Regaine Extra Strength 5% w/v Cutaneous Solution

SPC

.2         Posology and Method of Administration

Adults between 18 and 65 years of age:

Hair and scalp should be thoroughly dry prior to topical application of Regaine Extra Strength. A dose of 1 ml Regaine Extra Strength 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.

Clinical experience indicates that twice daily applications for six weeks may be required before evidence of a reduction in hair-loss can be seen and for two months or more before evidence of hair growth can be expected. Onset and degree of hair growth may be variable among patients.

Continuous twice-daily usage is necessary to maintain the results of treatment.

Relapse to pre-treatment appearance following discontinuation of medication has been reported to occur within 3-4 months.

In the absence of any clear response in men, the treatment should be discontinued after 12 months (8 months in women).

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.

The solution is flammable and exposure of the container and contents to naked flames should be avoided during use, storage and disposal.

.2         Posology and Method of Administration

Posology

Adults men and women between 18 and 65 years of age:

4.4       Special Warnings and Special Precautions for Use

The safety and efficacy of the product in patients aged fewer than 18 or over 65 is unknown.

Minoxidil should only be used on a normal healthy scalp. Do not use if scalp is red, inflamed, infected or painful or if using other medications on the scalp.

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 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 or irritation of the scalp.

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

Accidental ingestion may cause serious cardiac adverse events.  Therefore this product has to be kept out of the reach of children.

Regaine 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 Extra Strength Topical 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. Propylene Glycol, contained in this product, may cause skin irritation.

Some patients have experienced changes in hair colour and/or texture with Regaine use.

Some consumers reported increased hair shedding upon initiation of therapy with Regaine 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 Extra Strength and consult their doctor.

Users should be aware that, whilst extensive use of Regaine 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.

4.4       Special Warnings and Special Precautions for Use

The safety and efficacy of the product in patients aged fewer than 18 or over 65 is unknown.

Minoxidil Regaine should only be used on a normal healthy scalp. Do not use if scalp is red, inflamed, infected, irritated or painful. or if using other medications on the scalp.

Regaine should not be used concurrently with any other medicines on the scalp

Minoxidil Regaine 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 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 or irritation of the scalp, or other unexpected new symptoms occur (see section 4.8)..

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

Accidental ingestion may cause serious cardiac adverse events.  Therefore this product has to be kept out of the reach of children.

Regaine 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 Extra Strength Topical Solution contains ethanol (alcohol), which will may cause burning and/or 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. Propylene Glycol, contained in this product, may cause skin irritation.

Some patients have experienced changes in hair colour and/or texture with Regaine use.

Some consumers reported increased hair shedding upon initiation of therapy with Regaine 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 Extra Strength and consult their doctor.

Users should be aware that, whilst extensive use of Regaine 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.

Using more than the recommended dose or applying more often will not improve results.

Continued use is necessary to increase and maintain hair re-growth, or hair loss will begin again.

Unwanted hair growth may be caused by the transfer of the product to areas other than the scalp.

4.5       Interactions

Pharmacokinetic drug interaction studies in humans revealed percutaneous minoxidil absorption is enhanced by tretinoin and anthralin as a result of increased stratum corneum permeability; betmethasone dipropionate increases local tissue concentrations of minoxidil and decreases systemic minoxidil absorption.

4.5       Interactions

Topical minoxidil should not be used concurrently with any other medications on the scalp.

Pharmacokinetic drug interaction studies in humans revealed percutaneous minoxidil absorption is enhanced by tretinoin and anthralin as a result of increased stratum corneum permeability; betmethasone dipropionate increases local tissue concentrations of minoxidil and decreases systemic minoxidil absorption.

Guanethidine has been reported to interact with oral formulations of minoxidil resulting in rapid and pronounced lowering of blood pressure

4.6       Pregnancy and Lactation

Systemically absorbed minoxidil is secreted in human milk.

4.6       Fertility, Pregnancy and Lactation

Systemically absorbed minoxidil is secreted in human milk.

Topical minoxidil should not be used during pregnancy and lactation.

Fertility

There are no adequate and well controlled studies relating to female fertility.

Studies in animals have shown fertility toxicity - reduced conception and implantation rates as well as a reduction in the number of live pups 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.

Pregnancy

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. There is potentially a risk of foetal harm in humans (see section 5.3, Preclinical safety data).A low, albeit remote, risk of fetal harm is possible in humans.

Breastfeeding

Systemically absorbed minoxidil is secreted in human milk. The effect of minoxidil on newborns/infants is unknown.

4.7       Effects on ability to Drive and Use Machines

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

4.7       Effects on ability to Drive and Use Machines

Minoxidil may cause dizziness or hypotension. If patients are affected they should not drive or operate machinery.Based on the pharmacodynamic and overall safety profile of topical minoxidil, it is not expected that Regaine 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 (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1,000, <1/100); rare (≥1/10,000, <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data).

The following adverse events were associated with placebo controlled clinical trials:

* This adverse event was identified during a clinical trial for Minoxidil Foam

The following adverse events were associated with post marketing experience:

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.

The safety of topical minoxidil from clinical trial data is based on data from 7 placebo-controlled randomised clinical trials in adults evaluating either 2% or 5% minoxidil solution, and two placebo-controlled randomised clinical trials in adults evaluating a 5% foam formulation.

Adverse drug reactions (ADRs) identified during clinical trials and post-marketing experience with minoxidil are included in the table below by System Organ Class (SOC).

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 frequenciesy of adverse reactions to topical minoxidil solution is defined usingare provided according to  the following convention:

Very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1,000, <1/100); rare (≥1/10,000, <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data).

The following adverse events were associated with placebo controlled clinical trials:

4.9       Overdose

Signs and symptoms

Increased systemic absorption of minoxidil may potentially occur if higher-than-recommended doses of Regaine Extra Strength are applied to larger surface areas of the body or areas other than the scalp.  There is no evidence that topically applied minoxidil is absorbed in sufficient quantity to cause systemic effects. When used as directed, overdose is unlikely.

Because of the concentration of minoxidil in Regaine Extra Strength, accidental ingestion has the potential of producing systemic effects related to the pharmacological action of the drug (2ml of Regaine Extra Strength contains 100mg; the maximum recommended adult dose for oral minoxidil administration in the treatment of hypertension)..

If this product is applied to an area of decreased integrity of the epidermal barrier caused by trauma, inflammation, or disease process in the skin, there is a potential for a systemic overdose effect.

The following very rare adverse events may occur due to the systemic effects of minoxidil;

Very Rare: (< 1/10,000)

Cardiovascular disorders: Heart rate increased, hypotension

General Disorders: Fluid retention resulting in weight increase

Nervous System Disorders: Dizziness

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.

4.9       Overdose

Signs and symptoms

Increased systemic absorption of minoxidil may potentially occur if higher-than-recommended doses of Regaine Extra Strength are applied to larger surface areas of the body or areas other than the scalp which therefore may lead to adverse events. 

There is no evidence that topically applied minoxidil is absorbed in sufficient quantity to cause systemic effects. When used as directed, overdose is unlikely.

Overdose due to oral administration or excessive systemic exposure of minoxidil exaggerates its cardiovascular effects and may present as hypotension, tachycardia and lethargy.

Because of the concentration of minoxidil in Regaine Extra Strength, accidental ingestion has the potential of producing systemic effects related to the pharmacological action of the drug (2ml of Regaine Extra Strength contains 100mg; the maximum recommended adult dose for oral minoxidil administration in the treatment of hypertension)..

If this product is applied to an area of decreased integrity of the epidermal barrier caused by trauma, inflammation, or disease process in the skin, there is a potential for a systemic overdose effect.

The following very rare adverse events may occur due to the systemic effects of minoxidil;

Very Rare: (< 1/10,000)

Cardiovascular disorders: Heart rate increased, hypotension

General Disorders: Fluid retention resulting in weight increase

Nervous System Disorders: Dizziness

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.

5.3       Preclinical safety data

None that are relevant to human safety.

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.

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 seen 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 use.

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.

None that are relevant to human safety.

6.6       Instructions for use/handling

None.

6.6       Instructions for use/handlingSpecial precautions for disposal of a used medicinal product or waste materials derived from such medicinal product and other handling of the product

The solution is flammable and exposure of the container and contents to naked flames should be avoided during use, storage and disposal.

None.