Acetylcholinesterase Inhibitors and Memantine Clinical Indication: Treatment of Dementia in Alzheimer s Disease (AD)

Transcription

1 SHARED CARE PROTOCOL AND INFORMATION FOR GPS Acetylcholinesterase Inhibitors and Memantine Clinical Indication: Treatment of Dementia in Alzheimer s Disease (AD) Version: 3 Date Approved: June 2011 Review Date: June 2013 Acetylcholinesterase Inhibitors for the Treatment of Mild to Moderate Dementia, and Memantine for the Treatment of Moderate to Severe Dementia in Alzheimer s disease(ad). AREAS OF RESPONSIBILITY FOR THE SHARING OF CARE This shared care agreement outlines suggested ways in which the responsibilities for managing the prescribing of Acetylcholinesterase Inhibitors and Memantine can be shared between the specialist and general practitioner in primary care. GPs are invited to participate. If the GP is not confident to undertake these roles, then he or she is under no obligation to do so. In that case, the total clinical responsibility for the patient for the diagnosed condition remains with the specialist. If a specialist asks the GP to prescribe drugs for this treatment, the GP should reply to this request as soon as practicable. Sharing of care assumes communication between the specialist, GP and patient. The intention to share care should be explained to the patient or the patient s carer (where appropriate) by the doctor initiating treatment. It is important that patients are consulted about treatment and are in agreement with it. The doctor who prescribes the medication legally assumes clinical responsibility for the drug and the consequences of its use. RESPONSIBILITIES and ROLES Hospital specialist team responsibilities 1 Ask the GP whether he or she is willing to participate in shared care, and agree with the GP as to who will discuss the shared care arrangement with the patient. 2 Confirm diagnosis of Alzheimer s dementia. 3 Assess the need for treatment and the patient s fitness for medication. 4 Consideration of potential drug interactions. 5 Assessment of baseline mental state by testing and via the carer s view. 6 Provision of relevant information to the GP in writing including diagnosis, treatment to date, treatment to be undertaken by the GP review arrangements, possible side-effects of treatment, system for monitoring and recording adverse effects. 7 Selection and initiation of treatment with Acetylcholinesterase inhibitors and/or Memantine, or recommend GP to initiate treatment. 8 Review of the patient's compliance and response to treatment 6 months after initiation of treatment. 9 Evaluation of any adverse effects noted by the patient/ carer or GP. 10 Communicate promptly with the GP when any change of therapy occurs, such as change in dose, or if a patient is intolerant of a drug, or when discontinuing therapy if there is no longer evidence of benefit of treatment. 11 Patient review when requested by the GP. 12 Report adverse events to the MHRA via Yellow Card Scheme. 13 Ensure that clear backup arrangements exist for GPs to obtain advice and support. 14 The Consultant Psychiatrist is responsible for ensuring that an appropriate T2 or T3 is completed for patients detained under the Mental Health Act, and is responsible for sending a copy of a new or updated T2 or T3 to the GP.

2 General Practitioner responsibilities 1 Reply to the request for shared care as soon as practicable. 2 Undertake baseline investigations full blood count, urea & electrolytes, calcium, phosphate, liver function tests, thyroid function tests, serum glucose 3 Prescribe and administer Acetylcholinesterase inhibitors and/ or Memantine at the dose recommended by the hospital specialist team. 4 Adjust the dose as advised by the hospital specialist team. 5 Monitor patient for the emergence/ worsening of adverse effects, particularly bradycardia, asthma/copd or symptoms of peptic ulceration. 6 Report to and seek advice from the hospital specialist team on any aspect of patient care that is of concern and may affect treatment. 7 Refer patient to the hospital specialist team if there is concern about ongoing benefit. 8 Stop treatment on the advice of the hospital specialist team, or immediately if an urgent need to stop treatment arises. 9 Report adverse events to the hospital specialist, where appropriate, and to the MHRA via the Yellow Card Scheme. 10 Responsible for adhering to prescribing psychotropic medication as specified in a T2 or T3 for patients detained under the Mental Health Act. Patient's / Carer s role 1 Report to the specialist or GP if he or she does not have a clear understanding of the treatment. 2 Share any concerns in relation to treatment. 3 Report any adverse effects to the specialist or GP. BACK-UP ADVICE AND SUPPORT Contact details Telephone No. address: Specialist: Dr Pound Dr Thomas ext susan.pound@nhs.net ivor.thomas@nhs.net SUPPORTING INFORMATION Introduction Alzheimer s disease is the most common cause of dementia characterised by insidious onset of global mental impairment, and normally slow deterioration. Symptoms begin with decline in short-term memory and cognition and progress to disorientation, altered mood and behaviour then to severe dementia. Donepezil, galantamine and rivastigmine are reversible inhibitors of acetylcholinesterase which have been approved by the Scottish Medicines Consortium (SMC), SIGN (Guideline 86) and NICE (Technology appraisal guidance 217) as treatment options for mild to moderate Alzheimer s dementia. Memantine is also licensed and approved for treating moderate to severe dementia in Alzheimer s disease and has been approved by NICE (Technology appraisal guidance 217) and NHS Quality Improvement Scotland. Licensed indications

3 Acetylcholinesterase inhibitors are licensed and approved for the symptomatic treatment of mild to moderately severe dementia in AD. They should be initiated by or on the advice of a Consultant in Old Age Psychiatry or Care of the Elderly. Rivastigmine capsules and oral solution are also licensed for the symptomatic treatment of mild to moderate severe dementia in patients with idiopathic Parkinson s Disease. Rivastigmine patches are not licensed for this indication. Memantine is licensed and approved for the treatment of moderate to severe Alzheimer s disease. Dosage and Administration Donepezil is available as tablets or orodispersible tablets. It should be initiated at 5mg once daily at bedtime and increased to 10mg once daily at bedtime after at least one month if clinically appropriate. Galantamine is available as tablets, oral solution and modified release capsules. The tablets /solution should be initiated at a dose of 4mg twice daily, preferably with morning and evening meals and increased to 8mg twice daily after at least 4 weeks. Normal maintenance dose is 8-12mg twice daily. Galantamine MR capsules should be started at a dose of 8mg once daily in the morning, swallowed whole after food, and increased to 16mg MR once daily in the morning after at least 4 weeks. Normal maintenance dose is 16-24mg once daily. Adequate fluid intake should be maintained during therapy. Rivastigmine is available as capsules, oral solution and patches. The tablets /solution should be started at 1.5mg twice daily and increased in increments of 1.5mg twice daily at intervals of at least two weeks according to response and tolerance, to a maximum of 6mg twice daily. If therapy is interrupted by more than several days the dose should be re-titrated from 1.5mg twice daily. Usual range is 3-6mg twice daily. Rivastigmine transdermal patches should be started at a dose of 4.6mg/ 24 hours and increased to 9.5mg/ 24 hours if necessary after at least 4 weeks if well tolerated. This is the recommended daily maintenance dose. If therapy is interrupted by more than several days the dose should be re-titrated from 4.6mg/24hours. Patches should be applied to sites on the upper or lower back, upper arm or chest but not to the abdomen or thigh areas due to decreased bioavailability of rivastigmine when the transdermal patch is applied to these areas of the body. The patch should be removed after 24 hours, and the replacement patch sited on a different area (avoid using the same area for 14 days).patients with a body weight of less than 50kg are more likely to experience adverse effects leading to treatment discontinuation. Memantine is available as 5mg, 10mg, 15mg and 20mg tablets, and as a 5mg/pump oral solution. The recommended starting dose is 5mg once daily at the same time each day, increased stepwise in 5mg increments weekly to a maximum of 20mg daily. Oral solution - each pump activation gives 5mg in 0.5ml of solution. Memantine oral solution should be dosed onto a spoon or into a glass of water using the pump. It should not be poured or pumped into the mouth directly from the bottle or pump. See detailed instructions about administration of memantine oral solution in the Ebixa (memantine) Summary of Product Characteristics (SPC).. DRUG Donepezil (Aricept ) (Aricept Evess ) Galantamine (Reminyl ) (Reminyl XL ) Memantine ( Ebixa ) PRODUCTS AVAILABLE 5mg tablets x 28 10mg tablets x 28 5mg orodispersible tablets x 28 10mg orodispersible tablets x 28 8mg tablets x 56 12mg tablets x 56 4mg/ml oral solution (100ml) 8mg modified release capsules x 28 16mg modified release capsules x 28 24mg modified release capsules x 28 10mg scored tablets x 28 or 56 or mg scored tablets x 28 or 56 or 112 Treatment initiation pack: 7x5mg, 7x10mg, 7x15mg, 7x20mg Oral drops 5mg/actuation ( 50g or 100g) Rivastigmine (Exelon ) 1.5mg capsules x 28 or 56 3mg capsules x 28 or mg capsules x 28 or 56 6mg capsules x 28 or 56

4 2mg/ml oral solution (120ml) 4.6mg/24h transdermal patches x 30, 60 or mg/24h transdermal patches x 30, 60 or 90 Contraindications and precautions for use Known hypersensitivity to ingredients Breastfeeding Galantamine severe renal and hepatic impairment Rivastigmine severe hepatic impairment Cautions Anaesthesia, cardiac conduction abnormalities, glaucoma, seizures (rivastigmine and memantine); asthma or COPD, susceptibility to GI ulceration, urinary retention (galantamine, rivastigmine); recent MI, uncompensated congestive heart failure and uncontrolled hypertension, raised urine PH ( drastic changes in diet, massive intake of alkalising gastric buffers, renal tubulary acidosis, severe proteus UTIs) ( memantine) Memantine oral solution contains sorbitol, avoid in patients with fructose intolerance. Renal impairment Donepezil no dose adjustment necessary. Galantamine no dose adjustment in mild to moderate renal impairment. Severe - contraindicated if creatinine clearance is less than 9ml/min. Rivastigmine start with low dose and titrate slowly according to tolerability. Memantine moderate impairment (creatinine clearance 30-49ml/min ) maximum dose 10mg daily, if well tolerated after at least 1 week then dose can be increased to 20mg daily in steps using the usual titration procedure. Severe impairment ( creatinine clearance 5-29ml/min) maximum dose 10mg daily. Avoid if creatinine clearance less than 5ml/min. Hepatic impairment Donepezil titrate dose based on tolerability, Galantamine mild - no dose adjustment. Moderate immediate release preparations: commence with 4mg daily, preferably in the morning, for at least 7 days, increasing to 4mg twice a day for at least for weeks, maximum dose of 16mg daily. Modified release preparations: 8mg modified release on alternate days (preferably in the morning) for 1 week, then 8mg once daily for 4 weeks; maximum dose 16mg daily. Severe contraindicated Rivastigmine mild to moderate use with caution; severe contraindicated. Patch - patients with clinically significant hepatic impairment may experience more adverse effects. Memantine mild to moderate no dose adjustment required; severe not recommended. Patients with clinically significant hepatic impairment may experience more adverse effects. Discontinuation Treatment can be stopped quickly if the patient has an adverse drug reaction. In late stage Alzheimer s where there is doubt about ongoing efficacy, after consultation with the patient s Consultant, treatment doses could be reduced and symptoms observed. If there is deterioration then the dose can be increased again, or if there is no difference or improvement then treatment can be discontinued. Side Effects Acetylcholinesterase inhibitors Gastrointestinal side effects of nausea, vomiting, and diarrhoea are very common especially during initiation of therapy and after dose increases. Less common are peptic ulceration and GI bleeding. Syncope, fatigue, headache, dizziness, anorexia, muscle cramps are also common, and bradycardia, insomnia and extrapyridamal side effects can also occur. Nausea, vomiting and weight loss are more common in women taking rivastigmine.

5 Rivastigmine patches anxiety, pyrexia and delirium are more likely, but dizziness, agitation, somnolence, tremor, confusion, sweating, insomnia and cardiac arrhythmia probably less likely than with rivastigmine capsules. Memantine - most common - dizziness, headache, constipation, somnolence, dyspnoea and hypertension. Drug Interactions More severe side effects of peptic ulceration and GI bleeding are more likely where an acetylcholinesterase inhibitor is co-prescribed with an SSRI, a NSAID, aspirin, warfarin or oral steroids. There is an increased potential for decreased heart rate where an acetylcholinesterase inhibitor is coprescribed with digoxin, amiodarone, rate limiting calcium channel blockers verapamil or diltiazem, and beta blockers. Acetylcholinesterase inhibitors interact with muscle relaxants, antimuscarinics, erythromycin, itraconazole and fluconazole, fluoxetine and paroxetine, quinidine. Donepezil rifampicin, phenytoin and carbamazepine may reduce plasma levels of donepezil. Galantamine caution with other drugs that can potentially cause Torsade De Pointes. Rivastigmine less potential for interactions and no interaction expected with digoxin, fluoxetine, paroxetine, warfarin. Memantine avoid NMDA antagonists such as amantadine, ketamine and dextromethophan.cimetidine, ranitidine, quinine, quinidine and nicotine may increase levels of memantine; isolated cases of increased INR with warfarin; effects of L-dopa, dopaminergic agonists and anticholinergics may be enhanced; effects of barbiturates and neuroleptics may be reduced; dose adjustments of baclofen, antispasmodics and dantrolene may be necessary. Cost Donepezil standard and orodispersible tablets are the same price. Galantamine standard and modified release preparations are the same price. All doses of rivastigmine tablets are the same price. Oral solutions of galantamine and rivastigmine are more expensive than tablets/capsules and this cost increases with higher doses. Drug & daily dose Cost per 28 days Donepezil 5mg Donepezil 10mg Galantamine 16mg Galantamine 24mg Galantamine M/R 8mg Galantamine M/R 16mg Galantamine M/R 24mg Galantamine oral solution (4mg/ml) 24mg dose Memantine 10mg Memantine 20mg Memantine titration pack Memantine oral drops 20mg Rivastigmine 6mg, 9mg or 12mg Rivastigmine 4.6mg/24 hours or 9.5mg/24 hours Rivastigmine oral solution ( 2mg/ml) 12mg dose Rivastigmine Patch 4.6mg/24 hours or 9.5mg/24 hours (from BNF 61 March 2011) References: British National Formulary 61, March 2011.British Medical Association. Electronic Medicines Compendium. Summary of product Characteristics for Donepezil (Aricept ), Galantamine (Reminyl ), Rivastigmine (Exelon ) and Memantine (Ebixa ). National Institute for Clinical Excellence. (Technology appraisal guidance 217). March 2011.Donepezil, galantamine. rivastigmine and memantine for the treatment of Alzheimer s disease (review). Scottish Intercollegiate Guidelines Network (Guideline 86). February Management of patients with dementia.

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