apixaban
Direct oral anticoagulants· Brands: EliquisPO
Mechanism of action
Apixaban is a direct oral anticoagulant that selectively and reversibly inhibits factor Xa. It prevents the conversion of prothrombin to thrombin, thereby reducing thrombin generation and thrombus formation. It does not require antithrombin for its activity.
Pharmacokinetics
Apixaban is well absorbed after oral administration with a bioavailability of about 50%. It is metabolized in the liver primarily by CYP3A4 and CYP3A5, and undergoes renal and biliary excretion. Its half-life is approximately 12 hours, allowing twice-daily dosing. It is a substrate of P-glycoprotein and breast cancer resistance protein, so interactions with inhibitors or inducers of these transporters and CYP3A4 can affect its plasma levels.
Indications & dosing
Stroke prevention in non-valvular atrial fibrillation
- adult · PO: 5 mg BD
- adult · PO: 2.5 mg BD · Reduced dose if ≥2 of: age ≥80 years, weight ≤60 kg, or creatinine ≥1.5 mg/dL (133 micromol/L)
Contraindications & precautions
- Active major bleeding
- Mechanical heart valve
- Monitor patients for signs of bleeding and instruct them to report unusual bleeding or bruising.
- Use with caution in moderate hepatic impairment (Child-Pugh B) or severe renal impairment (CrCl < 15 mL/min) where dose adjustment may be required.
- Avoid concomitant use with strong inhibitors of both CYP3A4 and P-gp (e.g., ketoconazole, itraconazole, ritonavir) as they increase apixaban exposure and bleeding risk.
- Concomitant NSAIDs, antiplatelet agents, or other anticoagulants increase the risk of bleeding; use with caution only if the benefits outweigh the risks.
- Do not discontinue apixaban abruptly without adequate alternate anticoagulation, as this may increase the risk of thrombosis.
- For invasive procedures, stop apixaban at least 24-48 hours prior, depending on renal function and bleeding risk; consult local guidelines.
Adverse effects
- Bleedingserious
Interactions
- dabigatrancontraindicatedDo not co-prescribe apixaban and dabigatran. When switching therapy from one to the other, follow established switching guidelines: stop the first anticoagulant and start the second at the time of the next scheduled dose, taking renal function into account. Alternatives should be considered if temporary anticoagulation is needed for procedures or events.
- clarithromycinmajorAvoid co-prescription if possible. If combined use is essential, reduce the apixaban dose (for example, from 5 mg twice daily to 2.5 mg twice daily) and monitor the patient closely for signs of bleeding. Do not use this combination in patients already taking apixaban 2.5 mg twice daily. Consider alternative antibiotics that are not strong CYP3A4/P-gp inhibitors.
- phenytoinmajorAvoid co-prescription where possible. Consider alternative anticoagulants (e.g., warfarin with INR monitoring) or alternative antiepileptics (e.g., levetiracetam). If concurrent use is unavoidable, monitor for clinical signs of thrombosis and consider increasing the apixaban dose, though specific dosing recommendations are not well established.
- clopidogrelmajorAvoid the combination unless there is a clear indication for dual antithrombotic therapy as recommended by guidelines. If co-prescription is necessary, use the lowest effective doses and the shortest duration. Monitor closely for signs of bleeding (e.g., dark stools, haematuria, bruising) and check haemoglobin and haematocrit periodically. Consider omeprazole or other gastroprotective agents. Assess renal function and adjust apixaban dose accordingly.
- aspirinmajorAvoid co-prescription unless there is a clear indication for both. If used together, use the lowest effective doses, consider gastroprotection with a proton pump inhibitor, and monitor for signs of bleeding. Review the need for antiplatelet therapy regularly.
- naproxenmajorAvoid concomitant use unless strongly indicated. If co-prescription is necessary, use the lowest effective dose of naproxen for the shortest duration, consider gastroprotective therapy (e.g., a proton pump inhibitor), and monitor closely for signs of bleeding. Advise the patient to report any unusual bruising, black stools, or blood in vomit. Periodic full blood counts and stool occult blood testing may be considered.
- ibuprofenmajorAvoid co-prescription where possible. If an NSAID is required, use the lowest effective dose for the shortest duration and consider a gastroprotective agent such as a proton pump inhibitor. If combined, monitor for signs of bleeding (melena, haematemesis, bruising, anaemia) and assess haemoglobin and renal function periodically. For patients with a high bleeding risk, consider alternative analgesics such as paracetamol or a weak opioid.
- amiodaronemoderateConcomitant use of amiodarone and apixaban may require caution. Check the current apixaban prescribing information, as some formularies advise a reduced apixaban dose (e.g., 2.5 mg twice daily) when given with strong inhibitors of both CYP3A4 and P-gp. If no dose reduction is made, closely monitor the patient for clinical evidence of bleeding. Reassess the need for amiodarone and consider alternative anti-arrhythmic options when possible.
- warfarincontraindicatedCo-prescription is contraindicated. If switching therapy, discontinue one agent and start the other according to an accepted transition protocol, with close monitoring of INR and clinical bleeding signs. Do not overlap the agents except during supervised switching.
- diltiazemmajorAvoid co-prescription where possible, or use with caution. If combined, monitor the patient closely for signs of bleeding (e.g., bruising, melaena, haematuria). Consider reducing the apixaban dose according to local guidelines or product labelling. Re-evaluate the combination if other interacting drugs or bleeding risk factors are present.
Renal & hepatic adjustment
- eGFR 30+: No dose adjustment required for CrCl ≥30 mL/min.
- eGFR 15–29: For atrial fibrillation, reduce dose to 2.5 mg twice daily. For other indications, use with caution.
- eGFR 0–14: Not recommended; use with caution and only if no alternative. Consider specialist advice. (avoid)
- Hepatic impairment (mild): No dose adjustment required for Child-Pugh A.
- Hepatic impairment (moderate): Use with caution; no specific dose adjustment. Monitor for bleeding.
- Hepatic impairment (severe): Contraindicated in hepatic impairment with coagulopathy and clinically relevant bleeding risk (e.g. Child-Pugh C). (avoid)
Monitoring, pregnancy & toxicity
- Bleeding signs and symptoms · At each review
- Renal function (creatinine/eGFR) · Baseline then periodically; at least annually, more often if high risk
- Hepatic function (LFTs) · Baseline then periodically
- Haemoglobin · Baseline then periodically if bleeding risk
- Drug interactions (CYP3A4/P-gp inhibitors or inducers) · At start and when co-prescribed
- Anti-Xa activity · Not routine; consider in extremes of body weight or renal impairment
- Pregnancy: Contraindicated in pregnancy. If anticoagulation is required, use an alternative such as low molecular weight heparin.
- Toxicity: Bleeding (e.g., gastrointestinal, intracranial, retroperitoneal) · Discontinue apixaban and provide supportive care. Consider activated charcoal if ingestion within 2-3 hours. For severe bleeding, use specific reversal agent andexanet alfa or consider prothrombin complex concentrate (PCC).
- Toxicity: Anticoagulant effect (measured by anti-Xa activity) · Not usually monitored; if needed, anti-Xa assay can help assess exposure. Reverse if severe bleeding.
Antidotes & reversal
- Andexanet alfa · Specific factor Xa reversal; 4-factor PCC is the usual alternative where andexanet is unavailable.
Clinical notes
Apixaban is indicated for the prevention of stroke and systemic embolism in non-valvular atrial fibrillation, and for the treatment and prevention of recurrence of deep vein thrombosis and pulmonary embolism. Doses vary by indication and renal function. It is associated with a lower risk of major bleeding compared with warfarin. As with all DOACs, adherence is critical and missed doses can increase thrombotic risk. Restrictions exist in patients with mechanical heart valves or moderate-to-severe mitral stenosis. Renal function should be monitored, but dose adjustment is not required for mild or moderate renal impairment.
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BNF; local formulary