Proforma for the INITIATION of Direct Oral Anticoagulants (DOACs) therapy in Primary Care

Transcription

1 Proforma for the INITIATION of Direct Oral Anticoagulants (DOACs) therapy in Primary Care This proforma is for use in patients being commenced on DOAC therapy. Each stage of the proforma must be followed and completed during the patient consultation. A copy of the proforma must be saved on the patient medical record and a copy can be given to the patient. The GP must conduct a follow up appointment with the patient within 1 month of treatment initiation. This review should be conducted using the Proforma for the review of DOAC therapy in Primary Care. Patient eligibility for DOAC therapy Does the patient have any of the following: YES NO Atrial fibrillation Atrial flutter A continuing risk of arrhythmia recurrence after cardioversion back to sinus rhythm A mechanical prosthetic valve OR moderate-severe mitral stenosis (if the answer to this question is Yes, the patient is not eligible for DOAC therapy and must be started on warfarin) CHA 2DS 2VASc Congestive Heart Failure 1 Hypertension 1 Age 75 years 2 Diabetes 1 Prior stroke/tia 2 Vascular disease 1 Age Female 1 TOTAL SCORE Tick HASBLED Uncontrolled hypertension* 1 (systolic >160mmHg) Abnormal liver* (bilirubin >2x ULN, with 1 AST/ALT/ALP >3x ULN) Abnormal renal* (serum Cr>200µmol/L) 1 Prior stroke 1 History of major bleed 1 Labile INR (on warfarin)* 1 Age 65 years 1 Drugs (anti-platelets/nsaids)* Alcohol (>8 units/week)* 1 1 Tick TOTAL SCORE Consider anticoagulation in all men with CHA2DS2VASc = 1 Offer anticoagulation to all patients (male or female) with CHA2DS2VASc 2 *Offer methods of modifying and monitoring the bleeding risk factors A score of 3 or more indicates increased one year bleed risk on anticoagulation sufficient to justify caution (If necessary, seek specialist advice or refer to hospital) Anticoagulation therapy indicated YES NO Modifiable bleeding risk present YES NO Actions to modify bleeding risk: 1

2 Baseline Blood Tests Parameter Date of test Result In range to anticoagulate Monitoring frequency Clotting screen YES NO - (INR / APPT) Haemoglobin (g/l) YES NO ALT (unit/l) YES NO Annually <75 years ALP (unit/l) YES NO 6 monthly 75 years Bilirubin (µmol/l) YES NO OR when clinically Albumin (g/l) YES NO indicated AST (unit/l) YES NO Creatinine See Assessment of Renal Function below Assessment of Renal Function Use Cockcroft-Gault Equation. Contra-indications to DOAC therapy Contra-indications to treatment Yes No Any contra-indication to dabigatran / rivaroxaban / apixaban / edoxaban? Hypersensitivity to the active substance or any of the excipients Major bleeding potential or tendency (e.g. severe haemophilia) Active peptic ulcer, oesophageal varices, aneurysm, proliferative retinopathy Recent organ biopsy Lesion or condition at risk of significant major bleed e.g. recent trauma or surgery to the head, eyes, orbit or spine, malignant neoplasm, vascular aneurysm Confirmed intracranial or intraspinal bleed (usually within last 4 weeks) Uncontrolled hypertension (>160mmHg systolic BP) Infective endocarditis Pregnancy or breast feeding CrCl < 30ml/min (dabigatran) or CrCl < 15ml/min (rivaroxaban or apixaban or edoxaban) Liver disease with ascites, encephalopathy, coagulopathy, ALT>100 or bilirubin>35 (unless due to haemolysis or Gilbert s). Dabigatran only: LFTs: elevated liver enzymes > 2 ULN Coagulation screen: APTT > 1.5 x normal (does not apply if currently anticoagulated) INR > 1.4 (does not apply if currently anticoagulated) ALL DOACs: contra-indicated concomitant medications: dronedarone, other anticoagulant agents (except when switching therapy or unfractionated heparin for maintaining venous or arterial catheter patency), ritonavir, posaconazole, voriconazole, ketoconazole, itraconazole Dabigatran only - tacrolimus, ciclosporin Prosthetic heart valve(s) If the answer to any of the above is YES, patient is not suitable for a DOAC Patient eligibility Patient suitable to start anticoagulation Complete consultation below Patient unsuitable to start anticoagulation; document reason anticoagulation unsuitable: Tick relevant option 2

3 Patient Consultation The following points must be discussed with the patient and/or their relative/carer prior to starting anticoagulation therapy: Discussion point Explanation of atrial fibrillation and risk of stroke given to patient Explanation of the purpose of an anticoagulant and intended duration of treatment Explanation of the risks of bleeding whilst taking anticoagulation therapy; explain the options for management of bleeding whilst on oral anticoagulation (including the lack of specific antidote for rivaroxaban/apixaban/edoxaban) Consent Patient would like to commence an oral anticoagulant Patient would not like to commence an oral anticoagulant Reason patient does not want anticoagulation: Discussion taken place please tick Patient/carer signature Patient decision aid If there is no distinguishing clinical feature to warrant the choice of one oral anticoagulant over another, the patient should be provided with information about the options available in order to make an informed decision about the treatment option they wish to pursue. The NICE AF: anticoagulant options decision aid can be found here: Issue How many tablets or capsules would I have to take and how often? How important is this to me? IMPORTANT NOT IMPORTANT Options (circle option(s) preferred by patient) One tablet once a day fixed dose One tablet once a day variable dose One tab/cap twice a day fixed dose Suitable anticoagulant Rivaroxaban/edoxaban Warfarin Apixaban/dabigatran The need for regular blood tests How likely is it that I will forget to take my medication? The need to change what I eat or drink The availability of a direct antidote IMPORTANT NOT IMPORTANT LIKELY UNLIKELY IMPORTANT NOT IMPORTANT IMPORTANT NOT IMPORTANT Before you start treatment; then periodically (usually once a year) to check kidney and liver function Regularly (usually every 1-2 months) to guide the number of tablets you have to take Likely but I do not want any adherence support Likely - I use/want to use a dosette box/blister pack Unlikely I am good at remembering my medicines I want to drink cranberry juice I don t want to worry about whether I drink alcohol or not My diet often changes I want to take a medicine with an established direct antidote. I understand the limitations of the available direct antidotes I understand that general measures can be used to control bleeding which may be successful. I am happy with this option. Selection of anticoagulant DOAC Warfarin Warfarin (longer duration of action) Apixaban/rivaroxaban/ edoxaban All DOAC DOAC DOAC Warfarin/dabigatran Apixaban Dabigatran Edoxaban Rivaroxaban Warfarin All Arrange a follow up appointment in 1 month. 3

4 Proforma for the REVIEW of DOAC therapy in the Primary Care This proforma is for use in patients being reviewed on DOAC therapy. Each stage of the proforma must be followed and completed during the patient consultation. A copy of the proforma must be saved on the patient medical record and a copy can be given to the patient. The GP must conduct a follow up appointment with the patient within 1 month of treatment initiation. Patients taking DOACs do not need routine monitoring of INR/anticoagulation, but require periodic review of renal function and liver function, at least annually or 6-monthly depending on patient s renal function (see Appendix 2). In addition, adherence and tolerance should also be checked every 3 months. Ensure that the baseline creatinine clearance (calculated using Cockcroft-Gault formula within EMIS) is correct and verify dosage. Renal function: For patients with CrCl < 15ml/min: DOACs are contraindicated For patients with CrCl 15-29ml/min: - dabigatran is contraindicated; - apixaban / edoxaban / rivaroxaban should be used with CAUTION (no effectiveness or safety data for this patient cohort) Questions to ask the patient: Do you understand why you need anticoagulation? Have you been taking your anticoagulant medicine? Are you taking it AS prescribed (see Appendix 1: how to take section) and how are you getting on with it? Are you having problems with your new medicine or do you have any concerns? Do you think you are getting any side-effects, unexpected effects or new / worsening symptoms? Have you missed any doses or changed how you take the medicine? (see Appendix 1: Missed doses) Are you taking any new over the counter medicines since starting anticoagulant medicine? Do you have anything else you would like to know or anything you would like me to go over again? Enter diary date for next review on EMIS 4

5 Appendix 1: Counselling Check-list Counselling Point Reason for DOAC Mode of action Duration How to take Adherence Missed dose Guidance Atrial Fibrillation irregular heart beat = inefficient blood flow = clots = stroke/tia Anticoagulants thin the blood or reduce the ability of blood to form clots Lifelong Apixaban: TWICE a day, with or without food can be crushed Dabigatran: TWICE a day, with or without food DO NOT OPEN OR CHEW CAPSULES, DO NOT PUT IN DOSETTE BOX Edoxaban: ONCE a day, with or without food ADVISE NOT TO CRUSH (no data) Rivaroxaban: ONCE a day WITH FOOD can be crushed Importance of taking as prescribed if a dose/day of medicine is missed, the medicine will not work on that day putting the patient at risk of a stroke Advise on adherence aids e.g. reminders. ONCE-daily DOACs (rivaroxaban & edoxaban): the dose should be taken immediately and then be continued the following day with the once-daily intake as recommended. The patient should not take double the prescribed dose on the same day to make up for a missed dose. * resume 24 hour dosing from the new time of administration (if the patient wishes to return to their normal time of administration; the time at which the dose is taken each day may be gradually adjusted by 1 hour/day) *[Verbal advice from manufacturer] TWICE-daily DOACs: Dabigatran forgotten dose may still be taken up to 6 hours prior to the next scheduled dose. From 6 hours prior to the next scheduled dose on, the missed dose should be omitted Apixaban- If a dose is missed, the patient should take apixaban immediately and then continue with twice daily intake as before. Informing healthcare professionals Side-effects How to manage a bleed Monitoring Interactions Food and alcohol Women of child bearing age Alert card ESSENTIAL in an emergency situation, planning surgery, planning pregnancy, dentist, pharmacist (interactions), practice nurse (immunisations) Signs of bleeding and bruising (seek emergency help if severe) epistaxis (if lasts >10min seek medical assistance), haematuria, haemotypsis, haematemesis, melaena, abnormal genitourinary bleeding See individual patient packs for drug specific side effects e.g. fainting with rivaroxaban (counsel on safety with driving/operating machinery) Apixaban, edoxaban, rivaroxaban counsel on lack of specific antidote but that general measures (e.g. PCC) have been used successfully Dabigatran direct reversal agent licensed Periodically dependent on kidney or liver function Check with pharmacist if buying OTC medication e.g. NSAIDs, aspirin not recommended Check with pharmacist regarding use of herbal medicines avoid if possible No known food interactions No interaction with alcohol but staying within the recommended national guidelines is advised (3units/day for men and 2units/day for women) (NB: risk of falls with excessive alcohol consumption) Use reliable contraception whilst taking a DOAC Discuss with doctor if planning pregnancy or as soon as possible if they discover they are pregnant May experience heavier menstruation Carry alert card at ALL times 5

6 Appendix 2: Dosing guidance for patients on DOACs: DOAC Standard dose When to reduce Reduced dose Not recommended Apixaban 5mg TWICE daily CrCl < 30ml/min 2.5mg TWICE daily CrCl <15 ml/min Any two of the following: Age Weight Serum Cr 80 years 60kg 133 mmol/l Consider dose reduction (assess risk of stroke vs risk of bleed) a : High risk of bleeding (non-modifiable HASBLED score 3) Dabigatran 150mg TWICE daily CrCl < 50ml/min Age 80 years Concomitant treatment with verapamil Consider dose reduction (assess risk of stroke vs risk of bleed) a : years High risk of bleeding (non-modifiable HASBLED score 3) Patients with gastritis, esophagitis or gastroesophageal reflux Edoxaban 60mg ONCE daily CrCl <50ml/min 60kg Concomitant treatment with ciclosporin, dronedarone, erythromycin, ketoconazole Consider dose reduction (assess risk of stroke vs risk of bleed) a : High risk of bleeding (non-modifiable HASBLED score 3) Rivaroxaban 20mg ONCE daily CrCl <50ml/min Consider dose reduction (assess risk of stroke vs risk of bleed) a : High risk of bleeding (non-modifiable HASBLED score 3) a If unsure about whether a dose reduction is appropriate or not, seek specialist advice 110mg TWICE daily 30mg ONCE daily 15mg ONCE daily CrCl <30 ml/min CrCl <15 ml/min CrCl <15 ml/min 6

7 Appendix 3: Checklist for FOLLOW UP: Review Interval Guidance 1. Adherence Each visit Remind patient to bring DOAC card and remaining medication to assess average adherence (if patient is using adherence support technology review recorded data) Re-educate on importance of strict intake schedule Inform about adherence aids (dosette boxes, blister packs, smartphone applications) 2. Each visit Are there are new signs or symptoms the patient has experienced? Thromboembolism 3. Bleeding Each visit Nuisance bleeding (minor or clinically non-relevant bleeding) e.g. epitaxis: are preventative measures possible? e.g. PPI, haemorrhoidectomy Encourage patient to diligently continue with anticoagulation; do not stop treatment or adjust dose seek specialist advice if concerned Bleeding with impact on quality of life or with risk: are preventative measures possible? (also consider the onset of headaches carefully and send for review if concerned); particularly if combined with other symptoms such as weakness, nausea, confusion, slurred speech) If major bleeding refer for emergency care. If preventative measures not possible, contact AF anticoagulation service for advice OR refer immediately. 4. Other side effects 5. Other medications for interactions Each visit Carefully assess relation of other side effects to DOAC therapy: - is side effect likely to be transient? - can it be managed with symptomatic relief e.g. antihistamines, PPI - Encourage patient to diligently continue with anticoagulation If side-effect persistent and/or impacting on patient s quality of life, seek specialist advice or refer. Common side effects seen in real-life clinical practice are: rash or fainting with rivaroxaban, dyspepsia with dabigatran, nose bleeds with all DOACs Each visit Prescription drugs over the counter drugs including herbal remedies (especially aspirin and NSAID) see DOAC interaction checker (appendix 5) 6. Blood sampling Yearly Haemoglobin, renal and liver function 6 monthly 75 years or frail a x-monthly If CrCl 60ml/min: Recheck frequency (months) = CrCl/10 e.g. CrCl 30ml/min = 3 monthly On indication If intercurrent condition that may impact on renal or hepatic function a Frailty is defined as three or more criteria of unintentional weight loss, self-reported exhaustion, weakness assessed by handgrip test, slow walking speed, or low physical activity 7

8 Appendix 4: Things to consider Things to consider: Stroke risk Primary or secondary prevention % annual stroke risk ( Bleeding risk % annual bleed risk ( Including risk of intracranial haemorrhage (including history of head injury) Previous GI history Lifestyle activity/sport, etc Renal function For patients with CrCl < 15ml/min: DOACs are contraindicated For patients with CrCl 15-29ml/min: dabigatran is contraindicated; apixaban / edoxaban / rivaroxaban should be used with CAUTION (no effectiveness or safety data for this patient cohort) Co-morbidities Warfarin: some co-morbidities may make INR control challenging e.g. unstable severe COPD, recurrent cellulitis Patients with recurrent dehydration or UTIs risk of AKI = reduced clearance of DOACs Dementia: may have difficulty complying with warfarin requirements Liver function All DOACs are to some extent plasma protein bound; consider if patient has low albumin e.g. rivaroxaban is 98% bound to albumin (low albumin = increase in free drug in plasma care with nephrotic syndrome) Extreme age or weight Less evidence for the use of DOACs at the extreme of age and body weight (>130kg) Patient cognitive function Frailty Other medication Review DOAC drug interaction checker - appendix 5 Warfarin: - Long-term use of interacting drugs dose can be tailored to account for the effect of the interaction - Acute use of interacting drugs = disruption to INR control e.g. macrolide antibiotics Review use of other drugs which may increase the risk of bleeding (anti-platelet agents, NSAIDs, SSRIs/SNRIs, oral steroids) Consider use of drugs that may cause thrombocytopenia (DMARDs, chemotherapy) Time in therapeutic range (patients already on warfarin therapy ONLY) Aim >65% TTR What is contributing to fluctuating INR is the cause modifiable? Is patient eligible for DOAC switch? Patients with swallowing difficulties or nasogastric tube administration: Apixaban, rivaroxaban and warfarin can be crushed Dabigatran capsules MUST NOT be opened not suitable for patients with swallowing difficulties or NG tubes There is no data for edoxaban as yet Alcohol intake Warfarin: acute alcohol consumption may cause INR fluctuations Patient adherence Warfarin, edoxaban, rivaroxaban = ONCE daily dosing Apixaban, dabigatran = TWICE daily dosing Patients with adherence issues - Medication reminder apps - Family members - Consider compliance aids (self or relative-filled dosette box or pharmacy filled blister pack) Warfarin = benefit of long half-life and regular monitoring Patients who use compliance aids Apixaban, edoxaban and rivaroxaban can be dispensed into compliance aids (blister packs/dosette boxes) Warfarin is unsuitable for inclusion in compliance aids due to variable dosing Dabigatran is unsuitable for inclusion in compliance aids due to instability of capsule 8

9 Appendix 5: Interaction checker: Interacting agent Dabigatran Apixaban Edoxaban Rivaroxaban Amiodarone plasma No Pharmacokinetic data Minor effect (use with caution if CrCl <50ml/min Digoxin No effect No data yet No effect No effect Diltiazem No effect No data yet Dronedarone Quinidine Verapamil Atorvastatin Clarithromycin Erythromycin Rifampicin plasma plasma plasma (reduce DOAC dose and take simultaneously) plasma plasma Decreases plasma No Pharmacokinetic or Pharmacodynamic data: caution No data yet No Pharmacokinetic data (Reduce DOAC dose by 50%) (No dose reduction required) (pharmacokin etic data) but No dose reduction required Minor effect (use with caution if CrCl 15-50ml/min) Moderate effect but no Pharmacokinetic or Pharmacodynamic data: try to avoid Extent of increase unknown Minor effect (use with caution if CrCl 15-50ml/min) No data yet No effect No effect If on 5mg BD, reduce dose by 50%. Contact manufacturer. Decreases plasma (reduce DOAC dose by 50%) Avoid if possible: minus 35%, but with compensatory increase of active Decreases plasma metabolites No data yet Strong increase No data yet HIV protease inhibitors (e.g. ritonavir) Fluconazole No data yet No data yet No data yet (if systemically administered) Itraconazole Ketoconazole Posaconazole Voriconazole Ciclosporin Tacrolimus plasma Not recommended No data yet Naproxen No data yet H2 antagonists Proton Pump Inhibitors Al/Mg-hydroxide alginates Carbamazepine Phenytoin Phenobarbital St John s Wort Decreases plasma Decreases plasma (reduce DOAC dose by 50%) (reduce DOAC dose by 50%) No effect (but pharmacodynamica lly increased bleeding time) Extent of increase unknown No data yet No effect No effect No effect Decreases plasma Decreases plasma Decreases plasma 9

10 Other anticoagulants Pharmacodynamic interactions increased bleeding risk: Antiplatelet agents NSAIDs SSRIs Systemic steroid therapy Drugs associated with thrombocytopenia (e.g. chemotherapeutic agents) Key Contra-indicated or Not recommended Dose reduction of DOAC necessary Use with caution If 2 or more yellow factors present consider dose reduction of DOAC Significantly reduce DOAC level Not recommended Use with caution avoid if possible If concomitant use unavoidable consider monitoring anticoagulant effect of DOAC via Factor Xa level (apixaban, edoxaban, rivaroxaban) or dilute Thombin Time (dtt) Haemoclot assay (dabigatran) No data available Acknowledgments: Adapted from St George s Hospital proforma 10