What are the side effects and contraindications of oral diclofenac tablets?

Oral Diclofenac: Side Effects and Contraindications

Oral diclofenac carries black box warnings for serious cardiovascular thrombotic events (including myocardial infarction and stroke) and gastrointestinal bleeding, ulceration, and perforation—both of which can be fatal and occur without warning at any time during use. 1

Absolute Contraindications

Oral diclofenac is absolutely contraindicated in the following situations 1:

• Perioperative pain in coronary artery bypass graft (CABG) surgery 1
• Known hypersensitivity to diclofenac, including anaphylactic reactions or serious skin reactions 1
• History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs (severe, sometimes fatal anaphylactic reactions have been reported) 1

Major Cardiovascular Risks

Diclofenac carries the highest cardiovascular risk among commonly used NSAIDs, with particularly concerning mortality data 2:

• Vascular events: RR 1.63 (95% CI 1.12–2.37) versus placebo 2
• Cardiovascular events (mostly MI): RR 1.40 (95% CI 1.16–1.70) in observational studies 2
• Recurrent MI: RR 1.54 (95% CI 1.23–1.93) in registry data 2
• Mortality: RR 2.40 (95% CI 2.09–2.80)—the highest among NSAIDs 2

Risk increases with duration of use and may occur early in treatment. Patients with cardiovascular disease or risk factors are at substantially greater risk 1.

Gastrointestinal Adverse Effects

NSAIDs cause serious GI events including bleeding, ulceration, and perforation that can be fatal, occurring at any time without warning symptoms 1:

• Most common adverse effects (1-10% of patients): abdominal pain, constipation, diarrhea, dyspepsia, flatulence, heartburn, nausea, GI ulcers (gastric/duodenal), vomiting, and gross bleeding/perforation 1
• Elderly patients and those with prior peptic ulcer disease/GI bleeding are at greater risk 1
• Diclofenac causes fewer GI effects than aspirin or indomethacin in comparative studies 3, 4

Other Serious Adverse Reactions

Hepatotoxicity 1:

• Fulminant hepatitis with and without jaundice, liver failure, liver necrosis 1
• Elevated liver enzymes occur in approximately 1-10% of patients 1

Renal toxicity and hyperkalemia 1:

• Abnormal renal function in 1-10% of patients 1
• Respiratory depression, though rare 1

Hematologic toxicity 1:

• Agranulocytosis, hemolytic anemia, aplastic anemia, pancytopenia 1
• Increased bleeding time in 1-10% of patients 1
• Anemia in 1-10% of patients 1

Serious skin reactions 1:

• Toxic epidermal necrolysis, erythema multiforme, exfoliative dermatitis, Stevens-Johnson Syndrome 1
• Angioedema, urticaria 1

Cardiovascular effects beyond thrombosis 1:

• Arrhythmia, hypotension, myocardial infarction, palpitations, vasculitis 1
• Heart failure and edema 1

Neurological effects 1:

• Convulsions, coma, hallucinations, meningitis 1
• Dizziness and headaches in 1-10% of patients 1

Common Non-Serious Adverse Effects (1-10% incidence)

1:

• Pruritus and rashes
• Tinnitus
• Edema
• Appetite changes

Critical Prescribing Guidance

Use the lowest effective dose for the shortest duration necessary 2:

• Prescribe at 100-150 mg/day total (divided doses with meals) for osteoarthritis and ankylosing spondylitis 3
• 150-200 mg/day total for rheumatoid arthritis 3
• Preferably on-demand rather than continuous use 2

Pay particular attention to risk-benefit ratio in 2:

• Elderly patients (at greater risk for serious GI and cardiovascular events) 1
• Patients with cardiovascular disease or risk factors
• Patients with gastrointestinal disease history
• Patients with renal impairment
• Patients with hypertension or heart failure

Consider topical diclofenac as first-line alternative when appropriate, as it provides markedly fewer gastrointestinal adverse events while maintaining equivalent pain relief to oral NSAIDs 2, 5.