Voriconazole

Entry for voriconazole in respiratory / pulmonary fungal infection (e.g. invasive pulmonary aspergillosis); the SPC posology is the same across indications. Applies to patients aged 15 years and older. High oral bioavailability (96%) - switching between IV and oral is appropriate when clinically indicated. Dose adjustment: if IV 4 mg/kg twice daily is not tolerated, reduce to 3 mg/kg twice daily; if response is inadequate, oral maintenance may be increased to 300 mg twice daily (150 mg twice daily for patients less than 40 kg), then reduced in 50 mg steps if not tolerated. Duration should be as short as possible; more than 180 days requires careful benefit-risk assessment. Prophylaxis (transplant): same regimen as treatment for the age group; start on day of transplant, up to 100 (and up to 180) days. Elderly: no dose adjustment necessary. Hepatic impairment (mild-moderate, Child-Pugh A/B): use the standard loading dose but halve the maintenance dose. Coadministration: with rifabutin or phenytoin increase IV maintenance to 5 mg/kg twice daily; with efavirenz increase voriconazole to 400 mg every 12 hours and reduce efavirenz to 300 mg once daily. Correct hypokalaemia/hypomagnesaemia/hypocalcaemia before and during therapy.

SPC paediatric regimen for children 2 to under 12 years and low-weight adolescents (12 to 14 years, under 50 kg): IV loading 9 mg/kg every 12 hours for the first 24 hours; then IV maintenance 8 mg/kg twice daily OR oral maintenance 9 mg/kg twice daily (maximum 350 mg twice daily). Oral loading is not recommended. Initiate with the IV regimen; use oral only after significant clinical improvement. An 8 mg/kg IV dose gives voriconazole exposure about 2-fold higher than a 9 mg/kg oral dose. Adolescents 12 to 14 years and 50 kg or more, and 15 to 17 years regardless of body weight: dose as adults. Not studied in children under 2 years or with hepatic/renal insufficiency. Verify against a children's formulary.