Amphotericin B: Indications, Dosing, and Complications
Amphotericin B should be used primarily for treatment of progressive and potentially life-threatening fungal infections, with conventional amphotericin B administered at 0.5-1.5 mg/kg daily intravenously or lipid formulations at 3-5 mg/kg daily depending on the specific infection and patient factors. 1, 2
Indications
- Indicated for treatment of progressive and potentially life-threatening fungal infections; should not be used for noninvasive fungal diseases such as oral thrush, vaginal candidiasis, or esophageal candidiasis in patients with normal neutrophil counts 2
- Primary indications include:
Formulations and Dosing
Conventional Amphotericin B (Deoxycholate)
- Standard dosage: 0.5-1.5 mg/kg administered once daily intravenously over 1-2 hours 1, 3
- For severe or life-threatening infections: 0.7-1.0 mg/kg daily 1
- For neonates with disseminated candidiasis: 1 mg/kg daily 1, 3
- Maximum daily dose should never exceed 1.5 mg/kg due to risk of potentially fatal cardiac or cardiopulmonary arrest 2
- Recommended concentration for IV infusion: 0.1 mg/mL 1, 2
- Initial test dose recommended: 1 mg in 20 mL of 5% dextrose solution administered over 20-30 minutes 2
Lipid Formulations of Amphotericin B
- Three main lipid formulations available with different properties:
- Lipid formulations are preferred in patients with renal impairment or those who experience toxicity with conventional amphotericin B 5, 6
- Liposomal amphotericin B provides the greatest renal protection among lipid formulations 5, 6
Duration of Therapy
- For candidemia: Continue treatment for 14 days after the last positive blood culture and resolution of signs and symptoms 1, 3
- For sporotrichosis: At least 12 months of therapy 1
- For disseminated candidiasis: Treatment until all signs and symptoms of infection have resolved 1
- For cryptococcal meningitis: At least 2 weeks followed by fluconazole 3
- For rhinocerebral phycomycosis: Cumulative dose of at least 3g recommended 2
Complications and Adverse Effects
Nephrotoxicity
- Primary toxicity is nephrotoxicity, defined by substantial azotemia from glomerular damage 1
- Often accompanied by hypokalemia from tubular damage 1
- Exacerbated by concomitant use of other nephrotoxic drugs 1
- Permanent nephrotoxicity related to cumulative dose 1
- Can be ameliorated by hydration with 0.9% saline IV 30 minutes before infusion 1, 3
- Lipid formulations have significantly less nephrotoxicity compared to conventional amphotericin B 5, 6, 4
Infusion-Related Reactions
- Fever, chills, nausea, and vomiting commonly occur during infusion 1
- Typically begin within 1-3 hours after infusion starts and last <1 hour 1
- Less frequent in children than adults 1
- Tend to decrease in frequency over time 1
- Can be alleviated by pretreatment with acetaminophen or diphenhydramine 1, 3
- Significantly fewer infusion-related reactions with lipid formulations, particularly liposomal amphotericin B 6, 4
Other Adverse Effects
- Idiosyncratic reactions: hypotension, arrhythmias, allergic reactions including anaphylaxis 1
- Hepatic toxicity 1
- Thrombophlebitis 1
- Anemia 1
- Neurotoxicity (rare): confusion, delirium, hearing loss, blurred vision, seizures 1
- Overdose can result in potentially fatal cardiac or cardiopulmonary arrest 2
Special Populations
Pediatric Patients
- For children: 0.5-1.5 mg/kg daily IV or 50 mg/m²/day 1, 3
- For neonates with disseminated candidiasis: 1 mg/kg daily IV 1
- In patients with azotemia, hyperkalemia, or receiving high doses (>1 mg/kg), a longer infusion time of 3-6 hours is recommended 1
Pregnant Women
- Amphotericin B is the preferred antifungal for severe fungal infections during pregnancy 1
- Lipid formulations at 3-5 mg/kg daily are recommended 1
- Azoles should be avoided during pregnancy 1
Monitoring
- Monitor renal function, electrolytes, and liver function tests regularly 3
- For patients with persistent candidemia despite appropriate therapy, investigate for deep tissue focus of infection 1
- In neonates with candidemia, perform lumbar puncture, dilated retinal examination, and imaging of genitourinary tract, liver, and spleen 1
Important Considerations
- Central venous catheters should be removed when feasible in patients with fungemia 1
- For patients with mild-to-moderate disease, consider initiating at lower doses (0.25-0.5 mg/kg) and increasing as tolerated 1
- For life-threatening disease, target daily dose should be administered from the beginning 1
- Following stabilization and resolution of fever, amphotericin B can be administered as 1.5 mg/kg IV once every other day 1
- Combination therapy with flucytosine (100-150 mg/kg/day divided into 4 doses) may be considered for severe invasive candidiasis, particularly in CNS disease 1