Direct oral anticoagulant (factor Xa inhibitor)
Rivaroxaban is an anticoagulant (blood thinner) used to prevent stroke in people with atrial fibrillation, to treat and prevent blood clots, and to prevent clots after orthopaedic surgery. It is taken orally, usually with food at the 15/20 mg dose.
Also known as: Xarelto, rivaroxaban
Combining rivaroxaban with aspirin increases the risk of bleeding, particularly gastrointestinal.
Aspirin inhibits platelets and injures the gastric mucosa, and rivaroxaban inhibits factor Xa; the combination increases the risk of bleeding, particularly digestive, in an additive way. Risk factors: advanced age, renal or hepatic impairment, history of ulcer or bleeding and use of other antiplatelet agents. Anticoagulant + antiplatelet combinations are reserved for specific indications (for example, AF + recent coronary disease, or peripheral artery disease in which rivaroxaban 2.5 mg is intentionally used with aspirin). Outside these indications, avoid; if used, respect the approved regimen and monitor for bleeding signs.
Aspirin + rivaroxaban: additive bleeding risk (antiplatelet + anti-Xa + gastrointestinal injury). Assess the indication and dose.
Rivaroxaban inhibits factor Xa; aspirin blocks the platelet thromboxane pathway, with an additive bleeding effect.
Monitor haemoglobin, haematocrit and signs of bleeding.
GI bleeding, acute anaemia, dizziness from blood loss.
Weigh cardiovascular benefit against bleeding risk; use the lowest effective dose.
DailyMed (FDA) — approved Rivaroxaban label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=481b7802-5093-43e7-bbd9-1532197eb6e6 ; 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 bleeding risk with rivaroxaban.
Rivaroxaban inhibits factor Xa and ibuprofen adds platelet inhibition and gastrointestinal mucosal injury, increasing the risk of bleeding, particularly digestive. Risk factors: advanced age, renal or hepatic impairment, history of bleeding or ulcer and use of other antiplatelet agents. Prefer paracetamol for analgesia; if the NSAID is needed, use the lowest effective dose for the shortest time, consider gastroprotection and instruct the patient about bleeding signs (dark stools, haematuria, bruising, sudden headache).
Rivaroxaban + ibuprofen: additive bleeding risk. Avoid if possible; if unavoidable, use the lowest dose, shortest time and monitor for signs of bleeding.
Ibuprofen's antiplatelet and gastro-irritative effect adds to rivaroxaban.
Monitor for GI bleeding signs.
Melaena, haematemesis, abdominal pain with anaemia.
Avoid long-term NSAIDs; use the lowest dose for the shortest duration.
DailyMed (FDA) — approved Rivaroxaban label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=481b7802-5093-43e7-bbd9-1532197eb6e6 ; 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)
Rivaroxaban plus clopidogrel increases the risk of major bleeding.
Clopidogrel inhibits platelet aggregation and rivaroxaban inhibits factor Xa; the combination adds up the effects on haemostasis and increases the risk of major bleeding. The rivaroxaban label explicitly states that "clopidogrel and chronic NSAID use may increase the risk of bleeding" and recommends caution with the concomitant use of "antiplatelet agents, other antithrombotics, fibrinolytics and NSAIDs"; the clopidogrel label states that the risk increases with "the concomitant use of other drugs that increase the risk of bleeding". Dual therapy rivaroxaban 2.5 mg + aspirin/clopidogrel is approved in specific settings (coronary/peripheral artery disease with CAD/PAD) for defined periods, but the combination with clopidogrel in general should be avoided. Monitor for bleeding signs (including intracranial and GI) and renal function.
Clopidogrel + rivaroxaban: additive bleeding (antiplatelet + anticoagulant). Watch bleeding; short-duration combination in restricted settings.
Combined antithrombotic effect (factor Xa + P2Y12) with additive bleeding.
Monitor for bleeding signs and blood count.
Intracranial, GI or retroperitoneal bleeding.
Reserve for high thrombotic-risk indications; consider a gastroprotectant.
DailyMed (FDA) — approved Rivaroxaban label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=481b7802-5093-43e7-bbd9-1532197eb6e6 ; 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)
Switching between rivaroxaban and warfarin requires controlled overlap; prolonged simultaneous use increases bleeding.
The combination of warfarin and rivaroxaban (vitamin K antagonist + direct factor Xa inhibitor) has no therapeutic indication and substantially increases the risk of major bleeding, including intracranial haemorrhage. Switching between the two drugs must follow a protocol: when changing from warfarin to rivaroxaban, stop warfarin and start rivaroxaban when the INR is below the threshold (usually < 3.0); conversely, start warfarin overlapping with rivaroxaban until the INR is in the therapeutic range, then stop rivaroxaban. Prolonged dual anticoagulation is a medication error — alert the patient to bleeding signs.
Two anticoagulants at the same time: additive bleeding risk. Do not combine; switching between warfarin and rivaroxaban requires a protocol with controlled INR.
Overlap doubles anticoagulation; rivaroxaban's effect overlaps warfarin before it reaches the target INR.
Monitor INR per the transition protocol and bleeding signs.
Supratherapeutic INR, active bleeding during transition.
Follow the SmPC transition schedule: warfarin plus rivaroxaban for 2 days until INR ≥ 2.0 (and vice versa).
DailyMed (FDA) — approved Rivaroxaban label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=481b7802-5093-43e7-bbd9-1532197eb6e6 ; approved Warfarin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=541c9a70-adaf-4ef3-94ba-ad4e70dfa057 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Alcohol increases the bleeding risk in patients anticoagulated with rivaroxaban.
Limit alcohol intake during treatment.
EMC-UK (MHRA) — approved Rivaroxaban SmPC: https://www.medicines.org.uk/emc/product/100864/smpc
Rivaroxaban is contraindicated in hepatic disease with coagulopathy and a clinically relevant bleeding risk.
Do not use in Child-Pugh C or associated coagulopathy.
EMC-UK (MHRA) — approved Rivaroxaban SmPC: https://www.medicines.org.uk/emc/product/100864/smpc
Rivaroxaban is contraindicated in clinically significant active bleeding.
Do not use in patients with active bleeding.
EMC-UK (MHRA) — approved Rivaroxaban SmPC: https://www.medicines.org.uk/emc/product/100864/smpc
Rivaroxaban is contraindicated in pregnancy because of the bleeding risk for the mother and fetus.
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 Rivaroxaban SmPC: https://www.medicines.org.uk/emc/product/100864/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, reducing thrombin generation and thrombus formation. Factor Xa inhibition prolongs prothrombin time (PT) and aPTT dose-dependently; no routine monitoring required.
Rivaroxaban binds to the active site of factor Xa, both free and within the prothrombinase complex, inhibiting the conversion of prothrombin to thrombin. It does not directly inhibit thrombin nor affect platelet aggregation.
Absolute bioavailability is dose-dependent: 80–100% for 2.5 mg and ~66% for 20 mg fasted (food increases absorption of the 15/20 mg doses). Peaks occur 2–4 hours after intake; plasma protein binding is 92–95% and the steady-state volume of distribution is ~50 L.
Approximately 51% of the oral dose is recovered as inactive metabolites in urine (30%) and faeces (21%). Oxidative degradation by CYP3A4/5 and CYP2J2 and hydrolysis are the major sites of biotransformation; there are no major active circulating metabolites.
The terminal elimination half-life is 5–9 hours in healthy young adults (20–45 years) and 11–13 hours in the elderly (60–76 years). Systemic clearance is ~10 L/hour; ~36% of the dose is recovered unchanged in urine (actively secreted) and 7% in faeces.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
