Ketoconazole (Adrenal Indication)

SPECIALIST INITIATION (section 4.2): "Treatment should be initiated and supervised by physicians experienced in endocrinology or internal medicine and having the appropriate facilities for monitoring of biochemical responses since the dose must be adjusted to meet the patient's therapeutic need, based on the normalisation of cortisol levels." VERBATIM section 4.2 initiation: "The recommended dose at initiation in adults and adolescents is 400-600 mg/day taken orally in two or three divided doses and this dose can be increased rapidly to 800-1,200 mg/day in two or three divided doses. At treatment initiation, 24-hour urinary free cortisol should be controlled every few days/weeks." TITRATION: "A dose increase of 200 mg/day every 7 to 28 days may be considered if urinary free cortisol and/or plasma cortisol levels are above the normal range, as long as the dose is tolerated by the patient"; "A maintenance dose from 400 mg/day to a maximal dose of 1,200 mg/day taken orally in 2 to 3 divided doses may be required to restore normal cortisol levels"; "When the effective dose of ketoconazole is established, monitoring of urinary free cortisol and/or plasma cortisol levels may be performed every 3 to 6 months." ADRENAL INSUFFICIENCY: "In the case of adrenal insufficiency and depending on the severity of the event, the dose of ketoconazole should be decreased by at least 200 mg/day or the treatment should be temporarily discontinued and/or a corticosteroid therapy should be added until the resolution of the event. Ketoconazole can be reintroduced thereafter at a lower dose." STOPPING: "Treatment with ketoconazole can be stopped abruptly without a need for progressive dose decrease where a change in the therapeutic strategy (e.g. surgery) is desired." MAINTENANCE REGIMENS: "Block-only regimen: the maintenance dose of ketoconazole may be continued as described above; Block-and-replace regimen: the maintenance dose of ketoconazole should be further increased by 200 mg and concomitant corticosteroid replacement therapy should be added." HEPATIC: "Ketoconazole is contraindicated in patients with acute or chronic hepatic impairment. The treatment must not be initiated in patients with liver enzymes levels above 2 times the upper limit of normal." RENAL: "the pharmacokinetics of ketoconazole are not significantly different in patients with renal failure compared to healthy subjects, and no specific dose adjustment is recommended in this population." ELDERLY: "Data on the use of ketoconazole in patients older than 65 years are limited, but there is no evidence to suggest that specific dose adjustment is required." ABSORPTION (section 4.4): "Absorption is impaired when gastric acidity is decreased. Acid-neutralising medicines (e.g. aluminium hydroxide) should not be administered for at least 2 hours after the intake of ketoconazole." Some sections of the product information we used were incomplete — check the full SPC. NOT USED: the bundle's openFDA record is a ketoconazole 2% SHAMPOO (ANI Pharmaceuticals) — a topical antifungal with no oral posology and no endocrine indication; it was deliberately excluded.

THIS IS NOT A WEIGHT-BASED DOSE — no per-kg figure exists in the label, so dosePerKg is null. ADOLESCENTS: the UK SPC section 4.2 states "The recommended dose at initiation in adults and adolescents is 400-600 mg/day taken orally in two or three divided doses and this dose can be increased rapidly to 800-1,200 mg/day in two or three divided doses" — adolescents therefore receive the adult regimen. UNDER 12 YEARS: "The safety and efficacy of Ketoconazole Esteve in children aged less than 12 years have not been established. Currently available data are described in sections 4.8, 5.1 and 5.2 but no recommendation on a posology can be made." Verify against a children's formulary and current prescribing references before use.