CLINICAL USE

NSAID and analgesic

DOSE IN NORMAL RENAL FUNCTION

200 mg twice daily

PHARMACOKINETICS

  • Molecular weight                           :356.4
  • %Protein binding                           :95
  • %Excreted unchanged in urine     : 7
  • Volume of distribution (L/kg)       :No data
  • half-life – normal/ESRD (hrs)      :7.8/16.4 (metabolite)/Unchanged

    DOSE IN RENAL IMPAIRMENT

    GFR (mL/MIN)

  • 20 to 50     : Dose as in normal renal function. Avoid if possible
  • 10 to 20     : Give 50–100% of normal dose. Avoid if possible
  • <10           : Give 50–100% of normal dose. Avoid if possible

    DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

  • CAPD                :Unlikely to be 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      :Unknown dialysability. Dose as in GFR 10 to 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 possibly 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

    Rate of Administration

    –

    Comments

    –

    OTHER INFORMATION

    Sulindac has become the NSAID of choice in some centres for patients with renal impairment because of reports of its renal sparing effects. There is evidence that this sparing effect is dose-related and is lost if doses above 100 mg twice daily are usedInhibition of renal prostaglandin synthesis by NSAIDs may interfere with renal function, especially in the presence of existing renal disease – avoid NSAIDs if possible; if not, check serum creatinine 48–72 hours after starting NSAID – if increased, discontinue therapyUse normal doses in patients with CKD 5 on dialysis if they do not pass any urineUse with caution in renal transplant recipients (can reduce intrarenal autocoid synthesis).

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