New Medicines Committee Briefing May 2013 Emollients and Barrier preparations Emollient and Barrier preparations are to be reviewed for use within: Primary Care Secondary Care Formulary application: Consultant submitting application: Clinical Director supporting application: Dr Nicholas Craven (Consultant Dermatologist) Gareth Rowland (Clinical Director) Dr Craven has requested that the whole skin section of the formulary be reviewed as this was last undertaken in 2010. The Area Prescribing Committee agreed for this to be done in sections hence starting with emollients and barrier preparations. Dr Craven noted that there is a large variety of brands available on the market which suggests that there is no correct product for all individuals. Emollients are tailored to individual preference in order to improve adherence and compliance in patients. There are no clinical trials that state that one emollient is better than the other; but they are different based on their oil content. This resulted in the proposal to produce an emollient ladder for the treatment of dry skin based on constituents of the preparations, while bearing in mind suitability to patient s lifestyle and choice. Relevance in therapy: Dry skin is a common symptom of a number of skin conditions, including atopic dermatitis/eczema, ichthyosis, irritant contact dermatitis, psoriasis and asteatotic eczema. 1 Skin conditions are one of the most common diseases among all age groups, ranging from atopic eczema in children to problems associated with ageing. 2 Atopic eczema usually begins in childhood and accounts for 10-20% of referrals to dermatologists, as well as about 30% of dermatological consultations in general practice. 3 Promoting good skin health 1
prevents skin breakdown and improves comfort and quality of life, and emollients have a crucial role in maintaining skin health and patient wellbeing. 4 Emollients are first line therapy for all dry skin conditions including eczema and psoriasis. 1 Patients skin conditions and emollient needs change during their lives and these changes need to be considered when choosing which emollient to use. 5,6 Emollient is generally defined as something that smoothens and softens the skin. The aim of using emollient therapy is to correct some of the factors that contribute to dry skin, to restore the skin barrier, and to reduce the likelihood of further damage. 5 The constituent products of emollients vary hugely though they all have some quantity of lipid in them. The consistency of an emollient is affected by ambient temperature, type of lipid within the emollient, proportion of lipid to water and other additives. 7 They can be thought of as a continuum with greasy, high lipid content products being at one end, and less greasy, high water content products being at the other. Ointments are the greasiest while creams are less greasy making them more cosmetically acceptable. Lotions have higher water content than creams which makes them easier to spread but less effective as emollients. 7 Hence, prescribing should be guided by clinical need and informed patient choice. Emollient wash products and bath emollients are recommended to be used in conjunction with leave-on emollient products. Some products can be used as bath additives, soap substitutes and as leave-on emollients (3:1). Moncrief et al produced a table on the different types of emollient products available, categorising them by their adjuvant properties (Table 1). 5 Emollients work to moisturise the skin by increasing the amount of water held in the stratum corneum. Depending on the constituents of the emollients, they work either by occlusion, trapping moisture into the skin or in an active way drawing moisture into the stratum corneum from the dermis. 8,9 Occlusion is most effectively achieved if greasy emollients such as petrolatum are used. It has been reported to reduce water loss by 98% whereas other oils only manage to reduce 20-30%. 9 The active movement of water from the dermis to the epidermis is achieved by emollients that contain humectants such as urea and glycerine. These have a low molecular weight and water-attracting properties and as they penetrate the epidermis they draw water in from the dermis and therefore compensate for the reduced levels of natural moisturizing factors and other natural humectants in diseased and older skin. 10 Some emollients can be exfoliative (especially when combined with products such as salicylic acid) and may have anti-inflammatory 11, antipruritic effects when combined with other excipients such as lauromacrogols. 12 Some also have physiologic lipids such as ceramides, cholesterol and fatty acids that are naturally found in the stratum corneum hence they help to replenish and restore the intercellular lipid matrix. 5 Aqueous cream contains 1% sodium lauryl sulphate (SLS), an anionic surfactant known to be profoundly irritant. 5 Its high water content makes it a less effective leave-on emollient for those with dry skin as it weakens the epidermal barrier and increases trans-epidermal water 2
loss. 13,14 In March 2013 the MHRA 15 published a safety alert stating that aqueous cream may be associated with skin reactions, particularly in children with atopic eczema. These reactions may be due to the presence of SLS or other ingredients. Following a UK review the MHRA now recommends aqueous cream labelling and information leaflet to be updated with a warning on the potential for local skin reactions, and SLS will be listed as an ingredient. NICE guidelines for managing eczema in children advise that aqueous cream is associated with stinging when used as a leave-on emollient but can be used as a wash product 16, and the National Eczema Society advises that if aqueous cream is used as a leave-on emollient it can irritate the skin of children with eczema and make it worse rather than better 17. Despite the irritant effects reported, in clinical practice aqueous cream has been useful in the treatment of eczema in a very large proportion of patients. Emollients and Barrier Preparations currently on the North Staffordshire Joint Formulary: 13.2 EMOLLIENT AND BARRIER PREPARATIONS 13.2.1 Emollients Aqueous cream Emulsifying ointment Hydrous ointment (oily cream) Liquid and White Soft Paraffin Ointment (50:50) Diprobase E45 Contains hypoallergenic lanolin Aquadrate Contains urea Dermol 500 Lotion 13.2.1.1 Emollient bath and shower preparations APC Review: December 2010 Dermalo Hydromol Oilatum 1 st Line 2 nd Line Restriction: For patients with sensitivity to acetylated wool alcohol Contains lanolin 13.2.2 Barrier preparations Conotrane Sudocrem 3
EMOLLIENT GUIDE This guide is to aid in choice of product. The list is not exhaustive as there are other products which could be used when these have been tried first. 3:1 products can be used as bath additive, soap substitutes and as leave on emollients. Name Legal category Pack size Comments 50% liquid soft paraffin and 50% white soft paraffin (50:50) Hydromol ointment (3:1) Diprobase ointment Epaderm ointment (3:1) Very greasy 4 250g Greasy 125g 50g 125g Rich cream Doublebase Gel P Creamy Epaderm cream GSL 50g Diprobase cream GSL 50g Same formula as Hydromol but more expensive Preservative free Creamy with antimicrobial effect Dermol cream P Creamy with urea content Balneum (urea 5%) GSL 50g UHNS exc VAT 1.87 1.85 2.00 4.43 0.90 3.80 3.67 6.53 2.33 5.12 1.45 5.91 0.90 3.80 2.51 5.82 Cost Primary Care exc VAT 3.05 6.09 2.84 4.82 1.28 5.99 3.85 6.53 2.65 5.83 1.65 6.74 1.28 6.32 2.68 9.37 2.80 9.80 Aquadrate (urea 10%) P 4.02 4.37 LIGHT E45 cream GSL 50g 0.85 3.05 1.61 4.62 ZeroAQS GSL Light with antimicrobial effect Dermol 500 lotion P 500ml 5.30 6.04 Emollient bath and shower preparations Aqueous cream (only as a soap GSL 0.45 1.12 substitute) 0.84 5.60 Dermol 600 bath emollient P 600ml 6.63 7.55 1.45 2.89 2.86 6.63 1.65 3.29
Dermalo bath emollient P 500ml 3.02 3.44 Hydromol bath & shower P 350ml 3.32 3.61 emollient additive 500ml 3.78 4.11 Barrier preparation Conotrane P 0.81 0.88 *Prices are from Drug Tariff April 2013 and C+D monthly pricelist February 2013 Items recommended to be removed from the Joint Formulary Emulsifying ointment Hydrous ointment Oilatum cream Oilatum Junior bath & shower emollient Oilatum emollient Sudocrem Paraffin white soft BP Paraffin yellow soft BP 5
Table 1: Emollient products 5 Leave-on Products Wash Products Bath emollients Class Definition Usage Priority Patient Groups Occlusive emollient cream Occlusive ointment Occlusive ointment no water Humectantcontaining emollients Antipruritic emollient Emollient products Antiseptic products Bath oil wash wash Antiseptic Bath oil Oil-in-water emulsion intended to prevent water evaporation from the skin by providing a film of lipid Water in oil emulsions intended to provide a thicker film of lipid on the skin, 100% lipid ointments are also included Examples include white soft paraffin, liquid paraffin, 50/50 WSP/LP Emollient products containing humectants such as urea and glycerine. Humectants attract and hold water in the stratum corneum. Emollient products containing antipruritic agents Emollient products containing emulsifiers, designed for washing usage. Do not contain harsh detergents such as SLS Emollient wash products containing topically active antibacterial agents Deposit a layer of oil on the surface of bathwater, which coats the patient on exit bath oil containing topical antiseptic agent Moderately dry skin conditions. Patient choice regarding the thickness of barrier, variable lipid content, severity of condition, body site Drier skin conditions requiring a thicker lipid film. May be limited in use because of patient acceptability Very dry skin Dry skin where other products are not acceptable or effective Pruritus All patients for washing. Some simple emollients may also be used for washing Useful in managing/preventing flares of eczema. Should be used according to instructions Protection of the skin barrier during bathing Antipruritic Bath oil Bath oil containing antipruritic agent Protection of the skin barrier during bathing when pruritus is a problem 6 First line emollient therapy for mild/moderate severity dry skin conditions e.g. atopic eczema in children First line emollient therapy for more severe dry skin conditions e.g. severe atopic eczema Very severe dry skin conditions e.g. very severe atopic eczema First line use where simple emollients are not effective or greasier products are unacceptable e.g. older persons skin and psoriasis First line treatment for pruritus. Adjuvant to other emollient products where itch is not controlled, all dry skin conditions and other pruritic dermatses e.g. uraemic pruritus Should be used in conjunction with leave on emollients Recurrent infections in atopic eczema Should be used in conjunction with leave on emollients Prevention of infections Atopic eczema with frequent infective exacerbations Should be used in conjunction with antipruritic emollient cream when pruritus is not controlled
Guidance: National Institute for Health and clinical Excellence (NICE) Clinical Guideline 57: Atopic eczema in children 2007 16 NICE recommend that healthcare professionals should offer children with atopic eczema a choice of unperfumed emollients to use every day for moisturising, washing and bathing. This should be suited to the child s needs and preferences, and may include a combination of products or one product for all purposes. Leave-on emollients should be prescribed in large quantities (250 500 g weekly) and easily available to use at nursery, pre-school or school. They also recommended that healthcare professionals should offer an alternative emollient if a particular emollient causes irritation or is not acceptable to a child with atopic eczema. The guidelines also highlight that emollients and/or emollient wash products should be used instead of soaps and detergent-based wash products. The guidelines also reviewed the available evidence on aqueous cream emollients: an audit of children attending a paediatric dermatology clinic recorded the proportion of immediate cutaneous reactions to emollients (defined as one or more of burning, stinging, itching and redness developing within 20 minutes of application). Aqueous cream was the emollient used by most (71%), which was associated with an immediate cutaneous reaction in 56% of exposures, compared with 18% with other emollients used (details of the other emollients were not reported; n = 100). Based on the above evidence, NICE guidance concluded that Aqueous cream is associated with stinging when used as a leave-on emollient but can be used as a wash product. NICE also recommended that repeat prescriptions of individual products and combinations of products with children with atopic eczema and their parents or carers should be reviewed at least once a year to ensure that therapy remains optimal. Scottish Intercollegiate Guideline Network (SIGN) 125 March 2011 18 Management of atopic eczema in Primary Care SIGN recommends that patients with atopic eczema should have on-going treatment with emollients and to optimise adherence to emollient therapy, creams, lotions, ointments or a combination can be used depending on patient choice. Prescriptions should be reviewed regularly. 7
SIGN stated that although long-term emollient therapy is considered the mainstay of treating atopic eczema, a systematic review conducted in 2000 did not identify any high quality clinically relevant evidence in support of emollient monotherapy. Expert opinion supports the use of emollients in the treatment of atopic eczema to restore the defective skin barrier. SIGN recommends that healthcare professionals offer a range of emollients allowing selection of the most appropriate to the patient, and that prescription should be reviewed frequently. They also noted that emollients can become contaminated with bacteria and recommended the use of pump dispensers to minimise the risk of microbial contamination. If the emollient is in a pot the required amount should be removed with a clean spoon or spatula. Fingers should not be inserted into pots and emollients should not be shared with others. British Association of Dermatologists (BAD) & Primary Care Dermatology Society. Guidelines on the Management of Atopic Eczema 19 BAD recommended that emollients should be applied as liberally and frequently as possible. They are best applied when the skin is moist but they can and should be applied at other times as well. Ideally, emollients should be applied every 4 hours or at least 3 4 times per day. Continual treatment with complete emollient therapy (combinations of cream, ointment, bath oil and emollient soap substitute) will help provide maximal effect. Many patients underestimate the quantity needed and frequency of application to achieve maximal effect. They recommend that emollients should be prescribed in large quantities, with recommended quantities used in generalised eczema being 600g/week for an adult and 250g/week for a child. They also stated that intensive use of emollients will reduce the need for topical steroids. Best Practice in Emollient Therapy: A Statement for Healthcare Professionals 7 They stated that emollients have beneficial impact on barrier function, as it accelerates regeneration of skin barrier function following disruption, with the most lipid-rich emollients restoring the skin barrier more rapidly. They also stated that with a large variety of brands available on the market, there is no correct product for all individuals. They also said that using emollient effectively can make a significant improvement in chronic inflammatory skin conditions as well as positive impact on quality of life. 8
Costs Expenditure in Primary and Secondary Care for a 12-month period (January-December 2012): Product UHNS* Stoke-on-Trent CCG North Staffordshire CCG 50% liquid soft paraffin and 50% white soft paraffin 776.99 10,519.79 5,683.62 Hydromol Ointment 2.99 3,065.55 2,168.73 Diprobase Ointment 45.86 3,295.44 3,776.47 Epaderm Ointment 380.04 16,476.14 8,210.34 Doublebase Gel 981.51 36,552.52 23,490.52 Epaderm cream 423.99 9,010.22 8,732.05 Diprobase cream 1,736.57 27,491.81 28,922.85 Dermol cream 291.67 11,869.91 7,154.33 Balneum cream (5% urea) 11.05 869.47 482.52 Aquadrate Cream (10% urea) 67.41 1,526.28 1,293.19 E45 cream 1,003.96 40,608.59 20,918.44 Dermol 500 Lotion 3,058.95 22,095.41 8,977.92 Conotrane cream 2,285.44 10,512.33 6,688.78 Aqueous cream) 1,934.79 31,517.86 20,483.45 Emulsifying ointment 86.16 3,495.49 1,426.72 Hydrous ointment 0.00 761.74 280.43 Oilatum cream 22.46 0.00 0.00 Oilatum emollient 122.94 7,340.87 5,375.83 Sudocrem 520.64 5,118.92 4,254.04 Paraffin white soft BP 61.09 887.94 571.38 Paraffin yellow soft BP 11.79 26.77 28.88 *Expenditure for UHNS reflects items dispensed via UHNS dispensary (i.e. inpatients,) Lloyds pharmacy &FPHP10 prescriptions 9
Drug Estimated price comparison (based on 1000 patients) of switching from aqueous cream to either E45 or ZeroAQS (Primary Care) Pack size Cost (exc VAT) Usage per 1000 patients (Packs) Cost if using Aqueous Cream Cost if using E45 Cost if using ZeroAQS Aqueous 1.12 1000 1,120.00 1 x 50g 1,610.00 1 x 1,650.00 Cream 5.60 1000 5,600.00 1 x 4,620.00 1 x 3,290.00 Total 6,720.00 6,230.00 4,940.00 Alternative Treatment Costs E45-4.62 ZeroAQS - 1.65 E45-50g 1.61 ZeroAQS - 3.29 Price comparison of switching from aqueous cream to either E45 or ZeroAQS (Secondary Care) Drug Aqueous Cream Pack size Cost (inc VAT) Usage April 12 to March 13 (Packs) Actual Expenditure April 12 to March 13 Cost if using E45 Cost if using ZeroAQS 0.54 2204 1,190.16 1 x 50g 2,248.08 1 x 3,834.96 30g 0.46 1008 452.17 1 x 50g 1,028.16 1 x 1,753.92 1.01 200 201.60 1 x 732.00 1 x 693.60 Total 1,843.93 4,008.24 6,282.48 Alternative Treatment Costs E45-3.66 ZeroAQS - 1.74 E45-50g 1.02 ZeroAQS - 3.47 Points for consideration: There is a lack of data on the clinical effectiveness of emollients. There is currently no evidence that any emollient is better than another although there is wide inter-patient variability in response to treatments. Patient s preference is vital to enhance compliance and to engage patients in their treatment as well as reduce waste. Initial use of smaller pack is vital until patient satisfaction is gained to reduce waste Creams are easier to apply but ointments have a better emollient effect. Patients should be advised to keep away from fire and flames and not to smoke when using paraffin based emollients. 10
References 1 Proksch E, Lachapelle JM. The management of dry skin with topical emollients recent perspectives. J Dtsch Dermatol Ges 2005; 3: 768-74. 2 British Association of Dermatology 2008. Guidance for Commissioning Dermatology Services. BAD Clinical Advisory Unit.tinyUrl.com/dermatology-commissioning 3 McHenry PM, Williams HC, Bingham EA on behalf of a Joint Workshop of the British Association of Dermatologists and the Research Unit of the Royal College of Physicians of London. BMJ 1995; 310: 843-847. 4 Elson D. Use of emollients in dry skin conditions. Nursing Times 2011; 107: 18-21. 5 Moncrieff G, Cork M. et al. use of emollients in dry-skin conditions: consensus statement. Clinical and Experimental Dermatology December 2012. 6 Dyble T, Ashton J. use of emollients in the treatment of dry skin conditions. Br J Community Nurs 2011; 16: 214,216,218. 7 Best Practice Statement. Best practice in emollient therapy: a statement for healthcare professionals. Dermatological Nursing 2007; 1-19. 8 Flynn TC, Petros J. et al. Dry skin and moisturizers. Clin Dermatol 2001; 19: 387-92 9 Rawlings AV, Canestrari DA. et al. Moisturizer technology versus clinical performance. Dermatol Therap 2004; 17: 49-56. 10 Loden M. Role of topical emollients and moisturizers in the treatment of dry skin barrier disorders. Am J Clin Dermatol 2003; 4(11): 771-88. 11 Cork M. The importance of skin barrier function. J Dermatol Treat 1997; 8: s7-13. 12 Bettzueg-Pfaff B, Melze A. Treating dry skin and pruritus with a bath oil containing soya oil and lauromacragols. Curr Med Res Opin 2005; 21: 17350-90. 13 Cork MJ, Timmins J et al. An Audit of adverse drug reactions to aqueous cream in children with atopic eczema. Pharmaceutical Journal 2003; 271: 746-7. 14 Danby S, Al Enezi, et al. The effect of Aqueous cream BP on the skin barrier in volunteers with a previous history of atopic dermatitis. British Journal of Dermatology 2011. 15 Medicines and Healthcare products Regulatory Agency (MHRA) Drug Safety Update Volume 6, Issue 8, March 2013. Access via: drugsafetyupdate@mhra.gsi.gov.uk 16 National Institute for Health and Clinical Excellence (NICE): Atopic eczema in children: management of atopic eczema in children from birth up to the age of 12 years. London: National Collaborating Centre for Women s and Children s Health; 2007. 17 National Eczema Society: Factsheet on Emollients 2008. www.eczema.org 18 Scottish Intercollegiate Guidelines Network (SIGN). Management of atopic eczema in primary care SIGN no. 125. March 2011. Available via: www.sign.ac.uk 19 British Association of Dermatologists & Primary Care Dermatology Society. Guidelines on the management of atopic eczema. 2006, reviewed Jan 2010. Accessed via: http://www.bad.org.uk Produced by Sr. Maria Chidiamara Njoku Primary Care/Secondary Care Interface Pharmacist University Hospital of North Staffordshire Telephone: 01782 674541 e-mail: Maria.Njoku@uhns.nhs.uk Produced for use within the NHS. Not to be reproduced for commercial purposes. 11
Name 50% liquid soft paraffin and 50% white soft paraffin Appendix 1 (Initial ladder from which the recommended version came from) Legal category & Formulary status Yes EMOLLIENT LADDER Pack size VERY GREASY 250g GREASY Hydromol ointment Yes 125g 1kg Comments UHNS exc VAT 1.87 1.85 2.00 4.43 8.24 3.67 6.53 Primary Care exc. VAT 3.05 6.09 2.84 4.82 8.96 3.85 6.53 Epaderm ointment No 125g Same formula to hydromol Dermamist P/No 250ml 5.49 5.97 Emollin (liquid paraffin50%, No 150ml Same formula with 3.38 3.85 white paraffin 50% in 240ml 50:50 5.41 6.15 aerosol basis) RICH CREAM Unguentum M cream GSL/No 50g 1.41 2.57 7.80 2.78 8.48 Doublebase Gel P/No 2.33 5.12 2.65 5.83 GSL/No 3.79 3.77 Neutrogena dermatological cream CREAMY Zerobase MD/No 50g Zerocream (same as E45) GSL/No MD/No 50g Epaderm cream GSL/No 50g Diprobase cream GSL/Yes 50g Cetraben cream GSL/No 50g 125g 150g 0.75 3.84 Same formula as E45 0.77 3.80 1.45 5.91 0.90 3.80 1.00 4.20 1.04 5.26 1.17 4.08 1.65 6.74 1.28 6.32 1.40 2.38 3.98 5.99 12
Name Legal category & Formulary status Pack size Aquamol MD/No 50g Oilatum cream GSL/Yes 40g 150g 500ml 1.05L Aveno cream ACBS/No 100ml 300ml Comments UHNS exc VAT 1.07 5.62 1.30 2.46 4.99 8.76 3.97 5.97 Primary Care exc. VAT 1.22 6.40 1.30 2.46 4.99 9.98 3.97 6.80 E45 cream GSL/Yes 50g 125g 350g Hydromol cream GSL/Yes 50g Creamy with antimicrobial effect Dermol cream P/Yes 0.85 3.05 1.88 3.50 10.20 1.61 2.91 4.85 4.62 2.04 3.80 11.09 2.51 2.86 5.82 6.63 Eczmol GSL/No 250ml 3.25 3.70 Creamy with urea content E45 itch GSL/No 50g Balneum (urea 5%) GSL/No 50g Hydromol intensive (urea P/No 30g 10%) Flexitol (urea 10% Not in BNF but in drug tariff as appliance) No 150g 2.68 9.37 1.51 4.02 4.39 10.33 2.55 3.47 14.99 2.80 9.80 1.64 4.37 5.00 11.77 Aquadrate (urea 10%) P/Yes 4.02 4.37 Calmurid (contains urea 10%) P/No 7.75 8.83 34.00 Eucerin 5% cream GSL/No 75ml 5.75 5.08 Eucerin intensive (urea 10%) GSL/No 100ml 250ml 7.79 7.59 7.93 13
Name Legal category & Formulary status Pack size LIGHT E45 lotion GSL/Yes 250ml 500ml Comments UHNS exc VAT Primary Care exc. VAT 2.90 4.75 Aveeno lotion ACBS/No 500ml 5.86 6.66 Keri lotion No 190ml 380ml Aqueous cream (only to GSL/Yes wash, not as cream) ZeroAQS 2.91 4.74 0.45 0.84 1.45 2.89 1.12 5.60 1.65 3.29 Light with antimicrobial effect Dermol 500 lotion P/Yes 500ml 5.30 6.04 Light with urea content Eucerin lotion (contains 10% urea) GSL/No 250ml 7.93 7.93 Emollients not on the list but on our formulary Name Pack size UHNS exc VAT Primary Care exc VAT Diprobase ointment 50g 0.90 3.80 1.28 5.99 Dermol 200 shower emollient 200ml 3.12 3.55 Dermol 600 bath emollient 600ml 6.63 7.55 Dermalo bath emollient 500ml 3.02 3.44 E45 bath oil 250ml 3.19 3.19 Emulsifying ointment BP 0.80 1.32 Hydromol bath & shower emollient additive 350ml 500ml 3.78 Hydrous ointment 4.45 Conotrane 15 ml prepack Oilatum emollient Oilatum junior bath emollient additive 250ml 500ml 150ml 250ml 300ml 3.61 4.11 0.78 0.81 0.88 3.51 2.41 4.01 2.82 3.25 5.10 2.75 4.57 2.82 3.25 5.10 Paraffin white soft BP 2.47 Paraffin yellow soft BP 2.81 Sudocrem 60g 400g 0.89 3.70 1.38 4.71 Urea 20% oily cream (Manufacturing unit) 18.73 N/A 14