Rivaroxaban

Source: UK SPC (eMC) for Rivaroxaban 10 mg Film coated tablet, §4.2 (https://www.medicines.org.uk/emc/product/100864/smpc). Note that the fetched SPC is for the 10 mg strength but its §4.2 sets out the full DVT/PE treatment schedule including the 15 mg and 20 mg steps — the 15 mg and 20 mg tablets are separate products and their own SPCs should be checked before publishing. EXTENDED PREVENTION: when extended prevention of recurrent DVT and PE is indicated (following completion of at least 6 months therapy for DVT or PE), the recommended dose is 10 mg once daily; in patients whose risk of recurrent DVT or PE is considered high — such as those with complicated comorbidities, or who have developed recurrent DVT or PE on extended prevention with 10 mg once daily — a dose of 20 mg once daily should be considered. DURATION: short duration of therapy (at least 3 months) should be considered where DVT or PE was provoked by major transient risk factors (recent major surgery or trauma); longer duration should be considered for provoked DVT/PE not related to major transient risk factors, unprovoked DVT/PE, or a history of recurrent DVT/PE. Duration and dose selection should be individualised after careful assessment of treatment benefit against bleeding risk. VTE PROPHYLAXIS AFTER ELECTIVE HIP OR KNEE REPLACEMENT: 10 mg once daily, first dose 6 to 10 hours after surgery provided haemostasis has been established; 5 weeks after major hip surgery, 2 weeks after major knee surgery. MISSED DOSE: during the 15 mg twice daily phase (Days 1–21) take immediately to ensure intake of 30 mg per day — two 15 mg tablets may be taken at once — then continue the regular 15 mg twice daily schedule the next day; during a once daily phase take the missed dose immediately and continue the next day, without doubling the dose within the same day. CONVERTING FROM A VITAMIN K ANTAGONIST: for DVT/PE treatment and prevention of recurrence, stop the VKA and start rivaroxaban once the INR is ≤ 2.5; INR is falsely elevated after rivaroxaban intake and is not valid for measuring its anticoagulant activity. CONVERTING TO A VKA: give the VKA concurrently until the INR is ≥ 2.0, using standard initial VKA dosing for the first two days then INR-guided dosing; while on both drugs the INR should not be tested earlier than 24 hours after the previous rivaroxaban dose and should be taken before the next dose. CONVERTING FROM PARENTERAL ANTICOAGULANTS: stop the parenteral agent and start rivaroxaban 0 to 2 hours before the next scheduled parenteral dose would be due, or at the time of discontinuation of a continuous infusion (e.g. IV unfractionated heparin). CONVERTING TO PARENTERAL ANTICOAGULANTS: give the first parenteral dose when the next rivaroxaban dose would have been taken. HEPATIC IMPAIRMENT: contraindicated in hepatic disease associated with coagulopathy and clinically relevant bleeding risk, including cirrhotic patients with Child Pugh B and C. ELDERLY, BODY WEIGHT, GENDER: no dose adjustment. MONITORING: routine monitoring of exposure is not required, but rivaroxaban levels measured with a calibrated quantitative anti-factor Xa assay may be useful in exceptional situations such as overdose and emergency surgery — the INR must not be used. PAEDIATRIC: safety and efficacy of the 10 mg tablets in children aged 0 to 18 years have not been established and no data are available, so they are not recommended below 18 years — hence paedDose is null. (§4.8 notes that paediatric VTE trials used a body-weight-adjusted dose targeting adult 20 mg once daily exposure, but no per-kg figures are given in this bundle; verify any under-18 use against a children's formulary.) METHOD: oral use, with or without food; tablets may be crushed and mixed with water or apple puree immediately before use, or given via gastric tube. NOTE ON SOURCES: §4.5 was not retrieved in this bundle — the interactions below come from UK §4.4 plus §7 of the US label (Janssen XARELTO, https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=452610f0-5abb-448d-a1fc-9dd9be02bb66). §4.4 and §4.8 were truncated at the fetch limit.