ACTION AND MECHANISM - [ANTI-HAIR LOSS] with vasodilatory action. The exact mechanism by which minoxidil stimulates hair growth is not fully understood; a possible alteration of androgen metabolism in the scalp has been suggested, as well as a vasodilatory effect that may increase microcirculation around the hair follicle. Applied locally, minoxidil stimulates the growth of keratinocytes in vitro and in vivo ; it does not increase the number of hair follicles but partially converts miniaturized and intermediate hairs into terminal hairs, slowing the progression of androgenic alopecia in certain patients. This stimulation occurs after 4 or more months of treatment and varies in intensity among patients. After 6–12 months of uninterrupted treatment, one-third of patients have shown positive responses. However, discontinuing treatment stops hair growth, and the pre-treatment hair loss may return within 3–4 months. SPECIAL WARNINGS - Prior to its application, a medical history and a complete physical examination will be necessary. - Do not use in the presence of wounds or scalp dermatosis until these have healed, as there may be an increase in absorption and systemic adverse effects. - There is a possibility of minor 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 of ethanol and/or propylene glycol as excipients, frequent applications may cause skin irritation and dryness. - It is advisable to consult a dermatologist if there is no hair growth in women after 8 months using the 2% concentration and in men after 12 months using the 2% concentration or after 4 months with the 5% concentration. Topical minoxidil treatment is not indicated when there is no family history of hair loss, or if the hair loss is sudden (alopecia areata ) and/or patchy (e.g., scarring alopecia), if the hair loss is associated with pregnancy, childbirth, or serious illnesses (e.g., thyroid dysfunction, lupus, patchy hair loss associated with scalp inflammation, or others), or if the reason for the 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 causes a shift from the telogen (resting) phase of hair to the anagen (growth) phase (shedding of old hairs as new ones grow in their place). This temporary increase in hair loss generally occurs between 2 and 6 weeks after starting treatment and decreases within a couple of weeks (the first sign of minoxidils effect). If hair loss persists, patients should discontinue treatment and consult their doctor. PATIENT ADVICE - If you have any heart problems, even if they were in the past, you must consult your doctor before using minoxidil for the first time. Likewise, inform your doctor and/or pharmacist if you experience systemic effects such as a rapid heartbeat or palpitations; rapid and unexplained weight gain; swelling of the hands, elbows, and face; lightheadedness, dizziness, or fainting; blurred vision; chest, hand, or shoulder pain; scalp irritation; or any other reaction you suspect may be due to the use of this medication. In these cases, discontinue treatment. - This product is for application to the scalp, so avoid ingestion or inhalation. - For correct application, carefully read the instructions in the leaflet. - Apply to a perfectly dry scalp starting from the center of the area to be treated, and by massaging with your fingertips, spread the product over the area to be treated. - It is recommended to wash your hands thoroughly with water before and after application. Special care should be taken to wash your hands after application, especially for women, as there is a risk of hair growth in other areas of the body. - Do not use a hairdryer to speed up hair drying because hot air can evaporate the product and decrease its effectiveness. The recommended daily dose must be respected regardless of the extent of the alopecia. Using more than the recommended dose or applying it more frequently will not improve the result. - The patient should be advised that a 4-month pre-treatment may be necessary before any signs of hair growth are seen. - When treatment is stopped, growth may cease and return to the initial stage of alopecia within 3-4 months. CONTRAINDICATIONS - Hypersensitivity to any of the components of the preparation. ADVANCED AGE 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 in this age group is not recommended. 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 operate machinery. PREGNANCY Animal safety : Studies in animals have not demonstrated harmful effects on pregnancy, embryonal/fetal development, parturition, or 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 a lack of clinical data on the exposure of pregnant women to topical minoxidil, a risk of fetal harm in humans, although remote, is possible. Therefore, the use of minoxidil during pregnancy is not recommended and should only be used if the benefit to the mother outweighs the potential risk to the fetus. Effects on fertility : no specific studies have been conducted in humans. PHARMACOKINETICS - Absorption: slight absorption (bioavailability 1.4-1.7%). After 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 and 5.4 mg/day, some systemic effects could be expected. This dose could be reached if 5% minoxidil were applied to the entire scalp, not just the bald patch. The lowest dose of IV minoxidil that produces clinically significant hemodynamic effects in patients with mild to moderate hypertension has been observed to be 6.86 mg. The results of pharmacokinetic studies indicate that the three most important factors related to increased absorption of minoxidil in the skin are the following: - quantitative increase of the applied dose. - increased frequency of application. - 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 minoxidil absorption has not been determined. After application of minoxidil through the skin, its absorption is not influenced by factors such as: sex, exposure to ultraviolet rays, simultaneous application of a moisturizing product, occlusion (use of hairpieces), evaporation of the solvent (use of a hairdryer) or the surface of the application area. - Metabolism: The biotransformation of minoxidil absorbed after topical application is not well understood. It is believed that approximately 60% of absorbed minoxidil is metabolized to minoxidil glucuronide, primarily in the liver. - Elimination: Minoxidil and its metabolites are dialyzable; their elimination is primarily urinary. When topical application is discontinued, approximately 95% of the absorbed minoxidil is eliminated within 4 days. INDICATIONS - Treatment of moderate [ANDROGENIC ALOPECIA] (hair loss). 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 not clinically proven, there is a possibility that minoxidil may increase 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 to the same area with other topical products such as corticosteroids, retinoids, or occlusive ointments, due to the risk of increased absorption. LACTATION Animal safety: no data available. Safety in humans: Absorbed minoxidil is systematically excreted in breast milk. It is unknown whether it is excreted in breast milk, and the consequences this could have for the infant. When administered topically, it should only be used during breastfeeding if the benefit to the mother outweighs the potential risk to the infant. CHILDREN The safety and efficacy of minoxidil administered cutaneously in children and adolescents < 18 years has not been evaluated, therefore its use in this age group is not recommended. GUIDELINES FOR PROPER ADMINISTRATION - Using the dosing pump: Before applying the product, ensure that the hair and scalp are completely dry. Wash your hands thoroughly before and after applying the solution. a) Remove the lid from the jar and unscrew the cap that closes it. b) Attach by screwing the dosing pump onto the bottle. c) For application: direct the pump towards the center of the area to be treated. Press once and spread the product with your fingertips to cover the entire area, starting from the center. Repeat this process 6 times 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 application. Some presentations with a dosing pump also feature a cannula and nozzle for more localized administration, in less extensive areas of the scalp. - Treatment of large areas of the scalp: the applicator with a spray pump and dosing device 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 tightly. Remove the small transparent cap. d) Direct the spray nozzle towards the center of the area to be treated. Press once and spread the solution over the entire area with your fingertips. Perform 5 more presses (6 total), repeating the same operation each time. After 6 presses, the 1 ml dose will have been applied. e) After using the bottle, replace the outer transparent cap. - Treatment of small areas 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 tightly. Remove the small transparent cap. d) Pull upwards to remove the sprayer head. e) Insert the cannula nozzle into the headless end of the sprayer and press firmly. f) Direct the cannula towards the center of the area to be treated or under the hair, press once and spread the solution with your fingertips. Perform 5 more presses (6 total), repeating the same operation each time. After the 6 presses, the 1 ml dose will have been applied. POSOLOGY Cutaneous topical. Adults: 1 ml twice a day (one application in the morning and one at night) on the scalp, starting from the center of the area to be treated. - 1 ml of solution is calculated using the dosing syringe. Maximum daily dose: 2 ml, regardless of the surface treated. The applied dose and frequency of applications should not be increased: the recommended dose and method of administration should always be followed. The product should be applied as directed, 7 days a week, for at least 6 months. Hair growth is usually noticeable after approximately 4 months of treatment, although this may vary depending on the individual. Clinical experience has shown that after stopping treatment, the growth of new hairs stops, hair loss accelerates, and hair density decreases, potentially returning to pre-treatment levels after 3-4 months. - Children The safety and efficacy of minoxidil administered cutaneously in patients under 18 years of age have not been established. - Elderly: The safety and efficacy of minoxidil administered cutaneously in patients over 65 years of age have not been established. PRECAUTIONS - Scalp dermatosis: In patients with dermatosis or scalp skin lesions, greater percutaneous absorption of the active ingredient may occur, so it should be ensured that these do not exist before application. Although studies with topical minoxidil have not shown significant systemic absorption, there is a possibility of small local absorption through the scalp. Therefore, regular monitoring of blood pressure and heart rate is recommended in patients with any cardiac or cardiovascular problems such as: potential risk of [HYPERTENSION], [EDEMA], [PERIPHERAL ARTERY DISEASE], [CARDIAC ARRHYTHMIA], [HEART FAILURE] or [VALVULAR HEART DISEASE]. - Wearing wigs is not recommended during treatment. 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 frequent adverse reactions are mild dermatological alterations in the application area, such as: peeling, erythema, dermatitis, hypertrichosis (in distal areas), stinging, itching and dryness of the skin (mainly due to the ethanol content). However, the following adverse reactions may also be observed: - Cardiovascular: infrequent [TACHYCARDIA], [PALPITATIONS], [HYPOTENSION], increase or decrease in pulse. - Neurological/psychological: infrequent [HEADACHE], [PARESTHESIA]; very rare [DIZZINESS], [DYSGEUSIA]; frequency unknown [DEPRESSION]. - Respiratory: frequent [DYSPNEA]; infrequent [SINUSITIS], [RHINITIS]. - Dermatological/hypersensitivity: common [PRURITUS], [SKIN IRRITATION], [CONTACT DERMATITIS], [DRY SKIN], [EXFOLIATIVE DERMATITIS]; uncommon [ALOPECIA] (especially at the start of treatment), uneven hair, [HIRSUTISM]; very rare [ACNE]; frequency not known [ANGIOEDEMA]. - Genitourinary: [ERECTILE DYSFUNCTION]. - Allergic: very rare [HYPERSENSITIVITY REACTIONS], with [RHINITIS], [SKIN ERUPTIONS], generalized [ERYTHEMA] or facial edema. - Musculoskeletal: frequency unknown [MUSCULOSKELETAL PAIN]. - Ophthalmological: infrequent [TEARING], altered vision, visual disturbances. - Optic: infrequent [OTITIS], especially [OTITIS EXTERNA]. ADVERSE REACTIONS RELATED TO EXCIPIENTS - This medicine contains propylene glycol, so it may cause [SKIN IRRITATION]. OVERDOSE There is no evidence that minoxidil, when applied topically, is absorbed in sufficient quantities to cause systemic effects. Therefore, when used as directed, an overdose is unlikely. However, 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 possibility of a systemic overdose effect. - Symptoms: Accidental or intentional 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 a consequent increase in the likelihood of experiencing systemic effects, particularly cardiac ones, due to the vasodilatory 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 high blood pressure). Among the signs and symptoms of overdose, resulting from the rapid and almost complete absorption of the active ingredient at the level of the gastrointestinal tract, are: hypotension, tachycardia, hydrosaline retention with the appearance of edema, pleural effusion or congestive heart failure. - Treatment: Treatment of overdose resulting from 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 intravenous isotonic sodium chloride solution for hypotension. Sympathomimetics, such as adrenaline and noradrenaline, should be avoided due to the cardiac overstimulation they produce.