CLINICAL USE


Angiotensin-II receptor antagonist:Hypertension

DOSE IN NORMAL RENAL FUNCTION

10–40 mg once daily

PHARMACOKINETICS

  • Molecular weight &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :558.6
  • %Protein binding &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :99.7
  • %Excreted unchanged in urine &nbsp &nbsp : 35–50

  • Volume of distribution (L/kg) &nbsp &nbsp &nbsp :0.24

  • half-life – normal/ESRD (hrs)&nbsp &nbsp &nbsp :10–15/36

    DOSE IN RENAL IMPAIRMENT

    GFR (mL/MIN)

  • 20 to 50 &nbsp &nbsp : Dose as in normal renal function
  • 10 to 20 &nbsp &nbsp : Dose as in normal renal function. Start with low doses
  • <10 &nbsp &nbsp &nbsp &nbsp &nbsp : Dose as in normal renal function Initial dose 10 mg daily and gradually increase

    DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

  • CAPD &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp:Not dialysed. Dose as in GFR <10 mL/min

  • HD &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :Not dialysed. Dose as in GFR <10 mL/min
  • HDF/high flux &nbsp :Unlikely to be dialysed. Dose as in GFR <10 mL/min
  • CAV/VVHD &nbsp &nbsp &nbsp:Unknown dialysability. Dose as in GFR 10 to 20 mL/min

    IMPORTANT DRUG INTERACTIONS

    Potentially hazardous interactions with other drugs
  • Anaesthetics: enhanced hypotensive effect
  • Analgesics: antagonism of hypotensive effect and increased risk of renal impairment with NSAIDs; hyperkalaemia with ketorolac and other NSAIDs
  • Ciclosporin: increased risk of hyperkalaemia and nephrotoxicity
  • Diuretics: enhanced hypotensive effect; hyperkalaemia with potassium-sparing diuretics
  • Epoetin: increased risk of hyperkalaemia; antagonism of hypotensive effect
  • Lithium: reduced excretion (possibility of enhanced lithium toxicity)
  • Potassium salts: increased risk of hyperkalaemia
  • Tacrolimus: increased risk of hyperkalaemia and nephrotoxicity

    ADMINISTRATION

    Reconstition

    –

    Route

    Oral

    Rate of Administration

    –

    Comments

    –

    OTHER INFORMATION

    Hyperkalaemia and other side effects are more common in patients with impaired renal functionRenal failure has been reported in association with angiotensin-II antagonists in patients with renal artery stenosis, post renal transplant, and in those with congestive heart failureClose monitoring of renal function during therapy is necessary in those with renal insufficiencyIn mild, moderate and severe renal failure, the AUC is increased by 62, 82 and 179% respectively
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