Normopil 20Mg/Ml Cutaneous solution 90Ml 1 Bottle

Normopil (20 Mg/Ml 1 Bottle Cutaneous Solution 90 Ml)

ACTION AND MECHANISM

- [ANTALIOPECICO] with vasodilator action.

- The mechanism of action by which minoxidil stimulates hair growth is not exactly known; A possible alteration of androgen metabolism in the scalp has been suggested, as well as a vasodilator effect that can increase the microcirculation around the hair follicle.

Applied locally, minoxidil stimulates the growth of keratocytes in vitro and in vivo , it does not increase the number of hair follicles but rather partially converts miniaturized and intermediate hairs into terminal hairs, delaying the progression of androgenetic alopecia in certain patients.

This stimulation occurs after 4 or more months of treatment, and is of variable intensity between patients. After 6-12 months of uninterrupted treatment, 1/3 of patients have shown positive responses. However, discontinuation of treatment stops hair growth, and in 3-4 months it can return to pre-treatment alopecia.

PHARMACOKINETICS

- Absorption: slight absorption (bioavailability 1.4-1.7%). After the application of 1 ml, the amount of minoxidil absorbed is approximately 0.28 mg (20 mg/ml) and 0.85 mg (50 mg/ml).

Above doses between 2.4-5.4 mg/day, some systemic effect could be expected. This dose could be achieved if 5% minoxidil was applied to the entire surface of the scalp without being limited to the alopecic plaque. The smallest dose of IV minoxidil that produces clinically significant hemodynamic effects in patients with mild to moderate hypertension has been found to be 6.86 mg.

Results from pharmacokinetic studies indicate that the three most important factors in relation to increased absorption of minoxidil from the skin are as follows:

- quantitative increase of the applied dose.

- Increased application frequency.

- reduction of the barrier function of the stratum corneum of the epidermis.

Serum concentrations of minoxidil after topical application depend on the rate of percutaneous absorption. The influence of concomitant dermatological disorders on the absorption of minoxidil has not been determined.

After a cutaneous application of minoxidil, its absorption is not influenced by factors such as: sex, exposure to ultraviolet rays, the simultaneous application of a moisturizing product, occlusion (use of false hair), evaporation of the solvent (use of a dryer) or the surface of the application area.

- Metabolism: The biotransformation of minoxidil absorbed after topical application is not well known. Approximately 60% of absorbed minoxidil is believed to be metabolized to minoxidil glucuronide, primarily in the liver.

- Elimination: Minoxidil and its metabolites are dialyzable; its elimination is basically urinary. When topical application is discontinued, approximately 95% of absorbed minoxidil is eliminated within 4 days.

INDICATIONS

- Treatment of [ANDROGENIC ALOPECIA] (hair loss) of moderate intensity in men.

- Treatment of androgenetic alopecia in women.

RULES FOR CORRECT ADMINISTRATION

- Use of the dispensing syringe or pipette: Before applying the product, make sure that the hair and scalp are completely dry. Wash your hands well before and after applying the solution.

a) Measure an exact dose of 1 ml of solution with the dispensing syringe or pipette that is next to the bottle.

b) Apply to the scalp, spreading the product with the fingertips over the area to be treated, starting from the center of it.

c) Spread the product with the fingertips on the area to be treated, starting from the center of it

d) Do not apply the product to other parts of the body.

- Using the dosing pump: Before applying the product, make sure that the hair and scalp are completely dry. Wash your hands well before and after applying the solution.

a) Remove the bottle cap and unscrew the cap that closes.

b) Adapt by screwing the dosing pump to the bottle.

c) For the application: direct the pump towards the center of the area to be treated. Press once and spread the product with your fingertips in order to cover the entire area to be treated, starting from the center of it. Repeat the operation 6 times in order to apply a total dose of 1 ml.

d) Do not apply the product to other parts of the body, and avoid inhaling the product during its application.

Some presentations with a dosing pump also have a cannula and nozzle for a more localized administration, in less extensive areas of the scalp.

- Treatment of large areas of the scalp: the applicator with a spray and metering pump will be used.

a) Remove the outermost transparent cap.

b) Remove and discard the inner plug.

c) Place the sprayer inside the bottle and screw it on firmly. Remove the small transparent cap.

d) Direct the nozzle outlet of the sprayer towards the center of the area to be treated. Press once and spread the solution over the entire area with your fingertips. Carry out 5 more pulses (total 6) repeating the same operation each time. After 6 pulsations, the dose of 1 ml will have been applied.

e) After using the bottle, recap it with the outer transparent cap.

- Treatment of small surfaces or under the hair: the applicator with cannula and nozzle will be used.

a) Remove the outermost transparent cap.

b) Remove and discard the inner plug.

c) Place the sprayer inside the bottle and screw it on firmly. Remove the small transparent cap.

d) Pull up to remove spray head.

e) Insert the nozzle of the cannula into the headless end of the sprayer and press firmly.

f) Direct the cannula towards the center of the surface to be treated or under the hair, press once and spread the solution with your fingertips. Carry out 5 more presses (total 6), repeating the same operation each time. After 6 pulsations, the dose of 1 ml will have been applied.

CONTRAINDICATIONS

- Hypersensitivity to any of the components of the preparation.

ADVICE TO THE PATIENT

- In the case of any heart problem, even in the past, it is necessary to consult with the doctor before using minoxidil for the first time. Also, tell your doctor and/or pharmacist if systemic effects such as rapid heartbeat or palpitations occur; rapid and unexplained weight gain; swelling of hands, elbows and face; lightheadedness, dizziness, or fainting; blurry vision; chest, hand or shoulder pain or scalp irritation or any other reaction that you suspect may be due to the application of this medicine. In such cases, stop treatment.

- This product is to be applied to the scalp, so ingestion or inhalation should be avoided.

- For the correct application read carefully the instructions of the leaflet.

- Apply to a perfectly dry scalp starting in the center of the area to be treated, and by means of a massage with the fingertips, spread the product on the area to be treated.

- It is recommended to wash hands with plenty of water before and after application. Special care should be taken to wash hands after application, especially in the case of women, as there is a risk of hair growth on other parts of the body.

- Do not use a dryer to speed up the drying of the hair because the hot air can evaporate the product and reduce its effectiveness.

- The recommended daily dose should be respected regardless of the extent of the alopecia. Using more than the recommended dose or applying more frequently does not improve the result.

- The patient should be warned that a previous treatment of 4 months may be necessary before there are signs of hair growth.

- When the treatment is interrupted, the growth can stop and return to the initial stage of alopecia in 3-4 months.

SPECIAL WARNINGS

- Prior to its application, it will be necessary to carry out a clinical history and a complete physical examination.

- Do not use in the presence of wounds or dermatosis of the scalp until they have healed, because there may be increased absorption and systemic adverse effects.

- There is the possibility of a small local absorption through the scalp, so regular monitoring of blood pressure and heart rate is recommended, one month after starting treatment and every 6 months thereafter.

- Due to its content in ethanol and/or propylene glycol as excipients, frequent applications can cause irritation and dryness of the skin.

- It is advisable to consult a dermatologist if there is no hair growth in women at 8 months using the 2% concentration and in men at 12 months using the 2% concentration or at 4 months with the 5% concentration.

- Treatment with topical minoxidil is not indicated when there is no family history of hair loss, or if hair loss is sudden (alopecia areata ) and/or patchy (eg scarring alopecia), if hair loss is associated with pregnancy, childbirth, or serious illness (eg, thyroid dysfunction, lupus, loss of sections of hair associated with inflammation of the scalp, or others), or if the reason for hair loss is unknown.

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

- An increase in hair loss may occur due to the action of minoxidil, which initially produces a change from the telogen rest phase of the hair to the anagen growth phase (old hair falls while new ones grow in its place) . This temporary increase in hair loss usually occurs between 2 and 6 weeks after starting treatment and subsides within a couple of weeks (first sign of minoxidil effect). If hair loss persists, patients should stop treatment and consult their doctor.

INTERACTIONS

- Tretinoin: increases the percutaneous absorption of minoxidil as a result of increased permeability of the stratum corneum.

- Betamethasone dipropionate: increases minoxidil concentrations in local tissues and decreases systemic absorption of minoxidil.

- Antihypertensives: Although it has not been clinically confirmed, there is the possibility that minoxidil increases the risk of orthostatic hypotension in patients receiving concomitant treatment with peripheral vasodilators and antihypertensive drugs such as guanethidine and derivatives.

In general, minoxidil should not be applied concomitantly in the same area with other topical products such as corticosteroids, retinoids or occlusive ointments, due to the risk of increased absorption.

PREGNANCY

Animal Safety : Animal studies have not shown a harmful effect on pregnancy, embryonic/foetal development, parturition, or during postnatal development. A risk to the fetus has only been demonstrated at very high exposure levels (compared to those intended for human exposure).

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

Due to the lack of availability of clinical data on the exposure of pregnant women to topical minoxidil, it can be considered that, although remotely, a risk of fetal harm in humans is possible. Thus, the use of minoxidil during pregnancy is not recommended, and it should be used only if the benefit to the mother outweighs the potential risk to the foetus.

Effects on Fertility : No specific studies have been conducted in humans.

LACTATION

Absorbed minoxidil is excreted systemically in breast milk.

Therefore, topical minoxidil should only be used during lactation if the benefit to the mother outweighs the potential risk to the infant.

KIDS

The safety and efficacy of cutaneously administered minoxidil in children and adolescents <18 years of age have not been evaluated, so it is recommended that its use be avoided in this age group.

SENIORS

The safety and efficacy of topical minoxidil in patients over 65 years of age have not been established, so it is unknown whether they respond differently to the drug, and its use is not recommended in this age group.

EFFECTS ON DRIVING

Based on the pharmacodynamic and general safety profile of minoxidil when administered topically, it is unlikely to affect the ability to drive or use machines.

ADVERSE REACTIONS

Adverse reactions are described according to each frequency interval, being considered very common (>10%), common (1-10%), uncommon (0.1-1%), rare (0.01-0.1%) , very rare (<0.01%) or of unknown frequency (cannot be estimated from the available data).

The most common adverse reactions are mild dermatological changes in the area of ​​application, such as: peeling, erythema, dermatitis, hypertrichosis (in distal areas), burning, itching and dry skin (mainly due to the ethanol content). .

But the rest of the following adverse reactions could be observed:

- Cardiovascular: infrequent [TAQUICARDIA], [PALPITATIONS], [HYPOTENSION], increased or decreased pulse.

- Neurological/psychological: infrequent [CEFALEA], [PARESTHESIA]; very rare [MAREO], [DYSGEUSIA]; frequency unknown [DEPRESSION].

- Respiratory: frequent [DYSPNEA]; uncommon [SINUSITIS], [RHINITIS].  

- Dematological/hypersensitivity: frequent [PRURITO], [SKIN IRRITATION], [CONTACT DERMATITIS], [DRY SKIN], [EXFOLIATIVE DERMATITIS]; uncommon [ALOPECIA] (especially at the start of treatment), uneven hair, [HIRSUTISM]; very rare [ACNE]; unknown frequency [ANGIOEDEMA].

- Genitourinary: [ERECTILE DYSFUNCTION].

- Allergic: very rare [HYPERSENSITIVITY REACTIONS], with [RHINITIS], [SKIN ERUPTIONS], generalized [ERITEMA] or facial edema.

- Musculoskeletal: frequency unknown [OSTEOMUSCULAR PAIN].

- Ophthalmological: infrequent [LAGRIMEO], altered vision, altered vision.

- Otic: infrequent [OTITIS], especially [OTITIS EXTERNA].

OVERDOSE

There is no evidence that, when applied cutaneously, minoxidil is absorbed in sufficient quantity to cause systemic effects. Therefore, when used as directed, an overdose is unlikely to occur. But if this product is applied to an area where the integrity of the epidermal barrier is compromised (due to trauma, inflammation, or skin disease), there is a potential for a systemic overdose effect.

- Symptoms: Accidental or voluntary overdose after topical application will produce an increase in the intensity of dermatological adverse reactions, especially itching, dryness, skin irritation and eczema. Likewise, systemic absorption will be greater, with the consequent increase in the probability of suffering systemic effects, especially cardiac ones, due to the vasodilator action of minoxidil (5 ml of 2% solution contains 100 mg of minoxidil, which is the maximum dose used orally, in adults, for the treatment of arterial hypertension).

Among the signs and symptoms of overdose, as a result of the rapid and almost complete absorption of the active ingredient from the gastrointestinal tract, are: hypotension, tachycardia, hydrosaline retention with the appearance of edema, pleural effusion or congestive heart failure.

- Treatment: Treatment of overdose caused by accidental ingestion should be symptomatic and supportive, and may require the use of diuretics for edema, beta-blockers or other inhibitors of the sympathetic nervous system for tachycardia, and sodium chloride in isotonic solution. IV for hypotension. Sympathomimetics, such as epinephrine and norepinephrine, should be avoided due to the cardiac overstimulation they produce.

Normopil Leaflet  (20 Mg/Ml 1 Bottle Cutaneous Solution 90 Ml)