Dabigatran: Amber Drug Guidance for the prevention of stroke and systemic embolism in patients with non-valvular AF

Transcription

1 Leeds Dabigatran: Amber Drug Guidance for the prevention of stroke and systemic embolism in patients with non-valvular AF Amber Drug Level 3 (amber drug with monitoring requirements) We have started your patient on dabigatran. When the patient (and their condition) is stable on the medication, you will be asked to take over prescribing and monitoring responsibilities under this amber drug protocol. This drug requires monitoring. This guideline outlines the specific responsibilities of the Specialist, GP, and patient when dabigatran is prescribed. The general responsibilities for prescribing and monitoring amber drugs can be found here. Prescribing Information Indication for therapy (including licensing information): In Leeds dabigatran will be: Offered to people with non-valvular atrial fibrillation and a CHA 2 DS 2 -VASc score of 2 or above (taking bleeding risk into account) Considered for men with non-valvular atrial fibrillation and a CHA 2 DS 2 -VASc score of 1 for the prevention of stroke and systemic embolism, following an informed discussion with the patient about the anticoagulation options and basing the choice of treatment on their clinical features and preferences. Dabigatran is licensed for for prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation and one or more of the risk factors: Previous stroke, transient ischemic attack, or systemic embolism (SEE) Left ventricular ejection fraction < 40 % Symptomatic heart failure, (NYHA) Class 2 Age 75 years New York Heart Association Age 65 years associated with one of the following: diabetes mellitus, coronary artery disease, or hypertension It is not licensed for use in anyone less than 18 years of age. (Also note contraindications below) Classification: Amber Level 3 Monitoring: Required Baseline Tests: All patients should have their renal function (U&Es), full blood count (FBC) and liver function (LFTs) tested. 1

2 Prescribing Information (cont) Dabigatran is contraindicated if CrCl <30ml/min and is not recommended if liver enzymes are >2 times upper limit of normal. Baseline activated partial thromboplastin time (APTT) should be done if the patient is not on warfarin. If patients are switching from warfarin an international normalised ratio (INR) must be taken. Routine Tests/Monitoring: Monitor urea and electrolytes (U&E s), to ensure renal function is still adequate (see appendix 1) Monitor patients for signs of bleeding. FBC tests to monitor haemoglobin can be of assistance in monitoring for bleeding. Patients should be reviewed in terms of side effects, adherence to therapy, bleeding risk, safety of therapy and drug interactions see appendix 1. Dabigatran has a shorter half life than warfarin so the anticoagulant effect will reduce more rapidly on stopping treatment. o egfr > 80ml/min, half life 13 hours, o egfr 50-80ml/min half life 15 hours, o egfr ml/min half life 18 hours Monitor LFTs as these can be affected by dabigatran (see appendix 1). Adherence should be monitored. The APTT is raised in patients taking dabigatran but has limited sensitivity and cannot give precise quantification of anticoagulant effect. It may be useful in patients who are bleeding to assist in determining whether a significant anticoagulant effect is present. The following is a summary of prescribing information only. Consult the current BNF and SPC for full prescribing information. Dose: The usual recommended dose is 110mg or 150mg twice daily in adults. Patients aged 80 years or above, or those where there is concern around bleeding risk with the higher dose should be treated with 110mg twice daily (due to the increased risk of bleeding in this population) Formulation: Dabigatran (Pradaxa) is available as 110mg or 150mg capsules Adverse drug reactions: See current BNF and SPC for full list. The most common side effects (with a frequency of <1 in 10 to >1 in 100) are: anaemia, epistaxis, GI haemorrhage, diarrhoea, abdominal pain, dyspepsia, nausea, abnormal LFTs, genitourinary haemorrhage. 2

3 Prescribing Information (continued) Contra-indications: Hypersensitivity to the active substance or to any of the excipients Patients with severe renal impairment (CrCl <30 ml/min) Active clinically significant bleeding Recent intracranial haemorrhage Organic lesion at risk of bleeding Spontaneous or pharmacological impairment of haemostasis Hepatic impairment or liver disease expected to have any impact on survival Concomitant treatment with systemic ketoconazole, ciclosporine, itraconazole, tacrolimus, dronedarone, protease inhibitors Pregnancy and breast-feeding Cautions: Care should be taken to manage treatment for patients undergoing surgery or dental treatment and in cases of overdose or underdose. See LHP for advice in these circumstances or contact Medicines Information. Dabigatran should be used with caution in the following patient groups:- i. Hepatic impairment; Patients with elevated liver enzymes > 2 ULN were excluded from the study investigating the prevention of stroke and SEE associated with atrial fibrillation. No treatment experience is available for this subpopulation of patients, and therefore the use of dabigatran is not recommended in this population. ii. Haemorrhagic Risk; as with all anticoagulants, dabigatran should be used with caution in conditions with an increased risk of bleeding. Bleeding can occur at any site during therapy with dabigatran. An unexplained fall in haemoglobin and/or haematocrit or blood pressure should lead to a search for a bleeding site. iii. Factors, such as decreased renal function (CrCl ml/min), age 75 years, low body weight < 50 kg, or strong P-glycoprotein (Pgp) inhibitor co-medication (e.g. amiodarone, quinidine or verapamil) are associated with increased dabigatran plasma levels. iv. Patients requiring medication in a dosette box/compliance aid. Dabigatran is hydroscopic and should be kept in its original container. It cannot be put into a compliance aid. The manufacturers have developed their own compliance packaging which is available if required. 3

4 Prescribing Information (cont) Interactions: The prescriber will ensure that any changes to concurrent medication and prescribing of new drugs does not have implications for interacting with dabigatran, noting particular caution with: verapamil (P-gp inhibitor), restrict dose to 110mg BD, increased bleeding risk amiodarone (P-gp inhibitor), close clinical surveillance, increased bleeding risk ciclosporin, itraconazole, ketoconazole, tacrolimus, itraconazole (P-gp inhibitor), avoid due to increased bleeding risk clarithromycin (P-gp inhibitor), close monitoring due to increased bleeding risk carbamazepine, phenytoin, SSRI s, St John's Wort (P-gp inducers) - decreased dabigatran concentrations - avoid Anti-platelets, SSRIs and NSAIDs have been shown to increase the risk of bleeding so concomitant use should be reviewed and the risk v s benefit assessed. Note: This list is not exhaustive and the current BNF/SPC should be referred to for more information. Pregnancy/breast-feeding: Dabigatran is contraindicated in pregnancy and breast-feeding. Patients who are women of child-bearing age must be informed that they should use adequate contraception whilst on dabigatran. There are no known interactions between dabigatran and any contraceptives. Communication Hospital Specialist to GP The hospital specialist will inform the GP when they have initiated dabigatran and refer the GP to the amber drug guidance on LHP The hospital specialist will request that the GP accepts the patient after the first review see appendix 1.The patient will have at least 14 days supply of medication following the first review letter. Hospital specialist will ensure that arrangements are in place for GPs to obtain advice and support where needed. The hospital specialist will provide the GP with details of the prescription and any decisions regarding interacting medication/cautions, length of course if not lifelong, and will ask the GP to provide further care and ongoing prescription GP to Hospital Specialist If the GP has concerns over the prescribing of dabigatran, they will contact the NOAC clinic or initiating hospital specialist as soon as possible. Patients who develop a contraindication or CrCl < 30ml/min/ will have dabigatran stopped and a fast track referral made back to the specialist clinic (See also NICE CKD Guidelines) 4

5 Responsibilities of Specialist Assess the suitability of the patient for treatment in line with NICE CG 180 Assess bleeding risk with respect to reversibility of dabigatran. Assess renal function (contraindicated if CrCl <30ml/min). Confirm absence of any contra indication to dabigatran. Consider cautions to dabigatran use including GI bleeding Consider increased MI risk seen in RE-LY study with dabigatran compared to warfarin Confirm absence of any drug interaction with any of the patient s concurrent medication or put in place measures to reduce toxicity from the combination if essential i.e. dose reduction of dabigatran (See SPC) Baseline tests (see below) prior to initiation and communication of results to the GP. Inform GP of initiation. Assess patient at 3-6 weeks see appendix 1. If patient stable request GP take over responsibility for prescribing and monitoring. The patient will have at least 14 days supply of medication following the 3-6 week assessment. Inform patient of side effects of dabigatran, the need for long term monitoring, the lack of reversal agent, and the importance of reporting any symptoms of bleeding (or anaemia) to their GP or A&E if severe. Record that this information has been discussed. Inform patients to seek urgent medical advice if they fall or have a head injury Give patients a Pradaxa patient alert card and patient information leaflet and advise them to carry it with them and show it to any healthcare provider. Inform women of child-bearing age that they must use adequate contraception while on dabigatran Inform the Leeds anticoagulant clinic that the patient has been switched and add patient to the dabigatran database. When switching from warfarin ensure the INR is <2 before initiating dabigatran Inform patient that they are responsible for attending their GP practice when requested, for blood samples and assessment. Responsibilities of GP Only accept patients who meet the criteria in the NICE CG 180 Prescribe dabigatran as recommended by the specialist. Report adverse effects to the specialist and where appropriate the Commission on Human Medicines/MHRA (Yellow card scheme). Refer to NOAC clinic or initiating consultant if it is suspected that the patient is getting serious side effects (including significant dyspepsia, falling Hb, occurrence of thrombotic event, deteriorating LFTs) requiring investigation or termination of dabigatran. Ensure that if coagulation tests are requested dabigatran is noted on the extra information section. Alcohol doesn t interact with dabigatran but will increase the risk of 5

6 Responsibilities of GP (Continued) bleeding so patients should be advised to stick to safe limits and this should be re-enforced at review. Participate in audit when requested. GP practice must have systems to ensure reviews are undertaken as per appendix 1 Review the patient in terms of side effects, adherence to therapy, bleeding risk, safety of therapy and drug interactions see appendix 1 Monitor for adverse effects of dabigatran - including blood tests (U&E and FBC, LFTs).See appendix 1. NB. Renal function should be checked as per appendix 1, unless patient is at risk of deteriorating renal function (i.e. in hypovolaemia or dehydration acute illness e.g. sepsis, new heart failure, commencement of drugs which may impair renal function etc) when it should be checked more frequently. Responsibilities of Patient To take responsibility for taking dabigatran as prescribed. To adhere to their treatment. o Patients should be advised to take the doses at the same times every day (ideally 12 hours apart) to help them to remember to take it. o If the patient forgets to take a dabigatran dose, they should take it as soon as they remember, as long as it is more than 6 hours until the next dose. o If there are less than 6 hours until the next dose is due, the patient should just carry on as normal, omitting the forgotten dose. o All patients should be advised to contact their doctor immediately if they have taken too many dabigatran capsules, as this increases the risk of bleeding. o Patients should be advised not to stop taking dabigatran without talking to their doctor first. To attend their GP practice when requested, for blood samples. Immediately report any symptoms, side effects or bleeding to their GP or A&E depending on severity. To carry their Pradaxa (dabigatran) alert card and inform any healthcare providers that they are on dabigatran. To check with community pharmacist that there are no interactions with dabigatran, when buying any over the counter medicines or herbal/homoeopathic products. To contact the GP, Specialist, community pharmacist or Medicines Information patient helpline if further information or advice is needed about dabigatran. 6

7 Contact Details Contact Details NOAC clinic number; Medicines Information phone number; Medicines Information ; Medicines Information Patient Helpline phone number; Prepared by: Razvana Akbar Advanced Clinical Pharmacist Katherine Stirling Consultant Pharmacist Reviewed by Tony Jamieson Approved by: Shared Management of Medicines Group 7

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