MINOXIDIL
Minoxidil A white or off-white crystalline powder. Slightly soluble in water; soluble in alcohol and in propylene glycol; practically insoluble in acetone, in chloroform, in ethyl acetate, and in petroleum spirit; sparingly soluble in methyl alcohol.
Adverse Effects and Treatment
Adverse effects commonly caused by minoxidil include reflex tachycardia, fluid retention accompanied by weight gain, oedema, and sometimes deterioration of existing heart failure and changes in the ECG. Hypertrichosis develops in up to 80% of patients within 3 to 6 weeks of the start of minoxidil therapy but is slowly reversible on discontinuation. Pericardial effusion, sometimes with associated tamponade, has been reported in about 3% of patients. Pericarditis may also occur. Minoxidil may aggravate or uncover angina pectoris. Other less frequent adverse effects include headache, nausea, gynaecomastia and breast tenderness, polymenorrhoea, allergic skin rashes, Stevens-Johnson syndrome, and thrombocytopenia.
Reflex tachycardia can be overcome by the use of a beta blocker, or alternatively methyldopa, and a diuretic (usually a loop diuretic) is used to reduce fluid retention. If excessive hypotension occurs, an intravenous infusion of sodium chloride 0.9% can be given to maintain the blood pressure. If a pressor agent is necessary, drugs such as adrenaline, which can aggravate tachycardia, should be avoided; phenylephrine, angiotensinamide, vasopressin, or dopamine may be given if there is evidence of inadequate perfusion of a vital organ.
Topical application of minoxidil may be associated with contact dermatitis, pruritus, local burning, and flushing; sufficient may be absorbed to produce systemic adverse effects. Changes in hair colour or texture may occur.
Effects on the eyes.
Bilateral optic neuritis and retinitis occurred in a patient during treatment with minoxidil for hypertension after a renal transplant. The patient was also taking prednisolone and azathioprine.
Effects on the hair.
The hypertrichosis frequently associated with oral minoxidil makes it generally unsuitable for women. There have also been reports of changes in hair colour. In addition a case has been reported of increased hair loss, followed by subsequent regrowth of differently-coloured hair. Substantial hair loss occurred in a woman after withdrawal of minoxidil and she had to wear a wig.
Severe hypertrichosis has also been reported in 5 of 56 women applying minoxidil 5% solution topically for androgenetic alopecia. Facial, arm, and leg hypertrichosis were reported 2 to 3 months after starting treatment. Hypertrichosis had disappeared 5 months after discontinuation of minoxidil.
Effects on skeletal muscle.
A polymyalgia syndrome, manifesting as fatigue, anorexia, weight loss, and severe pain in the shoulders and pelvic girdle, was seen in 4 men using topical minoxidil. All symptoms improved within 2 to 4 weeks of stopping the drug. In 2 of the patients rechallenge produced a recurrence of symptoms.
Effects on the skin.
Although skin reactions to systemic minoxidil do not appear to be common, a case of classic Stevens-Johnson syndrome has been reported. The syndrome responded to withdrawal and corticosteroid therapy; subsequent rechallenge provoked a recurrence. In another patient an extensive erythematous weeping rash with lesions consistent with actinic keratosis also appeared to be due to minoxidil; bullous lesions recurred on re-exposure. After topical application itching, scaling, flushing, and dermatitis have been the most common adverse effects; allergic contact dermatitis has been reported in rare instances.
Neoplasms.
Two haemorrhagic lesions with Kaposi's features appeared on the forehead, an unusual location for HIV-associated Kaposi's sarcoma, in an HIV-positive patient who had applied topical minoxidil there for 3 months. In a healthy patient an angioma of the scalp developed after 2 months of topical minoxidil therapy. The patient had had a similar lesion as a baby. Minoxidil may induce angiogenesis or may stimulate endothelial cells, fibroblasts, and muscle cells to proliferate. Care should be taken when minoxidil is applied to the skin of people who are predisposed to neo-angiogenesis, or who are HIV-positive.
Precautions
Minoxidil is contra-indicated in phaeochromocytoma. It should be used with caution after a recent myocardial infarction, and in patients with pulmonary hypertension, angina pectoris, chronic heart failure, and significant renal impairment.
Topical application of minoxidil should be restricted to the scalp; it should not be applied to inflamed scalp skin or areas affected by psoriasis, severe sunburn, or severe excoriations, because of the risk of increased absorption. Patients being treated for hypertension should be monitored if topical minoxidil is used concurrently.
AIDS.
For recommendations that topical minoxidil should be used with caution in HIV-positive patients, see Neoplasms under Adverse Effects.
Breast feeding.
Study of a breast-feeding mother showed that minoxidil was rapidly distributed into breast milk, achieving similar concentrations to those in the maternal plasma. No adverse effects were seen in the infant after 2 months and the American Academy of Pediatrics considers that minoxidil is therefore usually compatible with breast feeding.
Porphyria.
Minoxidil is considered to be unsafe in patients with porphyria because it has been shown to be porphyrinogenic in animals or in-vitro systems.
Pregnancy.
A patient who took minoxidil, propranolol, and furosemide throughout pregnancy delivered a normal infant at 37 weeks. Pregnancy was uneventful.
Interactions
The antihypertensive effect of minoxidil may be enhanced by use of other hypotensive drugs. Severe orthostatic hypotension may occur if minoxidil and sympathetic blocking drugs such as guanethidine are given concurrently.
Topical minoxidil should not be used with other topical agents known to enhance absorption, such as corticosteroids, retinoids, or occlusive ointment bases.
Tretinoin.
Percutaneous absorption of minoxidil is enhanced by tretinoin as a result of increased stratum corneum permeability.
Pharmacokinetics
About 90% of an oral dose of minoxidil is absorbed from the gastrointestinal tract. The plasma half-life is about 4.2 hours although the haemodynamic effect may persist for up to 75 hours, presumably due to accumulation at its site of action. Minoxidil is not bound to plasma proteins. It is distributed into breast milk. Minoxidil is extensively metabolised by the liver. It requires sulfation to become active, but the major metabolite is a glucuronide conjugate. Minoxidil is excreted predominantly in the urine mainly in the form of metabolites. Minoxidil and its metabolites are dialysable, although the pharmacological effect is not reversed.
About 0.3 to 4.5% of a topical dose of minoxidil is absorbed from intact scalp.
Uses and Administration
Minoxidil is an antihypertensive that acts mainly by causing direct peripheral vasodilatation of the arterioles. It produces effects on the cardiovascular system similar to those of hydralazine. Minoxidil is given orally for the treatment of severe hypertension unresponsive to standard therapy. When applied topically to the scalp minoxidil may stimulate hair growth to a limited extent and is used in the treatment of alopecia.
In the treatment of hypertension minoxidil is given with a beta blocker, or with methyldopa, to diminish the cardiac-accelerating effects, and with a diuretic, usually a loop diuretic, to control oedema. After a single oral dose, the maximum hypotensive effect usually occurs after 2 to 3 hours, although the full effects may not occur until after 3 to 7 days of continuous treatment. An initial dose of 5 mg of minoxidil daily (or 2.5 mg daily in the elderly) is gradually increased at intervals of not less than 3 days to 40 or 50 mg daily according to response; in exceptional circumstances up to 100 mg daily has been given. If more rapid control of blood pressure is required, dosage changes may be made every 6 hours with careful monitoring. The daily dose may be given as a single dose or in 2 divided doses. For children, the initial dose is 200 micrograms/kg daily, increased in steps of 100 to 200 micrograms/kg at intervals of not less than 3 days, until control of blood pressure has been achieved or a maximum of 1 mg/kg or 50 mg daily has been reached.
Reduced doses may be required in patients with renal impairment.
In the treatment of alopecia androgenetica (male-pattern baldness) 1 mL of a 2% or 5% solution of minoxidil is applied twice daily to the scalp. The 5% solution is not recommended for women.
Administration in renal impairment.
A study of the pharmacokinetics of minoxidil in patients with varying degrees of renal impairment found that the non-renal clearance was also impaired as renal function worsened.1 Substantial accumulation of minoxidil might occur in these patients during multiple-dose therapy. It was advised that minoxidil be started with smaller doses or at longer dosage intervals in patients with renal impairment.
Alopecia.
Minoxidil is used topically to stimulate hair growth in alopecia , although its mechanism of action is poorly understood. Increases in pigmented non-vellus hair may be due to thickening and pigmentation of existing vellus rather than new growth. Measurement over 96 weeks showed that minoxidil in solutions of 2 or 5% had a greater effect on hair weight than number of hairs in men with androgenetic alopecia (male-pattern baldness) with the 5% solution being more effective; 24 weeks after treatment was stopped both values had returned to baseline. Another study also showed that 5% minoxidil had a greater effect than 2%, and produced an earlier response. However, 5% minoxidil has been found less effective than oral finasteride. Even with continued use there is a waning of effect with minoxidil. It may be more effective in retarding the progression of male-pattern baldness than in reversing it, and users are advised to abandon treatment if there is insufficient benefit after a year.
Minoxidil has also been used in women with female pattern hair loss, and as with men the 5% solution has been found more effective than the 2%. In women with no evidence of biochemical hyperandrogenism minoxidil 2% was more effective than oral cyproterone; where there was such evidence, cyproterone was superior.
Topical minoxidil has been shown to be safe in a large prospective study of men and women with androgenetic alopecia.
Minoxidil appeared to have no beneficial effect on alopecia areata, although one study indicated that topical minoxidil with 0.5% dithranol cream was more effective than either treatment alone.
Chemotherapy-induced alopecia.
Minoxidil 2% solution was applied daily to the scalp of a boy with acute lymphoblastic leukaemia whose hair had failed to regrow satisfactorily after intensive chemotherapy. Almost normal hair growth, achieved over a 9-month period, was attributed to the use of minoxidil.
A small study in women undergoing combination chemotherapy including doxorubicin found that topical minoxidil applied throughout therapy and for up to 4 months afterwards reduced the duration of alopecia by an average of 50 days.
MINTOPE ( brand )
Description: MINTOPE is a colorless liquid medication for use only on the top of the scalp to help regrow hair.
Active Ingredient: Minoxidil 2% w/v
Inactive Ingredients: Alcohol, 60% v/v, propylene glycol, and purified water.
Indication To regrow hair on the scalp.
Directions: FOR EXTERNAL USE ONLY. Apply 1 mL (2 times a day, every day, directly onto the top of the scalp) in the hair loss area. Using more or using more often will not improve results.
Warnings:
Do not use MINTOPE and see your doctor if you:
Have no family history of hair loss
Have sudden hair loss
Have patchy hair loss
Do not know the reason for your hair loss
Do not use MINTOPE if you:
Are less than 18 years old. Do not use on babies and children
Have ever had an allergic reaction to MINTOPE
Do not apply MINTOPE on scalp if the skin is:
Red or inflamed
Infected
Irritated
Painful to touch (such as severe sunburn)
Stop using MINTOPE and see your doctor if you get:
Unwanted facial hair growth
Chest pain
Rapid heartbeat
Faintness and/or dizziness
Sudden, unexplained weight gain
Swollen hands or feet
Redness or irritation on treated areas of your scalp
For external use only.
AVOID CONTACT WITH EYES. IN CASE OF ACCIDENTAL CONTACT, RINSE WITH LARGE AMOUNTS OF COOL TAP WATER. As with any drug, if you are pregnant or nursing a baby, seek the advice of a healthcare professional before using this product. Do not use if your hair loss is associated with childbirth. Keep this and all drugs out of the reach of children. In case of accidental ingestion, seek professional assistance or contact a Poison Control Center immediately.
Side Effects:
The most common side effects are itching and other skin irritations of the treated area of the scalp. If scalp irritation continues, stop use and see a doctor.
Although unwanted facial hair growth has been reported on the face and on other parts of the body, such reports have been infrequent. The unwanted hair growth may be caused by the transfer of MINTOPE to areas other than the scalp, or by absorption into the circulatory system of low levels of the active ingredient, or by a medical condition not related to the use of MINTOPE. If you experience unwanted hair growth, discontinue using MINTOPE and see your doctor for recommendations about appropriate treatment. After stopping use of MINTOPE, the unwanted hair, if caused by the use of MINTOPE, should go away over time.