REGAINE - PACKAGE LEAFLET - LEAFLETS

Home / leaflets / 2021

Regaine - Package Leaflet

Indications Contraindications Precautions for use Interactions Warnings Dosage and method of use Overdose Undesirable Effects Shelf Life and Storage

Active ingredients: Minoxidil

REGAINE 2% cutaneous solution
REGAINE 5% cutaneous solution
REGAINE 5% skin foam

Why is Regaine used? What is it for?

REGAINE is a medicine containing minoxidil, an active ingredient which, when used on the scalp, is able to stop hair loss and stimulate hair growth in patients who have hereditary hair loss (androgenic alopecia).

This condition manifests itself:

in women with widespread hair thinning affecting the top of the head, starting from the center;
in men with progressive hair loss in the frontal (receding hairline) and upper areas of the head (cleric).

REGAINE is available in two different concentrations: REGAINE 2% and REGAINE 5%.

If you are a woman you must use REGAINE 2% (See "What you need to know before you take REGAINE").

The onset and intensity of regrowth vary from patient to patient. As hair grows slowly, it may take up to 4 months to see the first results of the treatment. If you do not notice any improvement after this time, please contact your doctor.

Contraindications When Regaine should not be used

Do not use REGAINE if:

you are allergic to the active substance or to any of the other ingredients of this medicine (listed in section 6);
have heart disease such as coronary heart disease (coronary heart disease) or heart valve disease (valvulopathy), altered heart beat (arrhythmias), congestive heart failure;
are pregnant or breastfeeding.

Precautions for use What you need to know before taking Regaine

Talk to your doctor or pharmacist before using REGAINE:

if you have other heart and vascular problems, even mild ones, including hypertension (high blood pressure), as these problems can get worse.

REGAINE is not indicated in the following conditions:

there is no history of hair loss in his family;
your hair loss is sudden and / or patchy;
hair loss is present from birth (congenital alopecia);
your hair loss is due to childbirth, to toxic substances or drugs, to scars (for example after trauma, for infectious or psychic causes), or if you do not know the cause;
have a red, inflamed, infected or painful scalp;

ATTENTION, if you are a woman you must use REGAINE 2%, since the use of REGAINE 5% does not improve treatment results in the face of a higher incidence of side effects on the skin, such as irritation at the application site and abnormal growth of hair in other areas of the body (hypertrichosis).

During REGAINE therapy:

You may notice an increase in hair loss due to the action of minoxidil: old hair falls out when new hair grows in its place. Generally this temporary increase in hair loss occurs between the 2nd and 6th week after starting of treatment and tapers off within a couple of weeks. If the fall persists, stop using REGAINE and consult your doctor.
initially the regrowth consists of soft, weak hair with a different color than your normal hair. After further treatments, the "new hair" will have the same thickness and color as her hair. Results can be seen in less than 3-4 months. The effectiveness of the treatment varies from patient to patient.
some patients have experienced changes in hair color or hair texture.

Transferring the product to areas other than the scalp can cause unwanted hair to grow.

If you do not notice any improvement after 4 months of treatment, contact your doctor.

REGAINE 5% skin foam is extremely flammable: stay away from fire, flames or smoke during and immediately after application.

Stop taking REGAINE and see your doctor immediately if you notice:

severe allergic reactions which can occur with skin rashes, swelling of the hands, feet, face, eyes, lips, throat with difficulty in breathing (angioedema);
low or high blood pressure (hypotension or hypertension), rapid heartbeat (tachycardia), feeling of heart in the throat (palpitations), chest pain (possible angina), weakness, dizziness;
sudden and unexplained weight gain;
persistent redness or irritation of the scalp (which may also occur due to sensitization phenomena due to "prolonged use of the medicine), or if other new unexpected symptoms occur (See section 4." Possible side effects ").

Special populations

The use of REGAINE is not recommended in patients over 55 years of age.

Children and adolescents

The use of REGAINE is not recommended in patients under 18 years of age.

Interactions Which medications or foods can modify the effect of Regaine

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. This is especially important if you are using drugs that dilate blood vessels (peripheral vasodilators).

Do not use REGAINE together with other medicines applied directly to the scalp (corticosteroids, tretinoin, antralin).

Warnings It is important to know that:

Pregnancy, breastfeeding and fertility

Do not use REGAINE if you want to become pregnant, pregnant or breastfeeding.

Driving and using machines

REGAINE does not affect the ability to drive or use machines.

For those who carry out sporting activities: the use of medicines containing ethyl alcohol can determine positivity to doping tests in relation to the alcohol concentration limits indicated by some sports federations.

REGAINE 2% and 5% cutaneous solution contains:

propylene glycol: can it? cause skin irritation;
ethyl alcohol: it can cause burning and irritation to the eyes. In case of accidental contact with sensitive surfaces (eyes, bruised skin and mucous membranes), wet the area with large quantities of fresh water.

REGAINE 5% skin foam contains:

butylhydroxytoluene: can cause local skin reactions (eg contact dermatitis) or irritation of the eyes or mucous membranes;
cetyl alcohol and stearyl alcohol: they can cause local skin reactions (eg contact dermatitis);
anhydrous ethanol: can cause burning and irritation of the eyes. In case of accidental contact with sensitive surfaces (eyes, bruised skin and mucous membranes), wet the area with large quantities of fresh water.

Dose, Method and Time of Administration How to use Regaine: Posology

Always use this medicine exactly as described in this leaflet or as directed by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist.

The recommended dose is 1 ml of solution or 1 g of foam, twice a day, preferably in the morning and in the evening. Distribute this dose over all affected areas.

Do not exceed 2 ml or 2 g per day, whatever the extent of the area to be treated. Using more product or more often does not increase results.

Use in children and adolescents

The use of REGAINE is not recommended under the age of 18.

Method of administration

This medicine is for external (topical) use and should be applied to perfectly dry scalp. Do not use it in other areas of the body.

Avoid contact with eyes. If this happens, bathe the affected area with large amounts of fresh water.

Wash your hands thoroughly after using the medicine.

To use REGAINE, please read carefully and follow the instructions at the end of this leaflet "Instructions for using REGAINE".

If you forget to use REGAINE

Do not use a double dose to make up for a forgotten dose. Resume treatment as described in this leaflet.

If you stop using REGAINE, new hair growth stops and pre-treatment symptoms return within 3-4 months.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

Overdose What to do if you have taken too much Regaine

With doses of REGAINE higher than those recommended, or applied to areas of the body other than the scalp, or in case of accidental ingestion, you may notice: increased heart rate (tachycardia), lowering of blood pressure (hypotension), dizziness and weakness. Contact your doctor immediately or go to the nearest hospital.

Side Effects What are the side effects of Regaine

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Stop taking REGAINE and see your doctor immediately if you notice:

severe allergic reactions which can occur with skin rashes, swelling of the hands, feet, face, eyes, lips, throat with difficulty in breathing (angioedema);
low blood pressure (hypotension), fast heart rate (tachycardia), feeling of heart in the throat (palpitations), chest pain (possible angina), weakness, dizziness;
sudden and unexplained weight gain;
persistent redness or irritation of the scalp.

The side effects that can occur are the following:

Very common side effects (may affect more than 1 in 10 people)

Headache.

Common side effects (may affect up to 1 in 10 people)

Itching at the application site or throughout the body and eye, skin rashes at the application site or throughout the body, increased hair (hypertrichosis), increased blood pressure (hypertension), peripheral edema, dyspnoea (difficulty respiratory tract), dermatitis, acneiform dermatitis, weight gain.

Uncommon side effects (may affect up to 1 in 100 people)

Drop in blood pressure, irritation, redness (erythema, generalized erythema), swelling (edema), skin peeling, eczema, allergic reaction, sensitization, urticaria, swelling of the face, pain, dermatitis (including contact, application, allergic, atopic and seborrheic), dry skin (including dryness of the application site), blistering, acne, weakness, dizziness, dizziness, tingling, inflammation of a nerve (neuritis), taste changes, burning sensation , ear infection, otitis externa, visual disturbances.

Rare side effects (may affect up to 1 in 1,000 people)

Sensation of heart in the throat (palpitations), rapid heartbeat (tachycardia), bleeding and ulceration, blistering, hair loss (alopecia) or worsening of hair loss, eye irritation, kidney stones, liver inflammation (hepatitis ), sexual dysfunction.

Very rare side effects (may affect up to 1 in 10,000 people)

Chest pain, temporary hair loss, changes in hair color, abnormal hair structure, nausea, vomiting, angioedema, hypersensitivity, contact dermatitis.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at “www.agenziafarmaco.gov.it/it/responsabili.” By reporting side effects you can help provide more information on the safety of this medicine.

Expiry and Retention

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the package. The expiry date refers to the last day of that month.

Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.

REGAINE 2% and 5% cutaneous solution

This medicinal product does not require any special storage temperatures.

REGAINE 5% skin foam

Store below 25 ° C.
Pressurized container, extremely flammable. Do not spray on open flames or incandescent materials.
Protect from sunlight and do not expose to temperatures above 50 ° C.
Do not pierce or burn, even after use. Keep away from sources of ignition and do not smoke near the container.
Do not use near or place the container on polished or painted surfaces.

Other information

What REGAINE contains

The active ingredient is: minoxidil.

1 ml of REGAINE 2% cutaneous solution contains: 20 mg of minoxidil.
1 ml of REGAINE 5% cutaneous solution contains: 50 mg of minoxidil.
1 g of REGAINE 5% cutaneous foam contains: 50 mg of minoxidil.

The other ingredients are:

REGAINE 2% and 5% cutaneous solution: propylene glycol, ethyl alcohol, purified water.
REGAINE 5% skin foam: anhydrous ethanol, purified water, butylhydroxytoluene (E321), lactic acid, anhydrous citric acid, glycerol, cetyl alcohol, stearyl alcohol, polysorbate 60, propellant: propane / butane / isobutane.

Description of REGAINE's appearance and contents of the pack

REGAINE 2% and 5% cutaneous solution is available in a 60 ml bottle, equipped with a graduated dropper, spray applicator and relative extender. Each bottle contains the amount of treatment for 1 month.

REGAINE 5% skin foam is available in packs containing 1 or 3 pressurized containers, each of 60 grams, with child resistant cap. Each pressurized container holds the amount of treatment for 1 month.

Not all pack sizes may be marketed.

Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.

Further information on Regaine can be found in the "Summary of Characteristics" tab. 01.0 NAME OF THE MEDICINAL PRODUCT 02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION 03.0 PHARMACEUTICAL FORM 04.0 CLINICAL PARTICULARS 04.1 Therapeutic indications 04.2 Posology and method of administration 04.3 Contraindications 04.4 Special warnings and appropriate precautions for use 04.5 Interactions with other medicinal products and other forms of interaction04.6 Pregnancy and lactation04.7 Effects on ability to drive and use machines04.8 Undesirable effects04.9 Overdose05.0 PHARMACOLOGICAL PROPERTIES05.1 Pharmacodynamic properties05.2 Pharmacokinetic properties05.3 Preclinical safety data06.0 INFORMATION PHARMACEUTICALS 06.1 Excipients 06.2 Incompatibilities 06.3 Shelf life 06.4 Special precautions for storage 06.5 Nature of the immediate packaging and contents of the package 06.6 Instructions for use and handling 07.0 MARKETING AUTHORIZATION HOLDER08 .0 MARKETING AUTHORIZATION NUMBER 09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION 10.0 DATE OF REVISION OF THE TEXT 11.0 FOR RADIOPharmaceuticals, FULL DATA ON INTERNAL RADIATION DOSIMETRY 12.0 FOR RADIO DRUGS, ADDITIONAL DETAILED INSTRUCTIONS ON ESTEMPORANEA PREPARATION AND CONTROL

01.0 NAME OF THE MEDICINAL PRODUCT

REGAINE SKIN SOLUTION

02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION

REGAINE 2% cutaneous solution:

100 ml contain 2 g of minoxidil.

Excipients with known effects: ethyl alcohol, propylene glycol

REGAINE 5% cutaneous solution

100 ml contain 5 g of minoxidil.

Excipients with known effects: ethyl alcohol, propylene glycol

REGAINE 5% skin foam

1 g contains 50 mg of minoxidil.

Excipients with known effects: anhydrous ethanol, butylhydroxytoluene, cetyl alcohol, stearyl alcohol.

For the full list of excipients, see section 6.1.

03.0 PHARMACEUTICAL FORM

Skin solution

Skin foam

04.0 CLINICAL INFORMATION

04.1 Therapeutic indications

REGAINE is indicated for the symptomatic treatment of androgenetic alopecia in men and women.

The efficacy of REGAINE in the following forms has not been determined: localized or generalized congenital alopecia; cicatricial alopecia of various kinds (post-traumatic, psychic or infectious origin); acute alopecia diffused by toxic substances, medicaments in which the regrowth of hair is conditioned by the suppression of the specific cause; celsi area.

REGAINE 5% cutaneous solution and REGAINE 5% cutaneous foam are not recommended in women (see section 4.4).

04.2 Posology and method of administration

Dosage

REGAINE cutaneous solution

Apply a dose of 1 ml of REGAINE twice a day, preferably in the morning and in the evening, on the affected areas of the scalp. The dose is independent of the size of the area to be treated. The total daily dose should not exceed 2 ml.

REGAINE skin foam

Apply a 1 g dose (equivalent to the volume of half a cap) of REGAINE twice a day, preferably in the morning and evening, to the affected areas of the scalp. The dose is independent of the size of the area to be treated. The total daily dose should not exceed 2 g.

Using more or more often does not increase results.

Before evidence of hair growth can be expected, it may be necessary to wait 3-4 months of twice-daily applications. The onset of these signs and their intensity vary from patient to patient. In all cases, the doctor will have to evaluate the advisability of discontinuing treatment if no therapeutic result is observed within 4 months.

If regrowth occurs, it is necessary to continue applying REGAINE twice a day for hair growth to continue. Relapse to the pre-treatment state following discontinuation of therapy occurs within 3-4 months.

Special populations

REGAINE is not recommended for use in patients over 55 years of age due to a lack of data on safety and efficacy.

Pediatric population

REGAINE is not recommended for use in children below 18 years of age due to a lack of data on safety and efficacy.

Method of administration

Use REGAINE only following the instructions. Apply REGAINE only on completely dry hair and scalp. Hair should not be washed after applying REGAINE. Do not apply REGAINE to other areas of the body. After applying REGAINE, wash your hands carefully.

During the treatment with REGAINE, other cosmetic hair products can be used, following the instructions below:

- use a mild shampoo.

- REGAINE must be allowed to penetrate into the scalp before using hair styling products. Do not mix with other preparations to be applied to the scalp.

-There is no information available on whether hair dye or permanent treatments alter the effect of REGAINE. However, to avoid possible scalp irritation, the patient should make sure that REGAINE has been completely washed out of the hair and scalp before using these chemicals.

REGAINE cutaneous solution

Remove the external protection cap and the internal screw cap and insert the chosen applicator on the bottle.

A) Graduated dropper

This type of applicator is suitable for distributing REGAINE on small bald areas of the scalp.

§ Insert the graduated dropper on the bottle and after filling it up to the 1 ml mark, apply a few drops of REGAINE on the scalp and distribute the liquid with the fingertips on the entire bald area;

§ repeat until the full dose of 1 ml has been applied;

§ at the end of use, screw the dropper firmly onto the bottle and put the protective cap on.

B) Spray applicator

This type of applicator is suitable for distributing REGAINE on large bald areas of the scalp.

§ Insert the spray applicator on the bottle and screw tightly;

§ remove the transparent cap, direct the spray towards the center of the bald area, spray once and distribute REGAINE with the fingertips on the entire bald area;

§ repeat the operation for a total of 6 times to reach the application of the dose of 1 ml of solution;

§ avoid inhaling the vapors;

§ at the end of use, replace the protective cap.

C) Extender for the spray applicator

§ The extender, which must be inserted on the spray applicator, is suitable for distributing REGAINE under the hair;

§ Insert the spray applicator on the bottle and screw tightly. Remove the transparent cap and the dispenser head. Apply the extender on the stem, press to fix it firmly and remove the capsule from the nozzle;

§ orient the extender towards the area to be treated, spray once and distribute REGAINE with the fingertips on the area to be treated;

§ repeat the operation for a total of 6 times to reach the application of the dose of 1 ml of solution;

§ avoid inhaling the vapors;

§ at the end of use, put the capsule back on the nozzle.

REGAINE skin foam

Hold the can upside down and press the nozzle to release the foam. Use the cap as a dispenser (half cap is equivalent to a 1 g dose). Spread the product with your fingers over the entire bald area. After application, wash your hands thoroughly.

04.3 Contraindications

Hypersensitivity to minoxidil or to any of the excipients, listed in section 6.1.

REGAINE should not be used in the presence of coronary artery disease, arrhythmias, congestive heart failure or valvular heart disease.

Do not use during pregnancy and lactation.

04.4 Special warnings and appropriate precautions for use

Patients who are planned to undergo REGAINE therapy should have a medical history and undergo physical examinations. The physician should ascertain that the patient has a normal and healthy scalp, for example, not red, inflamed, infected, irritated or painful .

Minoxidil is not indicated when there is no family history of hair loss, hair loss is sudden and / or patchy, caused by childbirth or when its cause is unknown.

With the use of REGAINE, some patients have experienced changes in the color and / or texture of their hair.

Increased hair loss may occur due to the action of minoxidil in mutating hair from the resting telogen phase to the anagen growth phase (old hair falls out when new hair grows in its place). Generally this temporary increase in hair loss it occurs between two and six weeks after starting treatment and subsides within a couple of weeks (the first sign of minoxidil effectiveness). If the fall persists, users should stop using REGAINE and consult their doctor.

The use, especially if prolonged, of the products for topical use can give rise to sensitization phenomena. In this case, stop the treatment and consult the doctor to institute suitable therapy.

Although extensive clinical studies performed with REGAINE have not shown that there is sufficient absorption of minoxidil to cause systemic effects, some absorption of minoxidil occurs through the scalp and there is a potential risk of systemic effects such as salt and fluid retention, edema. generalized and local, pericardial effusion, pericarditis, cardiac tamponade, tachycardia, angina or increased orthostatic hypotension induced by antihypertensive drugs such as guanethidine and derivatives.

In the presence of cardiovascular disorders, including hypertension, careful medical evaluation is required.

The patient should stop using REGAINE and consult a physician if hypotension is detected or if the patient experiences chest pain, rapid heart rate, weakness, dizziness, sudden and unexplained weight gain, swollen hands or feet, persistent redness, reactions dermatological or scalp irritation, or if other unexpected new symptoms occur (see section 4.8).

Patients with a history of underlying heart disease should be advised that REGAINE may worsen these disorders. Patients should be monitored periodically for any suspicion of systemic effects caused by minoxidil.

Accidental ingestion can cause serious cardiac adverse events. Patients should avoid inhaling the product when using the spray applicator.

In the event of systemic side effects or dermatological reactions, discontinue administration of the drug.

The growth of unwanted hair can be caused by transferring the product to areas other than the scalp.

Studies carried out in women with REGAINE 5% solution applied twice a day have not shown a significant increase in efficacy compared to the 2% solution applied twice a day; on the other hand, a higher incidence of dermatological side effects, such as hypertrichosis and local irritation, was found.

Therefore REGAINE 5% solution is not recommended in women (see section 4.2).

Important information about some of the excipients

REGAINE 2% and 5% cutaneous solution contain:

§ ethyl alcohol: it can cause burning and irritation to the eyes. In case of accidental contact with sensitive surfaces (eyes, excoriated skin and mucous membranes), the area must be wet with large quantities of fresh tap water;

§ propylene glycol: can cause skin irritation.

REGAINE 5% skin foam contains:

§ butylhydroxytoluene: can cause local skin reactions (eg contact dermatitis) or irritation of the eyes or mucous membranes;

§ cetyl alcohol and stearyl alcohol: they can cause local skin reactions (eg contact dermatitis);

§ anhydrous ethanol: can cause burning and irritation of the eyes. In case of accidental contact with sensitive surfaces (eyes, excoriated skin and mucous membranes), the area should be wet with large quantities of fresh tap water.

For those who carry out sporting activities, the use of medicines containing ethyl alcohol can determine positive doping tests in relation to the alcohol concentration limits indicated by some sports federations.

04.5 Interactions with other medicinal products and other forms of interaction

REGAINE should not be used concomitantly with other medications applied topically to the scalp (corticosteroids, tretinoin and antralin).

No other interactions associated with the use of REGAINE are currently known. Although it has not been clinically demonstrated, there is a potential for increased orthostatic hypotension in patients receiving concomitant therapy with peripheral vasodilators.

04.6 Pregnancy and breastfeeding

REGAINE should not be used during pregnancy and breastfeeding and in women of childbearing age who do not use contraceptives.

Pregnancy

There are no adequate and well-controlled studies in pregnant women.

Animal studies have shown a risk to the fetus at exposure levels much higher than those intended for human exposure (see section 5.3). The potential risk in humans is unknown.

Feeding time

Systemically absorbed minoxidil is excreted in breast milk. The effect of minoxidil on infants / children is unknown.

Fertility

There are no adequate and well-controlled studies on female fertility.

Animal studies have shown fertility toxicity, a reduction in conception and implantation rates, as well as a reduction in the number of live offspring at exposure levels much higher than those intended for human exposure (see section 5.3). The potential risk in humans is unknown.

04.7 Effects on ability to drive and use machines

Based on the pharmacodynamics and overall safety profile of minoxidil, REGAINE is not expected to interfere with the ability to drive or use machines.

04.8 Undesirable effects

The frequency of adverse reactions to topical minoxidil is defined using the following convention:

very common (≥ 1/10); common (≥ 1/100,

Adverse reactions reported during clinical trials

The safety of minoxidil for cutaneous use is based on data from 7 randomized placebo-controlled clinical trials in adults evaluating minoxidil solution 2% and 5% (Table 1), and two randomized placebo-controlled clinical trials in adults evaluating a minoxidil foam. cutaneous 5% (Table 2).

Table 1: Adverse reactions reported with a frequency ≥1% in adult subjects receiving topical minoxidil 2% or 5% solution in randomized placebo-controlled clinical trials are reported.

System Organ Classification Adverse reactions Frequency General disorders and administration site conditions Peripheral edema Common Nervous system disorders Headache Very common Respiratory, thoracic and mediastinal disorders Dyspnea Common Skin and subcutaneous tissue disorders Dermatitis, Acneiform dermatitis, Hypertrichosis, Pruritus, Skin rash Common

Table 2: Adverse reactions reported with a frequency ≥1% in adult subjects receiving topical minoxidil 5% foam in randomized placebo-controlled clinical trials are reported.

System Organ Classification Adverse reactions Frequency Diagnostic tests Weight gain Common Nervous system disorders Headache Common Skin and subcutaneous tissue disorders Itching, Rash Common

Adverse reactions reported during post-marketing experience

In Table 3, the adverse reactions collected in post-marketing experience are reported, frequency based on the incidence of spontaneous reports.

Systemic organ classification Frequency Adverse reactions Nervous system disorders Uncommon Dizziness, Vertigo, Tingling, Neuritis, Changes in taste, Burning sensation. Eye disorders Uncommon Visual disturbances Rare Eye irritation Ear and labyrinth disorders Uncommon Ear infection, Otitis externa. Vascular pathologies Common Hypertension Uncommon Hypotension Cardiac pathologies Rare Palpitations, Tachycardia. Gastrointestinal disorders Very rare Nausea, Vomiting. Hepato-biliary disorders Rare Hepatitis Renal and urinary disorders Rare Kidney stones Diseases of the reproductive system and breast Rare Sexual dysfunction Skin and subcutaneous tissue disorders Uncommon Irritation, Pain, Erythema, Edema Peeling of the skin, Eczema, Allergic reaction, Sensitization, Urticaria, Generalized erythema and Edema of the face.Dermatitis (including contact, application site, allergic, atopic and seborrheic dermatitis). Dry skin (including dryness of the application site), Blisters, Acne. Rare Bleeding and ulceration, Vesiculation, Exacerbation of hair loss, Alopecia. Very rare Temporary hair loss, Changes in hair color, Abnormal hair structure. Disorders of the immune system Very rare Angioedema, Hypersensitivity, Contact dermatitis. General disorders and administration site conditions Uncommon Weakness Very rare Chest pain

The nature and severity of the reactions detected are similar in treatment with 2% and 5% minoxidil, but their incidence is higher in the latter.

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address" www.agenziafarmaco.gov.it/it/responsabili ".

04.9 Overdose

If higher than recommended doses of REGAINE are applied or to areas of the body other than the scalp, increased systemic absorption of minoxidil can potentially occur.

The accidental ingestion of REGAINE can lead to serious undesirable effects. Following accidental ingestion, minoxidil is totally absorbed through the gastrointestinal tract and can cause systemic effects related to its vasodilating action.

The signs and symptoms of minoxidil overdose are primarily cardiovascular associated with sodium hydroxide retention, and tachycardia, hypotension, weakness and dizziness may also occur.

Treatment

Treatment of minoxidil overdose should be symptomatic and supportive.

Fluid retention can be treated with appropriate diuretic therapy. Tachycardia can be controlled by administering a beta-blocking agent. Hypotension can be treated with intravenous administration of normal saline. Sympathomimetic drugs such as norepinephrine and adrenaline should be avoided due to their excessive cardiac stimulating activity.

05.0 PHARMACOLOGICAL PROPERTIES

05.1 Pharmacodynamic properties

Pharmacotherapeutic group: other dermatologicals, ATC code: D11AX01

Minoxidil stimulates growth and stabilizes hair loss in individuals with androgenic alopecia. The precise mechanism of action of minoxidil for the topical treatment of alopecia is not fully understood, but minoxidil can block the hair loss process and stimulate regrowth in androgenetic alopecia in the following ways:

• increase in the diameter of the hair shaft;

• stimulation of anagen growth;

• prolongation of the anagen phase;

• stimulation of anagen recovery from the telogen phase.

As a peripheral vasodilator, topical minoxidil improves microcirculation to the hair follicles. The Vascular Endothelial Growth Factor (VEGF) is stimulated by minoxidil and VEGF is probably responsible for the greater capillary fenestration, indicative of the high metabolic activity observed during the anagen phase.

Regarding REGAINE cutaneous solution, the stimulation of hair growth generally begins after about 3-4 months of application of the product and varies from patient to patient. On the basis of the non-fleece hair count, the stimulus to regrowth was found to be higher following the use of REGAINE 5% cutaneous solution instead of the 2% solution.

As for REGAINE 5% cutaneous foam the efficacy was evaluated in a clinical study in phase 3, conducted on men for a treatment period of 4 months. In this study, minoxidil in foam 5% was compared to the product without vehicle. of the active ingredient minoxidil.

Active treatment demonstrated a statistically significant greater increase in hair count compared to the vehicle foam group (21.0 versus 4.3 hair per cm2) at month 4. A clear difference between the treatment groups was already evident at the 2nd month, increasing to the 3rd month and again at the 4th month. The subject's assessment of treatment benefits was statistically significantly better for the 5% minoxidil foam group than placebo (1.4 versus 0.5) at month 4. use of REGAINE, new hair growth stops and pre-treatment symptoms return within 3-4 months.

05.2 Pharmacokinetic properties

Absorption

The systemic absorption of minoxidil applied topically by intact normal skin is reduced. The systemic absorption of minoxidil from topically applied solutions ranges from 1% to 2% of the total applied dose. The effect of dermatological diseases concomitants on absorption, is unknown.

In a study conducted in men only, the AUC curve of minoxidil for the 2% solution averaged 7.54 ng • h / ml compared to that for the oral formulation at 2.5mg which averaged 35.1 ng • h / ml. The mean peak plasma concentration (Cmax) for the topical solution was 1.25 ng / mL compared to that for the oral formulation at 2.5 mg which was 18.5 ng / mL.

The systemic absorption of minoxidil from a 5% foam formulation was estimated in a pharmacokinetic study in subjects with androgenetic alopecia, which included a topical 5% solution as a comparator. This study demonstrated that in men the systemic absorption of the minoxidil with two applications per day of 5% minoxidil foam was approximately half that observed with 5% minoxidil solution. The mean stationary AUC (0-12 h) and Cmax for 5% minoxidil foam, of 8.81 ng • h / ml and 1.11 ng / ml, respectively, were approximately 50% relative to the 5% solution. The mean (range) time to maximum minoxidil concentration (Tmax) was 6.0 (0-12) hours for both 5% foam and 5% solution.

Distribution

Minoxidil does not cross the blood brain barrier.

An in vitro ultrafiltration method demonstrated reversible binding to human plasma proteins between 37 - 39%.

Metabolism

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

Elimination

The half-life of topically administered minoxidil averages 22 hours, compared with 1.49 hours for the oral formulation.

Minoxidil and its metabolites are almost completely excreted in the urine, with a very small degree of elimination in the faeces.

Renal clearances of minoxidil and minoxidil glucuronide calculated from data from the oral formulation averaged 261 mL / min and 290 mL / min, respectively.

After discontinuation of treatment, approximately 95% of topically applied minoxidil is eliminated within four days.

05.3 Preclinical safety data

Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity or carcinogenic potential.

The data relating to the experimental animal are as follows:

LD50, oral administration:

• rat: between 1321 and 3492 mg / kg;

• mouse: between 2456 and 2648 mg / kg.

LD50, cutaneous administration:

• rat:> 2007 mg / kg.

Cases of mammary tumors in female mice and tumors of the adrenal glands and foreskin in male rats have been reported in carcinogenicity experiments performed on rats and mice. However, there is no evidence that these results are predictive of a similar risk for humans.

Teratogenicity

Animal reproductive toxicity studies in rats and rabbits showed signs of maternal toxicity and a risk to the fetus at exposure levels much higher than those intended for human exposure (19 to 570 times the human exposure). A small and remote risk of fetal harm is possible in humans.

Fertility

In rats, subcutaneous doses of minoxidil equal to or greater than 9 mg / kg (at least 25 times human exposure) were associated with reductions in conception and implantation rates and reductions in the number of live offspring.

06.0 PHARMACEUTICAL INFORMATION

06.1 Excipients

REGAINE 2% and 5% cutaneous solution: propylene glycol, ethyl alcohol, purified water.

REGAINE 5% skin foam: anhydrous ethanol, purified water, butylhydroxytoluene (E321), lactic acid, anhydrous citric acid, glycerol, cetyl alcohol, stearyl alcohol, polysorbate 60, propellant: propane / butane / isobutane.