itraconazole

CLINICAL USE

Antifungal agent

DOSE IN NORMAL RENAL FUNCTION

100–200 mg every 12–24 hours according to indication

PHARMACOKINETICS

Molecular weight :705.6

%Protein binding :99.8

%Excreted unchanged in urine : <0.03

Volume of distribution (L/kg) :10

half-life – normal/ESRD (hrs) :20–40/Unchanged

DOSE IN RENAL IMPAIRMENT

GFR (mL/MIN)

20 to 50 : Dose as in normal renal function

10 to 20 : Dose as in normal renal function

<10 : Dose as in normal renal function

DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

CAPD :Not dialysed. Dose as in normal renal function

HD :Not dialysed. Dose as in normal renal function

HDF/high flux :Not dialysed. Dose as in normal renal function

CAV/VVHD :Not dialysed. Dose as in normal renal function

IMPORTANT DRUG INTERACTIONS

Potentially hazardous interactions with other drugs

Analgesics: possibly inhibits alfentanil metabolism

Antibacterials: metabolism accelerated by rifabutin and rifampicin – avoid with rifabutin; possibly increased rifabutin concentration – reduce rifabutin dose; clarithromycin can increase itraconazole concentration

Anticoagulants: effect of coumarins enhanced

Antidepressants: avoid concomitant use with reboxetineAntidiabetics: can enhance effects of repaglinide

Anti-epileptics: concentration reduced by carbamazepine, barbiturates and phenytoin – avoid with phenytoinAntihistamines: inhibits mizolastine metabolism – avoid concomitant use

Antimalarials: avoid concomitant use with artemether/lumefantrine

Antipsychotics: possibly inhibits metabolism of aripiprazole – reduce aripiprazole dose; increased risk of ventricular arrhythmias with pimozide and sertindole – avoid concomitant use; possibly increased quetiapine concentration – reduce quetiapine dose

Antivirals: concentration possibly increased by amprenavir; concentration of indinavir increased – may need to reduce indinavir dose; with ritonavir concentration of both drugs may be increased; concentration of saquinavir possibly increased; concentration reduced by efavirenzAnxiolytics and hypnotics: concentration of buspirone, midazolam and alprazolam increased – reduce buspirone doseBosentan: possibly increased bosentan concentration

Calcium-channel blockers: negative inotropic effect possibly increased; metabolism of felodipine and possibly dihydropyridines inhibited; avoid concomitant use with lercanidipine and nisoldipineCardiac glycosides: concentration of digoxin increased

Ciclosporin: metabolism of ciclosporin inhibited (increased plasma ciclosporin levels)Cytotoxics: metabolism of busulfan inhibited, increased risk of toxicity; possibly inhibits metabolism of vincristine, increased risk of neurotoxicity; possibly increased side effects with cyclophosphamide

Diuretics: increased eplerenone levels – avoid concomitant use

Ergot alkaloids: increased risk of ergotism – avoid concomitant use5HT 1 agonists: increased eletriptan concentration – avoid concomitant useIvabradine: possibly increased ivabradine levels – reduce initial doseLipid-lowering drugs: increased risk of myopathy with atorvastatin and .iTrAConAZoLE 403simvastatin – avoid concomitant use with simvastatin, and maximum atorvastatin dose 40 mg.1Sirolimus: concentration increased by itraconazole

Tacrolimus: possibly increased tacrolimus levels

Ulcer-healing drugs: absorption reduced by histamine H2 antagonists and proton pump inhibitors

Vardenafil: possibly increased vardenafil concentration – avoid concomitant use

ADMINISTRATION

Reconstition

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Route

Oral,

IV infusion

Rate of Administration

Over 60 minutes

Comments

Add 250 mg vial to 50 mL sodium chloride 0.9%, administer 60 mL (increased volume due to large displacement value)

OTHER INFORMATION

Preparations absorbed at different rates: liquid is absorbed within 2.5 hours, capsules within 2–5 hoursOral bioavailability of itraconazole may be lower in some patients with renal insufficiency, e.g. those receiving CAPD Janssen-Cilag advise no dose alterations required in renal impairment as drug is extensively metabolised in the liver, and pharmacokinetics are unchanged in patients with ERF compared to normal

See how to identify renal failure stages according to GFR calculation

See how to diagnose irreversible renal disease

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