Amphotericin B

Indications

Amphotericin B is used for: Endocarditis, Systemic fungal infections, Visceral leishmaniasis, Primary amoebic meningoencephalitis, Thrush, Cryptococcal meningitis, Candidiasis, Aspergillosis, Candidal cystitis

Adult Dose

Adult: Dosing regimens are applicable to amphotericin B (conventional). PO Oral candidiasis Per loz contains amphotericin B 10 mg: Suck 1 loz 4 times/day, up to 8 loz/day if needed. IV Systemic Fungal Infections Test dose: 1 mg IV x1 infused over 20-30 min Load: 0.25-0.5 mg/kg IV infused over 2-6 hr Maintenance: 0.25-1 mg/kg IV qDay OR up to 1.5 mg/kg IV qOD (may increase gradually by 0.25 mg-increments/day)

Child Dose

Systemic Fungal Infections Test dose: 0.1 mg/kg IV, not to exceed 1 mg; administer over 20-60 min Initial dose: 0.25 mg/kg/dose IV qDay/qOD Maintenance: Increase by 0.25 mg/day increments as tolerated to 1-1.5 mg/kg/day

Renal Dose

Renal Impairment CrCl <10 mL/min: 0.5-0.7 mg/kg IV q24-48hr Consider other antifungal agents that may be less nephrotoxic Intermittent hemodialysis: 0.5-1 mg/kg IV q24hr after dialysis session Continuous renal replacement therapy: 0.5-1 mg/kg IV q24hr

Administration

IV Administration Use promptly after dilution. Infuse over 2-6 hr Reconstitution: For conventional amphotericin B: Reconstitute with sterile water for inj (without preservatives), then further dilute with glucose inj 5% (with a pH>4.2) to a final concentration not exceeding 0.1 mg/ml for peripheral infusion or 0.25 mg/ml for central infusion.

Contra Indications

Hypersensitivity; lactation; do not give to patients receiving antineoplastics.

Precautions

Renal and hepatic impairment; pregnancy; monitor renal and liver function changes. Lactation: Excretion in milk is unknown; due to the potential for serious adverse reactions in breast-fed infants, a decision should be made whether to discontinue nursing or whether to discontinue the drug, taking into account the importance of the drug to the mother

Pregnancy-Lactation

Pregnancy Category: B Lactation: Excretion in milk is unknown; due to the potential for serious adverse reactions in breast-fed infants, a decision should be made whether to discontinue nursing or whether to discontinue the drug, taking into account the importance of the drug to the mother

Interactions

Increased toxicity with flucytosine. Drug induced renal toxicity enhanced in presence of other nephrotoxic medications. Antagonises effects of azole antifungals. Potentially Fatal: Potentiates K loss by corticosteroids. Avoid diuretics. Enhances digitalis toxicity and neuromuscular blocker effects.

Adverse Effects

Side effects of Amphotericin B : >10% Anorexia, Chills, Diarrhea, Fever, Headache, Hypokalemia, Hypomagnesemia, Hypotension, Malaise, Nausea, Pain (generalized), Pain at injection site, Renal function abnormalities, Tachypnea, Vomiting 1-10% Arachnoiditis, Delerium, Flushing, Hypertension, Leukocytosis, Lumbar nerve pain, Paresthesia, Urinary retention <1% Agranulocytosis, Anuria, Bone marrow suppression, Cardiac arrest, Coagulation defects, Convulsions, Dyspnea, Hearing loss, Leukopenia, Maculopapular rash, Renal failure, Thrombocytopenia, Vision changes Potentially Fatal: Anaphylactic reaction; leucoencephalopathy. Overdosage can result in cardio-respiratory arrest.

Mechanism of Action

Amphotericin B is a polyene antifungal antibiotic which alters cell membrane permeability by binding to ergosterol, thus causing leakage of cell components and subsequent cell death. It is active against Absidia spp, Aspergillus spp, Basidiobolus spp, B. dermatitidis, Candida spp, C. immitis, Conidobolus spp, C. neoformans, H. capsulatum, Mucor spp, P. brasiliensis, Rhizopus spp, Rodotorula spp. and S. schenckii.