Itraconazole

SCOPE — this page (category 'Triazole antifungal', specialties Infectious Disease and Respiratory) leads with the onychomycosis pulse regimen and aspergillosis, by mouth or intravenously. Both of those indications and both of those routes are dosed above from labelled sources: the oral capsule regimens come from the US prescribing information and the intravenous regimen from the UK SPC, and the endemic mycoses (blastomycosis, histoplasmosis) are included because the same US label doses them. || DOSE ESCALATION (US label, blastomycosis and histoplasmosis), verbatim: 'The recommended dose is 200 mg once daily (2 capsules). If there is no obvious improvement, or there is evidence of progressive fungal disease, the dose should be increased in 100-mg increments to a maximum of 400 mg daily. Doses above 200 mg/day should be given in two divided doses.' ASPERGILLOSIS: 'A daily dose of 200 to 400 mg is recommended.' ONYCHOMYCOSIS, toenails: 'The recommended dose is 200 mg (2 capsules) once daily for 12 consecutive weeks.' ONYCHOMYCOSIS, fingernails only: 'The recommended dosing regimen is 2 treatment pulses, each consisting of 200 mg (2 capsules) b.i.d. (400 mg/day) for 1 week. The pulses are separated by a 3-week period without itraconazole.' || LIFE-THREATENING INFECTION — LOADING DOSE ABOVE THE STATED CEILING, verbatim: 'In life-threatening situations, a loading dose should be used. Although clinical studies did not provide for a loading dose, it is recommended, based on pharmacokinetic data, that a loading dose of 200 mg (2 capsules) three times daily (600 mg/day) be given for the first 3 days of treatment.' This is the only regimen in either label that exceeds 400 mg daily and it is limited to the first 3 days; it is deliberately not shown in the dose field. DURATION: 'Treatment should be continued for a minimum of three months and until clinical parameters and laboratory tests indicate that the active fungal infection has subsided. An inadequate period of treatment may lead to recurrence of active infection.' || INTRAVENOUS (UK SPC §4.2), verbatim: 'Itraconazole is given on the first two days in a loading dose twice daily, followed by once daily dosing. Day 1 and 2 of the treatment: 1-hour infusion of 200 mg (60 ml of the admixed solution) Itraconazole twice daily (see section 6.6). From day 3 on: one 1-hour infusion of 200 mg (60 ml of the admixed solution) Itraconazole each day. Safety for periods longer than 14 days has not been established.' || FORMULATIONS ARE NOT INTERCHANGEABLE (US label): 'Itraconazole capsule is a different preparation than itraconazole Oral Solution and should not be used interchangeably... Only the oral solution has been demonstrated effective for oral and/or esophageal candidiasis.' || PAEDIATRIC (why paedDose is null): US label, Pediatric Use — 'The efficacy and safety of itraconazole have not been established in pediatric patients. The long-term effects of itraconazole on bone growth in children are unknown.' UK IV SPC §4.2 — 'Clinical data on the use of itraconazole IV in paediatric patients are limited. The use of itraconazole IV in paediatric patients is not recommended unless it is determined that the potential benefit outweighs the potential risks.' Verify any paediatric use against a children's formulary. || ELDERLY (UK SPC §4.2): 'Since clinical data of the use of itraconazole in elderly patients are limited, it is advised to use itraconazole in these patients only if the potential benefit outweighs the potential risks.' || CARDIAC (UK SPC §4.4): 'Heart failure was more frequently reported among spontaneous reports of 400 mg total daily dose than among those of lower total daily doses, suggesting that the risk of heart failure might increase with the total daily dose of itraconazole. Itraconazole should not be used in patients with congestive heart failure or with a history of congestive heart failure unless the benefit clearly outweighs the risk.' || Confirm the whole regimen against the UK SPC for the specific product and formulation before use.