voriconazole: clinical use

Prescribing considerations

• Reserve for the licensed serious invasive infections or transplant prophylaxis represented by the selected products.
• Review all prescribed, non-prescription and herbal products before initiation and whenever treatment changes.
• Assess hepatic function, renal function, electrolytes and cardiac risk before treatment.
• Exposure varies substantially because of nonlinear pharmacokinetics, CYP2C19-related variability and interactions; plasma concentration monitoring may support management.
• Provide explicit photoprotection counselling and assess significant phototoxicity or suspicious skin lesions.
• Reassess ongoing need carefully where exposure is prolonged; investigate unexplained skeletal pain for periostitis.

Contraindications and cautions

• Hypersensitivity to voriconazole or the relevant formulation excipients
• Contraindicated CYP-inducing combinations, including rifampicin, carbamazepine, long-acting barbiturates and St John's wort
• Contraindicated combinations with sensitive CYP3A4 substrates where increased exposure can cause serious or life-threatening toxicity
• Product-specified contraindicated combinations involving certain ritonavir or efavirenz regimens

Monitoring

• Liver function before treatment and frequently after initiation, with ongoing monitoring if treatment continues
• Serum creatinine and clinical renal function
• Potassium, magnesium and calcium; correct abnormalities that increase arrhythmia risk
• ECG where QT prolongation or other proarrhythmic risk factors are present
• Plasma voriconazole concentration where clinically indicated, particularly with variable response, toxicity or interactions
• Skin examination where phototoxicity occurs or treatment is prolonged
• Visual symptoms; investigate severe, prolonged or worsening disturbance
• Pancreatic markers in patients with relevant risk factors

Clinical pharmacology

Voriconazole inhibits fungal lanosterol demethylation and ergosterol synthesis. It is extensively distributed, has nonlinear pharmacokinetics, is metabolised mainly through CYP2C19, CYP2C9 and CYP3A4, and is a strong CYP3A4 inhibitor. Its principal N-oxide metabolite has minimal antifungal activity.

Formulation and product differences

• Film-coated tablets contain lactose and are taken at least one hour before or after food.
• The oral suspension contains sucrose and sodium benzoate, has different food timing from tablets, must be shaken and should be measured using the supplied syringe.
• The intravenous powder requires reconstitution and further dilution. It contains sulfobutylether beta-cyclodextrin and a clinically relevant sodium load.
• The intravenous cyclodextrin vehicle can accumulate in moderate-to-severe renal dysfunction; oral treatment is preferred unless intravenous use is justified by individual benefit and risk.

Solution for infusion

Route: Intravenous

Strengths: 200 mg

Oral suspension

Route: Oral

Strengths: 40 mg/mL

Tablet

Route: Oral

Strengths: 50 mg, 100 mg, 200 mg