Is diclofenac (Nonsteroidal Anti-Inflammatory Drug (NSAID)) safe to use in patients with hepatitis?

Diclofenac Use in Patients with Hepatitis

Diclofenac should be avoided in patients with hepatitis due to its significant risk of hepatotoxicity and potential to worsen liver disease. 1, 2

Hepatotoxicity Risk of Diclofenac

• Diclofenac has been associated with severe hepatic reactions including liver necrosis, jaundice, fulminant hepatitis, and liver failure, with some cases resulting in fatalities or liver transplantation 1
• In clinical trials, meaningful elevations of liver enzymes (more than 3 times the upper limit of normal) were observed in about 2% of patients taking diclofenac 1
• In a large open-label controlled trial of 3,700 patients, approximately 4% developed significant ALT/AST elevations, including marked elevations (>8 times ULN) in about 1% of patients 1
• A prospective clinical trial with 17,289 arthritis patients showed that 3.1% of patients on diclofenac developed ALT/AST >3x ULN, with 0.5% developing ALT/AST >10x ULN 3

Specific Concerns in Hepatitis

• Diclofenac has been associated with features of autoimmune chronic active hepatitis, which could be particularly problematic in patients with pre-existing hepatitis 2
• Case reports document patients developing chronic active hepatitis after diclofenac use that progressed despite withdrawal of the drug 4
• The FDA label specifically warns about discontinuing diclofenac immediately if abnormal liver tests persist or worsen, or if clinical signs and symptoms consistent with liver disease develop 1
• Patients with pre-existing liver disease are at higher risk for diclofenac-induced hepatotoxicity due to already compromised liver function 1, 2

Monitoring and Risk Factors

• If diclofenac must be used (which is not recommended in hepatitis), transaminases should be monitored within 4-8 weeks after initiating treatment 1
• Aminotransferase elevations with diclofenac occur primarily within the first 4-6 months of therapy, but clinical liver events can develop early or late in therapy 3
• Warning signs of hepatotoxicity include nausea, fatigue, lethargy, diarrhea, pruritus, jaundice, right upper quadrant tenderness, and "flu-like" symptoms 1
• Patients with hepatitis are already at risk for these symptoms, making monitoring more challenging 1

Alternative Pain Management Options

• Acetaminophen may be a safer alternative for pain management in patients with hepatitis, though dose limitations must be observed to prevent additional hepatotoxicity 5
• For patients requiring an NSAID, naproxen has been shown to have a better hepatic safety profile than diclofenac 2, 6
• In case reports, patients who experienced hepatotoxicity with diclofenac were subsequently able to take naproxen without liver dysfunction 2

Additional Considerations

• Diclofenac can also cause renal toxicity and hypertension, which may further complicate management of patients with hepatitis 6, 1
• Diclofenac has been associated with a 54% increased risk of recurrent myocardial infarction and 140% increased mortality risk compared to placebo in patients with cardiovascular disease 6
• The combination of diclofenac with other potentially hepatotoxic medications should be strictly avoided in patients with hepatitis 1

In conclusion, given the significant risk of hepatotoxicity and potential to exacerbate existing liver disease, diclofenac should be avoided in patients with hepatitis. Alternative pain management strategies with better safety profiles should be considered instead.