General Information

• Diclofenac is the Most Commonly Used NSAID Worldwide

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Indications

• Arthritis
  • Acute Gout (see Gout)
  • Osteoarthritis (see Osteoarthritis)
  • Rheumatoid Arthritis
• Dysmenorrhea (see Dysmenorrhea)
• Fever (see Fever)
• Pain
  • Post-Operative Pain
  • Soft Tissue/Musculoskeletal Injury
• To Decrease the Risk of Malignancy
  • Breast Cancer (see Breast Cancer)
  • Colorectal Cancer (see Colorectal Cancer)
  • Prostate Cancer (see Prostate Cancer)

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Contraindications

• Aspirin-Exacerbated Respiratory Disease (AERD) (see Aspirin-Exacerbated Respiratory Disease)
  • Due to COX-1 Inhibition
• Chronic Kidney Disease (CKD) (see Chronic Kidney Disease)
  • Due to Risk of Worsening Chronic Kidney Disease
• Chronic Liver Disease (see Cirrhosis )
  • Due to Frequent Co-Existing Chronic Kidney Disease (and Risk of Hepatorenal Syndrome) (see Hepatorenal Syndrome)
  • Due to Risk of Gastrointestinal Hemorrhage (see Gastrointestinal Hemorrhage)

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Pharmacology

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Administration

• PO: xxx

Dose Adjustment

• Hepatic
• Renal

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Adverse Effects

Endocrinologic Adverse Effects

Drug-Induced Hyporeninemic Hypoaldosteronism (see Hypoaldosteronism)

• Physiology
  • Class effect, common to all NSAID’s
  • Dose-dependent COX-inhibition -> decreased renal prostaglandin synthesis -> results in drug-induced hyporeninemic hypoaldosteronism
• Clinical
  • Hyperkalemia (see Hyperkalemia)
  • Type 4 Renal Tubular Acidosis (RTA) (see Type 4 Renal Tubular Acidosis)

Gastrointestinal/Hepatic Manifestations

Fulminant Hepatic Failure with Massive Hepatic Necrosis(see Fulminant Hepatic Failure)

• xxx

Peptic Ulcer Disease (PUD) (see Peptic Ulcer Disease)

• Physiology: class effect, common to all NSAID’s

Transaminitis/Elevated Liver Function Tests (LFT’s) (see Drug-Induced Hepatotoxicity)

• Epidemiology
  • Class Effect: while transaminitis is common to all NSAID’s, diclofenac appears to induce a unique autoimmune hepatitis-like syndrome
• Diagnosis
  • Anti-Nuclear Antibody (ANA): positive
  • Liver Biopsy: consistent with chronic active hepatitis
• Clinical: resembles autoimmune hepatitis
• Treatment: change to another NSAID class (such as naproxen, etc) appears to be safe

Hematologic Manifestations

• Drug-Induced Autoimmune Hemolytic Anemia (see Hemolytic AnemiaMEDLINE]

Pulmonary Adverse Effects

Aspirin-Intolerant Asthma (see Asthma)

• Physiology: class effect, common to multiple NSAID’s

Drug-Induced Pulmonary Eosinophilia (see Drug-Induced Pulmonary Eosinophilia)

• Associated Agents
  • Acetylsalicylic Acid (Aspirin) (see Acetylsalicylic Acid)
  • Diclofenac (Aclonac, Cataflam, Voltaren) (see Diclofenac)
  • Diflunisal (Dolobid)
  • Fenbufen
  • Fenoprofen (see Fenoprofen): case reports
  • Ibuprofen (Advil, Brufen, Motrin, Nurofen) (see Ibuprofen): case reports
  • Indomethacin (Indocin) (see Indomethacin)
  • Loxoprofen
  • Meloxicam (see Meloxicam)
  • Naproxen (Naprosyn, Aleve) (see Naproxen): appears to be more frequent with naproxen than other NSAID’s
  • Nimesulide
  • Phenylbutazone
  • Piroxicam (Feldene) (see Piroxicam)
  • Pranoprofen
  • Sulindac (Clinoril) (see Sulindac): case reports
  • Tenidap
  • Tiaprofenic Acid
  • Tolfenamic Acid
• Diagnosis
  • Lung Biopsy: poorly defined granulomas with infiltrating eosinophils
• Clinical
  • Cough
  • Dyspnea
  • Fever
  • Peripheral Eosinophilia
  • Pulmonary Infiltrates

Renal Adverse Effects

Acute Kidney Injury (see Acute Kidney Injury)

• xxx

Acute Interstitial Nephritis (see Acute Interstitial Nephritis)

• Physiology: class effect, common to all NSAID’s

Hyperkalemia (see Hyperkalemia)

• Mechanism: due to drug-induced hyporeninemic hypoaldosteronism

Increased Renal Sodium Reabsorption with Peripheral Edema

• Risk Factors
  • Advanced Age
  • Diabetes Mellitus (see Diabetes Mellitus)
  • Volume Contraction
    • Cirrhosis (see End-Stage Liver Disease)
    • Congestive Heart Failure (CHF) (see Congestive Heart Failure)
    • Decreased Sodium Intake
    • Diuretics
• Physiology: decreased PGE2 -> increased renal sodium reabsorption
  • Class Effect: common to all NSAID’s
  • Dose-Dependent Effect
• Clinical: typically occurs during the first week of therapy
  • Exacerbation of Congestive Heart Failure (see Congestive Heart Failure)
  • Hypertension (see Hypertension: usually moderate
  • Peripheral Edema (see Peripheral Edema)
  • Weight Gain (see Weight Gain)

Type 4 Renal Tubular Acidosis (RTA) (see Type 4 Renal Tubular Acidosis)

• Physiology: due to NSAID-induced hyporeninemic hypoaldosteronism
• Clinical
  • Non-Anion Gap Metabolic Acidosis (NAGMA) (see Metabolic Acidosis-Normal Anion Gap)

Other Adverse Effects

• xxx

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References

• Diclofenac induced hepatitis. 3 cases with features of autoimmune chronic active hepatitis. Dig Dis Sci. 1993;38(4):744 [MEDLINE]
• Drug-induced immune haemolytic anaemia in the Berlin Case-Control Surveillance Study.  Br J Haematol   2011; 154:644-653.  Doi: 10.1111/j.1365-2141.2011.08784.x; First published online 12 July 2011 [MEDLINE]