In which disease should Diclofenac (Nonsteroidal Anti-Inflammatory Drug (NSAID)) be avoided?

Diclofenac Should Be Avoided in Multiple High-Risk Conditions

Diclofenac must be avoided in patients with cardiovascular disease (especially heart failure), chronic kidney disease, liver disease (particularly cirrhosis), and in those taking anticoagulants or the "triple therapy" combination of ACE inhibitors/ARBs plus diuretics. 1, 2, 3

Cardiovascular Disease - Highest Priority Contraindication

Diclofenac carries the highest cardiovascular mortality risk among commonly used NSAIDs, with a relative risk of death of 2.40 (95% CI: 2.09-2.80) and vascular events RR of 1.63. 4 The American Heart Association explicitly states that NSAIDs, including diclofenac, should be avoided in individuals with end-stage cardiovascular disease (ESCVD) because of cardiovascular toxicity, renal toxicity, and increased bleeding risk. 1

• Heart failure patients face a two-fold increase in hospitalization when taking diclofenac, and the drug can precipitate acute cardiac decompensation through sodium and water retention. 3
• The FDA black box warning specifically contraindicates diclofenac in the setting of coronary artery bypass graft (CABG) surgery. 3
• Diclofenac may impair renal function in patients with decreased effective circulating volume and promote fluid retention, resulting in increased risk of heart failure hospitalization. 1

Chronic Kidney Disease - Absolute Contraindication in Advanced Stages

NSAIDs including diclofenac should be avoided in patients with GFR < 30 mL/min/1.73 m² (CKD stages 4-5), and prolonged therapy is not recommended for GFR < 60 mL/min/1.73 m² (CKD stages 3-5). 2

• Even a single oral dose of diclofenac in the setting of pre-existing subclinical acute kidney injury can cause progression to chronic kidney disease. 5
• The combination of diclofenac with RAAS blockers (ACE inhibitors or ARBs) is specifically contraindicated due to dramatically increased acute kidney injury risk. 2
• The "triple therapy" of NSAIDs + ACE inhibitors/ARBs + diuretics creates a "perfect storm" that eliminates both vasodilatory mechanisms (prostaglandins) and pressure-maintaining mechanisms (angiotensin II) of the kidney. 2
• Approximately 2% of patients taking NSAIDs will develop renal complications significant enough to discontinue therapy. 2

Special CKD Considerations:

• Monitor renal function weekly for the first 3 weeks if diclofenac cannot be avoided in mild CKD. 2
• Patients on tenofovir disoproxil fumarate (TDF) for HIV should avoid diclofenac entirely, as drug-drug interaction exacerbates TFV-associated nephrotoxicity. 6
• Acetaminophen (up to 3 grams daily) is the preferred first-line analgesic for CKD patients. 2

Liver Disease - Absolute Contraindication in Cirrhosis

Diclofenac should be specifically avoided in patients with hepatic impairment due to additional hepatotoxicity concerns beyond other NSAIDs. 7

• Patients with cirrhosis and ascites must not use diclofenac due to extremely high risk of acute renal failure, hyponatremia, and diuretic resistance. 7
• Women and individuals over 50 years of age are at increased risk for NSAID-induced liver injury. 7
• Discontinue diclofenac immediately if liver function tests rise to 3 times the upper limit of normal, as hepatotoxicity can progress to fulminant hepatic failure and death. 7, 3
• For patients with FIB-4 scores > 2.67 (indicating high risk for advanced fibrosis), diclofenac is absolutely contraindicated. 7

Monitoring Requirements if Used in Early Liver Disease:

• Establish baseline liver function studies (alkaline phosphatase, LDH, SGOT, SGPT) and repeat every 3 months. 7
• Monitor within 4 to 8 weeks after initiating treatment, though severe hepatic reactions can occur at any time. 3

Gastrointestinal Risk - Highest Among NSAIDs

Diclofenac undergoes enterohepatic recirculation, resulting in significantly greater gastrointestinal toxicity due to prolonged gastric and duodenal mucosal exposure. 4

• The FDA black box warning states that diclofenac causes an increased risk of serious GI adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. 3
• Elderly patients and those with prior peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events. 3
• When combined with anticoagulants, diclofenac increases GI bleeding risk 3-6 fold and increases INR by up to 15%. 4

Gastroprotection Strategy if Diclofenac Cannot Be Avoided:

• PPI co-therapy reduces endoscopic NSAID-related ulcers by approximately 90% in patients with GI risk factors. 4
• Ibuprofen, etodolac, and nabumetone demonstrate superior GI safety compared to diclofenac. 4

Additional High-Risk Scenarios

Avoid diclofenac in patients taking anticoagulants (warfarin, heparin, DOACs), antiplatelets, SSRIs, or SNRIs due to significantly increased bleeding risk. 1

• Oral NSAIDs should be avoided in the setting of prophylactic or therapeutic anticoagulation; topical diclofenac gel or patch may be considered as an alternative. 1
• Diclofenac can exacerbate hypertension with an estimated mean blood pressure increase of 5 mm Hg. 1, 3
• Patients with aspirin-sensitive asthma (chronic rhinosinusitis with nasal polyps) should not receive diclofenac due to risk of severe, potentially fatal bronchospasm. 3

Common Pitfalls to Avoid

• Never combine diclofenac with other nephrotoxic medications (aminoglycosides, contrast dye, other NSAIDs) as this dramatically increases nephrotoxicity risk. 2
• Do not prescribe diclofenac to volume-depleted or hypovolemic patients without correcting volume status first, as this increases acute kidney injury risk. 3
• Avoid concomitant use with acetaminophen due to potential hepatotoxicity when drugs are combined. 3
• Diclofenac may blunt the cardiovascular effects of antihypertensive agents (diuretics, ACE inhibitors, ARBs), requiring blood pressure monitoring throughout therapy. 3