Regaine for Men Gel

Minoxidil 20 mg/g (2% w/w).

For excipients see section 6.1.

Cutaneous Gel (to be applied to the scalp).

Regaine for Men Gel is indicated for the treatment of alopecia androgenetica in men aged between 18 and 65.

Onset and degree of hair regrowth may be variable among users. Although trends in the data suggest that those users who are younger, who have been balding for a shorter period of time or who have a smaller area of baldness on the vertex are more likely to respond to Regaine for Men Gel, individual responses cannot be predicted.

Hair and scalp should be thoroughly dry prior to topical application of Regaine for Men Gel. A dose of 1 ml Regaine for Men Gel should be applied to the total affected areas of the scalp twice daily. The total daily dosage should not exceed 2 ml. If fingertips are used to facilitate drug application, hands should be washed afterwards.

It may take twice daily applications for four months or more before evidence of hair growth can be expected.

If hair regrowth occurs, twice daily applications of Regaine for Men Gel are necessary for continued hair growth. Anecdotal reports indicate that regrown hair may disappear three to four months after stopping Regaine for Men Gel application and the balding process will continue.

Users should discontinue treatment if there is no improvement after one year.

Children and the elderly

Not recommended. The safety and effectiveness of Regaine for Men Gel in users under 18 or over 65 years of age has not been established.

Regaine for Men Gel is contraindicated:

− in users with a history of sensitivity to minoxidil, ethanol, propylene glycol, carbomer and diisopropanolamine

− in users with treated or untreated hypertension

− in users with any scalp abnormality (including psoriasis and sunburn)

− in users with a shaved scalp

− if occlusive dressings or other topical medical preparations are being used.

Before using Regaine for Men Gel, the user should determine that the scalp is normal and healthy.

The user should stop using Regaine for Men Gel and see a doctor if hypotension is detected or if the patient is experiencing chest pain, rapid heart beat, faintness or dizziness, sudden unexplained weight gain, swollen hands or feet or persistent redness.

Users with known cardiovascular disease or cardiac arrhythmia should contact a physician before using Regaine for Men Gel.

Regaine for Men Gel is for external use only. Do not apply to areas of the body other than the scalp.

Hands should be washed thoroughly after applying the gel.

Regaine for Men Gel contains an alcohol base which will cause burning and irritation of the eye. In the event of accidental contact with sensitive surfaces (eye, abraded skin and mucous membranes) the area should be bathed with large amounts of cool tap water.

Regaine for Men Gel contains propylene glycol, which may cause skin irritation.

Some users have experienced changes in hair colour and/or texture with use of Regaine for Men Gel.

Users should be advised to consult their doctor or pharmacist if they are concerned at any time during treatment with Regaine for Men Gel.

Users should be aware that, whilst extensive use of Regaine for Men Gel has not revealed evidence that sufficient minoxidil is absorbed to have systemic effects, greater absorption because of misuse, individual variability, unusual sensitivity or decreased integrity of the epidermal barrier caused by inflammation or disease processes in the skin (e.g. excoriations of the scalp, or scalp psoriasis) could lead, at least theoretically, to systemic effects.

Topical drugs, such as corticosteroids, tretinoin, dithranol or petrolatum which alter the stratum corneum barrier, could result in increased absorption of minoxidil if applied concurrently. Although it has not been clinically demonstrated, there exists the theoretical possibility of absorbed minoxidil potentiating orthostatic hypotension in patients concurrently taking peripheral vasodilators.

There is no evidence as to drug safety in human pregnancy nor is there evidence from animal work that it is free from hazard. Regaine for Men Gel should not be used during pregnancy or lactation.

Based on the pharmacodynamic and overall safety profile of minoxidil, it is not expected that Regaine for Men Gel would interfere with the ability to drive or operate machinery.

In placebo controlled trials of Regaine, the overall frequency of medical events in females in all body system categories was approximately five times that of males.

Several thousand patients have used topical minoxidil in clinical trials where a comparison with an inactive solution was made. Dermatological reactions (e.g. irritation, itching) occurred in patients using both solutions. This has been explained by the presence of propylene glycol in both the active and inactive solution. Regaine for Men Gel also contains propylene glycol.

Reactions reported in commercial marketing experience include: hypertrichosis (unwanted non-scalp hair including facial hair growth in women), local erythema, itching, dry skin/scalp flaking, and exacerbation of hair loss. Users should stop using Regaine for Men Gel if they experience persistent redness or irritation of the scalp.

Some consumers reported increased hair shedding upon initiation of therapy with Regaine for Men Gel. This is most likely due to minoxidil's action of shifting hairs from the resting telogen phase to the growing anagen phase (old hairs fall out as new hairs grow in their place). This temporary increase in hair shedding generally occurs two to six weeks after beginning treatment and subsides within a couple of weeks. If shedding persists (>2 weeks), users should stop using Regaine for Men Gel and consult their doctor.

Particular attention has been paid to body systems, such as cardiovascular and metabolic, which might have some relevance based on the pharmacology of minoxidil. There was no increased risk to users due to drug related medical reactions in these, or other, body system categories.

Users should stop using Regaine for Men Gel if they experience chest-pain, tachycardia, faintness, dizziness, sudden unexplained weight gain, or swollen hands or feet. Rare cases of hypotension have been reported.

Increased systemic absorption of minoxidil may potentially occur if higher-than-recommended doses of Regaine for Men Gel are applied to larger surface areas of the body or areas other than the scalp. There are no known cases of minoxidil overdosage resulting from topical administration of Regaine for Men Gel.

Because of the concentration of minoxidil in Regaine for Men Gel, accidental ingestion has the potential of producing systemic effects related to the pharmacological action of the drug (5 ml of Regaine for Men Gel contains 100 mg minoxidil, the maximum recommended adult dose for oral minoxidil administration in the treatment of hypertension). Signs and symptoms of minoxidil overdosage would most likely be cardiovascular effects associated with sodium and water retention and tachycardia. Fluid retention can be managed with appropriate diuretic therapy. Clinically significant tachycardia can be controlled by administration of a beta-adrenergic blocking agent.

Minoxidil is a powerful vasodilator. It was noticed that in patients with severe hypertension, about 80% developed hypertrichosis as a side-effect.

Individual responses to Regaine are variable and unpredictable.

The effect of Regaine 2% solution has been assessed in phase III clinical trials in men conducted over a 48 week treatment period. In these studies Regaine 2% solution was compared to the product vehicle without the minoxidil active ingredient. The primary efficacy criterion was non-vellus hair count in a 1.0cm² reference area of affected scalp. The mean changes observed in this parameter in these studies were significantly in favour of Regaine 2% solution and were as follows:

Mean change in non-vellus hair count in reference 1cm2 area of scalp compared with baseline

In addition, efficacy was further assessed by comparing photographs taken at various timepoints with baseline. Assessment was undertaken by patients using a 100 mm visual analogue scale where point 0 represented much less scalp coverage, 50 mm no difference and 100 mm much more scalp coverage. The results were as follows:

Patient evaluation of change in scalp coverage

Assessment was also undertaken by two blinded reviewers who compared photographs taken at baseline and after 48 weeks. Differences were assessed using a 7 point categorical scale viz:

Dense growth

Moderate growth

Minimal Growth

No change

Minimal loss

Moderate loss

Dense loss

The results were as follows:

Photographic Evaluation of Clinical Response (Reviewer 1)

Photographic Evaluation of Clinical Response (Reviewer 2)

Based upon the photographic data around 40% of the patients experienced an increased scalp coverage after 48 weeks treatment with Regaine 2% solution as defined by regrowth of hair compared with 23% at an average for those who received vehicle alone. Around 19% treated with Regaine 2% solution experienced dense or moderate regrowth compared with around 7% who received vehicle alone. In addition 49% of patients who received Regaine 2% solution were adjudged to have no change between the photographic assessments of hair growth compared with 60% who received vehicle alone. Stabilisation of hair loss (i.e. regrowth or no loss) can therefore be expected in about 4 out of 5 patients using Regaine 2% solution compared with 3 out of 4 patients using vehicle alone.

The mechanism by which minoxidil stimulates hair growth is not fully understood, but minoxidil can reverse the hair loss process of androgenetic alopecia by the following means:

- increasing the diameter of the hair shaft

- stimulating anagen growth

- prolonging the anagen phase

- stimulating anagen recovery from the telogen phase

As a peripheral vasodilator minoxidil enhances microcirculation to hair follicles. The Vascular Endothelial Growth Factor (VEGF) is stimulated by minoxidil and VEGF is presumably responsible for the increased capillary fenestration, indicative of a high metabolic activity, observed during the anagen phase.

The failure to detect evidence of systemic effects during treatment with Regaine 2% solution reflects the poor absorption of topical minoxidil, which averages about 1.4% (range 0.3-4.5%) of the total applied dose from normal intact skin. Absorption is about 2% when applied topically to shaved scalps of hypertensive users.

Results of extensive pharmacokinetic studies indicate that the three major factors by which topical minoxidil absorption is increased are: increasing the dose applied, increasing the frequency of dosing and decreasing the barrier function of the stratum corneum.

Serum minoxidil levels and systemic effects resulting from administration of Regaine are governed by the drug's absorption rate through the skin. Following cessation of topical dosing, approximately 95% of the systemically absorbed drug is eliminated within 4 days. Minoxidil and its metabolites are excreted principally in the urine.

Preclinical data reveal no special hazards for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity or carcinogenic potential.

Cardiac effects of minoxidil in dogs are species-specific in terms of the low doses that cause profound haemodynamic effects and associated changes in the heart. Available data indicate that similar cardiac effects do not occur in humans treated topically or orally with minoxidil.

In rat fertility studies, minoxidil at dose levels between 3 and 80 mg/kg exhibited adverse effects on fertility. Animal reproduction toxicity studies have shown a risk to the foetus at exposure levels that in comparison to levels obtained in humans are very high (doses that ranged from 569- to 1139-fold anticipated human exposures) and showed signs of maternal toxicity.

Propylene glycol

Ethanol

Carbomer

Diisopropanolamine

Water

None known.

24 months

Do not store above 25˚C. Regaine for Men Gel is flammable.

Polyethylene bottle containing 60 ml of gel. An integral metered pump is included.

One press of the integral pump supplies 0.5 ml of gel. Regaine for Men Gel is flammable. Do not use while smoking, or near any naked flame or strong heat source. Avoid exposure of the container and contents to naked flames during use, storage and disposal.

McNeil Products Limited

Foundation Park

Roxborough Way

Maidenhead

Berkshire SL6 3UG

United Kingdom

PL 15513/0129

9 June 2005

11^th April 2008