Posaconazole

SOURCE: UK SPC for Noxafil 100 mg Gastro-resistant Tablets (https://www.medicines.org.uk/emc/product/5388/smpc). The dose above is the respiratory-relevant indication (treatment of invasive aspergillosis); recommended total duration of therapy is 6-12 weeks, and switching between intravenous and oral administration is appropriate when clinically indicated. FORMULATION WARNING: Noxafil tablets are NOT to be used interchangeably with Noxafil oral suspension, because the two formulations differ in frequency of dosing, administration with food and plasma drug concentration achieved — the specific dose recommendations for each formulation must be followed. Noxafil tablets generally provide higher plasma drug exposures than the oral suspension under both fed and fasted conditions, so tablets are preferred to optimise plasma concentrations. Other formulations are available for oral and intravenous use. OTHER LABELLED INDICATIONS, both using the same regimen (300 mg twice a day on the first day, then 300 mg once a day): refractory invasive fungal infections (IFI) / patients with IFI intolerant to first-line therapy, where duration should be based on the severity of the underlying disease, recovery from immunosuppression and clinical response; and prophylaxis of invasive fungal infections, where duration is based on recovery from neutropenia or immunosuppression, and for patients with acute myelogenous leukaemia or myelodysplastic syndromes prophylaxis should start several days before the anticipated onset of neutropenia and continue for 7 days after the neutrophil count rises above 500 cells per mm3. PRESCRIBING RESTRICTION: treatment should be initiated by a physician experienced in the management of fungal infections or in the supportive care of high-risk patients for whom posaconazole is indicated as prophylaxis. MISSED DOSE: take the dose as soon as possible unless it is almost time for the next dose; a double dose should not be taken to make up for a missed dose. MONITORING: liver function tests should be evaluated prior to the start of and during the course of therapy; patients who develop abnormal liver function tests must be routinely monitored for more severe hepatic injury and discontinuation should be considered if clinical signs and symptoms are consistent with liver disease. Electrolyte disturbances, especially potassium, magnesium and calcium, should be monitored and corrected before and during therapy because of the QTc prolongation risk. HEPATIC IMPAIRMENT: limited data (including Child-Pugh C) show increased plasma exposure but do not suggest that dose adjustment is necessary; caution is recommended due to the potential for higher plasma exposure. PAEDIATRIC (non per-kg, so not expressed as a mg/kg dose): the doses in the SPC table apply to paediatric patients from 2 years of age weighing MORE than 40 kg as well as adults — i.e. the same 300 mg twice daily on day 1 then 300 mg once daily. For paediatric patients 2 years of age and older weighing 40 kg or less, Noxafil gastro-resistant powder and solvent for oral suspension is recommended — refer to that SmPC for additional dosing information. Safety and efficacy in children aged below 2 years have not been established and no clinical data are available. Verify any under-18 use against a children's formulary.