not been clinically confirmed.

An interaction between guanethidine and oral minoxidil preparations has been reported, resulting in rapid and pronounced reduction in blood pressure. There is a theoretical possibility of interaction between topical minoxidil and guanethidine.

Special precautions for use.

Before starting treatment with Generolon, ensure that the scalp skin is healthy and not damaged.

Generolon must not be used if there is inflammation, infection, irritation, or pain of the scalp skin.

Generolon 2% topical solution is indicated for the treatment of male-pattern alopecia in women and men. It should not be used for other causes of hair loss, such as when there is no family history of hair loss, sudden and/or patchy hair loss, postpartum-related 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 when there is no family history of hair loss, sudden and/or patchy hair loss, or if the cause of hair loss is unknown.

Treatment should be discontinued and a physician consulted if hypotension, chest pain, tachycardia, weakness, dizziness, unexpected weight gain, swelling of hands or feet, persistent redness or irritation of the scalp skin, or any other unexpected new symptoms occur.

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

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

Increasing the dose or applying the product more frequently than recommended will not improve results.

Excessive hair growth may occur if the product is applied to areas other than the scalp skin.

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 (or 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.

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

In some patients, changes in hair color and/or texture may occur.

Some patients have reported increased hair loss after initiating treatment with topical minoxidil solution. This is most likely due to the transition from the resting phase (telogen phase) to the hair growth phase (anagen phase). During this process, old hair sheds and is replaced by new hair. This temporary increase in hair shedding usually occurs 2–6 weeks after starting treatment and resolves within several weeks. If hair loss persists for >2 weeks, treatment with topical minoxidil should be discontinued and a physician consulted.

Use with caution in patients with ischemic heart disease, angina pectoris, arrhythmia, or arterial hypotension. Patients with individual variability, unusual sensitivity, or impaired skin integrity due to inflammation or skin disorders (e.g., scalp skin injury or scalp psoriasis) may experience systemic effects of minoxidil.

Accidental ingestion of the product may lead to serious cardiovascular adverse effects. Therefore, this product should be stored out of reach of children.

Generolon topical solution contains ethanol, which may cause eye irritation. If the product 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, which may cause skin irritation.

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

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

Do not use under occlusive dressings or 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.

The use of this product is contraindicated in women who are pregnant or breastfeeding.

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 those in humans. There is a potential risk of fetal harm if used during pregnancy.

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

Ability to affect reaction speed when driving or operating machinery.

Due to the possible occurrence of dizziness or hypotension, caution should be exercised when driving or operating machinery. If such adverse effects occur, patients should refrain from these activities.

Method of Administration and Dosage

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

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

Before first use, the spray pump must be primed by pressing it several times until a consistent flow of solution is achieved. After this, the device is ready for use.

Before applying the solution, the scalp and hair must be thoroughly dried.

Using the spray pump, apply 1 mL of solution twice daily onto the dry scalp in the area of alopecia, gently massaging it in with movements from the center toward the periphery of the affected area. For each application, the spray pump should be pressed 10 times to deliver 1 mL of solution. The daily dose must not exceed 2 mL. Hands must be washed after each application.

To achieve a therapeutic effect, the 2% topical solution should be applied twice daily for at least 4 months. To achieve a therapeutic effect, the 5% topical solution should be applied twice daily for at least 2 months. After achieving clinical improvement, continued use of the medication is necessary to maintain hair growth. There have been reports of resumption of hair loss within 3–4 months after discontinuation of minoxidil treatment. Treatment should be discontinued if no effect is observed within 1 year of use.

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

The product must not be administered to children under 18 years of age.

Overdose

Accidental or intentional overdose of Genereolon topical solution may lead to an increased intensity of adverse dermatological reactions, particularly itching, dryness, and skin irritation. Enhanced systemic absorption of minoxidil may occur when applied to large body surfaces or areas other than the scalp, or when used at doses exceeding those recommended. Accidental ingestion of the solution may cause systemic effects due to the vasodilatory action of minoxidil (5 mL of Genereolon 2% contains 100 mg of minoxidil, which is the maximum recommended dose for the treatment of hypertension. 2 mL of Genereolon 5% contains 100 mg of minoxidil, which is the maximum recommended dose for the treatment of hypertension).

Symptoms of minoxidil overdose are primarily cardiovascular disturbances related to 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 correct fluid retention.

Adverse Reactions

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

Clinical trials involving several thousand patients compared topical minoxidil solution with a vehicle solution lacking the active ingredient. Dermatological reactions such as irritation and pruritus occurred in patients after application of both solutions, which is attributed to the presence of propylene glycol in both formulations.

Data from 7 placebo-controlled studies involving 1197 men and women who used topical minoxidil solution (20 mg/mL and 50 mg/mL in combination) report the occurrence of adverse reactions. Additionally, adverse reactions have been reported during the post-marketing period of this medicinal product.

The following frequency categories of adverse reactions are used in this section: 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 from available data).

Immune system disorders.

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

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

Psychiatric disorders.

Frequency not known – depressed mood.

Nervous system disorders.

Very common – headache.

Uncommon – dizziness.

Eye disorders.

Frequency not known – eye irritation.

Cardiac disorders.

Common – chest pain.

Uncommon – rapid heartbeat.

Frequency not known – increased heart rate.

Vascular disorders.

Frequency not known – decreased blood pressure.

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 outside the scalp, including facial hair growth in women), pruritus (including generalized rash with pruritus and eye pruritus), rash (including pustular, papular, generalized, vestibular, and macular rash), dermatitis (including application site contact dermatitis, allergic, atopic, and seborrheic dermatitis).

Rare – change in hair texture.

Frequency not known – dry skin, skin peeling (including exfoliative rash and exfoliative dermatitis), acne (acneiform rash), temporary hair loss, change in hair color.

General disorders and administration site conditions.

Common – peripheral edema.

Frequency not known – application site reactions (sometimes spreading to adjacent body areas, including ears and face), namely pruritus, irritation, pain, rash, swelling, dry skin, erythema, and erythematous rash, which may occasionally be more severe and include desquamation, dermatitis, blistering, bleeding, and ulceration.

Investigations.

Common – weight gain.

Treatment should be discontinued and a physician consulted if chest pain, rapid heartbeat, weakness, dizziness, unexpected weight gain, swelling of hands and feet, or persistent redness or irritation of the scalp occurs.

Shelf life. 3 years.

30 days after first opening of the bottle.

Storage conditions.

Store at temperatures not exceeding 25 °C.

Keep out of reach of children.

Packaging.

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

Availability.

Over-the-counter.

Manufacturer.

Belupo, pharmaceuticals and cosmetics, d.d., Croatia / 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.