Can you take diclofenac (nonsteroidal anti-inflammatory drug (NSAID)) long term and what are the precautions?

Long-term Diclofenac Use: Safety and Precautions

Long-term use of diclofenac requires careful monitoring due to significant cardiovascular, gastrointestinal, hepatic, and renal risks. It should be used at the lowest effective dose for the shortest duration possible, with appropriate protective measures for high-risk patients.

Cardiovascular Risks

• Diclofenac increases cardiovascular risk with a relative risk of 1.63 (95% CI 1.12-2.37) for vascular events compared to placebo 1
• It can elevate mean blood pressure by approximately 5 mm Hg while taking the medication 1, 2
• Diclofenac has been associated with a 54% increased risk of recurrent myocardial infarction and 140% increased mortality risk compared to placebo in registry studies 1
• Avoid diclofenac in patients with congestive heart failure and use with caution in patients with hypertension 2, 1
• Naproxen has a more favorable cardiovascular safety profile (RR 0.92,95% CI 0.67-1.26) and should be considered as an alternative for patients with cardiovascular risk factors 3

Gastrointestinal Risks

• Diclofenac can cause serious gastrointestinal adverse effects including ulceration, bleeding, and perforation 2, 4
• Risk factors for GI complications include increasing age, previous GI events, and concomitant use of anticoagulation therapy or corticosteroids 3
• Consider gastroprotection with proton pump inhibitors (PPIs) or misoprostol for high-risk patients 2, 5
• Misoprostol reduces gastric ulcer risk by 74% and duodenal ulcer risk by 53% compared to placebo when co-administered with NSAIDs 2
• Poor compliance with gastroprotective agents increases the relative risk of NSAID-induced upper GI adverse events 4-6 times 2

Hepatic Considerations

• Diclofenac has potential for hepatic complications including transaminitis and synthetic impairment 2
• Avoid diclofenac in patients with cirrhosis due to potential hematologic and renal complications 2
• Primary hepatic complications are rare and usually reversible 2
• Monitor for warning signs of hepatotoxicity (nausea, fatigue, lethargy, pruritus, diarrhea, jaundice, right upper quadrant tenderness, and "flu-like" symptoms) 4

Renal Considerations

• Approximately 2% of patients stop taking NSAIDs due to renal complications 2
• Avoid diclofenac in patients with renal disease 2
• Use with caution when combining with medications that potentially decrease renal function, such as ACE inhibitors and beta blockers 2, 1
• Monitor renal function periodically during long-term treatment 4

Drug Interactions

• Avoid combining diclofenac with:
  • Anticoagulants (increases risk of GI bleeding 3-6 times) 2
  • Other NSAIDs or salicylates (increases GI toxicity) 4
  • Methotrexate (increases risk for methotrexate toxicity) 4
  • Cyclosporine (increases nephrotoxicity) 4
  • Lithium (elevates plasma lithium levels) 4
  • Diuretics (may reduce diuretic efficacy) 4

Special Populations

• Elderly patients are at higher risk for NSAID-related complications, particularly gastrointestinal and cardiovascular events 5
• Use with caution in patients with asthma, especially those with nasal polyps or recurrent sinusitis 2
• Avoid diclofenac toward the end of pregnancy (six to eight weeks before term) 2
• May delay or prevent rupture of ovarian follicles, potentially causing reversible infertility in some women 4

Monitoring Recommendations

• Regular blood pressure monitoring 1
• Periodic liver function tests 4
• Renal function assessment 2
• Watch for signs of GI bleeding (epigastric pain, dyspepsia, melena, and hematemesis) 4
• Monitor for signs of cardiovascular events (chest pain, shortness of breath, weakness) 4

Long-term Safety Data

• Long-term studies show that maximal improvement with diclofenac tends to occur in the first 3-6 months of treatment and is generally maintained 6
• Most adverse effects occur within the first 6 months of treatment 6
• No changes in the nature, frequency, or severity of abnormal laboratory tests with increasing duration of treatment have been observed 6

Alternative Approaches

• Consider naproxen as an alternative for patients with cardiovascular risk factors 3
• Topical diclofenac formulations may provide local treatment with minimized systemic absorption 7
• SoluMatrix diclofenac (submicron particles) may provide efficacy at reduced doses with lower systemic absorption 7