What is the recommended dose of micofungin (antifungal agent) for adult and pediatric patients with normal and impaired renal (kidney function) and hepatic (liver function) function?

Micafungin Dosing Recommendations

For adults with invasive candidiasis or candidemia, administer micafungin 100 mg IV once daily; for pediatric patients ≥4 months of age, use 2 mg/kg once daily (maximum 100 mg); and for neonates <4 months, use 4 mg/kg once daily—no dose adjustment is required for renal or hepatic impairment. 1

Adult Dosing by Indication

Invasive Candidiasis and Candidemia

• Standard dose: 100 mg IV once daily 2, 1, 3
• Higher dose option: 150 mg IV once daily may be used, though 100 mg has demonstrated comparable efficacy 3
• Treatment duration: Continue for at least 14 days after documented clearance of Candida from bloodstream AND resolution of symptoms 2, 4, 5

Esophageal Candidiasis

• Dose: 150 mg IV once daily 2
• Treatment duration: 14-21 days until clinical improvement 2

Prophylaxis in Hematopoietic Stem Cell Transplant (HSCT)

• Dose: 50 mg IV once daily (1 mg/kg for patients <50 kg) 2, 6
• Initiate after last dose of chemotherapy and continue until neutrophil recovery 2
• Micafungin demonstrated superior efficacy compared to fluconazole 400 mg daily in this setting 6

Invasive Aspergillosis

• Micafungin is not FDA-approved for aspergillosis, though 100-150 mg daily has been studied in salvage therapy 2
• Optimal dosing for aspergillosis remains undefined 2

Pediatric Dosing

Children ≥4 Months of Age

• Invasive candidiasis: 2 mg/kg IV once daily (maximum 100 mg) 2, 1
• Higher doses of 2-4 mg/kg may be used for severe infections 2
• Body weight ≤30 kg: 2 mg/kg produces mean AUC of 109 mcg·h/mL 1
• Body weight >30 kg: 2 mg/kg produces mean AUC of 134 mcg·h/mL 1

Neonates and Infants <4 Months of Age

• Dose: 4 mg/kg IV once daily 1
• This higher dose is necessary because weight-normalized clearance is substantially higher in this age group (40-80 mL/h/kg in premature neonates vs. 20 mL/h/kg in older children) 1, 7
• The 4 mg/kg dose produces mean AUC of 131 mcg·h/mL, comparable to 2 mg/kg in older children 1

HSCT Prophylaxis in Pediatric Patients

• Dose: 1 mg/kg IV once daily 2
• Administer from last chemotherapy dose until neutrophil recovery 2

Renal Impairment

No dose adjustment required for any degree of renal impairment, including severe renal dysfunction (CrCl <30 mL/min) or patients on hemodialysis. 1

• Micafungin is highly protein-bound (>99%) and not dialyzable 1
• Supplementary dosing after hemodialysis is not necessary 1
• Pharmacokinetic studies showed no significant changes in Cmax or AUC in patients with severe renal impairment 1

Hepatic Impairment

No dose adjustment required for moderate or severe hepatic impairment. 1

Moderate Hepatic Impairment (Child-Pugh 7-9)

• Micafungin Cmax and AUC are approximately 22% lower compared to normal hepatic function 1
• This reduction does not warrant dose adjustment 1

Severe Hepatic Impairment (Child-Pugh 10-12)

• Micafungin Cmax and AUC are approximately 30% lower compared to normal hepatic function 1
• M-5 metabolite levels are 2.3-fold higher, but total exposure remains comparable to patients with systemic Candida infection 1
• No dose adjustment necessary 1

Rationale

• Micafungin undergoes minimal hepatic metabolism via CYP450 enzymes; primary metabolism is through arylsulfatase and catechol-O-methyltransferase 1, 7
• Unlike caspofungin, which requires dose reduction in moderate-to-severe hepatic dysfunction, micafungin maintains adequate exposure 2

Pharmacokinetic Considerations

Linear Dose Proportionality

• Micafungin exhibits linear, dose-proportional pharmacokinetics across the 0.15-8 mg/kg dose range 1, 7
• Mean AUC after 100 mg dose in healthy adults: 133 mg·h/L 7

Special Populations with Altered Clearance

• Critically ill patients and burn patients: Clearance is significantly higher than in healthy volunteers, potentially requiring higher doses 7
• Hematology patients: Lower exposure compared to healthy volunteers 7
• These populations may benefit from therapeutic drug monitoring, though routine monitoring is not standard practice 7

Species-Specific Efficacy

Candida glabrata and Candida krusei

• Micafungin 100 mg daily achieves clinical cure rates of 73.5% in infections due to these azole-resistant species 8
• No difference in outcomes between 100 mg and 150 mg doses 8
• Echinocandins (including micafungin) are strongly preferred for C. glabrata infections 4

Candida parapsilosis

• Micafungin has higher MICs against C. parapsilosis compared to other Candida species 2
• Despite this, clinical trials have not demonstrated reduced efficacy 2, 3
• Fluconazole may be preferred if susceptibility is confirmed, though continuing micafungin is reasonable if the patient is clinically stable 4

Common Pitfalls to Avoid

• Do not reduce dose in renal failure: Unlike many antimicrobials, micafungin requires no adjustment for renal impairment 1
• Do not reduce dose in hepatic impairment: Micafungin exposure actually decreases (not increases) in hepatic dysfunction, so dose reduction is inappropriate 1
• Do not underdose neonates: The 4 mg/kg dose in infants <4 months is necessary due to higher clearance 1, 7
• Do not prematurely discontinue therapy: Continue for at least 14 days after blood culture clearance and symptom resolution 2, 4, 5
• Do not assume higher doses are always better: The 100 mg dose is as effective as 150 mg for most indications 3, 8