Carexidil - Package Leaflet

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

Active ingredients: Minoxidil

CAREXIDIL 5% cutaneous spray, solution

Indications Why is Carexidil used? What is it for?

Carexidil is a solution for use on the scalp that contains a medicine called minoxidil.

Carexidil is indicated for the treatment of certain types of baldness (androgenic alopecia), a condition characterized by excessive hair loss, due to the action of certain hormones in the body (androgens).

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).

The onset and intensity of regrowth vary from patient to patient. As the hair grows slowly, it can 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 Carexidil should not be used

Do not use Carexidil:

  • if you are allergic to minoxidil or any of the other ingredients of this medicine (listed in section 6);
  • if you suffer from heart disease (coronary heart disease, arrhythmias, congestive heart failure or valvular heart disease);
  • if you are pregnant or breastfeeding.

Precautions for use What you need to know before taking Carexidil

Talk to your doctor or pharmacist before using Carexidil.

Before starting Carexidil treatment, your doctor will:

  • he will ask you about your medical history
  • will subject you to a complete physical exam.

Your doctor will take special care with you if:

  • have a family history of heart or circulation disorders,
  • have other heart and vascular disorders, even mild ones, including hypertension (high blood pressure), as these disorders can get worse;

Therefore, during treatment with Carexidil, your doctor may check your blood pressure, heart rate and swelling of the hands and feet (edema) periodically.

Carexidil 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.

During minoxidil therapy:

  • you may notice an increase in hair loss due to the action of minoxidil: old hair falls out when new hair grows in place. Generally this temporary increase in hair loss occurs between the 2nd and 6th week after starting treatment and tapers off within a couple of weeks. If the fall persists, stop using Carexidil 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 your 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.

Stop taking Carexidil 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 can also occur due to sensitization phenomena due to prolonged use of the medicine);
  • other unexpected new symptoms (See section 4. "Possible side effects").

Special populations

The use of Carexidil is not recommended in patients over the age of 55.

Children and adolescents

The use of Carexidil is not recommended in patients under the age of 18.

Interactions Which medications or foods can modify the effect of Carexidil

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 Carexidil 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 Carexidil if you want to become pregnant, pregnant or breastfeeding.

Driving and using machines

Based on the knowledge gained on this medicinal product, there are no known effects on the ability to drive and use machines.

However, during treatment with this medicine you may experience some side effects (including e.g. visual disturbances) which could affect your ability to drive or use machines. Take special care before driving a vehicle if you experience these symptoms while taking this medicine.

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.

Carexidil contains:

  • propylene glycol: can 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.

Dose, Method and Time of Administration How to use Carexidil: 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.

For external use only.

The recommended dose is 1 ml of cutaneous solution (corresponding to 10 sprays / sprays) to be applied twice a day on the scalp, preferably in the morning and in the evening.

The dose is independent of the size of the area to be treated.

The total daily dose should not exceed 2 ml. Using more or more often does not increase results.

How to apply Carexidil

Apply Carexidil only to completely dry hair and scalp. Start the application from the center of the area to be treated and distribute the dose over all affected areas.

Do not apply Carexidil to other areas of the body. Avoid contact with your eyes. If this happens, bathe the affected area with large amounts of fresh water.

After applying Carexidil, wash your hands thoroughly.

Instructions for Use

Unscrew the white polypropylene cap. Insert the spray applicator on the bottle and screw tightly. Apply the extender on the stem, press to fix it firmly. Orient the extender towards the area to be treated, spray once and distribute Carexidil with the fingertips on the area to be treated. Repeat the operation for a total of 10 times to reach the application of a dose of 1 ml of solution Avoid inhaling vapors.

Use in children and adolescents

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

If you forget to use Carexidil

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

If you stop using Carexidil, 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 Carexidil

In case of accidental ingestion / intake of an excessive dose of Carexidil, notify your doctor immediately or go to the nearest hospital.

Symptoms

The product, if accidentally ingested through the mouth or if applied in doses higher than those recommended on areas of the body other than the scalp, can cause:

  • low blood pressure (hypotension),
  • increased heart rate (tachycardia),
  • dizziness and weakness.

Treatment

The doctor will adopt appropriate supportive therapy.

Side Effects What are the side effects of Carexidil

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

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

  • severe allergic reactions which can occur with skin rashes, swelling of the hands, feet, face, 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 heart rate (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 http://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 carton after EXP.

The expiry date refers to the last day of that month.

This medicine does not require any special storage conditions.

The shelf life after first opening the container is 30 days under normal conditions of use.

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.

Deadline "> Other information

What Carexidil contains

  • The active ingredient is minoxidil (50 mg in 1 ml of cutaneous solution)
  • The other ingredients are 96% ethanol, propylene glycol, purified water.

Description of what Carexidil looks like and the contents of the pack

Carexidil is a clear cutaneous solution with an alcohol smell.

Carexidil is available in a pack containing 1 x 60ml high density polyethylene bottle with a polypropylene cap.

The bottle is equipped with a dosing pump.

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.

More information on Carexidil 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 interaction - 04.6 Pregnancy and lactation - 04.7 Effects on the ability to drive and use machines - 04.8 Undesirable effects - 04.9 Overdose - 05.0 PHARMACOLOGICAL PROPERTIES - 05.1 "Pharmacodynamic properties - 05.2 Pharmacokinetic properties" - 05.3 Preclinical safety data - 06.0 PHARMACEUTICAL PARTICULARS - 06.1 Excipients - 06.2 Incompatibility "- 06.3 Shelf life" - 06.4 Special precautions for storage - 06.5 Nature of the primary packaging and contents of the package - 06.6 Instructions for use and handling - 07.0 AUTHORIZATION HOLDER ALL "PLACING ON THE MARKET - 08.0 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 RADIO DRUGS, COMPLETE DATA ON INTERNAL RADIATION DOSIMETRY - 12.0 INSTRUCTIONS FOR RADIOPHONES ON EXTEMPORARY PREPARATION AND QUALITY CONTROL -

01.0 NAME OF THE MEDICINAL PRODUCT -

CAREXIDIL 5% SKIN SPRAY, SOLUTION

02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION -

100 ml of carexidil 5% cutaneous spray, solution contains 5 g of minoxidil.

Excipients with known effects: ethyl alcohol, propylene glycol

For the full list of excipients, see section 6.1.

03.0 PHARMACEUTICAL FORM -

Skin spray, solution.

04.0 CLINICAL INFORMATION -

04.1 Therapeutic indications -

Carexidil is indicated for the symptomatic treatment of androgenic alopecia in men and women.

The efficacy of Carexidil 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.

04.2 Posology and method of administration -

Dosage

Apply a dose of 1 ml of Carexidil twice a day, preferably in the morning and in the 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 ml.

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 with the application of Carexidil twice daily for hair growth to continue. Relapse to the pre-treatment state following discontinuation of therapy occurs within 3-4 months.

Special populations

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

Pediatric population

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

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

- use a mild shampoo.

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

• there is no information available on the possibility that treatments with hair dye or perm alter the effect of Carexidil. However, to avoid possible irritation of the scalp, the patient should ensure that Carexidil has been completely washed out of the hair and scalp before using these chemicals.

Instructions for Use

10 pulsations are equivalent to 1 ml of dispensed solution.

Unscrew the white polypropylene cap. Insert the spray applicator on the bottle and screw tightly. Apply the extender on the stem, press to fix it firmly. Orient the extender towards the area to be treated, spray once and distribute Carexidil with the fingertips on the area to be treated. Repeat the operation for a total of 10 times to reach the application of a dose of 1 ml of solution Avoid inhaling vapors.

04.3 Contraindications -

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

Carexidil 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 expected to undergo Carexidil therapy should have a medical history and undergo physical examinations. The physician should ascertain that the patient has a normal, 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.

Some patients have experienced changes in hair color and / or texture with the use of minoxidil.

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 efficacy). If the fall persists, users should stop using Carexidil and consult their physician.

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 minoxidil have not shown that there is sufficient absorption of this active ingredient 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. , generalized and local edema, 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 discontinue use of Carexidil 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 Carexidil 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.

Important information about some of the excipients

Carexidil 5% cutaneous spray, solution contains:

§ 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.

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

04.5 Interactions with other medicinal products and other forms of interaction -

Carexidil 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 minoxidil 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 -

Carexidil should not be used during pregnancy and breastfeeding and in women of childbearing potential 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, Carexidil 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" http://www.aifa.gov.it/responsabili ".

04.9 Overdose -

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

Accidental ingestion of minoxidil 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 vasodilatory 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.

The stimulation of hair growth generally begins after about 3-4 months of application of the product and varies from patient to patient.

When treatment is stopped, 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 minoxidil AUC curve for the 2% solution averaged 7.54 ng h / mL compared to that of a 2.5 mg oral formulation 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.

Distribution

Minoxidil does not cross the blood brain barrier.

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

Biotransformation

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 -

Ethyl alcohol, propylene glycol and purified water.

06.2 Incompatibility "-

Not relevant.

06.3 Period of validity "-

3 years.

The validity after first opening the container is 30 days under normal conditions of use.

06.4 Special precautions for storage -

No special storage precautions.

06.5 Nature of the immediate packaging and contents of the package -

60ml HDPE bottle with PP cap. The package contains a dosing pump for skin application.

10 pulsations are equivalent to 1 ml of dispensed solution.

Available in packs containing: 1, 2, 3 or 4 bottles of 60 ml. Not all pack sizes may be marketed.

06.6 Instructions for use and handling -

No special instructions.

Unused medicine and wastes derived from this medicine must be disposed of in accordance with local regulations.

07.0 HOLDER OF THE "MARKETING AUTHORIZATION" -

Difa Cooper S.p.A.

Via Milano, 160

21042 Caronno Pertusella (VA)

08.0 MARKETING AUTHORIZATION NUMBER -

"Carexidil 5% cutaneous spray, solution" 1 HDPE bottle of 60 ml equipped with dosing pump.

AIC n. 037291010

"Carexidil 5% cutaneous spray, solution" 2 HDPE bottles of 60 ml equipped with dosing pump.

AIC n. 037291059

"Carexidil 5% cutaneous spray, solution" 3 HDPE bottles of 60 ml equipped with dosing pump.

AIC n. 037291061

"Carexidil 5% cutaneous spray, solution" 4 HDPE bottles of 60 ml equipped with dosing pump.

AIC n. 037291073

09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION -

Determination no. 2058 of 10/10/2008 - GU n. 262 of 8/11/2008 - S.O. n. 247

10.0 DATE OF REVISION OF THE TEXT -

August 2016

11.0 FOR RADIO DRUGS, COMPLETE DATA ON THE INTERNAL RADIATION DOSIMETRY -

12.0 FOR RADIO DRUGS, FURTHER DETAILED INSTRUCTIONS ON EXEMPORARY PREPARATION AND QUALITY CONTROL -

none:  sexually transmitted diseases offal pregnancy