II. Indications
- Conditions
- Invasive Aspergillosis
- Invasive Mucormycosis
- Activity (broader spectrum Antifungal)
- Aspergillus species
- Candida species
- Dimorphic Fungi (e.g. Coccidioides, Blastomyces, Histoplasma)
- Fusarium species
- Mucorales or Zygomycetes (e.g. Mucor species, Rhizopus species)
- Secedosporium species
- Trichosporon species
III. Contraindications
- See Drug Interactions below
- Congenital Short QT Syndrome
- Children
IV. Mechanism
-
Azole Antifungal
- Second generation triazole
- Inhibits fungal CYP450 enzymes
- Inhibits fungal sterol demethylation (selectively at 14-alpha demethylase)
- Blocks the synthesis of plasma membrane steroids (conversion from lanosterol to ergosterol)
- Results in plasma membrane damage
V. Medications
- Oral Isavuconazonium Capsules: 186 mg
- Each 186 mg Isavuconazonium capsule of prodrug is equivalent to 100 mg of active Isavuconazole
- Intravenous Formulation
- Available in 372 mg Isavuconazonium single use vials of lipholized powder to be reconstituted
- Each 372 mg Isavuconazonium prodrug is equivalent to the active, 200 mg Isavuconazole
- Administer via filtered line over 1 hour
VI. Dosing: Invasive Aspergillosis or Mucormycosis (Adults)
- Load: 372 mg IV via filtered line over 1 hour or oral every 8 hours for 6 doses
- Next: 372 mg IV via filtered line over 1 hour or oral daily, starting at 12 to 24 hours after loading doses completed
VII. Adverse Effects
- Common
- Nausea or Vomiting
- Diarrhea or Constipation
- Cough
- Dyspnea
- Headache
- Hypokalemia
- Back Pain
- Uncommon (with IV infusion)
- Hypotension
- Chills
- Parasthesias
- Serious
- Shortens QTc Interval
- Hepatotoxicity
- Serum transaminase increase
- May be severe
- Monitor Liver Function Tests
VIII. Safety
- Avoid in Lactation
- Pregnancy Category C
- May be Teratogenic (use Shared Decision Making, based on pregnancy databases)
- Animal studies have demonstrated increased perinatal mortality and skeletal abnormalities
IX. Pharmacokinetics
- Oral Bioavailability: 98%
- Reaches peak serum levels at 2 to 3 hours after oral dose
- Elimination Half-Life: 130 hours (based on IV dose)
- Isavuconazonium is a prodrug of Isavuconazole
- After oral or IV dose, Isavuconazonium is hydrolyzed by plasma esterases to the active form Isavuconazole
- Isavuconazonium 372 mg is equivalent to Isavuconazole 200 mg
- Metabolism
- Hepatic metabolism via CYP3A4 and CYP3A5
- L-Glucuronidation
- No dose adjustments needed in mild to moderate hepatic Impairment
X. Drug Interactions
-
General
- CYP3A4 Inhibitor (moderate)
- P-Glycoprotein Inhibitor (P-gp inhibitor)
- Avoid with strong CYP3A4 Inhibitors or Inducers
- May affect levels of other agents
XI. Resources
- Isavuconazonium (DailyMed)
XII. References
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Related Studies
| cresemba (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
| CRESEMBA 186 MG CAPSULE | $96.89 each | |