Suffolk Drug & Therapeutics Committee Shared Care Guidelines for the Treatment of Atopic Dermatitis with TACROLIMUS ointment (Adopted by the CCG until review and further notice) What is a shared care document? Suffolk D&T operates a traffic light system in an attempt to clarify prescribing responsibility and improve consistency across Suffolk: Double Red Prescribing within hospital or general practice would not be supported. Red Hospital only Amber Hospital initiated but suitable for GP prescribing if a suitable shared care document is in place. Green Hospital initiated; GP prescribing Double Green GP prescribing The basic principles of a shared care arrangement are: 1) The shared care document will include a clear statement of the hospital specialist/gps responsibilities 2) Shared care documents must provide sufficient information such that after patient stabilisation under hospital supervision, prescribing responsibility could safely be transferred to primary care 3) Both hospital specialist and general practitioner have a duty of care for the overall management of the patient 4) Patient convenience may be a major factor for GPs taking on prescribing responsibility and not the cost of the therapy 5) The onus is on the hospital specialist to liase with the GP, and if the GP does not wish to undertake the clinical and legal responsibility for the drug he does not have to do so. Responsibility to prescribe will therefore remain with the hospital 6) Agreement to accept prescribing responsibility should be obtained from the GP before the patient is informed For more details please refer to the traffic light document on the Suffolk Extranet website. Document prepared on behalf of the dermatology departments at Ipswich, West Suffolk & James Paget hospitals contact details later in document Date received by Suffolk D&T and approved by the Local Medical Committee 10 th July 2003 This document is available on the Suffolk Extranet website under County Wide & Core Documents Prescribing Guidelines Persons consulted in developing this document: Dr T Cutler, Dr S Handfield- Jones, Jill Peters (dermatology nurse practitioner) and Dr. Hawkins (GPwSI)
Background to shared care document: Tacrolimus ointment was made a red drug (hospital only) by Suffolk D&T in January 2002. Local dermatology units since then have gained significant experience with this drug and further clinical trials have been published including long term safety and corticosteroid comparator studies 1,2. In March 2003, the Suffolk Drug & Therapeutics Committee reaffirmed that tacrolimus should remain a red drug, however they acknowledged that given the experience obtained with this drug, the development of a shared care guideline and reclassification as amber to assist GP prescribing may be an advantage. The British Association of Dermatologists Therapy Guidelines Committee recommended in Dec 02 that topical tacrolimus was suitable for initiation in secondary care with continuation in primary care under a shared care protocol. The role of tacrolimus ointment in the treatment of atopic dermatitis adapted from Drug & Therapeutics Bulletin Vol 40(10) Oct 02 & British Association of Dermatologists advice Dec 02. Tacrolimus ointment is the first non-steroidal topical immunomodulator for the treatment of atopic dermatitis. It is licensed for treatment of moderate to severe atopic dermatitis in adults who are not adequately responsive to or are intolerant of conventional therapies. Also treatment of moderate to severe atopic dermatitis in children (2 years of age and above) who have failed to respond adequately to conventional therapies. Adults (over 16 years) should be started on the 0.1% strength twice daily for up to three weeks before reducing strength and frequency. Children over 2 years should be started on the 0.03% ointment for up to three weeks then once-daily until clearance of the lesion. A double-blind study comparing 0.03% & 0.1% tacrolimus ointment with 1.0% hydrocortisone acetate in 560 children (aged 2-15 years) showed that tacrolimus at both strengths produced significantly greater response (using Eczema Area Severity Score) than the hydrocortisone 3. A similar study in 570 adults, which used the same index showed that the response with 0.1% tacrolimus ointment was similar to the potent steroid 0.1% hydrocortisone butyrate and was greater than with 0.03% tacrolimus ointment 4. In terms of long term side effects, although the current SPC states that the potential for local immunosuppression is unknown beyond two years of treatment, studies presented in 2002 1,2 suggest that there is no increased risk of non-melanoma skin cancers or other adverse effects up to 3 years. With regular application of 0.03% or 0.1% ointment to around 50% of body surface area in adults and children, overall systematic exposure to the drug is approximately 30-fold less than with oral immunosuppressive doses 5,6.
Patient Selection for tacrolimus ointment To be carried out by a hospital dermatology or paediatric specialist. Children > 2 years who are unresponsive to mild to moderate steroids (more potent steroids such as betamethasone 0.1% or clobetasol propionate 0.05% should generally be avoided in children)) Adults unresponsive to moderate to strong steroids. Adults or children with severe to moderate eczema with skin atrophy from steroids, as an alternative to systemic immunosuppressives, phototherapy or admission. Patient with severe hand or facial eczema. Hospital Specialist Responsibilities For the purposes of this document a hospital dermatology specialist may refer to either a dermatology clinician, paediatrician, GP with a special interest in dermatology, dermatology nurse specialist or dermatology nurse practitioner working under the supervision of a clinician Selection of patients suitable for tacrolimus, including discussion with the patient of the dosage and method of administration, side effect profile, special precautions exposure of the skin to sunlight, use of other topical preparations, pregnancy and breast-feeding risks, and risk of vaccination failure. The hospital specialist will also provide the patient with a drug information sheet (similar to that included in this document). The hospital specialist will be responsible for writing prescriptions for tacrolimus for the first two months of treatment. After patient review (within two months of initiation), the hospital specialist will write to the GP inviting them to partake in a shared care agreement and detailing the patient management strategy. After hand over to the GP, the hospital specialist will be responsible for: Review of the patient in clinic on at least an annual basis. Updating the GP with any recommended changes to therapy Advising and guiding the GP on therapy changes after any suspected adverse effects to tacrolimus therapy GP responsibilities After two months of treatment (with patient stabilised and free from any treatment-related adverse events) the patients GP will be asked to assume responsibility for prescribing tacrolimus ointment and sent a treatment plan Prescribing of topical tacrolimus will remain the responsibility of the hospital specialist until agreement confirming the shared care arrangement is obtained from the GP. No routine blood monitoring is required but the GP will take appropriate action in response to suspected adverse events (summarised in the prescribing information section), if necessary notifying the relevant dermatology specialist. For adults and children, tacrolimus ointment is usually prescribed twice daily for up to 3 weeks before reducing the frequency (and strength in adults) until the lesions clear. Use of the ointment should then only be intermittent at times of disease flare-up.
Prescribing information for Tacrolimus ointment Summary prescribing information for guidance only; please refer to the full SPC (available at www.emc.vhn.net (registration required)), local specialist or medicines information centre. The information is correct at the time of writing April 03 but maybe subject to change. Tacrolimus (Protopic ) Pharmacology Non-Steroidal Topical Immunomodulator, which blocks T- cell activation (thought to be central to the pathogenesis of Atopic Dermatitis) and produces a range of anti-inflammatory and immune system responses in the skin. Preparations available 0.03% and O.1% ointment Licensed indications Treatment of moderate to severe atopic dermatitis in adults who are not adequately responsive to or are intolerant of conventional therapies. Treatment of moderate to severe atopic dermatitis in children (2 years of age and above) who have failed to respond adequately to conventional therapies. Recommended dosage and administration Adults (16 years of age and above) - Treatment should be started with tacrolimus oint 0.1% twice a day for up to three weeks. Afterwards the strength should be reduced to 0.03% twice a day. An attempt should be made to reduce the frequency of application if the clinical condition allows. Treatment should be continued until clearance of the lesion. Children (2 years of age and above) Treatment with tacrolimus oint 0.03% should be started twice a day for up to 3 weeks. Afterwards the frequency of application should be reduced to once a day until clearance of the lesion. Tacrolimus ointment may be used on any part of the body, including face, neck and flexure areas, except on mucous membranes. Tacrolimus ointment should not be applied under occlusion. Generally, improvement is seen within one week of starting treatment. Contra-indications hypersensitivity to macrolides (e.g. erythromycin, clarithromycin) in general, to tacrolimus or to any of the excipients. Pregnancy or breast-feeding (females of child bearing age should be using suitable contraception). Cautions Due to the theoretical risk of skin cancer exposure of the skin to sunlight should be minimised and the use of ultraviolet (UV) light from a solarium, therapy with UVB or UVA in combination with psoralens (PUVA) should be avoided during use of tacrolimus oint. Emollients should not be
applied to the same area within 2 hours of applying tacrolimus oint. Before commencing treatment with topical tacrolimus, clinical infections at treatment
sites should be cleared. Transplant patients receiving immunosuppressive regimens (e.g. systemic tacrolimus) are at increased risk for developing lymphoma; therefore patients who receive topical tacrolimus and who develop lymphadenopathy should be monitored to ensure that the lymphadenopathy resolves. In the absence of a clear aetiology for the lymphadenopathy or in the presence of acute infectious mononucleosis, discontinuation of Protopic should be considered. Tacrolimus ointment should be used with caution in patients with hepatic failure. Tacrolimus oint should not be used in patients with Netherton s Syndrome (rare epidermal barrier defect). Drug interactions Formal topical drug interaction studies with tacrolimus ointment have not been conducted. Tacrolimus is not metabolised in human skin, indicating that there is no potential for percutaneous interactions that could affect the metabolism of tacrolimus. There is no experience of concomitant use of systemic steroids or immunosuppressive agents. Vaccinations The SPC states Because of the potential risk of vaccination failure, vaccination should be administered prior to commencement of treatment, or during a treatment-free interval with a period of 14 days between the last application of tacrolimus oint and the vaccination. In the case of live attenuated vaccination this period should be extended to 28 days or the use of alternative vaccines should be considered. Adverse effects Skin and Appendages Very common: some type of skin irritation at the site of application e.g. burning sensation, pruritis, erythema - usually mild to moderate in severity and tended to resolve within 1 week of starting treatment Common skin tingling, folliculitis, acne, herpes simplex (cold sores, eczema herpeticum) Nervous System Common: Hyperaesthesia (increased skin sensitivity, especially to hot and cold) Body as a whole Common: Alcohol intolerance (facial flushing or skin irritation after consumption of an alcoholic beverage) Prescribing costs (MIMS April 03) Basic NHS pricing 0.03% 0.1% Price per 30g 19.44 21.60 Price per 60g 36.94 41.04 Patient specific data have been collected to provide estimates of the cost per day of using tacrolimus ointment (Outcomes International Report Ltd, 2001). Assuming an average amount of ointment used per day is 1.63g, then the predicted mean cost per day for tacrolimus ointment 0.1% will be 1.11 per day or 31.22 for 28 days if using the 60g tube.
References 1. Caro I, Gordon KB, West DP, et al. Long term safety of topically applied tacrolimus ointment in adult patients with atopic dermatitis. The American Academy of Dermatology 60 th Annual Meeting; 2002 Feb 22-27; New Orleans, LA. P111. 2. Paller A, Hanifin J, Eichenfield L, et al. Long term safety of topically applied tacrolimus ointment (Protopic ) in pediatric patients 2-15 years of age with atopic dermatitis. The American Academy of Dermatology 60 th Annual Meeting; 2002 Feb 22-27; New Orleans, LA. P104. 3. Reitamo S, Van Leent EJM, Ho V, et al. Efficacy and safety of tacrolimus ointment compared with that of hydrocortisone acetate in ointment in children with atopic dermatitis. The Journal of Allergy and Clinical Immunology 2002a; 109(3): 539-546 4. Reitamo S, Rustin M, Ruzicka T, et al. Efficacy and safety of tacrolimus ointment compared with that of hydrocortisone butyrate in adult patients with atopic dermatitis. The Journal of Allergy and Clinical Immunology 2002b; 109(3): 547-555 5. Protopic 0.1% Summary of product characteristics, UK Fujisawa. Feb 2002. 6. Protopic 0.03% Summary of product characteristics, UK Fujisawa. Feb 2002
Dermatology Department Contact Details Ipswich Hospital Dermatology Department Dr. T Cutler, Consultant Dermatologist (01473) 704043 Dr. S Gibbs, Consultant Dermatologist (01473) 704039 Jill Peters, Nurse Practitioner (01473) 704599 Maureen Brown, Nurse Specialist (01473) 704717 Department Fax (01473) 704712 Dermatology Reception (01473) 704035 West Suffolk Hospital Dermatology Department Dr S Handfield-Jones, Consultant Dermatologist (01284) 713404 Dr R Jenkins, Consultant Dermatologist (01284) 712644 Marie Retzback, Dermatology Nurse Specialist (01284) 712646 Department Fax (01284) 713404 Dr D Mabin, Consultant Paediatrician (01284) 713903 James Paget Hospital Dermatology Department Dr I Salvary, Consultant Dermatologist (01493) 452313 Dr R Graham, Consultant Dermatologist (01493) 452613 Karen Peat, Dermatology Nurse Specialist (01493) 453545 Jill Ramsey, Dermatology Nurse Specialist (01493) 452613 Dermatology Clinic Reception (01493) 453602 Department Fax (01493) 452801 National Eczema Society Information Line (0870) 2413604
Tacrolimus Ointment Patient Information Leaflet The National Eczema Society 2002 This information sheet is a short guide to tacrolimus ointment (also known as Protopic ). It contains information that will help in understanding what tacrolimus ointment does, how it works, how it is used and what the possible side effects might be. What is it? Tacrolimus ointment is an ointment that is applied to the skin. It is not a steroid. Tacrolimus ointment is an immunomodulatory drug, which means it modulates or changes the immune system in some way. Tacrolimus has been used for a few years as a drug taken by mouth to suppress the immune system to prevent rejection of kidney transplants. The skin s immune system is normally responsible for protection against things such as infection, but in atopic eczema it is over-active to some degree. Tacrolimus helps to suppress this overactivity. When can tacrolimus ointment be used? Tacrolimus ointment 0.1% and 0.03% can be used for the treatment of moderate to severe atopic eczema that is unresponsive to conventional therapy. The ointment is available on prescription only. How does it work? Atopic eczema is a skin condition where the body reacts to things in the environment, which would normally do it no harm. This means that the immune system may be fighting things such as the house-dust mite and pollen allergens, that in turn cause the skin to become red, itchy and inflamed. Tacrolimus ointment acts on the cells in the body and the skin to dampen down the immune system. This will help to reduce inflammation and make the skin less itchy and red. How is it used? Tacrolimus ointment is used for people with atopic eczema and is available in two different strengths: 0.03% and 0.1%. It is applied thinly to the skin, twice a day, in the same way in which a topical steroid may be applied. It should only be applied to areas of the skin where there is atopic eczema. The patient information leaflet enclosed in the packaging will explain this in more detail. Please discuss the application of this ointment with your doctor. The manufacturers, Fujisawa, indicate its use in the UK is for children over the age of two and adults who have not responded adequately to conventional treatments, for example, if in your prescribing doctor s opinion, topical steroids fail to work on your eczema. Dermatologists and doctors who have experience in the treatment of atopic dermatitis will prescribe topical tacrolimus. Topical tacrolimus can be used on the skin on any part of the body, including the face, except mucosa (inside the nose, mouth and internal genital area).
Can it be used in combination with other treatments? It is important always to use plenty of emollient as often as possible to keep the skin smooth, supple and well moisturised. Emollients can be used alongside tacrolimus ointment. As topical tacrolimus works by damping down the immune system, it could worsen skin infections by reducing the skin s natural resistance. It should not therefore be applied to skin that is infected either with bacteria (e.g. impetigo) or viruses (e.g. chickenpox, cold sores or warts). Tacrolimus is not suitable for use under wet wraps. As yet no trials have been undertaken to assess the impact of using topical tacrolimus at the same time as other treatments such as topical steroids and antibiotics. Practice will be developed in the light of better understanding as more research is undertaken and the results become available. It is likely that doctors will use topical tacrolimus alongside topical steroids but on different parts of the body and it is more than likely that oral antibiotics will be used alongside topical tacrolimus for infected atopic eczema. Other treatments for severe atopic eczema such as oral steroids or ultraviolet light treatment will probably be stopped before a course of tacrolimus ointment is started, or tailed off soon after starting the tacrolimus ointment. Does it work? There have now been a number of trials using tacrolimus ointment to treat atopic eczema; it has been compared to placebo and to 15 hydrocortisone (a very weak topical steroid available over the counter) and the results look very good when compared against these. More recently it has been compared to hydrocortisone butyrate, which is a potent topical steroid. The results of this study suggest that stronger strength of tacrolimus (0.1%) is as effective at treating atopic eczema as hydrocortisone butyrate. Hydrocortisone butyrate was more effective than the 0.03% tacrolimus in that study. Even though tacrolimus is being developed for those for whom conventional treatment hasn t worked, none of the trials to date have tested tacrolimus with this particular group of people, so it is difficult to say how well it will work in such people. The skin begins to improve in about the first week of using the ointment, with an improvement in itching and redness, and this continues whilst treatment carries on. It is important to understand that topical tacrolimus is not a cure for atopic eczema; it is a new way of controlling the eruption of atopic eczema. What are the side effects? The trials that have been carried out involving tacrolimus ointment have looked into side effects and trials are ongoing to assess the long-term side effects of this new treatment. The main short term side effects identified are a burning feeling on the skin this occurs in around one third to half of all people using it; some itching and some infected hair follicles (folliculitis). As a patient you should be warned by your doctor about this burning sensation and be prepared to put up with it for a day or two as these symptoms disappear within the first few days of using the ointment.
Tests have also been performed to see whether tacrolimus ointment can pass through into the bloodstream. It can pass into the bloodstream but the risk of this happening to a significant degree appears to be small. Tests have also been conducted to see whether tacrolimus ointment can cause the skin to become thinner. These tests show that this does not happen. Rarely, skin thinning can occur in people using strong topical steroids for long periods on delicate sites such as the face without a break. It must be stressed that it is impossible to know what the long term side effects of using tacrolimus ointment might be as this treatment has not been available for very long. Studies have begun to monitor the long-term use of tacrolimus ointment. When drugs similar to tacrolimus are taken by mouth over very many years there is an increased risk of skin cancer occurring, although there is no evidence of this happening in any patients using tacrolimus as an ointment. Patients using long term tacrolimus ointment on sun-exposed areas should avoid excessive strong sun exposure until such time as the safety of sun exposure with this ointment has been established. Can anyone use it? Trials have included children from the age of two upwards. Tacrolimus ointment is available for adults and children aged two years and over. It is available on prescription only, to patients with moderate to severe atopic eczema, under the guidance and advice of the patient s doctor or specialist. Can it be used for other types of eczema? At present tacrolimus ointment has only been licensed to treat people with atopic eczema. Where can I obtain further information? If you would like further information about tacrolimus ointment please contact the information department at The National Eczema Society on 0870 241 3604, or if you have any concerns about your treatment, you should discuss this with your doctor. Remember to keep all medicines out of reach of children. The National Eczema Society 2002