Posaconazole

CLINICAL USE

Triazole antifungal agent

DOSE IN NORMAL RENAL FUNCTION

400 mg twice daily with food or 240 mL of a nutritional supplementOr 200 mg 4 times a day without food Oropharyngeal candidiasis severe infection or in immunocompromised patients: Loading dose of 200 mg once a day on the first day, then 100 mg once a day for 13 daysProphylaxis of invasive fungal infections: 200 mg 3 times a day

PHARMACOKINETICS

Molecular weight :700.8

%Protein binding :>98

%Excreted unchanged in urine : <0.2

Volume of distribution (L/kg) :1774 litres

half-life – normal/ESRD (hrs) :20–66 (average 35)/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 :Unknown dialysability. 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

Antidepressants: avoid concomitant use with reboxetine

Antibacterials: rifamycins may reduce posaconazole concentration; avoid concomitant administration unless benefit outweighs risk; rifabutin concentration increased

Anti-epileptics: phenytoin, carbamazepine, phenobarbital and primidone may reduce posaconazole concentration – avoid concomitant administration unless benefit outweighs risk

Antimalarials: avoid concomitant administration with artemether/lumefantrine

Antipsychotics: increased risk of ventricular arrhythmias with pimozide and sertindole – avoid concomitant use; possibly increase quetiapine levels – reduce dose of quetiapine

Antivirals: possibly increases saquinavir levelsAnxiolytics and hypnotics: increases midazolam levels

Ciclosporin: increases posaconazole concentration. Posaconazole can increase ciclosporin concentration, – dose reduction may be required

Ergot alkaloids: may increase ergot alkaloid concentration leading to ergotism – avoid concomitant administrationLipid-lowering drugs: possibly increased risk of myopathy with atorvastatin or simvastatinSirolimus: may increase concentration of sirolimus – adjust sirolimus dose as required according to levelsSulphonylureas: posaconazole can decrease glucose concentrations, monitor glucose levels in diabetic patients

Tacrolimus: concentration of tacrolimus increased – reduce dose of tacrolimus

Ulcer-healing drugs: cimetidine may reduce posaconazole concentration by 39% – avoid concomitant administration unless benefit outweighs risk; drugs which reduce gastric acidity may reduce bioavailability of posaconazoleVinca alkaloids: may increase vinca alkaloid concentration leading to neurotoxicity – avoid concomitant administration unless benefit outweighs risk. It is advised to reduce the dose of the vinca alkaloid

Tacrolimus: increases C max and AUC by 121% and 358% respectively of tacrolimus – reduce tacrolimus dose to about a third of current dose and adjust as required.594 PosAConAZoLE

ADMINISTRATION

Reconstition

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Route

Oral

Rate of Administration

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Comments

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OTHER INFORMATION

Use with caution in people with arrhythmias, electrolyte disturbances QT prolongation, sinus bradycardia and cardiomyopathyContains 7 g of glucose per 800 mg daily dose. Measure liver function tests as moderate increases have been noted.

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