Amphotericin

# Amphotericin ## Overview - **Classification**: Antifungal (polyene macrolide) - **Mechanism**: Binds to ergosterol in fungal cell membranes, forming pores and increasing permeability, leading to fungal cell lysis and death. ## Primary Indications 1. **Severe Systemic Fungal Infections**: Life-threatening infections like cryptococcosis, aspergillosis, candidiasis (disseminated), mucormycosis, histoplasmosis, blastomycosis, coccidioidomycosis. 2. **Visceral Leishmaniasis**: Treatment of severe forms of leishmaniasis. 3. **Empiric Therapy**: For febrile neutropenic patients unresponsive to broad-spectrum antibiotics. ## Adult Dosing ### Standard Dosing **Severe Systemic Fungal Infections (Amphotericin B deoxycholate)** - **Test Dose**: **1 mg** in **20 mL D5W** infused over **20-30 min**. Monitor for acute reactions. - **Initial Dose**: **0.25-0.5 mg/kg IV** daily. - **Gradual Increase**: Increase incrementally to **0.5-1 mg/kg IV** daily. - **Maximum Dose**: Typically **1 mg/kg IV** daily; up to **1.5 mg/kg IV** daily for severe infections (e.g., mucormycosis). - **Frequency**: Once daily. - **Route**: Intravenous infusion over **2-6 hours**. - **Duration**: Highly variable, from weeks to months, based on infection type and patient response. **Visceral Leishmaniasis (Amphotericin B deoxycholate)** - **Dose**: **0.5 mg/kg IV** daily for **10 days**, then **0.5 mg/kg IV** every other day for **10 days**. - **Cumulative Dose**: Target **20-21 mg/kg**. ### Dose Adjustments - **Renal Impairment**: No specific dose reduction generally recommended. Monitor renal function (BUN, Cr) closely. If Cr significantly increases, consider reducing dose, changing to every other day, or switching to a lipid formulation. - **Hepatic Impairment**: No specific dose adjustments. Hepatic metabolism is minimal. - **Elderly Patients**: No specific dose adjustments based on age. Monitor renal function more closely due to potential age-related decline. ## Pediatric Dosing ### Neonates (0-28 days) - **Dose**: Start with test dose **0.1 mg/kg IV**. - **Therapeutic Dose**: **0.25-1 mg/kg IV** daily. - **Frequency**: Once daily. - **Maximum**: **1 mg/kg/day**. - **Special Notes**: Premedicate to reduce infusion-related reactions. Monitor renal function and electrolytes frequently. ### Infants (1-12 months) - **Dose**: Start with test dose **0.1 mg/kg IV**. - **Therapeutic Dose**: **0.25-1 mg/kg IV** daily. - **Frequency**: Once daily. - **Maximum**: **1.5 mg/kg/day** (for severe, life-threatening infections). ### Children (1-12 years) - **Dose**: Start with test dose **0.1 mg/kg IV**. - **Therapeutic Dose**: **0.25-1 mg/kg IV** daily. - **Frequency**: Once daily. - **Maximum**: **1.5 mg/kg/day** (for severe, life-threatening infections). ### Adolescents (13-18 years) - **Dose**: Generally follows **adult dosing guidelines**. - **Maximum**: **1.5 mg/kg/day**. ## Safety Information ### Contraindications - **Absolute**: Hypersensitivity to amphotericin B or any component. (Though may be used in life-threatening infections if no alternatives). ### Common Adverse Effects - **Very Common (>10%)**: Nephrotoxicity (increased BUN/Cr, hypokalemia, hypomagnesemia), infusion-related reactions (fever, chills, rigors, headache, nausea, vomiting, hypotension). - **Common (1-10%)**: Anemia (normochromic, normocytic), abnormal liver function tests, phlebitis/pain at injection site. - **Serious but Rare**: Acute liver failure, cardiac arrhythmias, seizures, blood dyscrasias, anaphylaxis. ### Key Drug Interactions - **Nephrotoxic Agents**: **Aminoglycosides, cyclosporine, NSAIDs, tacrolimus**: Significantly increased risk of severe nephrotoxicity. Avoid concurrent use if possible, or monitor renal function very aggressively. - **Corticosteroids/ACTH**: May enhance potassium depletion. Monitor electrolytes closely. - **Digoxin**: Amphotericin B-induced hypokalemia can potentiate digoxin toxicity. Monitor potassium and digoxin levels. - **Flucytosine**: Increased flucytosine toxicity (especially hematologic) due to enhanced cellular uptake. Monitor CBC. - **Antineoplastic Agents**: Increased risk of renal toxicity, bronchospasm, and hypotension. - **Azole Antifungals**: Potential for antagonism (e.g., with fluconazole). Clinical significance varies by fungus. ## Monitoring & Follow-up - **Before Treatment**: Baseline renal function (BUN, creatinine, GFR), electrolytes (K, Mg), CBC with differential, liver function tests (LFTs), urinalysis. - **During Treatment**: - Renal function (BUN, Cr, GFR): Daily initially, then 2-3 times/week. - Electrolytes (K, Mg): Daily initially, then 2-3 times/week. Replete aggressively. - CBC: Weekly. - LFTs: Weekly. - Vital signs: Every 15-30 minutes during initial infusions for acute reactions. - **Clinical Signs**: Monitor for signs of infusion reactions (fever, chills, hypotension), fluid overload, and electrolyte imbalances. ## Clinical Pearls - 💡 **Premedicate**: Administer **acetaminophen**, **diphenhydramine**, and often **hydrocortisone** (e.g., **25-50 mg IV**) 30-60 minutes prior to infusion to reduce infusion reactions. - 💡 **Hydrate**: Administer **1 liter 0.9% Normal Saline** IV before and/or after each dose to help mitigate nephrotoxicity. - 💡 **Electrolyte Repletion**: Aggressively replete potassium and magnesium due to significant renal wasting caused by amphotericin. - 💡 **Lipid Formulations**: For patients unable to tolerate conventional Amphotericin B due to toxicity, or when higher doses are needed, consider **Amphotericin B lipid complex (ABLC)** or **liposomal amphotericin B (L-AMB)**. These have different dosing and significantly reduced toxicity. - 💡 **Drug Stability**: Protect reconstituted solutions from light. > **⚠️ Important**: This information is for educational purposes only. Always consult current prescribing information, local guidelines, and clinical judgment before prescribing.