Can diclofenac (nonsteroidal anti-inflammatory drug (NSAID)) injection be given as rescue therapy to a patient complaining of pain while on etoricoxib (cyclooxygenase-2 (COX-2) inhibitor)?

Combining Diclofenac with Etoricoxib: Not Recommended

Do not give diclofenac injection as rescue therapy to a patient already taking etoricoxib. Both medications are NSAIDs with similar COX-2 selectivity profiles and combining them provides no additional analgesic benefit while substantially increasing cardiovascular and gastrointestinal risks 1.

Why This Combination Should Be Avoided

Similar Mechanism of Action

• Both etoricoxib and diclofenac lie on the more COX-2-selective end of the NSAID spectrum, meaning they work through nearly identical mechanisms 1
• The MEDAL program demonstrated that etoricoxib and diclofenac have similar cardiovascular thrombotic event profiles (hazard ratio 0.95% CI 0.81-1.11), confirming their comparable risk profiles 1
• Combining two NSAIDs never increases efficacy but always increases toxicity 2

Cardiovascular Risks

• Both diclofenac and etoricoxib are associated with increased risk of thrombotic cardiovascular events compared to other NSAIDs 1
• The American Heart Association specifically cautions that neither etoricoxib nor diclofenac should be among first choices for pain relief, especially in individuals with or at risk for cardiovascular disease 1
• Combining these agents would compound the cardiovascular risk without providing additional benefit 1

Gastrointestinal Risks

• Never combine multiple NSAIDs, as this increases gastrointestinal bleeding risk without additional analgesic benefit 2
• Even though etoricoxib shows some GI safety advantage over traditional NSAIDs in long-term use, adding diclofenac negates any protective effect 3

Appropriate Rescue Therapy Options

First-Line Rescue Agents

• Acetaminophen (paracetamol) should be the first rescue option, as it provides analgesia through a different mechanism without compounding NSAID risks 1, 4, 2
• Acetaminophen up to 4g daily can be safely combined with etoricoxib for additional pain control 2

Second-Line Rescue Options

• Short-term opioid analgesics (tramadol or stronger opioids) can be used for breakthrough pain when acetaminophen is insufficient 1
• Opioids work through completely different pathways and do not increase NSAID-related cardiovascular or GI risks 1

Alternative Approaches

• Reassess the etoricoxib dose: If pain control is inadequate, consider whether the patient is on an appropriate dose (60-120 mg daily depending on indication) before adding rescue therapy 5
• Consider local/regional analgesia: For localized pain, topical NSAIDs or local anesthetic techniques may provide additional relief without systemic NSAID stacking 1, 2

Critical Clinical Pitfall

The most common error is assuming that switching from oral to injectable NSAID formulation somehow makes combination therapy safer—it does not. The route of administration does not change the fundamental problem of combining two drugs with overlapping mechanisms and toxicity profiles 1. The systemic effects and risks remain identical whether diclofenac is given orally, intramuscularly, or intravenously.