What is the dosage and treatment protocol for Amphotericin B (antifungal medication) calcium for severe fungal infections?

Amphotericin B Dosing and Treatment Protocol for Severe Fungal Infections

For severe fungal infections, conventional amphotericin B deoxycholate should be dosed at 0.5-1.0 mg/kg/day IV, with lipid formulations (liposomal amphotericin B 3-5 mg/kg/day, ABLC 5 mg/kg/day, or ABCD 3-6 mg/kg/day) preferred when nephrotoxicity is a concern or in patients with renal impairment. 1, 2, 3

Conventional Amphotericin B Deoxycholate Dosing

Initial Dosing Strategy

• Test dose: Administer 1 mg in 20 mL of 5% dextrose over 20-30 minutes, monitoring vital signs every 30 minutes for 2-4 hours 3
• Starting dose for stable patients: 0.25 mg/kg/day for those with good cardio-renal function and well-tolerated test dose 3
• Starting dose for severe/rapidly progressive infections: 0.3 mg/kg/day 3
• Starting dose for impaired cardio-renal function: 5-10 mg/day, gradually increasing by 5-10 mg increments 3

Target Maintenance Dosing

• Standard severe infections: 0.5-0.7 mg/kg/day 1, 2
• Life-threatening or less susceptible organisms: Up to 1.0 mg/kg/day 2, 3
• Maximum dose: Never exceed 1.5 mg/kg/day due to risk of potentially fatal cardiac or cardiopulmonary arrest 3

Administration Protocol

• Infuse over 2-6 hours at a concentration of 0.1 mg/mL (1 mg/10 mL) 3
• Administer 1 L of 0.9% normal saline 30 minutes before infusion to reduce nephrotoxicity 2, 4
• Pre-medicate with diphenhydramine or acetaminophen to minimize infusion-related reactions 4

Lipid Formulations of Amphotericin B

Lipid formulations provide equivalent efficacy with significantly reduced nephrotoxicity compared to conventional amphotericin B, making them the preferred choice for patients with renal impairment or those requiring prolonged therapy. 1, 2, 5

Liposomal Amphotericin B (L-AmB/AmBisome)

• Standard dosing: 3-5 mg/kg/day IV 1, 2
• CNS involvement: 10 mg/kg/day IV 6
• Cryptococcal meningitis: 4-6 mg/kg/day 4
• This formulation provides the greatest renal protection among all amphotericin B preparations 2, 4

Amphotericin B Lipid Complex (ABLC)

• Standard dosing: 5 mg/kg/day IV 1, 2
• Equivalent efficacy to conventional amphotericin B with improved tolerability 1, 5

Amphotericin B Colloidal Dispersion (ABCD)

• Standard dosing: 3-6 mg/kg/day IV 1, 2
• Note: More frequent infusion-related reactions compared to other lipid formulations, though less nephrotoxic than conventional formulation 5

Disease-Specific Dosing

Candidemia and Invasive Candidiasis

• Conventional amphotericin B: 0.5-0.6 mg/kg/day 1
• Alternative: 0.6-1.0 mg/kg/day for more severe infections 1
• Duration: Continue for 14 days after last positive blood culture and resolution of symptoms 2
• Combination therapy option: Fluconazole 800 mg/day plus amphotericin B deoxycholate 0.7 mg/kg/day for first 5-6 days only 1

Disseminated Candidiasis

• Neonates: 1 mg/kg/day of conventional amphotericin B 6
• Duration: 3-6 months until resolution or calcification of radiologic lesions 2

Aspergillosis

• Total cumulative dose: Up to 3.6 g over treatment course up to 11 months 3
• Lipid formulations: 3-5 mg/kg/day preferred for improved tolerability 1

Rhinocerebral Mucormycosis

• Minimum cumulative dose: 3 g recommended for deep tissue invasion 3
• Liposomal amphotericin B: 5-10 mg/kg/day for severe cases with CNS involvement 6
• Critical: Aggressive dosing required due to rapidly fatal course; must correct underlying diabetic ketoacidosis concurrently 3
• Duration: Continue for 4-6 weeks during induction and consolidation phases 6

Sporotrichosis

• Total cumulative dose: Up to 2.5 g over treatment course up to 9 months 3

Pediatric Dosing

• Conventional amphotericin B: 0.5-1.5 mg/kg/day IV 2
• Neonates: 0.6-1.0 mg/kg/day (similar to adult dosing) 1, 2
• Liposomal amphotericin B for cryptococcal meningitis: 2 mg/kg/day, up to 7.5 mg/kg/day for refractory cases 4
• Pharmacokinetics in neonates and children are similar to adults 1

Monitoring Requirements

Essential Laboratory Monitoring

• Renal function: Monitor serum creatinine regularly; expect mean increase from 0.9 to 1.1 mg/dL during treatment 2, 7
• Electrolytes: Check potassium and magnesium levels frequently (hypokalemia occurs in 6.2% of patients) 7
• Liver function tests: Monitor regularly (hepatotoxicity occurs in 5.2% of patients) 7

Clinical Monitoring

• Vital signs: Monitor every 30 minutes for 2-4 hours after test dose 3
• Infusion reactions: Watch for fever, chills, chest pain, dyspnea, hypoxia, severe abdominal/flank/leg pain, flushing, and urticaria 4
• Management of reactions: Temporarily interrupt infusion and administer IV diphenhydramine 4

Critical Safety Considerations

Absolute Contraindications and Warnings

• Never exceed 1.5 mg/kg/day - doses above this can result in potentially fatal cardiac or cardiopulmonary arrest 3
• Verify product name and dosage pre-administration, especially if dose exceeds 1.5 mg/kg 3
• Reserved for progressive and potentially life-threatening fungal infections only; should not be used for noninvasive disease like oral thrush or esophageal candidiasis in immunocompetent patients 3

Common Pitfalls to Avoid

• Persistent candidemia: If bloodstream remains positive despite appropriate therapy, investigate for deep tissue focus of infection (endocarditis, endophthalmitis, abscess) 2, 4
• Catheter management: Remove central venous catheters in candidemia when feasible 1
• pH of diluent: Ensure 5% dextrose injection has pH above 4.2; if below 4.2, buffer with sodium bicarbonate 3
• Infusion rate: Never administer as rapid infusion; maintain 2-6 hour infusion time 3

Alternative Dosing Strategy

Low-dose liposomal amphotericin B (1 mg/kg/day) may be equally effective as standard doses (3-5 mg/kg/day) for many indications with comparable clinical outcomes and reduced cost, though this approach requires further validation in guidelines. 8

• Research suggests 1 mg/kg/day liposomal amphotericin B achieved 47% clinical improvement rate, identical to 3 mg/kg/day dosing 8
• Survival to discharge was 68% vs 76% for low-dose vs standard-dose respectively 8
• Nephrotoxicity and hypokalemia rates were comparable between dosing strategies 8