What are the potential reactions to Diclofenac (Klafenac)?

Potential Reactions to Diclofenac (Klafenac)

Diclofenac (Klafenac) is associated with significant cardiovascular and gastrointestinal adverse reactions, including increased risk of serious cardiovascular thrombotic events, myocardial infarction, stroke, and gastrointestinal bleeding, ulceration, and perforation, all of which can be fatal. 1, 2

Cardiovascular Reactions

• Diclofenac significantly increases the risk of cardiovascular thrombotic events with a relative risk of 1.63 (95% CI 1.12-2.37) versus placebo 2
• Risk of recurrent myocardial infarction is elevated by 54% (RR 1.54,95% CI 1.23-1.93) and mortality risk increased by 140% (RR 2.40,95% CI 2.09-2.80) compared to placebo 2
• Cardiovascular risk increases with duration of use and is greater in patients with pre-existing cardiovascular disease or risk factors 1, 3
• Diclofenac can increase mean blood pressure by approximately 5 mm Hg, contributing to increased cardiovascular morbidity 3
• Heart failure and edema may occur due to fluid retention, with approximately two-fold increase in hospitalization for heart failure compared to placebo 1

Gastrointestinal Reactions

• Serious gastrointestinal adverse events including inflammation, bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal 1, 2
• Risk of serious upper gastrointestinal events is moderate with diclofenac compared to placebo 2
• Elderly patients are at greater risk for serious gastrointestinal events 1, 2
• Common gastrointestinal reactions include abdominal pain, constipation, diarrhea, dyspepsia, flatulence, heartburn, nausea, and vomiting 1

Hepatic Reactions

• Diclofenac is associated with large increase in risk for hepatic harms, particularly in the first 6 months of treatment 2
• Potential for elevated liver enzymes, fulminant hepatitis with and without jaundice, liver failure, and liver necrosis 1
• Warning signs include nausea, fatigue, lethargy, pruritus, diarrhea, jaundice, right upper quadrant tenderness, and "flu-like" symptoms 1

Renal Reactions

• Long-term administration can result in renal papillary necrosis and other renal injury 1
• Dose-dependent reduction in prostaglandin formation may precipitate overt renal decompensation 1
• Abnormal renal function, hyperkalemia, and fluid retention may occur 1
• Patients at greatest risk include those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors or ARBs, and the elderly 1

Dermatological Reactions

• Serious skin reactions including exfoliative dermatitis, Stevens-Johnson Syndrome, and toxic epidermal necrolysis 1
• Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported, which can be fatal or life-threatening 1
• Other skin reactions include angioedema, erythema multiforme, pruritus, and rashes 1

Hematologic Reactions

• Potential for anemia, increased bleeding time, agranulocytosis, hemolytic anemia, aplastic anemia, lymphadenopathy, and pancytopenia 1
• Diclofenac can interfere with platelet function, which may increase bleeding risk, especially when combined with anticoagulants 1

Neurological Reactions

• Headaches, dizziness, convulsions, coma, hallucinations, and meningitis have been reported 1
• Tinnitus and hearing impairment may occur 1

Special Considerations

• Diclofenac is contraindicated for perioperative pain in coronary artery bypass graft (CABG) surgery 2
• NSAIDs, including diclofenac, should be avoided in patients with cardiovascular disease when possible 2
• Combining diclofenac with other NSAIDs increases the risk of adverse effects without providing substantial additional therapeutic benefit 4
• Elderly patients are at particularly high risk for NSAID-related adverse effects 2

Risk Mitigation

• Use the lowest effective dose for the shortest duration possible 5
• Consider naproxen as a safer alternative for patients with cardiovascular risk factors (RR 0.92,95% CI 0.67-1.26 versus placebo) 5, 2
• Consider co-administration of gastroprotective agents such as proton pump inhibitors or misoprostol in high-risk patients 2
• Monitor renal function, blood pressure, and watch for signs of gastrointestinal bleeding in patients taking diclofenac 3, 1