Should I prescribe oral diclofenac for a 48‑year‑old man with end‑stage liver disease and bilateral hip pain?

Do Not Prescribe Oral Diclofenac to This Patient

Oral diclofenac is absolutely contraindicated in patients with end-stage liver disease and should never be prescribed in this clinical scenario. 1, 2

Why Diclofenac Is Contraindicated in End-Stage Liver Disease

Renal Failure Risk

• Patients with cirrhosis and ascites face an extremely high risk of acute renal failure when exposed to NSAIDs, including diclofenac, because their kidneys depend heavily on prostaglandin-mediated vasodilation to maintain adequate perfusion 1, 3, 2
• NSAIDs block prostaglandin synthesis, causing decreased renal blood flow and precipitating acute kidney injury in this vulnerable population 3, 2
• The risk of hepatorenal syndrome increases substantially with NSAID use in cirrhotic patients 2

Fluid Management Complications

• NSAIDs cause sodium and water retention by blocking renal prostaglandins, directly antagonizing diuretic therapy and making ascites management extremely difficult 2
• This leads to hyponatremia and diuretic resistance, both of which are Class A1 contraindications according to the European Association for the Study of the Liver 2

Hepatotoxicity Concerns

• Diclofenac and sulindac carry particularly high risk of drug-induced liver injury and must be strictly avoided in cirrhotic patients 1, 2, 4
• The FDA label reports that meaningful elevations of liver enzymes (>3 times upper limit of normal) occurred in approximately 4% of patients taking oral diclofenac, with marked elevations (>8 times ULN) in about 1% 5
• Postmarketing surveillance has documented cases of liver necrosis, fulminant hepatitis, and liver failure requiring transplantation with diclofenac use 5, 6, 7
• Most hepatotoxicity occurs within the first 2 months of therapy, but can happen at any time 5, 7

Bleeding Risk

• NSAIDs markedly increase the risk of gastrointestinal bleeding in cirrhosis, a population already predisposed to bleeding due to portal hypertension, varices, and coagulopathy 2, 4, 5
• Patients with advanced liver disease and coagulopathy are at increased risk for GI bleeding, with fatal GI events occurring most commonly in elderly or debilitated patients 5

Recommended Alternative Pain Management Strategy

First-Line: Acetaminophen

• Acetaminophen up to 3 g/day is the preferred analgesic for patients with cirrhosis and end-stage liver disease 1, 3
• This represents the safest option that avoids both renal and bleeding complications associated with NSAIDs 1, 3
• The European Association for the Study of the Liver specifically recommends acetaminophen for pain management in HCC patients with cirrhosis 1

Second-Line: Opioid Analgesics

• For moderate-to-severe pain insufficiently controlled by acetaminophen, opioids are the drugs of choice 1
• However, opioid prescription must be promptly associated with a purging program to prevent constipation and hepatic encephalopathy 1
• Pharmacologic treatments including osmotic laxatives should be initiated proactively, not waiting for severe adverse events 1

Topical Options

• Topical NSAIDs (such as topical diclofenac) may provide localized pain relief with less systemic absorption and fewer renal/hepatic complications compared to oral NSAIDs 1, 3
• This represents a potential middle-ground option if acetaminophen and opioids are insufficient, though caution is still warranted 1

Critical Clinical Pitfall to Avoid

No traditional NSAID is "safer" than another in cirrhosis with ascites—all carry the same fundamental risks, including COX-2 selective inhibitors which produce identical sodium retention and renal effects as non-selective NSAIDs 2. The patient's request for diclofenac specifically is particularly concerning given that diclofenac carries additional hepatotoxicity risk beyond other NSAIDs 1, 2, 4.

What to Tell the Patient

Explain that while you understand his pain is not adequately controlled, diclofenac could precipitate life-threatening kidney failure, worsen his liver disease, and cause dangerous bleeding given his end-stage liver disease 1, 2. Emphasize that acetaminophen (up to 3 g/day) combined with physical therapy remains the safest approach, and if pain persists, carefully monitored opioid therapy with aggressive constipation prevention is the appropriate next step 1.