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. See ‘Other Information’
DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES
CAPD                : Probably dialysed. Dose as in normal renal function
HD                     : Dialysed. Dose as in normal renal function
HDF/high flux   : Dialysed. Dose as in normal renal function
CAV/VVHD      : Probably dialysed. Dose as in normal renal function
IMPORTANT DRUG INTERACTIONS
Potentially hazardous interactions with other drugs
Analgesics: methadone concentration increased
Antibacterials: concentration reduced by rifabutin; increase dose of voriconazole from 200 to 350 mg and from 100 to 200 mg (depends on patient’s weight), and increase IV dose to 5 mg/kg if used in combination – avoid concomitant use if possible; increased rifabutin levels – monitor for toxicity; avoid concomitant use with rifampicin
Anticoagulants: enhanced effect of coumarins
Antidepressants: avoid concomitant use with reboxetine Antidiabetics: possibly increased concentration of sulphonylureas
Anti-epileptics: concentration reduced by carbamazepine, barbiturates and primidone – avoid concomitant use; phenytoin reduces voriconazole concentration and voriconazole increases phenytoin concentration – double oral voriconazole dose and increase IV to 5 mg/ kg dose if using with phenytoin; avoid concomitant use if possible
Antimalarials: avoid concomitant use with artemether/lumefantrine
Antipsychotics: increased risk of ventricular arrhythmias with pimozide and sertindole – avoid concomitant use; possibly increased quetiapine levels – reduce dose of quetiapine
Antivirals: concentration reduced by efavirenz and ritonavir; also concentration of efavirenz increased – avoid concomitant use with ritonavir; with efavirenz reduce dose by 50% and increase dose of voriconazole to 400 mg twice daily; possibly increased saquinavir levels Benzodiazepines: may inhibit metabolism of midazolam
Ciclosporin: AUC increased – reduce ciclosporin dose by 50% and monitor closely
Ergot alkaloids: risk of ergotism – avoid concomitant use Lipid-lowering drugs: possibly increased risk of myopathy with atorvastatin or simvastatin . Sirolimus: increased sirolimus concentration – avoid concomitant use
Tacrolimus: AUC increased – reduce tacrolimus dose to a third and monitor closely
Not compatible with sodium bicarbonate or TPN solutions Dilute to a concentration of 2–5 mg/mL with sodium chloride 0.9%, Hartmann’s solution or glucose 5%
OTHER INFORMATION
Haemodialysis clearance is 121 mL/min Oral bioavailability is 96% Only use IV in renal patients if patient is unable to tolerate oral, as intravenous vehicle (SBECD) accumulates in renal failure. The vehicle is dialysed at a rate of 55 mL/min Take oral dose 1 hour before or an hour after meals Monitor renal function as can enhance nephrotoxicity of other drugs and concurrent conditions Rare reports of acute renal failure and discoid lupus erythematosus occurring Also reports of haematuria, nephritis and tubular necrosis In clinical trials, 30% of patients had visual problems, usually with higher doses .