In which patients is diclofenac (Nonsteroidal Anti-Inflammatory Drug (NSAID)) contraindicated?

Contraindications and High-Risk Situations for Diclofenac

Diclofenac is absolutely contraindicated in patients undergoing coronary artery bypass graft (CABG) surgery, those with known hypersensitivity to diclofenac or aspirin-sensitive asthma, and should be avoided in patients with advanced renal disease, cirrhosis, congestive heart failure, and those at high cardiovascular risk. 1, 2

Absolute Contraindications

The FDA drug label explicitly lists the following absolute contraindications:

• Known hypersensitivity (anaphylactic reactions, serious skin reactions) to diclofenac or any drug components 1
• History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs, as severe and sometimes fatal anaphylactic reactions have been reported 1
• Perioperative pain management in CABG surgery, due to increased risk of cardiovascular thrombotic events 2, 1

High-Risk Cardiovascular Situations (Avoid Use)

Diclofenac carries particularly high cardiovascular risk compared to other NSAIDs and should be avoided in:

• Patients with cardiovascular disease or risk factors, as diclofenac increases vascular events by 63% (RR 1.63) compared to placebo 2
• Patients with history of myocardial infarction, where diclofenac increases recurrent MI risk by 54% (RR 1.54) and mortality by 140% (RR 2.40) 2
• Patients with congestive heart failure, as all NSAIDs can worsen heart failure through fluid retention and prostaglandin inhibition 2
• Patients with poorly controlled hypertension, as NSAIDs increase mean blood pressure by approximately 5 mm Hg 2

High-Risk Gastrointestinal Situations (Avoid or Use Extreme Caution)

Avoid diclofenac in patients with:

• History of NSAID-associated upper GI bleeding, as risk of bleeding recurrence is 5% in first 6 months 2
• Active peptic ulcer disease or GI bleeding, which can be fatal and occurs without warning 1
• Elderly patients (≥75 years) without gastroprotection, as they are at greater risk for serious GI events 2, 1

If diclofenac must be used in patients with prior complicated upper GI ulcer:

• Use COX-2 selective inhibitor plus proton pump inhibitor if GI bleed occurred within past year 2
• Use either COX-2 inhibitor OR nonselective NSAID plus proton pump inhibitor if no bleed in past year 2

High-Risk Hepatic Situations (Avoid Use)

Diclofenac has higher hepatotoxicity risk than other NSAIDs and should be avoided in:

• Patients with cirrhosis, due to potential for hematologic and renal complications 2
• Patients with hepatic dysfunction or active hepatitis, as diclofenac shows higher rates of hepatic injury and transaminase elevation (>3× upper limit of normal) compared to other NSAIDs 2, 3
• Patients with impaired hepatic function, as case reports document idiosyncratic liver toxicity 2

High-Risk Renal Situations (Avoid Use)

Avoid diclofenac in:

• Chronic kidney disease stage IV or V (eGFR <30 mL/min), as oral NSAIDs should not be used 2
• Patients with preexisting renal disease, as NSAIDs can cause volume-dependent renal failure 2, 1
• Dehydrated or hypovolemic patients until volume status is corrected 1
• Patients on ACE inhibitors, ARBs, or beta blockers, as these medications increase NSAID-related renal complications 2

Hematologic Contraindications

Avoid diclofenac in:

• Patients with platelet defects or thrombocytopenia, due to antiplatelet effects 2
• Patients on anticoagulants (warfarin, heparin), as risk of GI bleeding increases 3-6 times and INR increases up to 15% 2, 1
• Perioperative setting: Stop diclofenac for 5 elimination half-lives before surgery (approximately 2 days for diclofenac) 2

Pregnancy Contraindications

Avoid diclofenac:

• At approximately 30 weeks gestation and later, due to risk of premature closure of fetal ductus arteriosus 1
• At approximately 20 weeks gestation and later, due to risk of fetal renal dysfunction leading to oligohydramnios 1
• In the 6-8 weeks before term, as NSAIDs can prolong pregnancy or labor and cause fetal effects from antiplatelet activity 2

Special Population Considerations

In elderly patients (≥75 years):

• Strongly recommend topical rather than oral NSAIDs if NSAID therapy is necessary 2
• If oral NSAID required, use lowest dose for shortest duration with gastroprotection 2

In patients requiring low-dose aspirin for cardioprotection:

• Do NOT use ibuprofen due to pharmacodynamic interaction that renders aspirin less effective 2
• Use nonselective NSAID other than ibuprofen plus proton pump inhibitor 2
• Do NOT use COX-2 selective inhibitors in this setting 2

Common Clinical Pitfalls to Avoid

• Do not assume topical diclofenac is completely safe: Systemic absorption occurs and upper GI hemorrhage has been documented with cutaneous application 4
• Do not use diclofenac as first-line NSAID in cardiovascular disease: Naproxen has more favorable cardiovascular safety profile 2, 3
• Do not combine with other nephrotoxic drugs without close monitoring 2
• Do not ignore transaminase elevations: Monitor liver function and discontinue if levels exceed 3× upper limit of normal 2