Microsoft word - epiduo pcb final feb 2010.doc

London New Drugs Group
February 2010
RIMARY CARE BRIEFING: Epiduo 0.1%/2.5% gel
This Primary Care Briefing has been produced to inform healthcare professionals in primary care of the new Epiduo, which is used for mild to moderate acne when comedones, papules and pustules are present.
What is Epiduo?
What is Epiduo licensed for?
Epiduo is a topical gel which contains adapalene 1mg/1g Cutaneous treatment of Acne vulgaris when (0.1%) and benzoyl peroxide 25mg/1g (2.5%).1 A 45g comedones, papules and pustules are present. The safety of Epiduo has not been studied in children under Adapalene, a naphthoic acid derivative, has retinoid-like activity and binds to retinoic acid receptors. It How is Epiduo administered?
normalises the differentiation of follicular epithelial cells, A thin layer of Epiduo gel should be applied to the leading to a reduction in microcomedone formation and entire acne-affected area once a day, in the evening, has anti-inflammatory properties. Benzoyl peroxide on clean and dry skin.1 The eye and lip area should be (BPO) has antimicrobial activity against P. acnes, which is present in abnormal levels in acne. BPO also has exfoliative and keratolytic activities, as well as being What are the current recommendations for the
sebostatic and counteracting the excessive sebum treatment of acne?
The British Association of Dermatologists has advised the Clinical Knowledge Service on treatment recommendations for acne2 and there are European recommendations on the use of oral antibiotics.3 (see table below). Table 1: Treatment recommendations for acne2;3
First line
Second line
Alternative for women
Topical retinoid (tretinoin, isotretinoin, adapalene) or Topical antibiotic (clindamycin, erythromycin ± zinc) and can be used in women with who also require BPO± topical or oral (tetracyclines or erythromycin) antibiotics if topical treatment not tolerated. Moderate
Topical retinoid (isotretinoin/tretinoin) + BPO may be poorly tolerated. Use of topical retinoid with topical antibiotic may promote bacterial resistance. Oral antibiotic ± topical therapy whilst waiting for
What does Epiduo offer to the treatment of acne?
What did the main trials show?
Combination therapy is based on the premise that two There have been three 12-week placebo-controlled trials drugs targeting acne by different mechanisms should be in which Epiduo has been compared to monotherapy with more effective that either alone. The combination of BPO adapalene and BPO5-7 and one 12-month open-label and adapalene in Epiduo has been shown in trials to be study8 (see separate Appendix). The majority of consistently more effective in reducing the total number of subjects (aged 12-58 years) enrolled had moderate lesions (inflammatory and non-inflammatory) and to have acne. All treatments were applied once daily. Efficacy higher success rates than the monotherapies alone. For data were based on the intention-to-treat populations. A the patient, this means only one topical therapy needs to treatment effect with Epiduo was seen as early as after 1 be applied once a day, rather than two. If two topical week of treatment.6 Success rates and total lesion therapies are used, such as a topical retinoid and BPO, reductions were statistically significantly higher with one would be applied in the morning and one in the Epiduo treatment compared with the monotherapies. evening. A fixed combination of two active treatments Statistically significantly more patients were rated as opens up the possibility of triple topical therapy for having mild/almost clear/clear acne compared with the monotherapies. A synergistic effect of adapalene and BPO was seen. No subject discontinued Epiduo treatment because of lack of efficacy.5;6 What needs to be monitored?
THIS IS AN NHS DOCUMENT NOT TO BE USED FOR COMMERCIAL AND MARKETING PURPOSES.
Additional trial information is at http://www.nelm.nhs.uk/en/NeLM-Area/Evidence/Drug-Specific-Reviews/Primary- Care-Briefing-Epiduo-for-the-treatment-of-acne/ . For further details contact med.info@nwlh.nhs.uk. Early signs of clinical improvement usually appear within Does Epiduo interact with other medicinal
1-4 weeks of initiating treatment.1 If irritation occurs, the products?
patient should be advised to use non-comedogenic (non- No interaction studies have been carried out but, from pore blocking) moisturisers, apply Epiduo every other day, previous experience with adapalene and BPO, there are to temporarily stop using Epiduo or to discontinue use no known interactions with medicinal products that may altogether if the irritation is too great.1 be used topically and concurrently with Epiduo. Other retinoids, BPO or drugs with a similar mode of action Safety issues
should not be used concurrently. In a 30-day What are the side effects of Epiduo?
pharmacokinetic study the level of adapalene was not Dry skin, irritative contact dermatitis, burning and skin quantifiable in the majority of plasma samples taken. irritation commonly occurred in trials. Skin irritation is The percutaneous penetration of BPO is low and its generally mild to moderate with symptoms peaking during metabolite is rapidly eliminated. Interactions with the first few weeks and then subsiding spontaneously.1 systemic medicinal products are unlikely.1 Few subjects discontinued trials due to treatment-related
Cost comparison

Product Cost9
Adapalene
• Differin cream / gel: 45g = £11.40 (patent expired 200610) Azelaic acid
• 15% gel (Finacea): 30g = £7.48 • 20% cream (Skinoren): 30g = £3.74 • Strengths: 2.5% - 10% - lower concentrations seem as effective as higher concentrations. • Costs range from £1.51 (PanOxyl 5% gel 40g) to £4.17 (Acnecide 5% aqueous gel, 60g) • BPO 5% & clindamycin 1%: Duac Once Daily, 25g = £9.95, 50g: £19.90 • BPO 5% & potassium hydroxyquinoline sulphate 0.5% cream, 50g = £2.21 • Tetracycline, 500mg bd, 28x250mg= £9.09 • Erythromycin 500mg bd, 28x250mg caps = • Doxycycline 100mg od, 28x50mg = £1.76 Oral antibiotic
• Oxytetracycline 500mg bd, 28x250mg = £1.08 • Minocycline is not recommended, it is • Lymecycline 408mg od, 28 = £7.77; 56 = associated with lupus erythematosus-like Oral contraceptive
• Brevinor: 3x21: £1.99; Loestrin: 3x21 = £3.95; Microgynon: 3x21 = £2.87; Logynon: 3x21 = £3.96 • Dianette: 21 tablets = £2.92 Oral retinoid
• Isotretinoin, 500micrograms/kg daily increased if necessary to 1mg/kg (in 1–2 divided doses) for 16– 24 weeks; max. cumulative dose 150mg/kg per course; 56x5mg = £14.99; 56x20mg = £39.99. • Dalacin T (clindamycin 1% in aqueous alcoholic base): 30mL = £4.34, 50mL: £7.23 Topical antibiotic
• Stiemycin (erythromycin 2% in alcoholic base): 50mL = £7.69 • Zindaclin (clindamycin 1% gel): 30g = £8.66 • Zineryt (erythromycin 40mg & zinc 12mg/mL), 30mL = £7.71, 90mL = £22.24 • Adapalene, 0.1% cream or gel (Differin): 45g = £ 11.40 Topical retinoid
• Isotretinoin 0.05% gel (Isotrex): 30g = £ 5.94; with erythromycin 2% (Isotrexin): 30g = £7.47 • Tretinoin, 0.01% or 0.025% gel (Retin-A): 60g = £5.39 • Tretinoin 0.025% & erythromycin 4% in alcoholic base (Aknemycin Plus): 25mL = £7.05 (1) Summary of Product Characteristics. Epiduo 0.1%/2.5% gel. Galderma (UK) Ltd. Date of revision of the text: 11/11/2009. (2) Acne vulgaris. Updated July 2009. Clinical Knowledge Summaries. Accessed via: http://www.cks.nhs.uk/acne_vulgaris/in_the_right_clinical_topic#375456001 on 14/12/09. (3) Dreno B, Bettoli V, Ochsendorf F et al. European recommendations on the use of oral antibiotics for acne. Eur J Dermatol 2004; 14(6):391-399. http://www.john-libbey-eurotext.fr/e-docs/00/04/07/1B/vers_alt/VersionPDF.pdf (4) Summary of Product Characteristics: Dianette. Bayer Healthcare Ltd. Revised 01/05/08. Accessed via: http://emc.medicines.org.uk/medicine/1814/SPC/Dianette/ on 15/12/09. (5) Gollnick HPM, Draelos Z, Glenn MJ et al. Adapalene-benzoyl peroxide, a unique fixed-dose combination topical gel for the treatment of acne vulgaris: a transatlantic, randomized, double-blind, controlled study in 1670 patients. Br J Dermatol 2009; (6) Thiboutot DM, Weiss J, Bucko A et al. Adapalene-benzoyl peroxide, a fixed-dose combination for the treatment of acne vulgaris: results of a multicenter, randomized, double-blind, controlled study. J Am Acad Dermatol 2007; 57(5):791-799. (7) Stein Gold L, Tan J, Cruz-Santana A et al. A North American Study of adapalene-benzoyl peroxide combination gel in the treatment of acne. Cutis 2009; 84:110-116. (8) Pariser DM, Westmoreland P, Morris A et al. Long-term safety and efficacy of a unique fixed-dose combination gel of adapalene 0.1% and benzoyl peroxide 2.5% for the treatment of acne vulgaris. J Drugs Dermatol 2007; 6(9):899-905. (9) British National Formulary, 58th edition. September 2009. Ed. Martin J. British Medical Association and Royal Pharmaceutical Society of Great Britain. Accessed via www.bnf.org. (10) UKMi Central Patents database. UKMi Accessed via: www.ukmicentral.nhs.uk on 30/12/09. THIS IS AN NHS DOCUMENT NOT TO BE USED FOR COMMERCIAL AND MARKETING PURPOSES.
Additional trial information is at http://www.nelm.nhs.uk/en/NeLM-Area/Evidence/Drug-Specific-Reviews/Primary- Care-Briefing-Epiduo-for-the-treatment-of-acne/ . For further details contact med.info@nwlh.nhs.uk.

Source: http://www.medicinesresources.nhs.uk/upload/EpiDuo_PCB_FINAL_%20Feb2010.pdf