Diclofenac

General Information

  • Diclofenac is the Most Commonly Used NSAID Worldwide

Indications

  • Arthritis
    • Acute Gout (see Gout, [[Gout]])
    • Osteoarthritis (see Osteoarthritis, [[Osteoarthritis]])
    • Rheumatoid Arthritis
  • Dysmenorrhea (see Dysmenorrhea, [[Dysmenorrhea]])
  • Fever (see Fever, [[Fever]])
  • Pain
    • Post-Operative Pain
    • Soft Tissue/Musculoskeletal Injury
  • To Decrease the Risk of Malignancy

Contraindications

  • Chronic Kidney Disease (CKD) (see Chronic Kidney Disease, [[Chronic Kidney Disease]])
    • Due to Risk of Worsening Chronic Kidney Disease
  • Chronic Liver Disease (see End-Stage Liver Disease, [[End-Stage Liver Disease]])
    • Due to Frequent Co-Existing Chronic Kidney Disease (and Risk of Hepatorenal Syndrome) (see Hepatorenal Syndrome, [[Hepatorenal Syndrome]])
    • Due to Risk of Gastrointestinal Hemorrhage (see Gastrointestinal Hemorrhage, [[Gastrointestinal Hemorrhage]])

Pharmacology

Metabolism

  • Hepatic: predominantly

Administration

  • PO: xxx

Dose Adjustment

  • Hepatic
  • Renal

Adverse Effects

Endocrinologic Adverse Effects

Drug-Induced Hyporeninemic Hypoaldosteronism (see Hypoaldosteronism, [[Hypoaldosteronism]])

  • Physiology
    • Class effect, common to all NSAID’s
    • Dose-dependent COX-inhibition -> decreased renal prostaglandin synthesis -> results in drug-induced hyporeninemic hypoaldosteronism
  • Clinical

Gastrointestinal/Hepatic Manifestations

Fulminant Hepatic Failure with Massive Hepatic Necrosis(see Fulminant Hepatic Failure, [[Fulminant Hepatic Failure]])

  • xxx

Peptic Ulcer Disease (PUD) (see Peptic Ulcer Disease, [[Peptic Ulcer Disease]])

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

Transaminitis/Elevated Liver Function Tests (LFT’s) (see Drug-Induced Hepatotoxicity, [[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 Anemia, [[Hemolytic Anemia]]): most frequently implicated drug cause of autoimmune hemolytic anemia in Berlin Case-Control Surveillance Study (FAKOS) [MEDLINE]

Pulmonary Adverse Effects

Aspirin-Intolerant Asthma (see Asthma, [[Asthma]])

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

Drug-Induced Pulmonary Eosinophilia (see Drug-Induced Pulmonary Eosinophilia, [[Drug-Induced Pulmonary Eosinophilia]])

  • Associated Agents
    • Acetylsalicylic Acid (Aspirin) (see Acetylsalicylic Acid, [[Acetylsalicylic Acid]])
    • Diclofenac (Aclonac, Cataflam, Voltaren) (see Diclofenac, [[Diclofenac]])
    • Diflunisal (Dolobid)
    • Fenbufen
    • Fenoprofen (see Fenoprofen, [[Fenoprofen]]): case reports
    • Ibuprofen (Advil, Brufen, Motrin, Nurofen) (see Ibuprofen, [[Ibuprofen]]): case reports
    • Indomethacin (Indocin) (see Indomethacin, [[Indomethacin]])
    • Loxoprofen
    • Meloxicam (see Meloxicam, [[Meloxicam]])
    • Naproxen (Naprosyn, Aleve) (see Naproxen, [[Naproxen]]): appears to be more frequent with naproxen than other NSAID’s
    • Nimesulide
    • Phenylbutazone
    • Piroxicam (Feldene) (see Piroxicam, [[Piroxicam]])
    • Pranoprofen
    • Sulindac (Clinoril) (see Sulindac, [[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, [[Acute Kidney Injury]])

  • xxx

Acute Interstitial Nephritis (see Acute Interstitial Nephritis, [[Acute Interstitial Nephritis]])

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

Hyperkalemia (see Hyperkalemia, [[Hyperkalemia]])

  • Mechanism: due to drug-induced hyporeninemic hypoaldosteronism

Increased Renal Sodium Reabsorption with Peripheral Edema

  • Risk Factors
  • 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

Type 4 Renal Tubular Acidosis (RTA) (see Type 4 Renal Tubular Acidosis, [[Type 4 Renal Tubular Acidosis]])

  • Physiology: due to NSAID-induced hyporeninemic hypoaldosteronism
  • Clinical

Other Adverse Effects

  • xxx

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]