Leaflet VANIQA 11.5% cream

Vaniqa 11.5% cream

Each gram of cream contains 115 mg of eflornithine (as hydrochloride monohydrate).

Each gram of cream contains 47.2 mg of cetostearyl alcohol, 14.2 mg of stearyl alcohol, 0.8 mg ofmethyl parahydroxybenzoate and 0.32 mg of propyl parahydroxybenzoate.

For the full list of excipients, see section 6.1.

Cream.

White to off white cream

Treatment of facial hirsutism in women.

Vaniqa cream should be applied to the affected area twice daily, at least eight hours apart. Efficacy hasonly been demonstrated for affected areas of the face and under the chin. Application should belimited to these areas. Maximal applied doses used safely in clinical trials were up to 30 grams permonth.

Improvement in the condition may be noticed within eight weeks of starting treatment.

Continued treatment may result in further improvement and is necessary to maintain beneficial effects.

The condition may return to pre-treatment levels within eight weeks following discontinuation oftreatment.

Use should be discontinued if no beneficial effects are noticed within four months of commencingtherapy.

Patients may need to continue to use a hair removal method (e.g. shaving or plucking) in conjunctionwith Vaniqa. In that case, the cream should be applied no sooner than five minutes after shaving or useof other hair removal methods, as increased stinging or burning may otherwise occur.

Special population

Elderly: (> 65 years) no dosage adjustment is necessary.

The safety and efficacy of Vaniqa in children aged 0 to 18 years has not been established. There is nodata available to support use in this age group.

Hepatic/renal impairment: the safety and efficacy of Vaniqa in women with hepatic or renalimpairment have not been established. As the safety of Vaniqa has not been studied in patients withsevere renal impairment, caution should be used when prescribing Vaniqa for these patients. No dataare available.

A thin layer of the cream should be applied to clean and dry affected areas. The cream should berubbed in thoroughly. The medicinal product should be applied such that no visual residual productremains on the treated areas after rub-in. Hands should be washed after applying this medicinalproduct. For maximal efficacy, the treated area should not be cleansed within four hours ofapplication. Cosmetics (including sunscreens) can be applied over the treated areas, but no sooner thanfive minutes after application.

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Excessive hair growth can result from serious underlying disorders (e.g. polycystic ovary syndrome,androgen secreting neoplasm) or certain active substances (e.g. cyclosporin, glucocorticoids,minoxidil, phenobarbitone, phenytoin, combined oestrogen-androgen hormone replacement therapy).

These factors should be considered in the overall medical treatment of patients who might beprescribed Vaniqa.

Vaniqa is for cutaneous use only. Contact with eyes or mucous membranes (e.g. nose or mouth)should be avoided. Transient stinging or burning may occur when the cream is applied to abraded orbroken skin.

If skin irritation or intolerance develops, the frequency of application should be reduced temporarily toonce a day. If irritation continues, treatment should be discontinued and the physician consulted.

This medicinal product contains cetostearyl alcohol and stearyl alcohol which may cause local skinreactions (e.g. contact dermatitis) as well as methyl parahydroxybenzoate and propylparahydroxybenzoate which may cause allergic reactions (possibly delayed).

No interaction studies have been performed.

Throughout clinical trials data from a limited number of exposed pregnancies (22) indicate that there isno clinical evidence that treatment with Vaniqa adversely affects mothers or foetuses. Among the22 pregnancies that occurred during the trials, only 19 pregnancies occurred while the patient wasusing Vaniqa. Of these 19 pregnancies, there were 9 healthy infants, 5 elective abortions,4 spontaneous abortions and 1 birth defect (Down’s Syndrome to a 35 year old). To date, no otherrelevant epidemiological data are available. Animal studies have shown reproductive toxicity(see section 5.3). The potential risk to humans is unknown. Therefore, women who are pregnant orplanning pregnancy should use an alternative means to manage facial hair.

It is not known whether eflornithine/metabolites are excreted in human milk. Women should not use

Vaniqa whilst breastfeeding.

There are no data available.

Vaniqa has no or negligible influence on the ability to drive and use machines.

The mostly skin related adverse reactions reported were primarily mild in intensity and resolvedwithout discontinuation of Vaniqa or initiation of medical treatment. The most frequently reportedadverse reaction was acne, which was generally mild. In the vehicle-controlled trials (n= 596), acnewas observed in 41% of patients at baseline; 7% of patients treated with Vaniqa and 8% treated withvehicle experienced a worsening of their condition. Of those with no acne at baseline, similarpercentages (14%) reported acne following treatment with Vaniqa or vehicle.

The following listing notes the frequency of adverse skin reactions seen in clinical trials, according to

MedDRA convention. MedDRA conventions for frequency are very common (≥1/10), common(≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare(<1/10,000), or not known (cannot be estimated from the available data) including isolated reports.

Note that over 1350 patients were treated with Vaniqa in these trials for 6 months to one year, whileonly slightly more than 200 patients were treated with vehicle for 6 months. Most events werereported at similar rates between Vaniqa and vehicle. The skin effects of burning, stinging, tingling,rash and erythema were reported at higher levels in Vaniqa treated patients compared to vehicle, asindicated by the asterisk (*).

Frequency of adverse skin reactions seen in Vaniqa clinical trials, (according to MedDRA frequencyconvention).

Very common Acne(≥1/10)

Common Pseudofolliculitis barbae, alopecia, stinging skin*, burning skin*, dry skin,(≥1/100 to <1/10) pruritus, erythema*, tingling skin*, irritated skin, rash*, folliculitis

Uncommon Ingrown hair, oedema face, dermatitis, oedema mouth, papular rash, bleeding(≥1/1,000 to <1/100) skin, herpes simplex, eczema, cheilitis, furunculosis, contact dermatitis,abnormal hair texture and abnormal hair growth, hypopigmentation, flushingskin, lip numbness, skin soreness

Rare Rosacea, seborrheic dermatitis, skin neoplasm, maculopapular rash, skin(≥1/10,000 to cysts, vesiculobullous rash, skin disorder, hirsutism, skin tightness<1/1,000)

The adverse reactions observed in adolescents are similar to the ones observed in adults.

Reporting suspected adverse reactions after authorisation of the medicinal product is important. Itallows continued monitoring of the benefit/risk balance of the medicinal product. Healthcareprofessionals are asked to report any suspected adverse reactions via the national reporting systemlisted in Appendix V.

Given the minimal cutaneous penetration of eflornithine (see section 5.2), overdose is highly unlikely.

However, should very high dose cutaneous administration or accidental oral ingestion occur, attentionshould be paid to the effects seen with therapeutic doses of intravenous eflornithine (400 mg/kg/day orapproximately 24 g/day) used in the treatment of Trypanosoma brucei gambiense infection (Africansleeping sickness): hair loss, facial swelling, seizures, hearing impairment, gastrointestinaldisturbance, loss of appetite, headache, weakness, dizziness, anaemia, thrombocytopenia andleucopenia.

If symptoms of overdose occur the use of the medicinal product should be stopped.

Pharmacotherapeutic group: other dermatological preparations, ATC code: D11AX16.

Eflornithine irreversibly inhibits ornithine decarboxylase, an enzyme involved in the production of thehair shaft by the hair follicle. Vaniqa has been shown to reduce the rate of hair growth.

The safety and efficacy of Vaniqa was evaluated in two double-blind, randomised, vehicle-controlledclinical trials involving 596 women of skin types I-VI (395 on Vaniqa, 201 on vehicle) treated for upto 24 weeks. Physicians assessed the change from baseline on a 4-point scale, 48 hours after womenhad shaved the treated areas of the affected areas of the face and under the chin, consideringparameters such as hair length and density, and darkening of the skin associated with the presence ofterminal hair. Improvement was seen as early as 8 weeks after initiation of treatment.

The combined results of these two trials are presented below:

Outcome* Vaniqa 11.5% cream Vehicle

Clear/almost clear 6% 0%

Marked improvement 29% 9%

Improved 35% 33%

No improvement/worse 30% 58%

* At end of therapy (Week 24). For patients who discontinued therapy during thetrial last observations were carried forward to Week 24.

Statistically significant (p ≤ 0.001) improvement for Vaniqa versus vehicle was seen in each of thesestudies for women with marked improvement and clear/almost clear responses. These improvementsresulted in a corresponding reduction in the darkening appearance of the facial skin associated with thepresence of terminal hair. Subgroup analysis revealed a difference in treatment success where 27% ofnon-white women and 39% of white women showed a marked or better improvement. Subgroupanalysis also showed that 29% of obese women (BMI ≥ 30) and 43% of normal weight women(BMI < 30) showed a marked or better improvement. About 12% of women in the clinical trials werepostmenopausal. Significant improvement (p < 0.001) versus vehicle was seen in postmenopausalwomen.

Patient self-assessments demonstrated a significantly reduced psychological discomfort with thecondition, as measured by responses to 6 questions on a visual analogue scale. Vaniqa significantlyreduced how bothered patients felt by their facial hair and by the time spent removing, treating, orconcealing facial hair. Patient comfort in various social and work settings was also improved. Patientself-assessments were found to correlate with physician observations of efficacy. These patient-observable differences were seen 8 weeks after initiating treatment.

The condition returned to pre-treatment levels within eight weeks after discontinuation of treatment.

Steady state cutaneous penetration of eflornithine in women from Vaniqa on facial skin of shavingwomen was 0.8%.

The steady state plasma half-life of eflornithine was approximately 8 hours. Steady state was reachedwithin four days. The steady state peak and trough plasma concentrations of eflornithine wereapproximately 10 ng/ml and 5 ng/ml, respectively. The steady state 12-hour area under the plasmaconcentration versus time curve was 92.5 ng.hr/ml.

Eflornithine is not known to be metabolised and is eliminated primarily in the urine.

Non-clinical data reveal no special hazard for humans based on conventional studies of repeat dosetoxicity, genotoxicity and carcinogenic potential, including one photocarcinogenicity study in mice.

In a dermal fertility study in rats, no adverse effects on fertility were observed at up to 180 times thehuman dose. In dermal teratology studies, no teratogenic effects were observed in rats and rabbits atdoses up to 180 and 36 times the human dose, respectively. Higher doses resulted in maternal andfoetal toxicity without evidence of teratogenicity.

Cetostearyl alcohol;

Macrogol cetostearyl ether;

Dimeticone;

Glyceryl stearate;

Macrogol stearate;

Methyl parahydroxybenzoate (E218);

Liquid paraffin;

Phenoxyethanol;

Propyl parahydroxybenzoate (E216);

Purified water;

Stearyl alcohol;

Sodium hydroxide (E524) (to adjust pH)

Not applicable.

3 years.

Shelf-life after first opening: 6 months.

Do not store above 25°C.

High density polyethylene tube with a polypropylene screw cap containing 15 g, 30 g or 60 g ofcream. Not all pack sizes may be marketed.

Any unused medicinal product or waste material should be disposed of in accordance with localrequirements.

Almirall, S.A.

Ronda General Mitre, 151,08022 Barcelona,

Spain.

EU/1/01/173/001-003

Date of first authorisation: 20 March 2001

Date of latest renewal: 07 March 2011

Detailed information on this medicinal product is available on the website of the European Medicines

Agency http://www.ema.europa.eu