AMPHOTERICIN B
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AMPHOTERICIN B (AMPHOTERICIN B).
Binds to ergosterol in fungal cell membranes, forming pores that increase permeability and cause leakage of intracellular contents, leading to cell death.
| Metabolism | Primarily hepatic; exact enzymes not well characterized. |
| Excretion | Renal: ~2-5% unchanged; biliary/fecal: ~40% as metabolites; extensive tissue binding delays excretion. |
| Half-life | Terminal half-life: 24–48 hours initially, prolonged to 15 days with repeated dosing due to tissue redistribution. |
| Protein binding | 90–95% bound, primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 4–5 L/kg (extensive tissue binding, especially in liver, spleen, and lungs). |
| Bioavailability | IV: 100%; oral: <5%; topical: minimal systemic absorption. |
| Onset of Action | IV: 24–72 hours; topical: 3–5 days for fungal infections. |
| Duration of Action | IV: Up to 6 weeks post-therapy due to tissue retention; topical: apply 2–4 times daily for 1–4 weeks. |
| Molecular Weight | 924.09 |
0.5-1.5 mg/kg/day IV over 2-6 hours; for invasive aspergillosis, 1 mg/kg/day; for cryptococcal meningitis, 0.7 mg/kg/day IV in combination with flucytosine; liposomal formulation: 3-5 mg/kg/day IV. Maximum dose: 1.5 mg/kg/day for conventional amphotericin B deoxycholate.
| Dosage form | INJECTABLE |
| Renal impairment | Acute kidney injury: consider dose reduction or switch to liposomal formulation. No specific GFR-based dose adjustments for conventional formulation; monitor renal function and electrolytes. For liposomal amphotericin B, no dosage adjustment required for renal impairment. Continuous renal replacement therapy: conventional amphotericin not recommended due to nephrotoxicity; liposomal preferred. |
| Liver impairment | No specific Child-Pugh based dose adjustments. Use caution in hepatic impairment; monitor liver function tests. Dose adjustment not typically required. |
| Pediatric use | Conventional amphotericin B: 0.25-1.5 mg/kg/day IV; initial test dose 0.1 mg/kg. Liposomal amphotericin B: 3-5 mg/kg/day IV. For neonates: 1 mg/kg/day. Maximum daily dose: 1.5 mg/kg for conventional, 5 mg/kg for liposomal. |
| Geriatric use | Use with caution due to age-related renal function decline; monitor renal function and electrolyte levels carefully. Same dosing as adults; adjust for renal impairment if present. Lower doses may be considered based on clinical status. |
| 1st trimester | Avoid unless essential; associated with congenital anomalies in animal studies; human data limited. |
| 2nd trimester | Use if clearly needed; no known malformations but consider cumulative toxicity. |
| 3rd trimester | Use if clearly needed; risk of fetal nephrotoxicity and ototoxicity. |
Clinical note
Comprehensive clinical and safety monograph for AMPHOTERICIN B (AMPHOTERICIN B).
| Placental transfer | Crosses placenta; fetal serum levels approximately 30-50% of maternal levels. |
| Breastfeeding | Excreted in breast milk in low concentrations; consider risk of infant diarrhea and fungal microbiome disruption; use only if clearly needed. |
| Lactation Rating |
■ FDA Black Box Warning
Amphotericin B should be used primarily for progressive, potentially life-threatening fungal infections; it is not intended for non-invasive forms of fungal disease. It should be used under close medical supervision due to potential toxicity.
| Serious Effects |
Hypersensitivity to amphotericin B or any component of formulation
| Precautions | Monitor renal function, electrolytes, and liver function; risk of nephrotoxicity, hypokalemia, hypomagnesemia, and infusion-related reactions; caution in patients with renal impairment and those receiving other nephrotoxic drugs. |
| Food/Dietary | Avoid excessive salt intake; monitor for hypokalemia and hypomagnesemia. No specific food restrictions but maintain adequate hydration. |
Loading safety data…
| L3 (Moderately Safe) |
| Teratogenic Risk | FDA Pregnancy Category B. Animal studies show no evidence of fetal harm; no adequate human studies in first trimester. Use during pregnancy only if clearly needed. Limited data suggest no increased risk of major malformations across all trimesters. |
| Fetal Monitoring | Monitor renal function (BUN, serum creatinine), serum electrolytes (K+, Mg2+), liver function tests, CBC, and signs of infusion-related reactions. Fetal monitoring as clinically indicated. |
| Fertility Effects | No data on human fertility impairment. In animal studies, no effects on fertility observed. |
| Clinical Pearls | Premedicate with acetaminophen, diphenhydramine, and hydrocortisone to reduce infusion-related reactions. Monitor serum potassium and magnesium closely due to renal wasting. Use normal saline bolus before infusion to reduce nephrotoxicity. Lipid formulations allow higher doses with less nephrotoxicity. Amphotericin B deoxycholate is reserved for severe, refractory cases. |
| Patient Advice | You may experience fever, chills, and nausea during infusion; these are common and can be managed with premedications. · Report any signs of kidney problems such as decreased urine output, swelling in legs, or fatigue. · Avoid potassium and magnesium supplements unless prescribed, as levels may fluctuate. · This medication can cause low blood pressure during infusion; rise slowly from sitting or lying down. · Complete the full course even if you feel better to prevent the infection from returning. |