What are the side effects of Voltran (diclofenac)?

Side Effects of Voltaren (Diclofenac)

Diclofenac carries serious cardiovascular, gastrointestinal, and hepatic risks that require careful consideration before prescribing, with the FDA warning that it increases risk of myocardial infarction, stroke, and GI bleeding—risks that can be fatal even with short-term use. 1

Cardiovascular Side Effects

Diclofenac poses the highest cardiovascular risk among traditional NSAIDs, with substantially elevated rates of serious thrombotic events 2, 3:

• Mortality increases 2.4-fold (RR 2.40,95% CI 2.09-2.80) compared to non-users 2, 3
• Myocardial infarction risk increases 1.54-fold (RR 1.54,95% CI 1.23-1.93), with recurrent MI risk particularly elevated in post-MI patients 3
• Overall vascular events increase 1.63-fold (RR 1.63,95% CI 1.12-2.37) in randomized controlled trials 2, 1
• Risk begins as early as the first weeks of treatment and increases with higher doses and longer duration 1
• The mechanism involves diclofenac's high COX-2 selectivity, which eliminates protective prostaglandin effects during cardiac ischemia 3

High-Risk Cardiovascular Populations

• Absolutely avoid in patients with recent MI unless benefits clearly outweigh risks; if used, monitor closely for cardiac ischemia 1
• Contraindicated within 10-14 days post-CABG surgery due to increased MI and stroke incidence 1
• Avoid in established cardiovascular disease or multiple risk factors; choose naproxen instead (RR 0.92 for vascular events) 2, 3

Gastrointestinal Side Effects

GI complications occur in approximately 1% of patients treated for 3-6 months and 2-4% treated for one year, though serious events can occur without warning symptoms 1:

• Most common effects (1-10% of patients): abdominal pain, dyspepsia, nausea, diarrhea, constipation, flatulence, and heartburn 4, 1, 5
• Serious complications: GI ulceration, bleeding, and perforation of the esophagus, stomach, or intestines—which can be fatal 1
• Only one in five patients who develop serious upper GI events have warning symptoms 1
• Risk factors include: age ≥75 years, prior peptic ulcer disease or GI bleeding (>10-fold increased risk), concomitant corticosteroids, anticoagulants, SSRIs, aspirin use, smoking, alcohol use, and poor general health 1

GI Risk Mitigation

• Co-prescribe proton pump inhibitor for all patients at high risk, especially those with history of peptic ulcer disease 3
• Use topical rather than oral formulations in patients age ≥75 years 3
• If GI bleed occurred within past year, use COX-2 selective inhibitor plus PPI instead of diclofenac 3

Hepatotoxicity

Meaningful liver enzyme elevations (>3 times ULN) occur in approximately 2-4% of patients, with marked elevations (>8 times ULN) in about 1% 1:

• Warning signs include: nausea, fatigue, lethargy, pruritus, diarrhea, jaundice, right upper quadrant tenderness, and flu-like symptoms 1
• Serious hepatic reactions reported: fulminant hepatitis with and without jaundice, liver failure, and liver necrosis 1
• Higher incidence in osteoarthritis patients compared to rheumatoid arthritis patients 1
• Monitor liver enzymes at 8 weeks for chronic use, then periodically 1

Renal and Hypertensive Effects

Diclofenac causes renal toxicity and worsens blood pressure control 2, 3:

• Absolute contraindication: chronic kidney disease stage IV-V (eGFR <30 mL/min) 3
• Use with extreme caution: stage III CKD (eGFR 30-59 mL/min) only after careful risk-benefit assessment 3
• Effects include: abnormal renal function, edema, hyperkalemia, and exacerbation of heart failure 4, 1
• Monitor renal function and blood pressure in all patients on chronic therapy 2, 1

Hematologic Side Effects

Blood dyscrasias are rare but serious complications 1, 6:

• Reported effects: agranulocytosis, hemolytic anemia, aplastic anemia (including two fatal cases in early surveillance), lymphadenopathy, pancytopenia 1, 6
• Increased bleeding time occurs commonly 1
• Monitor CBC periodically for patients on long-term treatment 1

Dermatologic Reactions

Serious skin reactions can be life-threatening 1:

• Severe reactions: toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, exfoliative dermatitis 1
• Common reactions: rash, pruritus, urticaria, angioedema 1, 5
• Instruct patients to stop immediately if any rash or fever develops and contact healthcare provider 1

Central Nervous System Effects

CNS side effects occur less frequently than with indomethacin but still require monitoring 5, 6:

• Common: dizziness, headaches 1, 5
• Rare but serious: convulsions, coma, hallucinations, aseptic meningitis 1
• Tinnitus reported in approximately 1-10% of patients 1

Anaphylactic Reactions

Anaphylaxis can occur without prior exposure 1:

• Symptoms: difficulty breathing, swelling of face or throat, hypotension 1
• Instruct patients to seek immediate emergency help if symptoms occur 1

Critical Drug Interactions Increasing Side Effect Risk

Concomitant medications significantly amplify adverse effects 1:

• Low-dose aspirin: increases GI bleeding risk without clear cardiovascular protection benefit 1
• Anticoagulants: increase bleeding risk 3-6 fold; requires extreme caution or avoidance 3
• ACE inhibitors and diuretics: increase renal toxicity risk 3
• Other NSAIDs or salicylates: increase GI toxicity without efficacy benefit 1
• Corticosteroids and SSRIs: increase GI bleeding risk 1

Special Populations at Highest Risk

Certain populations require avoidance or extreme caution 3, 1:

• Elderly patients (≥75 years): higher absolute incidence of fatal GI events; prefer topical formulations 3, 1
• Pregnant women after 20 weeks gestation: risk of premature ductus arteriosus closure and oligohydramnios; avoid after 30 weeks 1
• Patients with advanced liver disease or coagulopathy: increased GI bleeding risk 1
• Perioperative trauma patients: avoid for pain management; use tramadol or opioids instead 3

Safer Alternatives to Consider

When diclofenac risks outweigh benefits, consider these alternatives 4, 3:

• Acetaminophen up to 4 g daily as first-line for mild pain 4, 3
• Naproxen has the most favorable cardiovascular safety profile among NSAIDs (RR 0.92) 2, 3
• Topical NSAIDs for localized pain, especially in elderly 3
• Tramadol for moderate pain 4, 3
• Opioid analgesics for severe pain when NSAIDs contraindicated 4, 3

Essential Monitoring and Risk Minimization

To minimize serious adverse events, implement these strategies 1:

• Use lowest effective dose for shortest duration possible 2, 1
• Never combine with other NSAIDs 1
• Monitor CBC and chemistry profile periodically for long-term use 1
• Remain alert for warning symptoms throughout treatment, even without prior symptoms 1
• Promptly discontinue and evaluate if serious adverse event suspected 1