indometacin

CLINICAL USE

NSAID:Pain and inflammation in rheumatic disease and other musculoskeletal disordersAcute gout Dysmenorrhoea Closure of ductus arteriosus

DOSE IN NORMAL RENAL FUNCTION

Oral: 50–200 mg daily in divided doses, after foodPR: 100 mg twice daily if required Gout: 150–200 mg daily in divided doses Dysmenorrhoea: up to 75 mg daily Maximum combined oral and PR: 150– 200 mg daily

PHARMACOKINETICS

Molecular weight &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :357.8

%Protein binding &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :90–99

%Excreted unchanged in urine &nbsp &nbsp : 5–20 (60% as metabolites)

Volume of distribution (L/kg) &nbsp &nbsp &nbsp :0.34–1.57

half-life – normal/ESRD (hrs)&nbsp &nbsp &nbsp :1–16/unchanged

DOSE IN RENAL IMPAIRMENT

GFR (mL/MIN)

20 to 50 &nbsp &nbsp : Dose as in normal renal function, but avoid if possible

10 to 20 &nbsp &nbsp : Dose as in normal renal function, but avoid if possible

<10 &nbsp &nbsp &nbsp &nbsp &nbsp : Dose as in normal renal function, but only use if CKD 5 and on dialysis

DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

CAPD &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp:Not dialysed. Dose as in normal renal function

HD &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :Not dialysed. Dose as in normal renal function

HDF/high flux &nbsp :Unlikely to be dialysed. Dose as in normal renal function

CAV/VVHD &nbsp &nbsp &nbsp: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 and phenindione enhanced; possibly increased risk of bleeding with heparins

Antidepressants: increased risk of bleeding with SSRIs and venlafaxineAntidiabetic agents: effects of sulphonylureas enhancedAnti-epileptic agents: effects of phenytoin enhanced

Antipsychotics: possible severe drowsiness with haloperidol

Antivirals: increased risk of haematological toxicity with zidovudine; concentration possibly increased by ritonavir

Ciclosporin: increased risk of nephrotoxicityCytotoxic agents: reduced excretion of methotrexate

Diuretics: increased risk of nephrotoxicity, hyperkalaemia with potassium-sparing diuretics; antagonism of diuretic effect

Lithium: lithium excretion reduced Pentoxifylline: possibly increased risk of bleedingProbenecid: excretion of indometacin reduced

Tacrolimus: increased risk of nephrotoxicity

ADMINISTRATION

Reconstition

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Route

Oral, PR, IV

Rate of Administration

20–30 minutes

Comments

–.382 indoMETACin

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 raised, discontinue NSAID therapyUse normal doses in patients with ERF on dialysis if they do not pass any urineUse with caution in renal transplant recipients – can reduce intrarenal autocoid synthesis.

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