Antifungal agent
Fungi: Candida albicans, C. tropicalis, C. parapsilosis, C. krusei, C. guilliermondii, Cryptococcus neoformans, Aspergillus fumigatus, A. flavus, A.niger, Absidia corymbifera, Rhizopus oryzae, R. rhizopodiformis, Blastomyces dermatitidis, Coccidioides immitis, Histoplasma capsulatum, Paracoccidioides brasiliensis, Sporothrix schencki, Malasezzia furfur
Induces membrane permeability by forming complexes with ergosterol located in fungal membranes, leading to intracellular leakage and cell death.
Peak serum level in relation to MIC is the pharmacodynamic parameter of best predictive outcome, while the AUC:MIC ratio and T > MIC are only slightly less predictive.
Absorption: generally classified as a non-absorbable drug, however, oral administration may result in low but detectable blood concentrations
Distribution: minimal amounts enter the aqueous humor, bile, CSF (inflamed or noninflamed meninges), amniotic fluid, pericardial fluid, pleural fluid, and synovial fluid
Metabolism: elimination half life is approximately 24 hours; only 3% of the toal administered dose of amphotericin B is excreted as unchanged drug
Elimination: urine; ~ 40% eliminated over 7 day period
Plasma protein binding: ~90 to 95%
Volume of distribution: 4 L/kg
CNS – headache, chills, fever
Renal – nephrotoxicity
Gastrointestinal – dyspepsia, epigastric pain, anorexia, cramping, weight loss
Cardiovascular – hypotension
Respiratory – tachypnea
Hematologic – normochromic normocytic anemia
Other – muscle and joint pain, anaphylaxis (rare), hypomagnesemia, hypokalemia
Renal Failure: In case of deterioration of renal function (defined as a doubling of serum creatinine from baseline), a brief cessation of drug administration for one or several days has been advocated.
Hepatic failures: No dosage adjustment required.
Abbreviations:
CVVH (Continuous venovenous hemofiltration)
CVVHD (Continuous venovenous hemodialysis)
CVVHDF (Continuous venovenous hemodiafiltration)
Amphotericin B deoxycholate:
CVVH: 0.4-1mg/kg q24h
CVVHD or CVVHDF: 0.4-1mg/kg q24h
Amphotericin B lipid complex
CVVH: 3-5mg/kg q24h
CVVHD or CVVHDF: 3-5mg/kg q24h
Amphtericin B liposomal
CVVH: 3-5mg/kg q24h
CVVHD or CVVHDF: 3-5mg/kg q24h
Note: CVVH is mainly for fluid removal alone. Many institutions will employ more CVVHD or CVVHDF which combine dialysis with fluid removal.
Contraindications: Hypersensitivity to amphotericin B
Precautions: Anaphylaxis has been reported. During initial dosing, the drug should be administered under close observation.
Aminoglycosides, cyclosporine, antineoplastic agents (cisplatin, nitrogen mustard compounds) – nephrotoxic effects
Skeletal muscle relaxants and digitalis glycosides – hypokalemia may be exaggerated
Flucytosine – amphotericin B may increase the toxicity of flucytosine
Category B: No evidence of risk in humans but studies inadequate.
Renal function (monitor Scr), Electrolyes (especially potassium and magnesium)