Direct oral anticoagulant (factor Xa inhibitor)
Apixaban is an anticoagulant (blood thinner) used to prevent clots and stroke in people with atrial fibrillation, and to treat and prevent deep vein thrombosis and pulmonary embolism. It is taken orally, with or without food. Like any anticoagulant, it increases the risk of bleeding.
Also known as: Eliquis, apixaban
Combining apixaban with aspirin increases the risk of bleeding, particularly gastrointestinal, although it may be beneficial in specific indications.
Aspirin irreversibly inhibits platelet COX-1 and injures the gastrointestinal mucosa; apixaban inhibits factor Xa. Together, the risk of bleeding — particularly digestive — increases in an additive and clinically relevant way, especially in the elderly, with reduced renal function, a history of ulcer or bleeding, or with other antiplatelet agents. Dual therapy with an anticoagulant and an antiplatelet is reserved for specific indications (for example, AF with recent coronary disease). Outside these situations, avoid the combination; if unavoidable, use the lowest aspirin dose, consider gastroprotection and instruct the patient about bleeding signs.
Apixaban + aspirin: additive bleeding risk (antiplatelet + anticoagulant + gastrointestinal injury). Assess the indication carefully.
Apixaban inhibits factor Xa and aspirin inhibits platelet COX-1; the anti-haemostatic effects are additive with no relevant pharmacokinetic interaction.
Monitor for bleeding signs, haemoglobin and gastrointestinal symptoms.
Uncontrolled bleeding, melaena, haematemesis, haematuria.
Assess bleeding risk; when indicated (e.g. AF with arterial disease), use the lowest effective dose and a gastroprotectant.
DailyMed (FDA) — approved Apixaban label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a454cd24-0c6d-46e8-b1e4-197388606175 ; approved Aspirin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3ba0a9f2-062a-401e-82eb-54383a822366 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Ibuprofen increases the risk of bleeding in patients treated with apixaban.
Apixaban inhibits factor Xa, reducing coagulation, and ibuprofen adds reversible platelet inhibition and gastrointestinal mucosal injury — two independent mechanisms that increase the risk of bleeding, including upper gastrointestinal and intracranial haemorrhage. The risk is higher in the elderly (over 75 years), in patients with reduced renal function, with a history of ulcer or bleeding, or with concomitant use of other antiplatelet agents. Whenever possible, avoid the combination; if unavoidable, use the lowest effective ibuprofen dose for the shortest time, consider gastroprotection and instruct the patient about alarm signs (blood in the stool, haematuria, extensive bruising, sudden headache).
Apixaban + ibuprofen: additive bleeding risk (platelet inhibition + gastrointestinal mucosal injury). Avoid or use with extreme caution and monitor for signs of bleeding.
Ibuprofen inhibits platelet aggregation and irritates the GI mucosa, adding to the anticoagulant effect.
Monitor dyspepsia, melaena and blood count.
GI bleeding, acute iron-deficiency anaemia.
Prefer paracetamol or a COX-2 selective NSAID where possible; limit NSAID duration.
DailyMed (FDA) — approved Apixaban label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a454cd24-0c6d-46e8-b1e4-197388606175 ; approved Ibuprofen label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=291602fa-8ebe-4200-bba7-9798c90f8a50 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Apixaban with clopidogrel raises bleeding risk; the combination is used in selected cases (e.g. post-ACS with AF).
Apixaban inhibits factor Xa and clopidogrel inhibits platelet aggregation: the apixaban label states that "co-administration with antiplatelet agents, fibrinolytics, heparin, aspirin and chronic NSAID use increases the risk of bleeding" and documents a trial with clopidogrel "terminated early due to a higher rate of bleeding with apixaban compared to placebo"; the clopidogrel label states that the risk increases with "the concomitant use of other drugs that increase the risk of bleeding". The combination should only be used in restricted settings (e.g. short duration after acute coronary syndrome with atrial fibrillation) and with close monitoring: watch for bleeding (including GI and intracranial), blood count and renal function, and reassess the duration of the combined therapy.
Apixaban + clopidogrel: additive bleeding (anticoagulant + antiplatelet). Watch bleeding; short-duration combination in restricted settings.
Combined inhibition of factor Xa and platelet aggregation with an additive bleeding risk.
Monitor occult bleeding, bruising and blood count.
GI or intracranial bleeding; extensive spontaneous bruising.
Use only with a clear indication; reduce the apixaban dose according to patient profile.
DailyMed (FDA) — approved Apixaban label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a454cd24-0c6d-46e8-b1e4-197388606175 ; approved Clopidogrel label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=55731d95-0c99-ff61-e063-6394a90a1ab5 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Alcohol intake may increase bleeding risk and interact with anticoagulation.
Limit alcohol intake during apixaban treatment.
EMC-UK (MHRA) — approved Apixaban SmPC: https://www.medicines.org.uk/emc/product/102130/smpc
Apixaban is contraindicated in severe hepatic impairment because of altered coagulation and drug metabolism.
Do not use in Child-Pugh C; assess liver function before starting.
EMC-UK (MHRA) — approved Apixaban SmPC: https://www.medicines.org.uk/emc/product/102130/smpc
Apixaban is an anticoagulant and is contraindicated in clinically significant active bleeding.
Do not use in patients with active bleeding; investigate the cause and treat the bleeding.
EMC-UK (MHRA) — approved Apixaban SmPC: https://www.medicines.org.uk/emc/product/102130/smpc
Apixaban is contraindicated in pregnancy: direct oral anticoagulants may cause maternal-fetal bleeding.
Do not use in pregnancy; use LMWH when anticoagulation is needed.
Contraindicated during breastfeeding.
Women of childbearing age must use effective contraception during treatment.
EMC-UK (MHRA) — approved Apixaban SmPC: https://www.medicines.org.uk/emc/product/102130/smpc
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Direct-acting oral anticoagulant that selectively and reversibly inhibits factor Xa, at the apex of the intrinsic and extrinsic coagulation pathways. Factor Xa inhibition reduces thrombin generation and thrombus formation, without requiring antithrombin III or routine coagulation monitoring.
Apixaban binds directly to the active site of factor Xa, preventing the conversion of prothrombin to thrombin (factor IIa). Pharmacodynamics are assessed by anti-Xa activity inhibition; it does not inhibit thrombin (factor IIa) directly nor affect platelet aggregation.
Absolute bioavailability is approximately 50% for doses up to 10 mg, with peak concentrations 3–4 hours after oral administration; food does not affect bioavailability. Plasma protein binding is ~87% and the volume of distribution is ~21 L. Absorption is dissolution-limited at doses ≥25 mg.
Approximately 25% of an oral dose is recovered in urine and faeces as metabolites. It is metabolised mainly via CYP3A4, with minor contributions from CYP1A2, 2C8, 2C9, 2C19 and 2J2; O-demethylation and hydroxylation are the major sites of biotransformation. Unchanged apixaban is the major plasma component — there are no active circulating metabolites.
Apixaban has a total clearance of approximately 3.3 L/hour and an apparent half-life of about 12 hours. Renal excretion accounts for about 27% of total clearance; the remainder is eliminated by biliary and direct intestinal excretion in the faeces.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
