dosage adjustment of Candesartan cilexetil in renal failure




Candesartan cilexetil.JPG

Candesartan cilexetil

CLINICAL USE

Angiotensin-II antagonist:
  • Hypertension
  • Heart failure

    DOSE IN NORMAL RENAL FUNCTION

    2–32 mg daily

    PHARMACOKINETICS

  • Molecular weight                           :610.7
  • %Protein binding                           :>99
  • %Excreted unchanged in urine     : 26
  • Volume of distribution (L/kg)       :0.1
  • half-life – normal/ESRD (hrs)      :9/18

    DOSE IN RENAL IMPAIRMENT

    GFR (mL/MIN)

  • 20 to 50     : Dose as in normal renal function
  • 10 to 20     : Initial dose 2 mg and increase according to response
  • <10           : Initial dose 2 mg and increase according to response

    DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

  • CAPD                :Unlikely to be dialysed. Dose as for GFR <10 mL/min
  • HD                     :Not dialysed. Dose as for GFR <10 mL/min
  • HDF/high flux   :Not dialysed. Dose as for GFR <10 mL/min
  • CAV/VVHD      :Unlikely to be dialysed. Dose as for 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 toxicityP
  • otassium salts: increased risk of hyperkalaemia.
  • Tacrolimus: increased risk of hyperkalaemia and nephrotoxicity

    ADMINISTRATION

    Reconstition

    Route

    Oral

    Rate of Administration

    Comments

    OTHER INFORMATION

  • In patients with mild–moderate renal impairment Cmax and AUC are increased by 50% and 70% respectively. Corresponding changes in patients with severe renal impairment are 50% and 110% respectively
  • Adverse reactions, especially hyperkalaemia, are more common in patients with renal impairment
  • Renal 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 failure
  • Close monitoring of renal function during therapy is necessary in those with renal insufficiency