Ketoconazole

CLINICAL USE

Antifungal agent

DOSE IN NORMAL RENAL FUNCTION

200–400 mg once daily

PHARMACOKINETICS

Molecular weight :531.4

%Protein binding :>90

%Excreted unchanged in urine : 13

Volume of distribution (L/kg) :0.36

half-life – normal/ESRD (hrs) :2/3.3

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 :Unknown dialysability. Dose as in normal renal function

CAV/VVHD :Unknown dialysability. Dose as in normal renal function

IMPORTANT DRUG INTERACTIONS

Potentially hazardous interactions with other drugs

Analgesics: inhibits buprenorphine metabolism – reduce buprenorphine dose

Anti-arrhythmics: increased risk of ventricular arrhythmias with disopyramide – avoid concomitant use

Antibacterials: metabolism increased by rifampicin; may reduce rifampicin concentration; concentration possibly reduced by isoniazid; avoid concomitant use with telithromycin in severe renal and hepatic impairment

Anticoagulants: anticoagulant effect of coumarins enhanced

Antidepressants: avoid concomitant use with reboxetine; ketoconazole increases concentration of mirtazepine

Anti-epileptics: concentration of ketoconazole reduced by phenytoin; concentration of carbamazepine possibly increasedAntihistamines: concentration of loratidine possibly increased; avoid concomitant use with mizolastine

Antimalarials: manufacturer advises avoid artemether and lumefantrine with ketoconazole

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

Antivirals: concentration of both drugs increased with darunavir; inhibits metabolism of indinavir; concentration reduced by nevirapine – avoid concomitant use; ketoconazole and ritonavir can increase concentration of each other; concentration of saquinavir increased; concentration increased by amprenavirAnxiolytics and hypnotics: concentration of alprazolam and midazolam increased (risk of prolonged sedation)

Calcium-channel blockers: increased concentration of felodipine; avoid with lercanidipine and nisoldipine; possibly inhibits metabolism of dihydropyridines

Ciclosporin: increased ciclosporin concentrationCilostazol: possibly increased concentration of cilostazol, avoid concomitant useCinacalcet: increased cinacalcet concentration

Diuretics: increased eplerenone concentration – avoid concomitant useDomperidone: possibly increased risk of arrhythmias

Ergot alkaloids: increased risk of ergotism with ergotamine and methysergide – avoid concomitant use5HT 1 agonists: increased concentration of eletriptan – avoid concomitant use; increased almotriptan concentration (increased toxicity).KEToConAZoLE 407Ivabradine: concentration of ivabradine increased – avoid concomitant useLanthanum: reduces absorption of ketoconazole – give at least 2 hours apartSirolimus: concentration increased by ketoconazole – avoid concomitant useStatins: possibly increased risk of myopathy with atorvastatin and simvastatin – avoid concomitant use with simvastatin

Tacrolimus: increased tacrolimus concentrationTheophylline; possibly increased concentration of theophylline

Vardenafil: increased concentration of vardenafil, avoid concomitant use

ADMINISTRATION

Reconstition

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Route

Oral, topical

Rate of Administration

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Comments

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OTHER INFORMATION

Monitor LFTs especially if on long-term treatment.

See how to identify renal failure stages according to GFR calculation

See how to diagnose irreversible renal disease

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