Pharm

Isavuconazole

search

Isavuconazole, Isavuconazonium, Cresemba

  • See also
  1. Antifungal Medication
  2. Topical Antifungal
  3. Fluconazole
  4. Itraconazole
  5. Posaconazole
  6. Voriconazole
  • Indications
  1. Conditions
    1. Invasive Aspergillosis
    2. Invasive Mucormycosis
  2. Activity (broader spectrum Antifungal)
    1. Aspergillus species
    2. Candida species
    3. Dimorphic Fungi (e.g. Coccidioides, Blastomyces, Histoplasma)
    4. Fusarium species
    5. Mucorales or Zygomycetes (e.g. Mucor species, Rhizopus species)
    6. Secedosporium species
    7. Trichosporon species
  • Contraindications
  1. See Drug Interactions below
  2. Congenital Short QT Syndrome
  3. Children
  • Mechanism
  1. Azole Antifungal
    1. Second generation triazole
  2. Inhibits fungal CYP450 enzymes
  3. Inhibits fungal sterol demethylation (selectively at 14-alpha demethylase)
    1. Blocks the synthesis of plasma membrane steroids (conversion from lanosterol to ergosterol)
    2. Results in plasma membrane damage
  • Medications
  1. Oral Isavuconazonium Capsules: 186 mg
    1. Each 186 mg Isavuconazonium capsule of prodrug is equivalent to 100 mg of active Isavuconazole
  2. Intravenous Formulation
    1. Available in 372 mg Isavuconazonium single use vials of lipholized powder to be reconstituted
    2. Each 372 mg Isavuconazonium prodrug is equivalent to the active, 200 mg Isavuconazole
    3. Administer via filtered line over 1 hour
  1. Load: 372 mg IV via filtered line over 1 hour or oral every 8 hours for 6 doses
  2. Next: 372 mg IV via filtered line over 1 hour or oral daily, starting at 12 to 24 hours after loading doses completed
  • Adverse Effects
  1. Common
    1. Nausea or Vomiting
    2. Diarrhea or Constipation
    3. Cough
    4. Dyspnea
    5. Headache
    6. Hypokalemia
    7. Back Pain
  2. Uncommon (with IV infusion)
    1. Hypotension
    2. Chills
    3. Parasthesias
  3. Serious
    1. Shortens QTc Interval
    2. Hepatotoxicity
      1. Serum transaminase increase
      2. May be severe
      3. Monitor Liver Function Tests
  • Safety
  1. Avoid in Lactation
  2. Pregnancy Category C
    1. May be Teratogenic (use Shared Decision Making, based on pregnancy databases)
    2. Animal studies have demonstrated increased perinatal mortality and skeletal abnormalities
  • Pharmacokinetics
  1. Oral Bioavailability: 98%
    1. Reaches peak serum levels at 2 to 3 hours after oral dose
  2. Elimination Half-Life: 130 hours (based on IV dose)
  3. Isavuconazonium is a prodrug of Isavuconazole
    1. After oral or IV dose, Isavuconazonium is hydrolyzed by plasma esterases to the active form Isavuconazole
    2. Isavuconazonium 372 mg is equivalent to Isavuconazole 200 mg
  4. Metabolism
    1. Hepatic metabolism via CYP3A4 and CYP3A5
    2. L-Glucuronidation
    3. No dose adjustments needed in mild to moderate hepatic Impairment
  • Drug Interactions
  1. General
    1. CYP3A4 Inhibitor (moderate)
    2. P-Glycoprotein Inhibitor (P-gp inhibitor)
  2. Avoid with strong CYP3A4 Inhibitors or Inducers
  3. May affect levels of other agents
    1. Cyclosporine
    2. Digoxin
    3. Sirolimus
    4. Tacrolimus
  • Resources
  1. Isavuconazonium (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8f7f73b8-586a-4df0-935f-fecd4696c16c
  • References
  1. (2016) Med Lett Drugs Ther 58(1490):37 [PubMed]