What is the proper administration protocol for amphotericin (antifungal medication) in a patient with a fungal infection and potential impaired renal function?

Amphotericin B Administration Protocol

Formulation Selection Based on Renal Function

For patients with normal renal function (CrCl >50 mL/min), use conventional amphotericin B deoxycholate at 0.7-1.0 mg/kg/day IV, while patients with impaired renal function or pre-existing renal disease should receive lipid formulations to minimize nephrotoxicity. 1

Conventional Amphotericin B Deoxycholate

• Dosing: 0.7-1.0 mg/kg/day IV for patients at low risk for nephrotoxicity 1
• Infusion duration: 2-6 hours to avoid hypotension, arrhythmias, and shock 2
• Maximum daily dose: Never exceed 1.5 mg/kg/day due to risk of fatal cardiac or cardiopulmonary arrest 2
• Concentration: Dilute to 0.1 mg/mL (1 mg/10 mL) in 5% dextrose with pH >4.2 2

Lipid Formulations (for renal impairment or intolerance)

• Liposomal amphotericin B (AmBisome): 3-5 mg/kg/day IV for standard infections; 5-10 mg/kg/day for mucormycosis 1, 3
• Amphotericin B lipid complex (ABLC/Abelcet): 5 mg/kg/day IV over 2 hours 1, 3
• Amphotericin B colloidal dispersion (ABCD): 3-6 mg/kg/day IV (note: more infusion reactions than other formulations) 1

The KDIGO guidelines specifically recommend lipid formulations over conventional amphotericin B when equal therapeutic efficacy can be assumed, to reduce nephrotoxicity risk. 1

Pre-Infusion Preparation and Premedication

Fluid Loading (Critical for Nephrotoxicity Prevention)

• Administer 1 L normal saline 30 minutes before amphotericin B infusion in patients who can tolerate fluids 4
• Sodium supplementation (via IV saline or sodium-containing antibiotics like ticarcillin disodium 5.2 mEq/g) reduces nephrotoxicity by interfering with physiologic feedback responses that worsen renal impairment 5
• Avoid dehydration throughout treatment course 5

Premedication for Infusion Reactions

• Diphenhydramine or acetaminophen should be given before infusion to reduce fever, chills, and allergic reactions 4, 1
• For lipid formulations, premedication with diphenhydramine specifically reduces acute reactions (chest pain, dyspnea, flushing) that occur in ~20% of patients 1

Test Dose Protocol

Administer a test dose of 1 mg in 20 mL of 5% dextrose over 20-30 minutes before initiating full therapy. 2

• Monitor temperature, pulse, respiration, and blood pressure every 30 minutes for 2-4 hours post-test dose 2
• If test dose is poorly tolerated or patient has impaired cardio-renal function, start with 5-10 mg daily doses 2

Dose Escalation Strategy

For Patients with Good Cardio-Renal Function

• Initial dose: 0.25 mg/kg/day (or 0.3 mg/kg/day for severe, rapidly progressive infections) 2
• Escalation: Increase by 5-10 mg per day to reach target of 0.5-0.7 mg/kg/day 2
• Maximum: Up to 1.0 mg/kg/day, or 1.5 mg/kg when given on alternate days 2

For Patients with Impaired Cardio-Renal Function

• Initial dose: 5-10 mg daily 2
• Escalation: Gradual increases of 5-10 mg per day based on tolerance 2

Resuming After Treatment Interruption

• If therapy is interrupted for >7 days, restart at lowest dosage (0.25 mg/kg) and re-escalate gradually 2

Monitoring Requirements

Renal Function (Most Critical)

• Monitor serum creatinine and creatinine clearance frequently throughout therapy 2, 1
• Dose adjustment or switch to lipid formulation indicated if creatinine rises to ≥2.5 mg/dL (adults) or ≥1.5 mg/dL (children) 1

Additional Laboratory Monitoring

• Serum electrolytes: Particularly potassium and magnesium (amphotericin B causes renal wasting) 2
• Liver function tests 2
• Complete blood count and hemoglobin 2
• Monitor regularly and use results to guide dosage adjustments 2

Critical Drug Interactions and Contraindications

Avoid Concurrent Use

• Leukocyte transfusions: Separate infusions as far as possible due to risk of acute pulmonary toxicity 2
• Nephrotoxic agents (aminoglycosides, cyclosporine, pentamidine): Use only with intensive renal monitoring if absolutely necessary 2

Use with Caution and Monitoring

• Corticosteroids/ACTH: Potentiate hypokalemia; monitor electrolytes and cardiac function closely 2
• Digitalis glycosides: Hypokalemia increases digitalis toxicity risk 2
• Skeletal muscle relaxants: Hypokalemia enhances curariform effects 2
• Flucytosine: May increase flucytosine toxicity; monitor levels (target 40-60 μg/mL) 1

Potentially Antagonistic

• Imidazole antifungals (ketoconazole, fluconazole, etc.): May induce fungal resistance to amphotericin B; use combination therapy with caution 2

Special Clinical Situations

Severe Pulmonary Involvement with Hypoxemia

• Consider adding methylprednisolone 0.5-1.0 mg/kg/day IV during first 1-2 weeks for patients with respiratory complications 1

Combination Therapy

• Flucytosine 100 mg/kg/day divided q6h may be added for CNS candidiasis or cryptococcal meningitis 1
• Adjust flucytosine dose to maintain levels 40-60 μg/mL, especially in renal impairment 1

Common Pitfalls to Avoid

• Rapid infusion: Associated with hypotension, hypokalemia, arrhythmias, and shock—always infuse over 2-6 hours 2
• Inadequate hydration: Failure to provide sodium loading significantly increases nephrotoxicity risk 5
• Ignoring electrolyte depletion: Hypokalemia and hypomagnesemia are common and can cause cardiac complications 2
• Using wrong dextrose pH: Ensure 5% dextrose has pH >4.2 before dilution 2
• Exceeding maximum dose: Never give >1.5 mg/kg/day due to fatal cardiac arrest risk 2