Amphotericin B

SCOPE: the source bundle is LIPOSOMAL amphotericin B only (UK SPC: Amphotericin B Gilead liposomal 50 mg, eMC product 1022; US cross-check: amphotericin B liposome for injection, Sun Pharmaceutical). It contains no dose for conventional amphotericin B deoxycholate, so none is given. UK SPC 4.2 warns: 'Different amphotericin products (sodium deoxycholate, liposomal, lipid complex) are not equivalent in terms of pharmacodynamics, pharmacokinetics and dosing and so the products should not be used interchangeably without accounting for these differences. Both the trade name, common name and dose should be verified pre-administration. There is a risk of under-dose if Amphotericin B Gilead liposomal is administered at a dose recommended for amphotericin B deoxycholate.' MYCOSES (UK SPC 4.2): 'Therapy is usually instituted at a daily dose of 3 to 5 mg/kg of body weight for a minimum of 14 days. Dosage of amphotericin B as Amphotericin B Gilead liposomal must be adjusted to the specific requirements of each patient.' MUCORMYCOSIS (UK SPC 4.2): 'For suspected or confirmed infection, the recommended starting dose is 5 to 10 mg/kg/day. In patients with brain involvement or solid-organ transplant, dose at 10 mg/kg/day. Avoid slow escalation of doses.' Courses of up to 6 - 8 weeks are commonly used and longer may be needed for deep seated infections. 'Although doses greater than 5 mg/kg and up to a maximum of 10 mg/kg have been used in clinical trials and clinical practice, data on the safety and efficacy of Amphotericin B Gilead liposomal for the treatment of mucormycosis at these higher doses are limited.' A benefit:risk assessment should be made at individual patient level. HIV ASSOCIATED CRYPTOCOCCAL MENINGITIS (UK SPC 4.2): 'Administer a single dose of 10 mg/kg Amphotericin B Gilead liposomal on day 1, in combination with daily flucytosine 100 mg/kg and daily fluconazole 1200 mg, both administered for 14 days. After the 2-week induction period, patients should receive fluconazole 800 mg daily for 8 weeks and then at a dose of 200 mg daily thereafter at the treating physician's discretion.' VISCERAL LEISHMANIASIS (UK SPC 4.2): 'A total dose of 21.0 - 30.0 mg/kg of body weight given over 10-21 days may be used in the treatment of visceral leishmaniasis.' FEBRILE NEUTROPENIA (UK SPC 4.2): treatment should be continued until the recorded temperature is normalised for 3 consecutive days and in any event discontinued after a maximum of 42 days. US LABEL initial doses (mg/kg/day, adult and paediatric patients): empirical therapy 3; systemic fungal infections (Aspergillus, Candida, Cryptococcus) 3 to 5; cryptococcal meningitis in HIV-infected patients 6; visceral leishmaniasis - immunocompetent 3 on days 1 to 5 and 3 on days 14 and 21, immunocompromised 4 on days 1 to 5 and 4 on days 10, 17, 24, 31 and 38 (US labelling - verify vs UK SPC). NO MAXIMUM: neither label prints a non-weight-based ceiling for the 3 to 5 mg/kg/day regimen, so maxDose is blank. ADMINISTRATION: UK SPC recommended concentration for intravenous infusion is 0.20 mg/ml to 2.00 mg/ml. US label: reconstitute each 50 mg vial with 12 mL Sterile Water for Injection to give 4 mg/mL, then dilute with 5% Dextrose Injection to a final concentration of 1 mg/mL to 2 mg/mL (lower concentrations, 0.2 mg/mL to 0.5 mg/mL, may be appropriate for infants and small children); do not reconstitute with saline or mix with other drugs; flush an existing line with 5% Dextrose or use a separate line; an in-line filter must have a mean pore diameter of not less than 1.0 micron. ELDERLY (UK SPC 4.2): 'No alteration in dose or frequency of dosing is required.' TRUNCATION: UK SPC 4.8 and the US drug-interaction and adverse-reaction sections were cut off at the source-fetch limit.

LIPOSOMAL PRODUCT ONLY - not interchangeable with conventional amphotericin B deoxycholate. UK SPC 4.2: 'Amphotericin B Gilead liposomal has been studied in paediatric patients aged one month to 18 years old. Doses used in these clinical studies were the same as those used in adults on a mg/kg body weight basis.' It 'is not recommended for use in children below 1 month old due to lack of data on safety and efficacy.' US label: 'Since pediatric patients have received amphotericin B liposome for injection at doses comparable to those used in adults on a per kilogram body weight basis, no dosage adjustment is required in this population'; its initial doses apply to adult and pediatric patients (empirical therapy 3 mg/kg/day; systemic fungal infections 3 to 5 mg/kg/day; cryptococcal meningitis in HIV-infected patients 6 mg/kg/day). No single per-kg multiplier is published for a weight calculator because the label dose is a range that varies by indication (a range cannot be used as a multiplier). Verify against a children's formulary before administration.