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

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Route

Oral

Rate of Administration

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Comments

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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

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