Apixaban × Ketorolac

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. Apixaban is a direct factor Xa inhibitor, and its SmPC notes that NSAIDs usually increase bleeding risk, so the risks add up.

Gum bleeding, epistaxis, bruising without trauma, blood in urine or stool, menorrhagia. Severe cases include gastrointestinal or intracranial haemorrhage. Risk rises in patients over 65 and with prior 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 apixaban. 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 apixaban SmPC asks for caution when it is combined with NSAIDs (apixaban SmPC, EMA), and the US apixaban label asks doctors to explain the signs of blood loss and to tell patients to report them at once (US apixaban label). 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).