1. Name Of The Medicinal Product
Regaine for Men Extra Strength
2. Qualitative And Quantitative Composition
Minoxidil 50 mg/ml (5% w/v).
Contains propylene glycol.
For full list of excipients, see section 6.1.
3. Pharmaceutical Form
Cutaneous Solution.
4. Clinical Particulars
4.1 Therapeutic Indications
Regaine for Men Extra Strength is indicated for the treatment of alopecia androgenetica in men.
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 Extra Strength, individual responses cannot be predicted.
4.2 Posology And Method Of Administration
Men aged 18-65:
Hair and scalp should be thoroughly dry prior to topical application of Regaine for Men Extra Strength. A dose of 1 ml Regaine for Men Extra 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 2 months or more before evidence of hair growth can be expected.
If hair re-growth occurs, twice daily applications of Regaine for Men Extra Strength are necessary for continued hair growth. Anecdotal reports indicate that re-grown hair may disappear three to four months after stopping Regaine for Men Extra 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 Men Extra Strength over the entire bald area until chamber is empty.
Children and the Elderly
Not recommended. The safety and effectiveness of Regaine for Men Extra Strength in users aged under 18 or over 65 has not been established.
4.3 Contraindications
Regaine for Men Extra Strength is contraindicated:
− in women
− 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.
4.4 Special Warnings And Precautions For Use
Before using Regaine for Men Extra Strength, the user should determine that the scalp is normal and healthy.
Minoxidil is only indicated for the treatment of alopecia androgenetica and should not be used in other types of hair loss for example when there is no family history of hair loss, hair loss is sudden and/or patchy, hair loss is due to childbirth or the reason for hair loss is unknown.
The patient should stop using Regaine for Men Extra 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 Men Extra Strength.
Regaine for Men Extra 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 Men Extra Strength cutaneous solution contains ethanol (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 Men Extra 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 Men Extra Strength.
Some consumers reported increased hair shedding upon initiation of therapy with Regaine for Men Extra Strength. 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 Extra Strength and consult their doctor.
Users should be aware that, whilst extensive use of Regaine for Men Extra 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.
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
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.
4.6 Pregnancy And Lactation
There are no adequate and well-controlled studies in pregnant women.
Animal studies have shown a risk to the foetus at exposure levels that are very high compared to those intended for human exposure (see section 5.3). The potential risk in humans is unknown.
Systemically absorbed minoxidil is secreted in human milk.
Regaine for Men Extra Strength should not be used during pregnancy or lactation.
4.7 Effects On Ability To Drive And Use Machines
Based on the pharmacodynamic and overall safety profile of minoxidil, it is not expected that Regaine for Men Extra Strength would interfere with the ability to drive or operate machinery.
4.8 Undesirable Effects
In placebo controlled trials, the overall frequency of adverse 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.
Data from 7 placebo controlled trials are available with a population of 1,197 males and females treated with topical minoxidil solution (2% and 5% combined) where adverse events were assessed. Additionally, adverse events reported in post-marketing are included.
The frequency of adverse reactions to topical minoxidil solution is defined using the following convention:
Very common (
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| |
|
|
|
Users should stop using Regaine for Men Extra Strength solution if they experience chest-pain, tachycardia, faintness, dizziness, sudden unexplained weight gain, swollen hands or feet or persistent redness or irritation of the scalp.
4.9 Overdose
Increased systemic absorption of minoxidil may potentially occur if higher-than-recommended doses of Regaine for Men Extra Strength solution 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 Solution, accidental ingestion has the potential of producing systemic effects related to the pharmacological action of the drug (2 ml of Regaine for Men Extra Strength 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 and hypotension..
Treatment
Treatment of minoxidil overdosage should be symptomatic and supportive.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
Pharmacotherapeutic group: other dermatologicals, ATC code: D11AX
The effect of Regaine for Men Extra Strength has been assessed in a phase III clinical trial conducted over a 48 week treatment period.
In this study Regaine for Men Extra Strength (5% minoxidil cutaneous solution) was compared to the product vehicle without the minoxidil active ingredient and also to 2% minoxidil cutaneous solution.
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 active treatment. A significant dose effect was also demonstrated. The results are summarized in the following table:
Mean change in non-vellus hair count in reference 1cm2 area of scalp compared with baseline | ||||
|
|
|
| |
|
|
|
| |
|
|
| ||
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
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 and assessing scalp coverage where point 0 represented much less scalp coverage, 50 mm no difference and 100 mm much more scalp coverage. In addition, an assessment was undertaken by 2 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 of these analyses were as follows:
| ||||
|
|
|
| |
|
|
| ||
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| ||||||
|
|
|
|
|
| |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| ||||||
|
|
|
|
|
| |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Based upon these photographic data, around 60% of the patients experienced an increased scalp coverage after 48 weeks treatment with Regaine for Men Extra Strength as defined by re-growth of hair; compared with around 23% as an average for those who received vehicle alone. Of these, around 35% treated with Regaine for Men Extra Strength experienced dense or moderate re-growth compared with around 7% who received vehicle alone. In addition 30% of patients who received Regaine for Men Extra Strength were adjudged to have no change between the photographic assessments of hair growth compared with 60% who received vehicle alone. Stabilisation of hair loss (expressed both as re-growth of hair and no continuation of hair loss) can therefore be expected in about 4 out of 5 of patients using Regaine for Men Extra Strength compared with 3 out of 4 patients using vehicle alone.
Regaine for Men Extra Strength may therefore be considered by men who wish to achieve a faster onset and greater degree of hair re-growth than would be expected through the use of Regaine Regular Strength.
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 telegon 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.
5.2 Pharmacokinetic Properties
The failure to detect evidence of systemic effects during treatment with Regaine solution 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% solution formulation has been estimated in a pharmacokinetic study in subjects with androgenetic alopecia, which included 5% topical foam as a comparator. This demonstrated that in men, the systemic absorption of minoxidil from twice daily application of 5% minoxidil solution was about twice that observed with 5% minoxidil foam. The mean steady state AUC(0-12 h) and Cmax for 5% minoxidil foam, 8.81 ng·h/ml and 1.11 ng/ml, respectively, were both approximately 50% of AUC(0-12 h) and Cmax of the 5% solution, 18.71 ng·h/ml and 2.13 ng/ml, respectively. The time to maximum minoxidil concentration (Tmax) for the 5% solution, 5.79 hours, was similar to Tmax for the 5% foam, 5.42 hours.
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.
5.3 Preclinical Safety Data
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.
Mutagenicity
Minoxidil showed no evidence of mutagenic/genotoxic potential in a number of in vitro and in vivo assays.
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 (from 19 to 570-fold human exposure). A low, albeit remote, risk of foetal harm is possible in humans.
Fertility
Preclinical fertility studies in rats have shown minoxidil doses equal to or greater than 3 mg/kg/day (at least 8-fold human exposure) when administered orally and greater than 9 mg/kg/day (at least 25-fold human exposure) when administered subcutaneously were associated with reduced conception and implantation rates as well as a reduction in the number of live pups.
6. Pharmaceutical Particulars
6.1 List Of Excipients
Propylene glycol
Ethanol
Water
6.2 Incompatibilities
Not applicable.
6.3 Shelf Life
36 months
6.4 Special Precautions For Storage
Regaine for Men Extra Strength is flammable. Store below 25°C.
6.5 Nature And Contents Of Container
HDPE bottle with spray-pump/dabbing applicator containing 60 ml of solution. Packs contain either one or three bottles.
6.6 Special Precautions For Disposal And Other Handling
The solution is flammable. Do not use while smoking, or near any naked flame or heat source. Avoid exposure of the container and contents to naked flames during use, storage and disposal. Any unused product or waste material should be disposed of in accordance with local requirements.
7. Marketing Authorisation Holder
McNeil Products Limited
Foundation Park
Roxborough Way
Maidenhead
Berkshire SL6 3UG
United Kingdom
8. Marketing Authorisation Number(S)
PL 15513/0148
9. Date Of First Authorisation/Renewal Of The Authorisation
28 June 2005
10. Date Of Revision Of The Text
6 October 2010
No comments:
Post a Comment