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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