Increased systemic absorption of minoxidil may potentially occur if higher-than-recommended doses of Regaine for Men Extra Strength Scalp Foam 5% w/w Cutaneous Foam are applied to larger surface areas of the body or areas other than the scalp.
Because of the concentration of minoxidil in Regaine for Men Extra Strength Scalp Foam 5% w/w Cutaneous Foam, accidental ingestion has the potential of producing systemic effects related to the pharmacological action of the drug (2 g of Regaine for Men Extra Strength Scalp Foam 5% w/w Cutaneous Foam 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 primarily be cardiovascular effects associated with sodium and water retention. Tachycardia, hypotension, dizziness and lethargy can also occur.
Treatment
Treatment of minoxidil overdosage should be symptomatic and supportive.
Fluid retention can be managed with appropriate diuretic therapy. Clinically significant tachycardia can be controlled by administration of a beta-adrenergic blocking agent.
3 years.
Not applicable.
Ethanol, Anhydrous
Purified Water
Butylated hydroxytoluene (E321)
Lactic acid
Citric acid anhydrous
Glycerol
Cetyl alcohol
Stearyl Alcohol
Polysorbate 60
Propane/Butane/Iso-butane (as propellant)
Mutagenicity
Minoxidil showed no evidence of mutagenic/genotoxic potential in a number of in vitro and in vivo assays.
Carcinogenicity
A high incidence of hormone-mediated tumours was observed in mice and rats. These tumours are due to the secondary hormonal (hyperprolactinemia) effects observed only in the rodents at extremely high doses by a mechanism similar to that seem with reserpine. Application of topical minoxidil has not demonstrated any effect on hormonal status in women. Therefore, hormonally mediated tumour promotion by minoxidil does not represent a carcinogenic risk to humans.
Teratogenicity
Animal reproduction toxicity studies in rats and rabbits have shown signs of maternal toxicity and a risk to the foetus at exposure levels that are very high compared to those, intended for human exposure. A low, albeit remote, risk of foetal harm is possible in humans.
Fertility
Minoxidil doses greater than 9 mg/kg (at least 25-fold human exposure) administered subcutaneously in rats were associated with reduced conception and implantation rates as well as reduction in the number of live pups.
Pharmacotherapeutic group: Other dermatologicals, ATC code: D11AX.
Minoxidil stimulates hair growth in persons with early and moderate stages of hereditary hair loss (alopecia androgenetica). This hair loss appears in men as a receding hairline and balding in the vertex area. The exact mechanism of action of minoxidil for topical treatment of alopecia 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 telegen 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 efficacy of 5% minoxidil foam has been assessed in a Phase 3 clinical trial conducted over a 16-week treatment period. In this study 5% minoxidil foam was compared to the product vehicle without the minoxidil active ingredient.
The primary efficacy endpoints were a) mean change in non-vellus hair count within the target region between Baseline and Week 16, as determined by validated computer-assisted dot-mapping technique; and b) subject rating of treatment benefit via use of global photographs of the vertex region, assessed as an overall improvement from baseline, collected on a subject questionnaire.
The active treatment showed a statistically significant greater increase in hair count than the vehicle foam group (21.0 versus 4.3 hairs cm2) at week 16. A clear difference between treatment groups was already evident at week 8, increasing at week 12 and again at week 16. The subject`s rating of treatment benefit was statistically significantly better for the 5% minoxidil foam treatment group than placebo (1.4 vs 0.5) at week 16.
The secondary efficacy endpoints were a) expert panel review (EPR) of hair regrowth when comparing global photographs obtained at baseline with photographs obtained at Week 16 and b) percent change from baseline in non-vellus hair counts within a pre-specified area of clipped hair.
The 5% minoxidil foam group showed a better score in the expert panel review (EPR) than the placebo foam group (adjusted mean 0.5 vs 0.1, p<0.0001).
At weeks 8, 12 and 16, the difference in adjusted means for percent change in non-vellus hair counts between vehicle foam and minoxidil foam were statistically significant (p<0.0001 at all 3 visits).
Regaine Foam Data: Mean change in non-vellus hair count in reference 1cm2 area of scalp compared with baseline
|
|
Regaine for Men Extra Strength Foam (n=180)
|
Placebo (n=172)
|
Difference (p-value) |
|
Baseline haircount |
170.8 |
168.9 |
|
|
|
Mean change from baseline |
Mean change from baseline |
|
|
8 weeks |
16.0 |
4.9 |
11.1 (<0.0001) |
|
12 weeks |
19.9 |
4.5 |
15.4 (<0.0001) |
|
16 weeks |
21.0 |
4.3 |
16.7 (<0.0001) |
The failure to detect evidence of systemic effects during treatment with Regaine Foam reflects the poor absorption of topically applied minoxidil from normal intact skin. Systemic absorption of minoxidil from topically applied solution ranges between 1% and 2% of the total applied dose.
The systemic absorption of minoxidil from a 5% foam formulation has been estimated in a pharmacokinetic study in subjects with androgenetic alopecia, which included 5% topical solution as a comparator. This demonstrated that in men, the systemic absorption of minoxidil from twice daily application of 5% minoxidil foam was about half of that observed with 5% minoxidil solution. The mean steady state AUC (0-12 hr) and Cmax for 5% minoxidil foam, 8.81 ng·hr/mL and 1.11 ng/mL, respectively, were both approximately 50 % of AUC (0-12 hr) and Cmax of the 5% solution, 18.71 ng·hr/mL and 2.13 ng/mL, respectively. The time to maximum minoxidil concentration (Tmax) for the 5% foam, 5.42 hr, was similar to Tmax for the 5% solution, 5.79 hr.
There is some evidence from in vitro studies that minoxidil reversibly binds to human plasma proteins. However, since only 1 - 2% of topically applied minoxidil is absorbed, the extent of plasma protein binding occurring in vivo after topical application would be clinically insignificant. The volume of distribution of minoxidil after intravenous administration has been estimated at 70 litres.
Approximately 60% minoxidil absorbed after topical application is metabolised to minoxidil glucuronide, primarily in the liver. Minoxidil and its metabolites are excreted almost entirely in the urine, with a very minor degree of elimination via the faeces. Following cessation of dosing, approximately 95% of topically applied minoxidil will be eliminated within four days.
01 May 2018
McNeil Products Limited
Foundation Park
Roxborough Way
Maidenhead
Berkshire SL6 3UG
United Kingdom
Store below 25°C.
Regaine for Men Extra Strength Scalp Foam 5% w/w Cutaneous Foam is extremely flammable.
A lined aluminium pressurised container with a child-resistant plastic or polypropylene overcap, containing 60 gram of product.
Packs contain either one or three cans. Not all pack sizes may be marketed.
PL 15513/0366
Precautions during use, storage and disposal:
Pressurized container: May burst if heated. Protect from sunlight and do not expose to temperatures above 50°C. Do not pierce or burn, even after use. Do not spray on a naked flame or any incandescent material. Keep away from heat, hot surfaces, sparks, open flames and other ignition sources. No smoking. Do not use near or place container on polished or painted surfaces.
Any unused product or waste material should be disposed of in accordance with the local requirements.
30/11/2010
