- 1. NAME OF THE MEDICINAL PRODUCT
- 2. QUALITATIVE AND QUANTITATIVE COMPOSITION
- 3. PHARMACEUTICAL FORM
- 4. CLINICAL PARTICULARS
- 4.1 Therapeutic indication
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Fertility, pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. PHARMACOLOGICAL PROPERTIES
- 6. PHARMACEUTICAL PARTICULARS
- 7. MARKETING AUTHORISATION HOLDER
- 8. MARKETING AUTHORISATION NUMBERS
- 9. DATE OF FIRST AUTHORISATION / RENEWAL OF THE AUTHORISATION
- 10. DATE OF REVISION OF THE TEXT
1.NAME OF THE MEDICINAL PRODUCT
Vaniqa 11.5% cream
2.QUALITATIVE AND QUANTITATIVE COMPOSITION
Each gram of cream contains 115 mg of eflornithine (as hydrochloride monohydrate).
Excipients with known effect:
Each gram of cream contains 47.2 mg of cetostearyl alcohol, 14.2 mg of stearyl alcohol, 0.8 mg of methyl parahydroxybenzoate and 0.32 mg of propyl parahydroxybenzoate.
For the full list of excipients, see section 6.1.
White to off white cream
Treatment of facial hirsutism in women.
4.2Posology and method of administration
Vaniqa cream should be applied to the affected area twice daily, at least eight hours apart. Efficacy has only been demonstrated for affected areas of the face and under the chin. Application should be limited to these areas. Maximal applied doses used safely in clinical trials were up to 30 grams per month.
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
Use should be discontinued if no beneficial effects are noticed within four months of commencing therapy.
Patients may need to continue to use a hair removal method (e.g. shaving or plucking) in conjunction with Vaniqa. In that case, the cream should be applied no sooner than five minutes after shaving or use of other hair removal methods, as increased stinging or burning may otherwise occur.
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 no data available to support use in this age group.
Hepatic/renal impairment: the safety and efficacy of Vaniqa in women with hepatic or renal impairment have not been established. As the safety of Vaniqa has not been studied in patients with
severe renal impairment, caution should be used when prescribing Vaniqa for these patients. No data are available.
Method of administration
A thin layer of the cream should be applied to clean and dry affected areas. The cream should be rubbed in thoroughly. The medicinal product should be applied such that no visual residual product remains on the treated areas after
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
4.4Special warnings and precautions for use
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
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 or broken skin.
If skin irritation or intolerance develops, the frequency of application should be reduced temporarily to once 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 skin reactions (e.g. contact dermatitis) as well as methyl parahydroxybenzoate and propyl parahydroxybenzoate which may cause allergic reactions (possibly delayed).
4.5Interaction with other medicinal products and other forms of interaction
No interaction studies have been performed.
4.6Fertility, pregnancy and lactation
Throughout clinical trials data from a limited number of exposed pregnancies (22) indicate that there is no clinical evidence that treatment with Vaniqa adversely affects mothers or foetuses. Among the
22 pregnancies that occurred during the trials, only 19 pregnancies occurred while the patient was using 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 other relevant 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 or planning 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.
4.7Effects on ability to drive and use machines
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 resolved without discontinuation of Vaniqa or initiation of medical treatment. The most frequently reported adverse reaction was acne, which was generally mild. In the vehicle controlled trials (n= 596), acne was observed in 41% of patients at baseline; 7% of patients treated with Vaniqa and 8% treated with vehicle experienced a worsening of their condition. Of those with no acne at baseline, similar percentages (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, while only slightly more than 200 patients were treated with vehicle for 6 months. Most events were reported 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, as indicated by the asterisk (*).
Frequency of adverse skin reactions seen in Vaniqa clinical trials, (according to MedDRA frequency convention).
Skin and subcutaneous tissue disorders
Pseudofolliculitis barbae, alopecia, stinging skin*, burning skin*, dry skin,
(≥1/100 to <1/10)
pruritus, erythema*, tingling skin*, irritated skin, rash*, folliculitis
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, flushing
skin, lip numbness, skin soreness
Rosacea, seborrheic dermatitis, skin neoplasm, maculopapular rash, skin
cysts, vesiculobullous rash, skin disorder, hirsutism, skin tightness
The adverse reactions observed in adolescents are similar to the ones observed in adults.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed 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, attention should be paid to the effects seen with therapeutic doses of intravenous eflornithine (400 mg/kg/day or approximately 24 g/day) used in the treatment of Trypanosoma brucei gambiense infection (African sleeping sickness): hair loss, facial swelling, seizures, hearing impairment, gastrointestinal disturbance, loss of appetite, headache, weakness, dizziness, anaemia, thrombocytopenia and leucopenia.
If symptoms of overdose occur the use of the medicinal product should be stopped.
Pharmacotherapeutic group: other dermatological preparations, ATC code: D11AX16.
Mechanism of action
Eflornithine irreversibly inhibits ornithine decarboxylase, an enzyme involved in the production of the hair shaft by the hair follicle. Vaniqa has been shown to reduce the rate of hair growth.
Clinical efficacy and safety
The safety and efficacy of Vaniqa was evaluated in two
The combined results of these two trials are presented below:
Vaniqa 11.5% cream
Clear / almost clear
No improvement / worse
* At end of therapy (Week 24). For patients who discontinued therapy during the trial last observations were carried forward to Week 24.
Statistically significant (p ≤ 0.001) improvement for Vaniqa versus vehicle was seen in each of these studies for women with marked improvement and clear/almost clear responses. These improvements resulted in a corresponding reduction in the darkening appearance of the facial skin associated with the presence of terminal hair. Subgroup analysis revealed a difference in treatment success where 27% of
(BMI < 30) showed a marked or better improvement. About 12% of women in the clinical trials were postmenopausal. Significant improvement (p < 0.001) versus vehicle was seen in postmenopausal women.
The condition returned to
Steady state cutaneous penetration of eflornithine in women from Vaniqa on facial skin of shaving women was 0.8%.
The steady state plasma
Eflornithine is not known to be metabolised and is eliminated primarily in the urine.
5.3Preclinical safety data
6.1List of excipients
Macrogol cetostearyl ether;
Methyl parahydroxybenzoate (E218);
Propyl parahydroxybenzoate (E216);
Sodium hydroxide (E524) (to adjust pH)
6.4Special precautions for storage
Do not store above 25°C.
6.5Nature and contents of container
High density polyethylene tube with a polypropylene screw cap containing 15 g, 30 g or 60 g of cream. Not all pack sizes may be marketed.
6.6Special precautions for disposal
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
7.MARKETING AUTHORISATION HOLDER
Ronda General Mitre, 151,
8.MARKETING AUTHORISATION NUMBERS
9.DATE OF FIRST AUTHORISATION / RENEWAL OF THE AUTHORISATION
Date of first authorisation: 20 March 2001
Date of latest renewal: 07 March 2011
10.DATE OF REVISION OF THE TEXT
Detailed information on this medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu