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Diclofenac

Class
  • Antipyretic/analgesic NSAID
Indications
  • pain
  • dysmenorrhea
  • ocular inflammation
  • osteoarthritis
  • rheumatoid arthritis
  • ankylosing spondylitis
  • actinic keratosis
Administration/Absorption
  • Completely absorbed from the gastrointestinal tract
  • Topical cream
Dosage

Distribution

Mechanism
  • 2-(2,6-dichloranilino) phenylacetic acid
  • The most potent NSAID on a broad basis
  • COX-1 and COX-2 inhibition
    • => peripheral inhibition of prostaglandin synthesis
    • Approximately 10-fold for the COX2-isoenzyme
  • Somewhat lower incidence of gastrointestinal complaints than noted with indomethacin and aspirin
  • Inhibition of leukocyte migration
  • Antipyretic effects may be due to action on the hypothalamus, resulting in peripheral dilation, increased cutaneous blood flow, and subsequent heat dissipation
  • There is some evidence that diclofenac inhibits the lipoxygenase pathways thus reducing formation of the leukotrienes
  • There is also speculation that diclofenac may inhibit phospholipase A2
Excretion
  • The action of one single dose is much longer (6 to 8 hours) than the very short half-life that the drug indicates
    • This could be partly because it persists for over 11 hours in synovial fluids
Side effects

Interactions

Alendronate Increased risk of gastric toxicity
Anisindione The NSAID, diclofenac, may increase the anticoagulant effect of anisindione.
Cyclosporine Monitor for nephrotoxicity
Dicumarol The NSAID, diclofenac, may increase the anticoagulant effect of dicumarol.
Ginkgo biloba Additive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.
Lithium The NSAID, diclofenac, may decrease the renal excretion of lithium. Increased risk of lithium toxicity.
Methotrexate The NSAID, diclofenac, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
Rifampin Rifampin, a CYP2C9 inducer, may increase the metabolism of diclofenac.
Tacrine The metabolism of Tacrine, a CYP1A2 substrate, may be reduced by Diclofenac, a CYP1A2 inhibitors. Monitor the efficacy and toxicity of Tacrine if Diclofenac is initiated, discontinued or if the dose is changed.
Telmisartan Concomitant use of Telmisartan and Diclofenac may increase the risk of acute renal failure and hyperkalemia. Monitor renal function at the beginning and during treatment.
Timolol The NSAID, Diclofenac, may antagonize the antihypertensive effect of Timolol.
Tizanidine Diclofenac may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
Trandolapril The NSAID, Diclofenac, may reduce the antihypertensive effect of Trandolapril. Consider alternate therapy or monitor for changes in Trandolapril efficacy if Diclofenac is initiated, discontinued or dose changed.
Treprostinil The prostacyclin analogue, Treprostinil, may increase the risk of bleeding when combined with the NSAID, Diclofenac. Monitor for increased bleeding during concomitant thearpy.
Voriconazole Voriconazole, a strong CYP2C9 inhibitor, may increase the serum concentration of diclofenac by decreasing its metabolism. Renal impairment may increase the risk of diclofenac adverse effects. Monitor for changes in therapeutic and adverse effects of diclofenac if voriconazole is initiated, discontinued or dose changed.
Warfarin The antiplatelet effects of oral diclofenac may increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for signs and symptoms of bleeding during concomitant therapy.
Warfarin The NSAID, diclofenac, may increase the anticoagulant effect of warfarin

Contraindications
  • Hypersensitivity against diclofenac
  • History of allergic reactions (bronchospasm, shock, rhinitis, urticaria) following the use of Aspirin or another NSAID
  • Third-trimester pregnancy
  • Active stomach and/or duodenal ulceration or gastrointestinal bleeding
  • Inflammative intestinal disorders such as Crohn's disease or ulcerative colitis
  • Severe insufficiency of the heart (NYHA III/IV)
  • Recently, a warning has been issued by FDA not to use to treat patients recovering from heart surgery
  • Severe liver insufficiency (Child-Pugh Class C)
  • Severe renal insufficiency (creatinine clearance <30 ml/min)
  • Caution in patients with preexisting hepatic porphyria, as diclofenac may trigger attacks
  • Caution in patients with severe, active bleeding such as cerebral hemorrhage
  • NSAIDs in general should be avoided during dengue fever.
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