Apixaban for stroke prevention in atrial fibrillation - Wirral Medicines ...

Clinical Guideline

Apixaban (Eliquis®) for stroke prevention in atrial fibrillation NICE TA275 published in March 2013. Apixaban is recommended as an option for the prevention of stroke and systemic embolism within its licensed indication, that is, in people with nonvalvular atrial fibrillation with one or more risk factors such as: 

symptomatic heart failure



hypertension



age 75 years or older



diabetes mellitus,



prior stroke or transient ischaemic attack.

1. Baseline assessment prior to initiation of apixaban (Eliquis®) 1.1 Baseline Activated Partial Prothrombin Time (aPTT), International Normalised Ratio (INR), haemoglobin, urea & electrolytes and liver function tests 1.2 Weigh patient 1.3 Calculate baseline creatinine clearance (CrCL) 1.4 Establish bleeding risk for individual patient – (See table 1) 1.5 Complete initiation checklist for apixaban and file in patient records. 1.6 Informed discussion with patient regarding risks and benefits of apixaban This MUST include that there is currently no available antidote for reversing apixaban in the event of a major bleed 1.7 Confirm if patient already taking other anticoagulants and switch according to Section 3 1.8 ALL patients MUST be given the apixaban alert card.

2. Dose of apixaban (Eliquis®) 5mg daily twice daily. Therapy should be continued long term. Some patients require a lower dosage of apixaban (See table 1)

Apixaban for stroke prevention in atrial fibrillation – clinical guideline, v1 Approved by Wirral Drug & Therapeutic Panel: May 2013

Principal author: Alice Foster Review by: May 2016

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Table 1. Bleeding risks and recommended dosage adjustments Patient Factors

Dose of apixaban

If your patient has any of these MAJOR risk factors:  Hypersensitivity to the active substance or to any of the excipients  Severe renal impairment (CrCL < 15ml/min)  Active clinically significant bleeding or organic lesion at risk of bleeding  High risk of falls that are likely to cause injury and contraindicate the use of anticoagulation  Hepatic disease associated with coagulopathy and clinically relevant bleeding risk  Concomitant treatment with any other anticoagulant. Except under the circumstances of switching therapy from apixaban. Or when unfractionated heparin is given at doses necessary to maintain a central venous or arterial catheter.  Concomitant treatment with systemic ketoconazole, voriconazole, posaconazole and itraconazole. HIV protease inhibitors e.g. ritonavir  Breastfeeding and pregnancy  Rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption  Diseases/procedures with special haemorrhagic risks  current or recent gastrointestinal ulceration,  presence of malignant neoplasms at high risk of bleeding  recent brain or spinal injury, recent brain, spinal or ophthalmic surgery,  recent intracranial haemorrhage,  known or suspected oesophageal varices, arteriovenous malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities

Avoid as contraindicated

If your patient has either (AMBER):



CrCL 15-29mls/min

   

OR if TWO of the following criteria are present: Age > 80 years old Weight < 60kg SrCr >133 micromols/litre

If both RED and AMBER factors are excluded


Initiate reduced dose of apixaban 2.5mg twice daily

Initiate standard dose of apixaban 5mg twice daily


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3. Switching anticoagulants Apixaban treatment to parenteral anticoagulant. Switching treatment to parenteral anticoagulants from apixaban can be done at the next scheduled dose Parenteral anticoagulants to apixaban - Switching treatment from parenteral anticoagulants to apixaban can be done at the next scheduled dose Apixaban treatment to Vitamin K antagonists (VKA) e.g. warfarin - when converting patients from apixaban to VKA therapy, continue administration of apixaban for at least 2 days after beginning VKA therapy. After 2 days of coadministration of apixaban with VKA therapy, obtain an INR prior to the next scheduled dose of apixaban. Continue coadministration of apixaban and VKA therapy until the INR is ≥ 2.0. Vitamin K antagonists to apixaban - When converting patients from Vitamin K antagonist (VKA) therapy to apixaban, discontinue warfarin or other VKA therapy and start apixaban when the international normalized ratio (INR) is < 2.0.

4. Monitoring There is no routine anticoagulant blood monitoring for apixaban Clotting tests (e.g., PT, INR, and aPTT) are affected as expected by the mechanism of action of apixaban. Changes observed in these clotting tests at the expected therapeutic dose are small and subject to a high degree of variability. Apixaban is a black triangle drug. ANY adverse effects must be reported to the Committee on Safety of Medicines (CSM). http://yellowcard.mhra.gov.uk/ 4.1. Renal Function Assess renal function at baseline and every six months thereafter. Close clinical supervision is required in patients with stage 3 chronic kidney disease (CKD) CrCL 30-60ml/min, e.g. monitor renal function every three months or more frequently if clinically appropriate. ***Remember reduce dose to 2.5mg twice daily if TWO of the following (AMBER) factors change **** Age > 80 years old, Weight < 60kg or SrCr >133 micromols/litre While on treatment, renal function should be assessed in certain clinical situations when it is suspected that renal function could decline or deteriorate (such as hypovolemia, dehydration, and with certain co-medications — e.g. high dose diuretics). The dose of apixaban should be reviewed in these circumstances.

4.2 Hepatic Impairment Patients with elevated liver enzymes (ALT/AST >2 x ULN) or total bilirubin ≥1.5 x ULN were excluded in clinical trials. Apixaban should be used with caution in this population (see sections 4.4 and 5.2). Prior to initiating apixaban, liver function testing should be performed.

4.3 Bleeding risk As with all anticoagulants, apixaban should be used with caution in conditions with an increased risk of bleeding. Bleeding may occur at any site during therapy with apixaban. An Apixaban for stroke prevention in atrial fibrillation – clinical guideline, v1 Approved by Wirral Drug & Therapeutic Panel: May 2013


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unexplained fall in haemoglobin and/or haematocrit or blood pressure should lead to an investigation to identify a bleeding site. Close clinical surveillance is recommended throughout the treatment period, especially if risk factors are combined.

5. Problem Solving 5.1 Drug Interactions Table 2. Selected interactions and recommended dosage adjustments: (Refer to BNF/SPC for a full up-to-date list of interactions) Drug Interactions with apixaban HIV Protease Inhibitors e.g. ritonavir and systemic Avoid co-prescribing. azole antifungals. e.g. ketoconazole Phenytoin, rifampicin, Phenobarbital, St Johns Wort

carbamazepine, Co-administer with caution. May lead to a reduction in apixaban concentrations.

Antiplatelets, NSAIDs, SSRIs and SNRIs.

Increased risk of GI bleeding. Use combination with extreme caution – consider GI protection.

UFH, LMWH, heparin derivatives (fondaparinux), thrombolytic agents, GPIIb/IIIa receptor Increased risk of bleeding. antagonists, dextran, sulphinpyrazone, dabigatran, prescribing (See table 2). rivaroxaban and vitamin K antagonists

Avoid

co-

Amiodarone, diltiazem, quinidine, verapamil and No recommendation regarding concomitant dronedarone, digoxin use. HIV Protease Inhibitors e.g. ritonavir and systemic Avoid co-prescribing. azole antifungals. e.g. ketoconazole

Digoxin

No interactions reported to date

Beta - blockers

No interactions reported to date

5.2. Acute Bleeding See Bleeding — Management in patients taking oral anticoagulants.

5.3. Surgery Apixaban should be discontinued at least 48 hours prior to elective surgery or invasive procedures with a moderate or high risk of bleeding. This includes interventions for which the probability of clinically significant bleeding cannot be excluded or for which the risk of bleeding would be unacceptable. Apixaban should be discontinued at least 24 hours prior to elective surgery or invasive procedures with a low risk of bleeding. This includes interventions for which any bleeding that occurs is expected to be minimal, non-critical in its location or easily controlled. If surgery or invasive procedures cannot be delayed, appropriate caution should be exercised, taking into consideration an increased risk of bleeding. This risk of bleeding should be weighed against the urgency of intervention. Apixaban for stroke prevention in atrial fibrillation – clinical guideline, v1 Approved by Wirral Drug & Therapeutic Panel: May 2013


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Apixaban should be restarted after the invasive procedure or surgical intervention as soon as possible provided the clinical situation allows and adequate haemostasis has been established. 5.4. Acutely unwell patients While on treatment with apixaban renal function should be assessed in clinical situations where it is suspected that renal function could decline or deteriorate. Consider temporarily substituting apixaban with prophylactic low molecular weight heparin in patients who are admitted to hospital with sepsis, acute kidney injury, hypovolaemia, dehydration or who are started on high dose diuretics. It is recommended to wait until the next dose of apixaban is due before starting parenteral anticoagulation. 5.5. Compliance Aids – If a patient has been assessed as being appropriate for a multicompartment compliance aid (MCA), often known as a dosette box, consideration can be given to including apixaban tablets as they do not have any special storage requirements. Patients should be able to identify the apixaban tablet in the compliance aid so that it can be omitted if bleeding occurs. 5.6. Swallowing difficulties Data from an open label study looking into the effects of crushing apixaban tablets and administration via enteral feeding tubes showed pharmacokinetic profile is broadly comparable to whole tablets in terms of absorption profile. However the study only involved 14 patients. 5.7. Overdose with apixaban There is no antidote to apixaban. Overdose of apixaban may result in a higher risk of bleeding. In the event of haemorrhagic complications, treatment must be discontinued and the source of bleeding investigated. Refer to Bleeding — Management in patients taking oral anticoagulants if patient is bleeding acutely. In controlled clinical trials, orally-administered apixaban in healthy subjects at doses up to 50 mg daily for 3 to 7 days (25 mg twice daily (bid) for 7 days or 50 mg once daily (OD) for 3 days) had no clinically relevant adverse effects. The use of activated charcoal to reduce absorption in case of apixaban overdose may be considered when administered 2 and 6 hours after apixaban ingestion.

6. Patient information    

All patients should be given the apixaban alert card and counselled on the details Patient understands the potential bleeding risks with apixaban and is aware that there is currently no readily available antidote for its effects and the potential ramifications of this. All patients should be advised on what action to take if they miss a dose of apixaban All patients should be counselled to inform their dentist or any other healthcare professional performing invasive treatments or surgery that they are taking apixaban.

Patients should be able to identify the apixaban tablet in the compliance aid so that it can be omitted if bleeding occurs. Apixaban for stroke prevention in atrial fibrillation – clinical guideline, v1 Approved by Wirral Drug & Therapeutic Panel: May 2013


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7. References    

Apixaban for preventing stroke and systemic embolism in people with nonvalvular atrial fibrillation: Available http://publications.nice.org.uk/apixaban-for-preventing-stroke-and-systemicembolism-in-people-with-nonvalvular-atrial-fibrillation-ta275 Summary of product characteristics for Eliquis: Accessed available online at www.medicines.org.uk British National Formulary, March 2013 Apixaban patient alert card available at: https://www.eliquis.co.uk/Images/5829_FINAL_Patient%20Alert%20Card_WEB_.pdf



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