naproxen

Mechanism

Similar to apixaban + meloxicam. Additive GI bleeding risk with an anticoagulant and NSAID.

Symptoms

Black or tarry stools (melena), vomiting blood or coffee-ground material, epigastric pain. Risk multiplies in older patients and with prior peptic ulcer disease.

Management

Avoid prolonged combination. If naproxen is needed for a short course, use the minimum effective dose for 5–7 days with pantoprazole cover. For chronic analgesia: paracetamol or celecoxib.

Mechanism

Contrast and NSAID (naproxen) – additive nephrotoxicity, especially in chronic kidney disease and dehydration.

Symptoms

Reduced urine output, rising creatinine and potassium, oedema. Symptoms appear earlier in older patients and chronic kidney disease.

Management

Stop naproxen 48 hours before planned contrast and resume 48 hours after with stable renal function. Alternative analgesic: paracetamol. Provide contrast nephroprotection with adequate saline hydration.

Mechanism

Dual NSAID therapy – sharp rise in GI bleeding risk (3- to 5-fold), acute kidney injury, and cardiovascular events.

Symptoms

Black or tarry stools, vomiting blood, epigastric pain. Risk multiplies in older patients and with prior peptic ulcer disease.

Management

The combination is not prescribed. One NSAID at a time. For enhanced analgesia: paracetamol or a short opioid course, not a second NSAID. Ketorolac courses never exceed 5 days.

Mechanism

NSAIDs reduce renal lithium clearance via prostaglandin-dependent renal blood flow blockade. Lithium plasma levels rise 1.5- to 2-fold with toxicity risk.

Symptoms

Tremor, muscle twitching, nausea, diarrhoea, confusion, ataxia. Symptoms emerge when serum lithium exceeds 1.2 mmol/L.

Management

Avoid prolonged combination. If naproxen is needed for a short course, reduce lithium by 25–30% and check lithium level at 5–7 days. For chronic analgesia: paracetamol or celecoxib (with lithium monitoring).

Mechanism

NSAIDs reduce renal methotrexate clearance via renal blood flow blockade and can displace methotrexate from plasma protein binding. Fatal cases have been reported at high oncologic methotrexate doses.

Symptoms

Mouth ulcers (mucositis), nausea, diarrhoea, hair loss. Blood counts fall: leukocytes, platelets, erythrocytes. Severe cases: fatal pancytopenia, nephrotoxicity.

Management

At oncologic methotrexate doses, the combination is not prescribed. At low rheumatologic doses, a short naproxen course is acceptable with blood count and creatinine monitoring. For chronic analgesia: paracetamol or celecoxib.

Mechanism

Direct oral anticoagulant (rivaroxaban) + NSAID (naproxen) – additive GI bleeding risk.

Symptoms

Black or tarry stools, vomiting blood, epigastric pain. Risk multiplies in older patients and with prior peptic ulcer disease.

Management

Avoid prolonged combination. If naproxen is needed for a short course, use the minimum effective dose for 5–7 days under pantoprazole cover. For chronic analgesia: paracetamol or celecoxib.

Mechanism

NSAID (naproxen) + nephrotoxic calcineurin inhibitor (tacrolimus) – additive acute kidney injury risk in transplant patients.

Symptoms

Reduced urine output, rising creatinine and potassium, oedema. Symptoms appear earlier in older patients and chronic kidney disease.

Management

Avoid prolonged combination. For post-transplant analgesia: paracetamol (up to 2 g/day) or a short opioid course. For neuropathic pain: gabapentin or pregabalin.

Mechanism

Naproxen (NSAID) inhibits platelet aggregation and injures the gastric mucosa. On warfarin, GI bleeding risk multiplies, particularly in older patients and with prior peptic ulcer disease.

Symptoms

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.

Management

Avoid chronic naproxen on warfarin. For analgesia, choose paracetamol. For chronic NSAID needs, use a selective COX-2 inhibitor (celecoxib) under pantoprazole cover.