Regaine^® (Solution, Foam) Instructions for Use

ATC Code

D11AX01 (Minoxidil)

Active Substance

Minoxidil (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Drug for the treatment of alopecia in men and women

Pharmacotherapeutic Group

Other drugs used in dermatology

Pharmacological Action

As a peripheral vasodilator, Minoxidil enhances microcirculation in the area of hair follicles when applied topically. It stimulates vascular endothelial growth factor (VEGF), which is believed to be responsible for increased capillary permeability, indicating the high metabolic activity observed in the anagen phase.

Minoxidil stimulates hair growth in patients with hereditary hair loss (androgenic alopecia) in the initial and moderate stages. The exact mechanism of action of topical minoxidil for hair loss is not fully understood.

Pharmacokinetics

Absorption

When applied topically to intact skin, approximately 1-2% of the minoxidil solution undergoes systemic absorption.

In a clinical study, the systemic absorption of the 5% topical foam was approximately half that of the 5% topical solution. The mean values for the area under the concentration-time curve (AUC_{0-12 h}) and maximum concentration (C_max) for the 5% foam were 8.81 ng×h/ml and 1.11 ng/ml, respectively, representing approximately 50% of the corresponding values for the 5% solution (18.71 ng×h/ml and 2.13 ng/ml, respectively).

The time to reach the maximum concentration of minoxidil (T_max) for the 5% foam is 5.42 h and is similar to that for the 5% solution (5.79 h). The effect of minoxidil on hemodynamics is not pronounced until the average serum concentration of minoxidil reaches 21.7 ng/ml.

Distribution

Although it was previously reported that Minoxidil does not bind to plasma proteins, later in vitro ultrafiltration demonstrated its reversible binding to human plasma proteins in the range of 37-39%.

Since only 1-2% of topically applied minoxidil is absorbed, the extent of plasma protein binding observed in vivo after topical application will be clinically insignificant.

The V_d of minoxidil after intravenous administration of 4.6 mg and 18.4 mg doses is 73.1 L and 69.2 L, respectively.

Biotransformation

Approximately 60% of the minoxidil absorbed after topical application is metabolized to form minoxidil glucuronide, primarily in the liver.

Excretion

The half-life of topically applied minoxidil averages 22 hours, compared to 1.49 hours for oral administration. 97% of minoxidil and its metabolites are excreted by the kidneys and 3% through the intestines.

After discontinuation of the drug, approximately 95% of the topically applied minoxidil is eliminated within 4 days.

Indications

• Treatment of androgenic alopecia in men and women.

ICD codes

Dosage Regimen

Foam

The drug is for topical use. Before using the drug Regaine^®, hair and scalp should be thoroughly dried.

For the drug’s effectiveness and its delivery to the hair follicles, it is important to apply the drug to the scalp skin, not to the hair.

Dose for men – Apply 1 g (1/2 capful) of foam 2 times/day (morning and evening) to the affected areas of the scalp. Do not use Regaine^® more than once every 12 hours. The total daily dose should not exceed 2 g of the drug (100 mg of minoxidil).

Dose for women – Apply 1 g (1/2 capful) of foam once a day to the affected areas of the scalp. Do not use Regaine^® more than once a day. The daily dose should not exceed 1 g of the drug (50 mg of minoxidil).

Do not apply the drug Regaine^® to other parts of the body.

Instructions for using the canister

1. Turn the cap so that the arrows on the dispenser and cap are opposite each other (Fig. 1).
2. Tilt the cap back and remove it.
3. Before dispensing the foam, it is recommended to first rinse your fingers with cold water and dry them thoroughly, as the foam may dissolve upon contact with warm skin.
4. Turn the canister upside down, press the dispenser, and dispense the required amount of foam onto your fingers (Fig. 2).
5. Spread the foam with your fingertips over the balding areas and gently rub into the scalp skin (Fig. 3 and 4).
6. After using the drug Regaine^®, put the cap back on the canister. To keep the packaging protected from accidental opening by children, ensure that the arrows on the dispenser and cap are not aligned.

After applying the drug Regaine^®, wash your hands thoroughly.

The first signs of reduced hair loss and restored hair growth may appear after using the drug Regaine^® twice a day in men for 2-4 months and once a day in women for 3-6 months.

To achieve and maintain the achieved effect of restored hair growth, the patient should not interrupt the use of the drug, otherwise hair loss will resume.

Increasing the dose of the drug or using it more frequently will not lead to improved treatment results.

If enhanced hair growth is not observed after using the drug Regaine^® in men for 16 weeks and in women for 24 weeks, the use of the drug should be discontinued.

After starting the use of the drug Regaine^®, increased hair loss may be observed. This effect is caused by the action of minoxidil. It is expressed in stimulating the transition of hair from the resting phase (telogen) to the growth phase (anagen). Thus, old hair falls out and new hair grows in its place. Temporary increased hair loss usually lasts for 2-6 weeks from the start of treatment and then decreases within 2 weeks.

Solution

The drug is intended only for topical application to the scalp skin. Do not apply the drug Regaine^® to other parts of the body.

Regaine^® is applied to the affected areas of the scalp at a dose of 1 ml twice a day, starting from the center of the affected area. The drug is used at this dose regardless of the size of the treated areas of the scalp. The total daily dose should not exceed 2 ml.

Patients who do not experience cosmetically satisfactory hair growth with the 2% solution and patients for whom faster hair growth is desirable can use the 5% solution.

For men, Regaine^® is most effective for hair loss on the crown; for women, for hair loss in the mid-parting area.

Rules for using the drug

Regaine^® is applied only to dry scalp skin. The method of application depends on the applicator used, as described below. If the drug is applied with the fingertips, hands should be washed thoroughly after treating the head.

A. Sprayer

This nozzle is suitable for applying the drug to large areas of the scalp.

1. Remove the large outer cap and the inner screw cap from the bottle.
2. Attach the sprayer nozzle to the bottle and screw it on tightly.
3. Remove the transparent cap.
4. Direct the sprayer head to the center of the affected area, press the valve, and distribute the drug with your fingertips over the entire balding area. To apply a dose of 1 ml of solution, repeat this operation a total of 6 times.
5. Avoid inhaling the aerosol. After use, put the transparent cap and the large outer cap back on the bottle.

B. Extended spray nozzle

This nozzle is suitable for applying the drug to small balding areas or for treating the skin under remaining hair.

1. To use the extended nozzle, the sprayer must be installed on the bottle. Perform steps A₁ and A₃ (see above).
2. Remove the small spray head from the sprayer, attach the extended spray nozzle to the sprayer bushing. Remove the small cap from the end of the extended nozzle.
3. Directing the nozzle to the center of the balding area, press the sprayer once, then distribute the drug with your fingertips over the entire area, gently rubbing it into the skin. To apply a dose of 1 ml of solution, repeat this operation a total of 6 times.
4. Avoid inhaling the aerosol. After use, you can put the cap on the end of the extended nozzle.

C. Rubbing applicator

This applicator is suitable for applying the drug to small balding areas.

1. Remove the large outer cap and the inner screw cap from the bottle.
2. Attach the rubbing applicator to the bottle and screw it on tightly.
3. Holding the bottle vertically, squeeze the bottle to fill the upper chamber up to the black line. The chamber holds one full dose (1 ml of solution).
4. Turn the bottle upside down and massage the scalp with the applicator to treat the entire balding area until the chamber is empty. After use, put the large outer cap back on the bottle.

Clinical experience with the drug shows that the first signs of hair growth stimulation may appear after using the drug twice a day for 4 months or more. The onset and degree of hair growth, as well as hair quality, may vary among different patients.

According to individual reports, restoration of the original appearance can be expected within 3-4 months after discontinuation of treatment.

Adverse Reactions

The frequency of adverse reactions is presented using the following gradation: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10000, <1/1000); very rare (<1/10000), unknown (cannot be estimated from the available data).

Adverse events observed in patients during clinical trials

Nervous system disorders common – headache.

Skin and subcutaneous tissue disorders: common – skin itching, rash;

Laboratory and instrumental data: common – increased body weight; rare – dermatitis, manifested as redness, scaling, and inflammation.

Post-marketing data

Immune system disorders: very rare – angioedema (lip swelling, swelling of oral tissues, oropharyngeal swelling, pharyngeal swelling, and tongue swelling), hypersensitivity (facial swelling, generalized erythema, generalized skin itching, feeling of throat tightness), allergic contact dermatitis.

Psychiatric disorders very rare – depressed mood.

Nervous system disorders: very rare – dizziness, headache.

Eye disorders: very rare – eye irritation.

Cardiac disorders very rare – tachycardia, palpitations.

Vascular disorders uncommon – decreased BP.

Thoracic and mediastinal disorders very rare – dyspnea.

Gastrointestinal disorders: very rare – nausea, vomiting.

Skin and subcutaneous tissue disorders: very rare – application site reactions (these reactions may spread to the ears and face, include skin itching, irritation, pain, rash, swelling, dry skin, erythema; however, in some cases reactions may be more severe, including exfoliation, dermatitis, blistering, bleeding, ulceration), temporary hair loss, hair color changes, altered hair texture, hypertrichosis (unwanted hair growth outside the application site).

General disorders and administration site conditions: very rare – peripheral edema, chest pain.

If any of the side effects listed in the instructions get worse, or if any other side effects not listed in the instructions are noticed, the patient should inform the doctor.

Contraindications

• Hypersensitivity to minoxidil or other components of the drug;
• Impaired skin integrity;
• Scalp dermatoses;
• Concurrent use of other medicinal products on the scalp;
• Pregnancy;
• Breastfeeding period;
• Age under 18 years;
• Age over 65 years.

With caution

Patients with cardiovascular diseases, arrhythmia, renal and hepatic insufficiency. Before starting the drug, such patients should consult a doctor.

Use in Pregnancy and Lactation

The drug Regaine^® in the form of foam is contraindicated in women during pregnancy and breastfeeding.

Use in Hepatic Impairment

The drug should be prescribed with caution to patients with hepatic insufficiency.

Use in Renal Impairment

The drug should be prescribed with caution to patients with renal insufficiency.

Pediatric Use

The drug is contraindicated for use in patients under 18 years of age.

Geriatric Use

The drug is contraindicated for use in patients over 65 years of age.

Special Precautions

Before starting treatment with Regaine^®, a general examination, including collection and review of medical history, should be performed. The doctor should ensure that the scalp skin is healthy.

The drug Regaine^® should be applied only to healthy scalp skin. Do not use the drug in case of inflammation, infection, irritation, soreness of the skin, or simultaneously with other medicinal products applied to the scalp skin.

The drug Regaine^® should not be used in cases of sudden hair loss, alopecia areata, when alopecia develops after childbirth, in case of baldness caused by medication, improper diet (iron deficiency, vitamin A deficiency), as a result of styling hair in “tight” hairstyles, and also when the cause of hair loss is unknown.

If BP decreases or chest pain, rapid heartbeat, weakness or dizziness, sudden unexplained weight gain, swelling of the hands or feet, persistent redness or irritation of the scalp skin occurs, the patient should stop using Regaine^® and consult a doctor.

If symptoms persist or worsen, or if new symptoms appear, the patient must discontinue the drug and consult a doctor.

The drug may activate the growth of unwanted hair if applied to areas of the skin other than the scalp.

Some components of the drug may cause burning and irritation. If the drug gets on sensitive surfaces (eyes, irritated skin, mucous membranes), the affected area should be rinsed with plenty of cool water. The drug contains butylated hydroxytoluene, cetyl and stearyl alcohol, which may cause local skin reactions (e.g., contact dermatitis).

Accidental ingestion of the drug may lead to the development of serious cardiac adverse events. Therefore, this drug should be stored in places inaccessible to children.

The canister contents are under pressure. Do not puncture or incinerate the canister. The drug is flammable, so the contents of the canister should not be sprayed near an open flame, polished or painted surfaces. Contact of the canister with open flame sources should be avoided during use, storage, and disposal. Do not heat the canister above 50°C (122°F). When applying the drug, refrain from smoking.

If the medicine has deteriorated or the expiration date has passed, it should not be poured down the drain or thrown out on the street. The drug should be placed in a bag and put in a trash container. These measures will help protect the environment.

Recommendations for using the drug together with hair care products

The drug will not be effective when used with:

• A hairdryer after applying the foam to the scalp;
• Hair care products that can cause scarring, as well as deep burns of the scalp;
• Hair care methods that require strong pulling of hair away from the scalp (e.g., braiding “tight” braids (braiding) or a “ponytail” hairstyle).

It is not necessary to wash your hair to apply the drug. If you wash your hair before using the drug, you must dry your hair and scalp.

When using hair styling products, first apply the foam and wait for it to dry, then use the hair styling products.

Washing your hair is allowed no less than 4 hours after applying the drug.

There is no data on the effect of dyeing, perming, hair straighteners on the effectiveness of the drug. Since perming and dyeing can cause scalp irritation, the following precautions are recommended

• Before dyeing and/or perming, make sure that the drug has been washed off the hair and scalp to avoid possible scalp irritation;
• For best results, do not apply the drug on the same day as chemical hair treatment;
• After using any chemicals, do not apply the drug for 24 hours to ensure that the scalp is not irritated after perming and/or dyeing.

Effect on ability to drive vehicles and operate machinery

Due to the possible development of headache, dizziness, hypotension, eye irritation, caution should be exercised when driving vehicles and engaging in certain activities requiring increased concentration and quick motor reactions. If the described adverse events occur, you should refrain from performing these activities.

Overdose

If doses exceeding the recommended ones are applied to large areas of the body or to other parts of the body besides the scalp, an increase in the systemic absorption of minoxidil is possible, which may lead to the development of adverse events.

Symptomsundesirable effects from the cardiovascular system associated with sodium and water retention, as well as tachycardia, decreased blood pressure, and dizziness.

Treatmentsymptomatic and supportive therapy should be administered. Beta-blockers may be prescribed to treat tachycardia, and diuretics may be used to eliminate edema. In case of decreased blood pressure, intravenous 0.9% sodium chloride solution should be administered. Sympathomimetic agents, such as epinephrine and norepinephrine, which have excessive cardiac stimulatory activity, should not be used. If the drug is swallowed, the patient should seek medical help immediately.

Drug Interactions

There is a theoretical possibility of enhanced orthostatic hypotension in patients receiving concomitant treatment with peripheral vasodilators, which, however, has not received clinical confirmation.

A very slight increase in minoxidil blood levels cannot be ruled out in patients with arterial hypertension taking Minoxidil orally in case of simultaneous use of the drug Regaine^®, although relevant clinical studies have not been conducted.

It has been established that topical Minoxidil may interact with some other topical medicines.

When using Minoxidil topically, it should not be used simultaneously with any other medicines ( corticosteroids, tretinoin, anthralin) applied to the skin of the scalp.

Concomitant use of minoxidil in the form of a topical foam and a cream containing betamethasone (0.05%) leads to a decrease in the systemic absorption of minoxidil.

Concomitant use of a cream containing tretinoin (0.05%) leads to an increase in the absorption of minoxidil.

Concomitant application of minoxidil and topical preparations, such as tretinoin and dithranol, which cause changes in the skin’s protective functions, may lead to increased absorption of minoxidil.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C (77°F).

Shelf Life

The shelf life is 3 years. Do not use the drug after the expiration date.

Dispensing Status

The drug is available without a prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.