What is the proper administration protocol for liposomal amphotericin B in a patient with a severe fungal infection and potentially impaired renal function?

Administration of Liposomal Amphotericin B

For severe fungal infections with potential renal impairment, administer liposomal amphotericin B at 3-5 mg/kg/day intravenously over 2-6 hours, with premedication using diphenhydramine or acetaminophen and 1 liter of normal saline before and after infusion to minimize nephrotoxicity. 1, 2

Dosing by Clinical Scenario

Standard Severe Fungal Infections (Without CNS Involvement)

• Administer 3-5 mg/kg/day intravenously for 1-2 weeks, followed by oral azole therapy 3, 1
• For moderately severe to severe acute pulmonary histoplasmosis: 3-5 mg/kg daily IV for 1-2 weeks, then transition to itraconazole 3
• For progressive disseminated histoplasmosis: 3 mg/kg daily for 1-2 weeks, followed by itraconazole for at least 12 months 3

CNS Involvement or Severe Infections

• Increase dose to 10 mg/kg/day intravenously for infections with CNS involvement 1
• For cryptococcal meningitis: 4-6 mg/kg daily 2
• Continue for 4-6 weeks during induction and consolidation phases 1

Fungal Endocarditis

• Use liposomal amphotericin B as an alternative for patients with moderate to severe renal impairment or unacceptable infusion-related toxicities 3
• Surgery in conjunction with antifungal agents is required for most patients 3

Infusion Protocol

Preparation and Administration

• Infuse over 2-6 hours depending on dose 4
• The recommended concentration is 0.1 mg/mL (1 mg/10 mL) 4
• Use a dedicated IV line to allow precise control of infusion rate without interference from other medications 2
• Avoid rapid infusion, which has been associated with hypotension, hypokalemia, arrhythmias, and shock 4

Premedication Strategy

• Administer diphenhydramine or acetaminophen 30 minutes before infusion to reduce infusion-related reactions (fever, chills, nausea, vomiting) 1, 2, 5
• Infuse 1 liter of normal saline before and after liposomal amphotericin B in patients who can tolerate fluids to reduce nephrotoxicity 1, 2
• Reserve glucocorticosteroids (such as hydrocortisone) only for severe infusion-related reactions that occur despite standard premedication 2
• If glucocorticosteroids are needed, administer approximately 30 minutes before the infusion 2

Monitoring During Infusion

• Monitor for infusion-related reactions including chest pain, dyspnea, hypoxia, severe abdominal/flank/leg pain, flushing, and urticaria 2
• Temporarily interrupt the infusion and administer intravenous diphenhydramine if reactions occur 2

Renal Function Considerations

Patients with Impaired Renal Function

• Liposomal amphotericin B is strongly preferred over conventional amphotericin B deoxycholate in patients with pre-existing renal dysfunction 5, 3
• No dosage adjustment is required based on renal impairment 6
• Liposomal amphotericin B has significantly less nephrotoxicity compared to conventional amphotericin B 2, 6

Nephrotoxicity Monitoring

• Monitor renal function, serum creatinine, and electrolytes (especially potassium and magnesium) frequently during therapy 5, 4
• Most nephrotoxicity occurs within the first 9 days of treatment 7
• In critically ill patients, the development of acute kidney injury is multifactorial and liposomal amphotericin B administration appears safe 8
• Mean serum creatinine typically increases modestly from 0.9 mg/dL to 1.1 mg/dL during treatment 9

Duration of Therapy

Initial Treatment Phase

• Continue for 1-2 weeks until clinical stabilization 3, 1
• For candidemia: treat for 14 days after the last positive blood culture and resolution of signs and symptoms 5

Maintenance Therapy

• After initial response, transition to oral azole therapy (posaconazole or isavuconazole) 1
• Continue maintenance therapy for 3-6 months until resolution of clinical signs and symptoms 1
• For cryptococcal meningitis: at least 2 weeks of amphotericin B followed by fluconazole 5

Special Populations and Situations

Transplant Recipients

• For solid organ or hematopoietic stem cell transplant recipients with clinically stable acute or chronic pulmonary coccidioidomycosis: initiate fluconazole 400 mg daily 3
• For very severe and/or rapidly progressing infections: use amphotericin B until stabilized, then switch to fluconazole 3
• Consider reducing immunosuppression in transplant recipients with severe or rapidly progressing infections 3

Alternative Routes

• For lung transplant prophylaxis: nebulized liposomal amphotericin B 25 mg three times weekly 3, 1
• For endophthalmitis: intravitreal liposomal amphotericin B injection may be considered in addition to systemic therapy 1

Common Pitfalls to Avoid

• Never exceed 1.5 mg/kg/day of conventional amphotericin B deoxycholate as overdoses can result in potentially fatal cardiac or cardiopulmonary arrest 4
• Do not use conventional amphotericin B deoxycholate when liposomal formulations are available, especially in patients with renal impairment 5
• Do not administer liposomal amphotericin B during or shortly after leukocyte transfusions due to risk of acute pulmonary reactions; separate these infusions as far as possible 4
• If therapy is interrupted for more than 7 days, resume with the lowest dosage level (0.25 mg/kg) and increase gradually 4
• Monitor liver function tests regularly as liver enzyme abnormalities can occur 6