Ketorolac × Rivaroxaban

Ketorolac inhibits platelet aggregation, prolongs bleeding time and damages the gastric mucosa; according to its SmPC it causes serious gastrointestinal toxicity more often than equivalent doses of other NSAIDs. Rivaroxaban is a direct factor Xa inhibitor, and its SmPC notes that NSAIDs increase bleeding risk on their own, so the risks add up.

Black or tarry stools (melena), vomiting blood or coffee-ground material, epigastric pain. Risk is higher in older patients and with a history of peptic ulcer disease.

Spanish ketorolac SmPCs list anticoagulants among combinations that are not recommended, and for patients on full (therapeutic) doses of anticoagulants the interaction section calls the combination contraindicated (ketorolac 10 mg and 30 mg/ml SmPCs). Ketorolac is therefore not given to patients on a therapeutic dose of rivaroxaban. At any anticoagulant dose, the FDA allows the combination only after weighing benefits against risks, with extreme caution and close monitoring (US ketorolac label). The rivaroxaban SmPC asks for caution with any NSAID and allows ulcer prophylaxis in patients at risk of peptic ulcer disease (rivaroxaban SmPC, EMA). In older patients and those at high risk of gastrointestinal complications, start ketorolac at the lowest dose and consider gastroprotection with misoprostol or a proton pump inhibitor; oral treatment lasts no more than 7 days (ketorolac 10 mg SmPC). Stop ketorolac at once if bleeding is suspected (ketorolac SmPCs).