Micagin

Approved Indications (FDA/EMA):

• Candidemia and Other Invasive Candidiasis
• Treatment of candidemia (Candida bloodstream infections)
• Acute disseminated candidiasis
• Candida abscesses, peritonitis, and other deep-tissue Candida infections in adults and children, including neonates
• Esophageal Candidiasis
• Approved for treatment in patients ≥16 years
• Effective in azole-resistant or refractory cases
• Prophylaxis of Candida Infections
• In patients undergoing hematopoietic stem cell transplantation (HSCT) expected to develop neutropenia
• Approved for both adult and pediatric patients (≥4 months)

Off-label and Clinically Accepted Uses:

• Empiric antifungal therapy in febrile neutropenic patients
• Prophylaxis or treatment of invasive Candida infections in preterm neonates or critically ill ICU patients
• Fungal infections involving CNS or intra-abdominal compartments
• Oropharyngeal candidiasis in immunocompromised patients

Route: Intravenous infusion only; administer over 1 hour.
Preparation: Reconstitute and dilute using sterile technique. Do not shake.

Adults

• Invasive Candidiasis (Candidemia, Abscesses, Peritonitis):
  • 100 mg IV once daily
  • May increase to 150 mg/day in severe infections
• Esophageal Candidiasis:
  • 150 mg IV once daily
  • Duration: At least 14 days, including 7 days after symptom resolution
• Prophylaxis in HSCT Recipients:
  • 50 mg IV once daily

Pediatric Patients (≥4 months to <16 years)

• Invasive Candidiasis:
  • 2–4 mg/kg IV once daily (maximum 100 mg/day)
• Esophageal Candidiasis:
  • 3 mg/kg IV once daily (maximum 150 mg/day)
• Prophylaxis:
  • 1 mg/kg IV once daily (maximum 50 mg/day)

Neonates and Infants (<4 months) (Off-label use)

• Invasive Candidiasis (including CNS infections):
  • 4–10 mg/kg IV once daily
  • Higher doses used for severe or CNS involvement

Renal Impairment:

• No dose adjustment necessary

Hepatic Impairment:

• No adjustment required, but use with caution in moderate to severe hepatic dysfunction; monitor liver function closely

Micafungin Sodium is an antifungal agent in the echinocandin class. It exerts its effect by inhibiting the synthesis of (1,3)-β-D-glucan, an essential component of the fungal cell wall. This inhibition disrupts cell wall integrity, resulting in osmotic instability, cellular lysis, and fungal cell death. Micafungin demonstrates fungicidal activity against Candida species and fungistatic activity against Aspergillus species, although it is not indicated for invasive aspergillosis.

• Absorption: Not orally absorbed; administered intravenously
• Distribution:
  • Volume of distribution: 0.2–0.3 L/kg
  • Highly protein-bound (~99.8%)
• Metabolism:
  • Metabolized via non-CYP hepatic enzymes (arylsulfatase, catechol-O-methyltransferase)
  • Does not induce or inhibit CYP450 isoenzymes
• Elimination:
  • ~90% excreted via feces (mostly as metabolites)
  • ~10% via urine
• Half-life: 10–17 hours (dose-dependent)
• Time to Steady-State: 4–5 days with once-daily dosing

• Pregnancy:
  • FDA Pregnancy Category C
  • Animal studies show fetal toxicity at high doses; no adequate human studies
  • Use only if the potential benefit justifies the risk
• Lactation:
  • Unknown whether excreted in human milk
  • Due to possible serious adverse reactions in nursing infants, a risk-benefit assessment is essential
  • Consider discontinuation of drug or breastfeeding

• Primary Class: Antifungal Agent
• Subclass: Echinocandin

• Known hypersensitivity to micafungin or other echinocandins
• Hypersensitivity to any excipients in the formulation

• Hepatic Effects:
  • Elevations in ALT, AST, bilirubin possible
  • Hepatic failure has been reported; monitor liver enzymes regularly
• Hypersensitivity Reactions:
  • Anaphylaxis, rash, facial swelling, pruritus, bronchospasm
  • Discontinue immediately if signs occur
• Hematologic Effects:
  • Neutropenia, thrombocytopenia, anemia
  • Monitor complete blood count with prolonged therapy
• Use in Pediatrics and Neonates:
  • Safety in neonates is off-label but supported by clinical use
  • Liver function should be closely monitored
• Superinfections:
  • May promote non-susceptible fungal or bacterial overgrowth

Common (≥1%)

• Gastrointestinal: Nausea, vomiting, diarrhea
• Liver: Elevated transaminases, bilirubin
• Hematologic: Neutropenia, anemia, thrombocytopenia
• Infusion-related: Fever, headache, phlebitis

Serious

• Hepatic failure
• Anaphylaxis
• Acute renal failure (rare)
• Hemolysis
• Seizures (very rare)

Timing and Severity

• Most adverse effects are mild to moderate and appear early in therapy
• Infusion-related reactions may be mitigated by slower administration

• Cyclosporine: May increase hepatic enzyme levels; monitor LFTs
• Sirolimus, Nifedipine: Levels may increase due to weak CYP3A4 inhibition
• Tacrolimus: No clinically significant effect
• Other Antifungals: No major interaction with amphotericin B or fluconazole

CYP450 Involvement:

• Micafungin is not a significant inducer, inhibitor, or substrate of CYP450 enzymes
• Low potential for drug-drug interactions

Food/Alcohol: Not applicable (parenteral use only)

• IDSA Guidelines:
  • Endorse micafungin as first-line therapy for candidemia and empiric use in febrile neutropenia
• WHO & EMA:
  • Support use in pediatrics and prophylaxis in HSCT
• FDA Safety Notices:
  • Reinforced hepatic monitoring recommendations, especially with prolonged use

• Unopened Vials:
  • Store at 20°C to 25°C (68°F to 77°F)
  • Protect from light; retain in original carton until use
• After Reconstitution and Dilution:
  • Stable for up to 24 hours at 2°C to 8°C (36°F to 46°F)
  • Do not freeze
  • Use within recommended time; discard any unused portion
• Handling:
  • Reconstitute only with sterile water
  • Dilute with 0.9% sodium chloride or 5% dextrose
  • Use aseptic preparation technique