Month/Year (Leave blank) Issue No New Medicines Profile February 2005 Issue No. 05/04 Eflornithine cream Concise evaluated information to support the managed entry of new medicines in the NHS Introduction Summary Hirsutism affects 5-15% of women.2 It is Eflornithine cream (Vaniqa®) is licensed in the UK for the treatment defined as the excessive growth of coarse of facial hirsutism in women. It irreversibly inhibits an enzyme hairs in women which may appear in a (ornithine decarboxylase) involved in controlling hair growth and male-like pattern i.e. face, chest, stomach proliferation. and thighs. It is usually due to increased androgen production and increased Treatment does not remove hairs but slows down hair growth such sensitivity to androgens of the skin. Some that users require less frequent hair removal by other methods. drugs e.g. ciclosporin, steroids, danazol, Unpublished clinical trial data indicate that eflornithine improves valproate and phenytoin, may also induce symptoms of hirsutism, reduces darkening of facial skin and reduces hirsutism.3 Diagnosis of hirsutism associated psychological discomfort. Once treatment stops, hair re- requires exclusion of any underlying grows to pre-treatment levels within eight weeks. causes, such as polycystic ovaries, prior to treatment. Eflornithine cream is a prescription only medicine and the first topical preparation licensed for an indication that is generally self- There are currently 3 common classes of treated without consultation with a healthcare professional. Its treatment for hirsutism in women:2 availability may prompt increased GP consultations. · Mechanical or cosmetic e.g. waxing. Dianette® is the only other UK licensed product for hirsutism and · Androgen suppression e.g. Dianette®. costs about £3.70 per month. Eflornithine cream (Vaniqa®) costs · Peripheral androgen blockade e.g. £13 per month. cyproterone, spironolactone, finasteride. With the exception of Dianette®, the Brand Name, (Manufacturer): Vaniqa® (Shire Pharmaceuticals other drugs listed above are not licensed Li mited). for this indication. BNF Therapeutic Class: Ornithine decarboxylase inhibitor . Proposed Eflornithine cream (Vaniqa®) was BNF section 13.9 (Shampoos and other preparations for scalp launched in July 2004 specifically for the conditions) treatment of facial hirsutism in women. It Licensed Indications: Treatment of facial hirsutism in women. has a different mechanism of action to existing treatments in that it irreversibly Dosage and Administration: A thin layer is applied to the affected inhibits ornithine decarboxylase, an areas twi ce a day, at least 8 hours apart. Patient must be counselled enzyme involved in controlling hair not to cl ean the treated ar ea within four hours of application. growth and proliferation. Maximum dose 30 grams per month.1 Discontinue treatment if no effects are seen within 4 months. Evidence Marketed: July 2004 The efficacy of eflornithine has been demonstrated in a number of trials, none Cost Comparisons: Cost per month based on MIMS December of which have been fully published. The 2004. majority of trials used eflornithine 15% cream, which equates to 11.5% monohydrate chloride as in the UK S pironolac tone* 50-200m g O D day s 4-21 £5.60 licensed product.1,3 After reviewing the trials submitted for licensing purposes, M etform in* 500m g TD S £2.19 the EMEA concluded that the data demonstrated that eflornithine cream Cy proterone* 100m g O D day s 5-14 £12 improves symptoms of hirsutism, reduces darkening appearance of facial skin, and D ianette 1 O D £4 reduces psychological discomfort with the condition.3 V aniqa B D £13 £0 £2 £4 £6 £8 £10 £12 £14 The two main randomised, double blind, multicentre vehicle controlled studies (DE140-001 and ­002) involved a total *Hirsutism is an unlicensed indication. of 596 women who had facial hirsutism N.B. Doses shown for general comparison and do not imply that required removal at least twice a therapeutic equivalence. week.4,5 The subjects applied (in a ratio Eflornithine Cream of 2:1) either eflornithine 15% or upper lip and chin.6 Study 010 Vaniqa® cream has been available in a vehicle-cream twice a day for was a 12-month study: 18% of the USA since July 2000 and, as yet, 24 weeks, and were followed for subjects were rated clinical there are no significant post 8 weeks when they received no successes after 20 weeks of marketing data. treatment. The primary efficacy treatment, rising to 24% at 52 measure was a four point weeks. Study 011 was a 6-month Place in Therapy Physicians Global Assessment study: at 26 weeks 47.3% of Hirsutism is largely subjective and (PGA) of improvement or subjects were rated clinical has an impact on the patient's quality worsening of the condition successes. of life. Many women currently use compared to baseline. mechanical or cosmetic methods for Secondary efficacy measures Safety removing unwanted facial hair were a self assessment Systemic absorption of without asking advice from a GP. questionnaire and video analysis eflornithine after topical use is of reduction in hair growth and very low (<1%).7 The most Eflornithine cream appears to be spatial mass. frequently reported adverse effective in improving symptoms of reaction is acne, which is hirsutism for up to one year. It does Statistically significant generally mild. not provide permanent hair removal. improvements in facial hair Methods for permanent hair removal growth were seen after week 4 Four dermal safety studies are available e.g. electrolysis and (001 study) and week 8 (002 evaluated the potential of laser hair removal. The latter does study) in favour of eflornithine eflornithine and the vehicle to not work well in darker-skinned based on PGA. The differences cause contact sensitisation, people so eflornithine cream may became clinically significant at cumulative irritation, phototoxicity appear to have a place in this group. week 16 (001 study) and week and photocontact allergy.8 All four However, success rates in the trials 24 (002 study). At 24 weeks, studies were open-label and within- have been greater in women with fair at least 70% of subjects using subject, vehicle controlled. skin.3 eflornithine had at least some improvements in their condition, The results indicated that Eflornithine cream has not been compared to 41% using the eflornithine is unlikely to be compared to other hair reduction vehicle.4 Overall, when the data photoallergic or phototoxic treatments; hence it is difficult to from the two studies were reactive. However the possibility comment on its place in therapy. combined, 35% of the of allergic sensitisation cannot be eflornithine treated subjects ruled out. With regards to were classed as treatment irritation, when compared to Append Appen ix I: Bibliograph ix I: Bibliogr y aph successes versus only 9% of the sodium lauryl sulphate (classed as The full Lo The full L n o d n on New Drugs Group d vehicle treated subjects.4 A `extremely irritant'), eflornithine Document is found on Document clinical success was defined as a was classed as `irritating'. The Drug infozon Drug e infozon . grade 2 score based on PGA, conditions in the studies were i.e. reduced visibility of terminal exaggerated i.e. eflornithine hair on face and minimal Risk Management Issues: cream was applied and darkening of skin due to maintained under occlusive terminal hair. Success rates The USA marketed product dressings for 21 days. Occluded varied according to race: in contains eflornithine 13.9% exposure to eflornithine (which is DE140-001 the success rates whereas the UK marketed product not recommended) produced for Caucasians was 30.6%, contains eflornithine 11.5%. dermal irritation in most subjects. compared to 13.8% for non- No subjects discontinued therapy Caucasians. In DE140-002, the Vaniqa is a "black triangle" drug ­ due to adverse events and all success rates were 46.2% and any side effects must be reported were included in the final analysis. 34.9% respectively. All to the CSM. statistically significant The SPC of Vaniqa® states that differences for reduction in hair irritated skin is a common length and spatial hair mass adverse effect however it were lost at 32 weeks, after 8 occurred at a similar rate to weeks of no active treatment. vehicle in clinical trials.1 Two open-label studies (DE140- There are no known interactions 010 and ­011) evaluated the with Vaniqa® cream.1 use of eflornithine in 970 women who removed hair at least twice a week from their Produced for the UK Medicines Information Service By Iram Reza (Husain), London Medicines Information Service, Pharmacy Department, Northwick Park Hospital, Watford Road, Harrow HA1 3UJ. Tel: 020 8869 3973. The information contained in this document will be superseded in due course. Not to be used for commercial purposes. May be copied for use within the NHS. Eflornithine Cream Appendix I Bibliography References 1) Summary of Product Characteristics: Vaniqa 11.5% 7) Malhotra B, Noveck R, Behr D, Palmisano M. cream Shire Pharmaceutical Contracts Ltd 2001 Percutaneous absorption and pharmacokinetics of www.emc.medicines.org.uk eflornithine HCl 13.9% cream in women with unwanted facial hair. J Clin Pharmacol 2001; 41:972- 2) Azziz R. The evaluation and management of 978. hirsutism. Obstet Gynecol 2003; 101:995-1007. 8) Hickman JG, Huber F, Palmisano M. Human dermal 3) Scientific Discussion: Vaniqa Shire Pharmaceuticals safety studies with eflornithine HCl 13.9% cream 2004 (Vaniqa), a novel treatment for excessive facial hair. http://www.emea.eu.int/humandocs/Humans/EPAR/ Curr Med Res Opin 2001; 16(4): 235-244. vaniqa/vaniqa.htm Acc essed: 28-7-0004 4) Schrode K, Huber F, Staszak J, Altman DJ, Shander D, Morton J Randomized, double-blind, vehicle- controlled safety and efficacy evaluation of eflornithine 15% cream in the treatment of women with excessive facial hair. 58th Annual meeting of the American Academy of Dermatology. 2000 March 10-15, San Francisco (CA). 2000 5) Huber F, Schrode K, Staszak J, Altman DJ, Funkhouser M, Shander D Use of a video imaging system to obtain hair measurement data in controlled clinical trials evaluating the safety and efficacy of eflornithine 15% cream in the treatment of excessive facial hair in women. 58th Annual meeting of the American Academy of Dermatology. 2000 March 10-15, San Francisco (CA). 2000 6) Schrode K, Huber F, Staszak J, Altman DJ, and the Eflornithine Study Group. Evaluation of the long-term safety of eflornithine 15% cream in the treatment of women with excessive facial hair. 58th Annual meeting of the American Academy of Dermatology. 2000 March 10-15, San Francisco (CA). 2000