Amphotericin B

• Approved Indications:
• Treatment of systemic fungal infections including candidiasis, cryptococcosis (including cryptococcal meningitis), aspergillosis, mucormycosis, histoplasmosis, blastomycosis, coccidioidomycosis, and other serious fungal infections.
• Treatment of leishmaniasis (visceral and cutaneous forms).
• Empirical therapy in febrile neutropenic patients suspected of fungal infections.
• Off-label Uses:
• Fungal infections resistant to other antifungal agents.
• Intrathecal use for fungal meningitis (rare, under specialist supervision).

• Route: Intravenous infusion (slow). Liposomal and lipid formulations are preferred for reduced toxicity.
• Adults:
• Conventional Amphotericin B deoxycholate: 0.3–1.0 mg/kg/day IV infusion over 2–6 hours.
• Liposomal formulations: 3–5 mg/kg/day IV.
• Pediatrics:
• Similar dosing adjusted for weight and clinical response.
• Elderly:
• No specific dosage adjustment; monitor renal function closely.
• Renal/Hepatic Impairment:
• Use with caution; dosage adjustments not well defined; renal function monitoring essential.
• Duration: Depends on infection severity and clinical response; often several weeks to months.

Amphotericin B binds to ergosterol, a key sterol in fungal cell membranes, forming pores that increase membrane permeability. This disrupts membrane integrity causing leakage of intracellular ions and molecules, leading to fungal cell death. It exhibits broad-spectrum fungicidal activity.

• Absorption: Not absorbed orally; administered IV only.
• Distribution: Widely distributed in body tissues, especially liver, spleen, lungs, and kidneys; poor penetration into cerebrospinal fluid.
• Metabolism: Minimal hepatic metabolism.
• Half-life: Approximately 15 days due to slow tissue release.
• Elimination: Primarily via renal excretion of unchanged drug and metabolites.

• Pregnancy: FDA Category B; animal studies show no harm but controlled human studies are lacking; use only if clearly needed.
• Lactation: Excreted in breast milk in small amounts; caution advised due to potential toxicity.

• Polyene antifungal agent.

• Known hypersensitivity to Amphotericin B or formulation excipients.
• Caution in patients with pre-existing renal impairment.

• High risk of nephrotoxicity and electrolyte imbalances; monitor renal function and serum potassium/magnesium regularly.
• Infusion-related reactions (fever, chills, hypotension) common; premedication with antipyretics and antihistamines recommended.
• Risk of anemia due to bone marrow suppression.
• Use cautiously in patients with cardiac disease or electrolyte disturbances.
• Monitor liver enzymes during therapy.

• Common: Fever, chills, headache, nausea, vomiting, infusion site reactions.
• Renal: Nephrotoxicity, increased serum creatinine, hypokalemia, hypomagnesemia.
• Hematologic: Anemia, thrombocytopenia.
• Rare/Severe: Anaphylaxis, arrhythmias, hepatic dysfunction.

• Additive nephrotoxicity with other nephrotoxic drugs (e.g., aminoglycosides, cyclosporine).
• Increased risk of electrolyte disturbances with corticosteroids, diuretics.
• Avoid concurrent use with drugs prolonging QT interval.
• May increase toxicity of digoxin and other cardiac glycosides due to hypokalemia.

• Lipid-based formulations recommended over conventional deoxycholate formulation for reduced toxicity.
• Monitoring protocols for renal function and electrolytes emphasized in recent guidelines.
• No new major indications; focus on antifungal stewardship to prevent resistance and toxicity.

• Store at 2°C to 8°C (refrigerated).
• Protect from light; keep vial in carton until use.
• Do not freeze.
• Reconstituted solutions should be used promptly or stored as per manufacturer guidelines, typically not exceeding 24 hours refrigerated.