Regaine for Women Regular Strength

Minoxidil 20 mg/ml (2% w/v).

For excipients see section 6.1.

Cutaneous Solution (to be applied to the scalp)

Regaine for Women Regular Strength is indicated for the treatment of alopecia androgenetica in women 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, whose hair has been thinning for a shorter period of time or who have a smaller area of thinning on the vertex are more likely to respond to Regaine for Women Regular Strength, individual responses cannot be predicted.

Women aged 18-65:

Hair and scalp should be thoroughly dry prior to topical application of Regaine for Women Regular Strength. A dose of 1 ml Regaine for Women Regular Strength cutaneous solution should be applied to the total affected areas of the scalp twice daily. The total 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 Women Regular Strength are necessary for continued hair growth. Anecdotal reports indicate that regrown hair may disappear three to four months after stopping Regaine for Women Regular Strength application and the balding process will continue.

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

The method of application varies according to the disposable applicator used:

Pump spray applicator: this is useful for large areas. Aim the pump at the centre of the bald area, press once and spread with fingertips over the entire bald area. Repeat for a total of 6 times to apply a dose of 1 ml. Avoid breathing spray mist.

Extended spray-tip applicator: this is useful for small areas, or under hair. The pump spray applicator must be in place in order to use this additional applicator. Use in the same way as the pump spray.

Rub-on applicator: squeeze the upright bottle once to fill the 1 ml chamber to the black line. Invert bottle, dab on scalp, and spread Regaine for Women Regular Strength over the entire bald area until chamber is empty.

Children and the Elderly

Not recommended. The safety and effectiveness of Regaine for Women Regular Strength in users aged under 18 or over 65 has not been established.

Regaine for Women Regular Strength is contra-indicated:

− in users with a history of sensitivity to minoxidil, ethanol, or propylene glycol

− 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 Women Regular Strength, the user should determine that the scalp is normal and healthy.

The patient should stop using Regaine for Women Regular Strength 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.

Patients with known cardiovascular disease or cardiac arrhythmia should contact a physician before using Regaine for Women Regular Strength.

Regaine for Women Regular Strength 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 solution. Inhalation of the spray mist should be avoided.

Regaine for Women Regular Strength contains alcohol, 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 Women Regular Strength contains propylene glycol, which may cause skin irritation.

Some patients have experienced changes in hair colour and/or texture with use of Regaine for Women Regular Strength.

Patients should be advised to consult their doctor or pharmacist if they are concerned at any time during treatment with Regaine for Women Regular Strength.

Users should be aware that, whilst extensive use of Regaine for Women Regular Strength 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 demonstrated clinically, there exists the theoretical possibility of absorbed minoxidil potentiating orthostatic hypotension caused by peripheral vasodilators.

There are no adequate data from the use of minoxidil in pregnant women. Studies in animals have shown reproductive toxicity (see Section 5.3). The potential risk for humans is unknown. Regaine should not be used during pregnancy.

In pregnant rats administered a single subcutaneous dose of 0.9 mg/kg minoxidil, the concentrations in foetuses were 19% to 28% of the maternal plasma concentration.

It is recommended that breast-feeding should be discontinued during treatment with Regaine.

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

In placebo controlled trials, 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.

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 if they experience persistent redness or irritation of the scalp.

Some consumers reported increased hair shedding upon initiation of therapy with Regaine. 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 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 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 Women Regular Strength 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 Women Regular Strength.

Because of the concentration of minoxidil in Regaine for Women Regular Strength, accidental ingestion has the potential of producing systemic effects related to the pharmacological action of the drug (5ml of Regaine for Women Regular Strength contains 100mg minoxidil; the maximum recommended adult dose for oral minoxidil administration in the treatment of hypertension). Signs and symptoms of minoxidil overdosage would primarily 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.

Individual responses to Regaine for Women Regular Strength are variable and unpredictable.

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

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

Using non-vellus hair count as an efficacy criteria, Regaine for Women Regular Strength has also been shown to stabilise hair loss (defined as regrowth or no loss) in 88% of patients compared with 69% of patients who received vehicle in one trial following 48 weeks treatment and in 87% of patients compared with 73% of patients who received vehicle in a further trial following 32 weeks treatment.

Female patients' own evaluations in clinical studies have shown that hair growth was reported by approximately 60% of females after 8 months of Regaine for Women Regular Strength usage.

Patient evaluation of visible hair growth

In addition, Regaine for Women Regular Strength has been shown to stabilise hair loss (shown as regrowth or no loss) in 4 out of 5 females as calculated from two clinical studies that showed stabilisation with 88 and 87% respectively while corresponding figures for vehicle were 69 and 74%.

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:

- increase the diameter of the hair shaft

- stimulate anagen growth

- prolong the anagen phase

- stimulate 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 for Women Regular Strength 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. Increasing the amount of drug applied or increasing the frequency of application of Regaine for Women Regular Strength also results in increased absorption.

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 for Women Regular Strength are governed by the drug's absorption rate through the skin. Following cessation of topical dosing of Regaine for Women Regular Strength, 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

Water

None known.

48 months

Regaine for Women Regular Strength is flammable. Do not store above 25°C.

HDPE bottle with spray-pump/dabbing applicator containing 60 ml of solution.

Pack size: 1 x 60 ml.

The solution 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 15513/0149

7^th March 2005/27 Feb 2009