CLINICAL USE

NSAID and analgesic

DOSE IN NORMAL RENAL FUNCTION

Rheumatic disease: 20–30 mg daily Acute gout: 40 mg in single or divided dosesAcute musculoskeletal disorders: 40 mg daily for 2 days, then 20 mg daily

PHARMACOKINETICS

  • Molecular weight                           :331.3
  • %Protein binding                           :99
  • %Excreted unchanged in urine     : <5
  • Volume of distribution (L/kg)       :0.14
  • half-life – normal/ESRD (hrs)      :50/Unchanged

    DOSE IN RENAL IMPAIRMENT

    GFR (mL/MIN)

  • 20 to 50     : Dose as in normal renal function, but avoid if possible
  • 10 to 20     : Dose as in normal renal function, but avoid if possible
  • <10           : Dose as in normal renal function, but only use if on dialysis

    DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

  • CAPD                :Not dialysed. Dose as in GFR <10 mL/min.
  • HD                     :Not dialysed. Dose as in GFR <10 mL/min.
  • HDF/high flux   :Unknown dialysability. Dose as in GFR <10 mL/min.
  • CAV/VVHD      :Not dialysed. Dose as in GFR=10–20 mL/min

    IMPORTANT DRUG INTERACTIONS

    Potentially hazardous interactions with other drugsACE inhibitors and angiotensin-II antagonists: antagonism of hypotensive effect; increased risk of nephrotoxicity and hyperkalaemia

  • Analgesics: avoid concomitant use of 2 or more NSAIDs, including aspirin (increased side effects); avoid with ketorolac (increased risk of side effects and haemorrhage)
  • Antibacterials: possibly increased risk of convulsions with quinolones
  • Anticoagulants: effects of coumarins enhanced; possibly increased risk of bleeding with heparins and coumarins
  • Antidepressants: increased risk of bleeding with SSRIs and venlafaxineAntidiabetic agents: effects of sulphonylureas enhanced
  • Anti-epileptics: possibly increased phenytoin concentration
  • Antivirals: increased risk of haematological toxicity with zidovudine; concentration increased by ritonavir
  • Ciclosporin: may potentiate nephrotoxicity Cytotoxic agents: reduced excretion of methotrexate; increased risk of bleeding with erlotinib
  • Diuretics: increased risk of nephrotoxicity; antagonism of diuretic effect; hyperkalaemia with potassium-sparing diuretics
  • Lithium: excretion decreased Pentoxifylline: increased risk of bleeding
  • Tacrolimus: increased risk of nephrotoxicity

    ADMINISTRATION

    Reconstition

    –

    Route

    Oral, IM, topical

    Rate of Administration

    –

    Comments

    –

    OTHER INFORMATION

    Inhibition of renal prostaglandin synthesis by NSAIDs may interfere with renal function, especially in the presence of existing renal disease – avoid if possible; if not, check serum creatinine 48–72 hours after starting NSAID – if serum creatinine is increased, stop NSAIDUse normal doses in patients with CKD 5 if on dialysis and do not pass any urineUse with caution in renal transplant recipients – can reduce intrarenal autocoid synthesisWater soluble inactive metabolites may be removed by HD and CAPD

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