Prescribing info on Minoxidil (Rogaine)

ROGAINE®
Pharmacia & Upjohn Minoxidil Hair Growth Stimulant

Action And Clinical Pharmacology:

When applied topically, minoxidil topical solution has been shown to stimulate hair growth in individuals with alopecia androgenetica (male pattern baldness). Although the exact mechanism of action of minoxidil in the treatment of alopecia androgenetica is not known, there may be more than one mechanism by which minoxidil stimulates hair growth; they include: vasodilation of the microcirculation around the hair follicles which may stimulate hair growth; direct stimulation of the hair follicle cells to enter into a proliferative phase: resting phase (telogen) follicles being stimulated to pass into active phase (anagen) follicles; alteration of the effect of androgens on genetically predetermined hair follicles: minoxidil may affect the androgen metabolism in the scalp by inhibiting the capacity of androgens to affect the hair follicles.

Following topical application of minoxidil topical solution, minoxidil is poorly absorbed from normal intact skin, with an average of 1.4% (range 0.3 to 4.5%) of the total applied dose reaching the systemic circulation. The effects of concomitant dermal diseases or occlusion on absorption are unknown. Serum minoxidil levels resulting from topical administration are governed by the drug's percutaneous absorption rate; increases in surface area of application do not result in proportionate increases in the serum minoxidil level. Steady state is achieved by the end of the third dosing interval (36 hours) when the drug is administered twice daily. Approximately 95% of the systemically absorbed minoxidil from topical dosing is eliminated within 4 days. The metabolic biotransformation of minoxidil absorbed following topical application has not been fully determined.

Absorption from the gastrointestinal tract following oral administration of minoxidil tablets is essentially complete (at least 95%). Approximately 90% of orally administered minoxidil is metabolized, predominantly by conjugation with glucuronic acid at the N-oxide position in the pyrimidine ring and by conversion to more polar products.

Known metabolites exert much less pharmacologic effect than minoxidil itself and all are excreted principally in the urine. Minoxidil does not bind to plasma proteins; its renal clearance corresponds to glomerular filtration rate and it does not cross the blood brain barrier. Minoxidil and its metabolites are hemodialyzable, although this does not rapidly reverse its pharmacological effect.

Increased hair growth has not been associated with increased systemic absorption of topical minoxidil. The onset of hair growth stimulation requires twice daily applications of minoxidil topical solution for 4 or more months, and is variable among patients. Upon discontinuation of topically applied minoxidil, new hair growth has been anecdotally reported to stop and restoration of pretreatment appearance to occur within 3 to 4 months.

Indications And Clinical Uses:
The treatment of alopecia androgenetica (male pattern baldness).

Contra-Indications:
Hypersensitivity to minoxidil, propylene glycol or ethanol.

Pregnancy and Lactation: Minoxidil topical solution should not be used by pregnant or nursing women.

Manufacturers' Warnings In Clinical States:
Although the following systemic effects have not been associated with the topical use of minoxidil topical solution, there is some absorption of minoxidil from the skin and the potential exists for systemic effects such as tachycardia, angina, edema or potentiation of the orthostatic hypotension produced by guanethidine. Patients should be observed periodically for any suggestion of systemic effects of minoxidil. In the event of systemic side effects discontinue administration of the drug. If necessary, fluid retention and edema can be managed with diuretic treatment. Tachycardia and angina can be controlled by administration of beta-adrenergic blocking drugs or other sympathetic nervous system suppressants. Patients should discontinue use of minoxidil topical solution and contact their physician in the event of systemic effects and/or severe dermatologic reactions.

Pregnancy and Lactation: The safety for use of minoxidil topical solution in pregnancy has not been established. Orally administered minoxidil has been shown to reduce the conception rate in rats and to show evidence of increased fetal resorption in rabbits when administered at 5 times the human oral dose. There was no evidence of teratogenic effects in rats and rabbits.

Systemically absorbed minoxidil is secreted in human milk.

Children: Safety and effectiveness of minoxidil topical solution in patients under 18 years of age has not been established.

Patients With Underlying Cardiovascular Disease: Patients should not use minoxidil topical solution if they have a history of underlying coronary artery disease, cardiac dysrhythmias, congestive heart failure, or valvular heart disease. Patients with hypertension, including those under treatment with antihypertensive agents, should be monitored closely and their medication adjusted if necessary. Minoxidil topical solution should be used with caution in patients with any other cardiovascular disease present.

Precautions:
Before prescribing minoxidil topical solution, ensure that the patient reads and understands the contents of the patient-package insert including the application instructions.

Minoxidil topical solution will cause burning and irritation of the eye. In the event of accidental contact with sensitive surfaces (eye, abraded skin, mucous membranes), the area should be bathed with copious amounts of cool tap water.

Inhalation of the spray mist should be avoided.

Accidental ingestion of minoxidil topical solution could lead to serious adverse effects.

The effects of minoxidil topical solution in patients with concomitant dermal diseases, or in those using topical corticosteroids or other dermatologic preparations are unknown. It has not been clearly determined whether occlusion will increase the absorption of minoxidil after administration of the topical solution. As is the case with other topically applied drugs, decreased integrity of the epidermal barrier caused by inflammation or disease processes in the skin, may increase percutaneous absorption of minoxidil.

Geriatrics: Studies involving subjects over the age of 65 years have not been performed hence the safety and effectiveness of minoxidil topical solution in these patients has not been established.

Drug Interactions:
There are currently no known drug interactions associated with the use of minoxidil topical solution. Although it has not been clinically demonstrated, there exists the possibility of potentiating orthostatic hypotension in patients concurrently taking guanethidine.

Adverse Reactions:
The most frequently encountered adverse effects in clinical trials with minoxidil topical solution were minor dermatologic reactions. In light of the findings that systemic levels of minoxidil from topical application are low in relation to systemic levels from oral dosing, this distribution of encountered adverse effects is to be expected. Local irritation was the most common adverse reaction reported, including scaling, erythema/flushing, dermatitis, dry skin, hypertrichosis (in areas other than where minoxidil topical solution was applied), burning sensation and rash.

Infrequent adverse reactions including allergic reactions (sensitivity, hives, generalized erythema and facial swelling); dizziness; tingling sensation; headache; weakness; neuritis; edema; eye irritation; altered taste; ear infection (otitis externa); and visual disturbances have been reported. Rarely reported adverse reactions included alopecia, hair abnormalities, chest pain, blood pressure changes, pulse changes, hepatitis, and kidney stones.

The occurrence rates for adverse reactions derived from the total adverse reactions of all patients (placebo [one-third of these patients received placebo treatment for 4 months] 2% minoxidil and 3% minoxidil treated) enrolled in 2 pivotal efficacy/safety studies (2 326 patients), are as follows: Dermatological: itching (3%); scaling, erythema, dermatitis, dry skin (1 to 2%); hypertrichosis, burning sensation, rash, folliculitis, desquamation, alopecia (hair loss), skin abscess, acne, eczema, eruptions, excoriation, flaking scalp, hair abnormalities, nail disorders, seborrhea, other skin irritations (0.1 to 1.0%).

Cardiovascular: flushing (1 to 2%); chest pain, changes in blood pressure, changes in pulse rate, fainting (0.1 to 1.0%).

CNS: headache, dizziness (1 to 2%).

Allergic: fever (1 to 2%); allergic reaction, non-specific allergic reaction, hives, allergic rhinitis, facial swelling and sensitivity, chills (0.1 to 1.0%).

Renal: edema (1 to 2%); kidney stones (0.1 to 1.0%).

Respiratory: shortness of breath (0.1 to 1.0%).

Neurological: neuritis (1 to 2%); weakness (0.1 to 1.0%).

Hepatic: hepatitis (0.1 to 1.0%).

Special senses: eye irritations, bitter taste, ear infection (otitis externa), taste alteration, visual disturbance (0.1 to 1.0%).

Symptoms And Treatment Of Overdose:
Symptoms and Treatment: Accidental ingestion of minoxidil topical solution may produce systemic effects related to the vasodilatory action of minoxidil (5 mL of the 2% topical solution contains 100 mg minoxidil, the maximum recommended adult oral dose for the treatment of hypertension). There have been only a few instances of deliberate or accidental overdosage with oral minoxidil (Loniten tablets).

In a reported case of accidental ingestion, a 3-year-old male swallowed 1 to 2 mL of a 3% concentration of topical minoxidil solution. After vomiting he was treated in an emergency room. The child was found to be alert and active with no obvious signs of distress. His temperature was 37°C, pulse 152, respiration 32, and systolic blood pressure 110 by palpation. Cardiovascular, chest, lungs, abdomen, head, skin and neurological examinations were normal. Blood levels taken indicated a total minoxidil level (glucuronide and unchanged) of 320.6 ng/mL. The child was discharged without sequelae.

Signs and symptoms of drug overdosage would most likely include cardiovascular effects associated with fluid retention, lowered blood pressure and tachycardia. Fluid retention can be managed with appropriate diuretic therapy. Tachycardia can be controlled by administration of a beta-adrenergic blocking agent.

If exaggerated hypotension is encountered, it is most likely to occur in association with residual sympathetic nervous system blockade from previous therapy (guanethidine-like effects or alpha-adrenergic blockade). The recommended treatment is i.v. administration of normal saline.

Sympathomimetic drugs, such as norepinephrine or epinephrine, should be avoided because of their excessive cardiac-stimulating action. Phenylephrine, angiotensin II, vasopressin and dopamine, which reverse the effects of orally administered minoxidil, should only be used if inadequate perfusion of a vital organ is evident.

Oral LD50 in rats has ranged from 1 321 to 3 492 mg/kg; in mice 2 457 to 2 648 mg/kg. Minoxidil and its metabolites are hemodialyzable, although this does not rapidly reverse its pharmacological effect.

Dosage And Administration:
For external use only. Use only as directed.

A total dose of 1 mL minoxidil topical solution should be applied twice per day to the scalp, beginning at the centre of the affected area. This dose should be used regardless of the size of the affected area. The total daily dose should not exceed 2 mL. The method of application varies according to the disposable applicator used, as indicated below. After applying minoxidil topical solution, wash hands thoroughly. Do not apply the topical solution to any other area of the body.

Apply minoxidil topical solution when the hair and scalp are thoroughly dry. Do not use a hairdryer to speed the drying of the topical solution, because blowing air on the scalp may decrease the effectiveness of the drug.

A. Pump-Spray Applicator: (Works best for applying minoxidil topical solution to large areas): (1) Remove large outer cap and keep it. (2) Remove small inner cap and discard it. (3) Insert the pump spray applicator into bottle and screw on firmly. (4) After aiming the pump toward the centre of the bald area of the scalp, press the pump once and spread minoxidil topical solution with fingertips to cover all of the bald area. Repeat for a total of 6 times, to apply a dose of 1 mL. Avoid breathing spray mist. (5) Replace large outer cap over the pump spray applicator when not in use.

B. Rub-On Applicator: Works best for applying minoxidil topical solution to small areas of the scalp. (1) Remove large outer cap and keep it. (2) Remove small inner cap and discard it. (3) Insert the rub-on applicator into bottle and screw on firmly. (4) Hold the bottle upright and squeeze it once to fill the upper chamber to the black line. The chamber now contains 1 full dose (1 mL). (5) Hold the bottle upside down, then rub applicator on the scalp to apply minoxidil topical solution over the entire bald area - until the chamber is completely empty. (6) Replace large outer cap over the rub-on applicator when not in use.

C. Extended Spray-TIp Applicator: Works best for applying minoxidil topical solution to small areas of the scalp, or under hair. (1) Remove large outer cap and discard it. (2) Remove small inner cap and discard it. (3) Insert the pump spray applicator into the bottle and screw on firmly. (4) Remove small spray head from top of pump spray applicator. (5) Fit the extended spray tip applicator onto the spray shaft and push down firmly. (6) Remove the small cap on the end of the extended tip and keep it. (7) After aiming the applicator toward the centre of the bald area of the scalp, press the pump once and spread the minoxidil topical solution with fingertips to cover all of the bald area. Repeat for a total of 6 times, to apply a dose of 1 mL. Avoid breathing spray mist. (8) If desired, replace the small cap onto the end of extended tip when not in use.

Clinical experience with minoxidil topical solution indicates that twice daily application for 4 or more months may be required before evidence of hair growth stimulation can be expected. Onset and degree may be variable among patients. Relapse to pretreatment appearance following discontinuation of medication has been anecdotally reported to occur within 3 to 4 months.

Availability And Storage:
Each mL of clear, colorless to slightly yellow solution contains: minoxidil 20 mg (2%) in alcohol (63%), propylene glycol and water. Bottles containing 60 mL of solution with the following metered disposable applicators: pump spray, extended tip and rub-on assemblies.