Direct oral anticoagulants (factor Xa inhibitors)
ATC code: B01AF01 (Rivaroxaban)
Brand names
Xarelto
Selective reversible direct factor Xa inhibitor. Blocks the final step of the coagulation cascade upstream of thrombin formation. Unlike apixaban, the maintenance phase uses once-daily dosing, improving adherence but making missed doses more impactful. Half-life is 5–13 hours depending on age and renal function.
First line
First-line DOAC for stroke prevention in non-valvular AF per 2024. The ROCKET-AF trial showed non-inferiority versus warfarin for stroke and systemic embolism. Bleeding profile: fewer intracranial, slightly more GI bleeds than warfarin. Standard dose 20 mg once daily with food. At eGFR 15–49 mL/min/1.73 m², 15 mg once daily.
First line
First-line treatment of DVT and PE in outpatients without contraindications. Loading 15 mg twice daily for 21 days, then 20 mg once daily for up to 6 months. Long-term secondary prevention: 10 mg once daily. In active cancer, DOAC evidence (apixaban, rivaroxaban, edoxaban) accumulated through SELECT-D, Hokusai-VTE Cancer, and ADAM-VTE: non-inferior to LMWH, but GI and genitourinary tumors carry an increased bleeding risk.
Individual decision
The COMPASS trial (over 27,000 patients with chronic CAD or peripheral artery disease) showed that rivaroxaban 2.5 mg twice daily plus aspirin 100 mg reduced MACE (vascular death, MI, stroke) by 24 % compared with aspirin alone, at the cost of a 70 % increase in major bleeding. Use is justified in patients at high ischemic and low hemorrhagic risk. The decision is individualized using , age, and comorbidities.
Low «vascular» dose 2.5 mg twice daily combined with aspirin 100 mg.
Not recommended
After the COVID-19 pandemic some patients took up the habit of taking rivaroxaban, apixaban, and other DOACs at the first symptoms of an upper respiratory infection «for thrombosis prevention». International guidelines do not support this. Outpatient viral URI is self-limiting, clinically meaningful thromboembolism risk is not elevated, and major bleeding risk on rivaroxaban remains the same. , , ASH, and ISTH do not mention anticoagulants for outpatient URI. Evidence-based management is rest, hydration, symptomatic measures; antivirals (oseltamivir, nirmatrelvir/ritonavir) are reserved for confirmed influenza or COVID-19 in high-risk patients.
Not recommended
For mild and moderate outpatient COVID-19, rivaroxaban and other DOACs are not prescribed for thrombosis prophylaxis. The ACTIV-4B RCT (Connors et al., JAMA 2021) compared aspirin, prophylactic-dose apixaban, therapeutic-dose apixaban, and placebo in symptomatic outpatients – the trial was stopped early for futility at very low event rates. Anticoagulants did not reduce hospitalisations, thromboses, or mortality, while bleeding events rose. The updated ASH 2024 living guideline (Blood Advances) issued a conditional recommendation against routine post-discharge thromboprophylaxis in COVID-19; the Therapeutics Living Guideline and NG191 do not support routine DOAC use in outpatients. Non-severe hospitalised patients benefit from low-molecular-weight heparin under supervision, not oral DOACs. One exception is MICHELLE (Ramacciotti et al., Lancet 2022): post-discharge rivaroxaban 10 mg for 35 days reduced VTE in high-thrombotic-risk patients (IMPROVE-DD ≥ 4 or ≥ 2 with D-dimer ≥ 500 ng/mL). ISTH 2023 discusses this tactic only for that selected post-discharge cohort. This narrow scenario does not justify self-administered Xarelto «just in case» for outpatient COVID-19.
1 pair found. Sorted from critical to minor.
Mechanism
Кетоконазол – сильный ингибитор CYP3A4 и P-gp. Концентрация ривароксабана возрастает в 2.6 раза, риск кровотечений критический.
Management
Сочетание противопоказано. Выбрать альтернативный антимикотик (флуконазол с осторожностью, тербинафин для онихомикоза).
Boxed warning
FDA boxed warning: premature discontinuation increases the risk of thrombotic events. With neuraxial anesthesia (epidural or spinal), the risk of epidural hematoma is increased — careful timing and monitoring are required.
FDA categories were retired in 2015. The drug crosses the placenta. The manufacturer label states a contraindication. LMWHs are the standard for anticoagulation in pregnancy.
Excreted in breast milk. The manufacturer states a contraindication. Switch breastfeeding patients to LMWH or warfarin (compatible per LactMed).
rivaroxaban is evaluated for the following indications with varying evidence strength: Venous thromboembolism (evidence tier A), Stroke prevention in non-valvular atrial fibrillation (evidence tier A), Established ASCVD, secondary prevention (evidence tier B). See the full indication matrix with dosing and citations above on this page.
Common side effects of rivaroxaban (≥ 1 in 100): Epistaxis, gum bleeding, Gastrointestinal bleeding (somewhat more frequent than other DOACs), Hematuria, Bruising, Anemia. See the Safety section for uncommon and serious reactions.
FDA categories were retired in 2015. The drug crosses the placenta. The manufacturer label states a contraindication. LMWHs are the standard for anticoagulation in pregnancy.
Excreted in breast milk. The manufacturer states a contraindication. Switch breastfeeding patients to LMWH or warfarin (compatible per LactMed).
rivaroxaban is contraindicated in: Active clinically significant bleeding; Lesion or condition at high risk of major bleeding; Concomitant anticoagulant therapy; Severe hepatic impairment (Child-Pugh B and C); Pregnancy and breastfeeding (per manufacturer). Full list in the Safety section.
FDA boxed warning: premature discontinuation increases the risk of thrombotic events. With neuraxial anesthesia (epidural or spinal), the risk of epidural hematoma is increased — careful timing and monitoring are required.