• Invasive aspergillosis.
• Mucormycosis.

Contraindicated in:

• Hypersensitivity
• Strong CYP3A4 inhibitors
• Familial short QT syndrome
• Strong CYP3A4 inducers
• OB: Pregnancy
• Lactation: Lactation.

Use Cautiously in:

• Severe hepatic impairment (use only if benefits outweigh risks, monitor carefully for adverse reactions)
• Rep: Women of reproductive potential
• Pedi: Safety and effectiveness not established in children.

CV: peripheral edema, chest pain, hypotension.

Derm: pruritus, rash, STEVENS-JOHNSON SYNDROME.

F and E: hypokalemia, hypomagnesemia.

GI: ↑ liver enzymes, constipation, diarrhea, nausea, vomiting, ↓ appetite, dyspepsia.

GU: renal failure.

Local: injection site reactions.

MS: back pain.

Neuro: fatigue, headache, insomnia, anxiety, delirium.

Resp: cough, dyspnea, respiratory failure.

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS), infusion-related reactions.

Drug-Drug:

• ↑ levels and risk of toxicity with strong inhibitors of CYP3A4, including ketoconazole or high-dose ritonavir; concurrent use is contraindicated.
• Lopinavir/ritonavir significantly ↑ levels and risk of toxicity; concurrent use should be undertaken with caution.
• Isavuconazonium ↓ levels and effectiveness of lopinavir/ritonavir.
• Isavuconazonium ↑ levels and risk of toxicity with atorvastatin, cyclosporine, digoxin, midazolam, mycophenolate, sirolimus, tacrolimus; undertake concurrent use with caution, monitoring drug effects and making adjustments if necessary.
• Strong inducers of CYP3A4 including long-acting barbiturates, carbamazepine, or rifampin ↓ levels and effectiveness; concurrent use is contraindicated.
• ↓ levels and effectiveness of bupropion; bupropion dose may need to be ↑ but should not exceed maximum recommended dose.

Drug-Natural Products:

• St. John's wort ↓ blood levels and effectiveness; concurrent use is contraindicated.

• Capsules: 186 mg isavuconazonium (equivalent to 100 mg isavuconazole);
• Lyophilized powder for injection: 372 mg isavuconazonium (equivalent to 200 mg isavuconazole)/vial;

• PO, IV (Adults ≥18 yr): Loading dose: 372 mg isavuconazonium (equivalent to 200 mg isavuconazole) every 8 hr for six doses; Maintenance dose: 372 mg isavuconazonium (equivalent to 200 mg isavuconazole) once daily starting 12–24 hr after last loading dose.

Cresemba

• A prodrug that is converted (rapidly hydrolyzed) to isavuconazole. Inhibits the synthesis of ergosterol, a key component of fungal cell walls.

• Resolution of invasive fungal infections.

Spectrum:

• Active against Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger, and Mucormycetes species including Rhizopus oryzae.

Therapeutic Classification: antifungals

Pharmacologic Classification: azoles

Absorption: Prodrug is rapidly converted to isavuconazole, the active component. 98% absorbed following oral administration. Similar conversion follows intravenous administration, resulting in complete bioavailability.

Distribution: Extensively distributed.

Protein Binding: >99%.

Metabolism/Excretion: Extensively metabolized (mostly by CYP3A4 and CYP3A5); inactive metabolites are mostly renally eliminated, <1% excreted unchanged in urine.

Half-life: 130 hr.

(plasma concentrations)

• Instruct patient to take isavuconazonium as directed. Do not stop taking isavuconazonium without consulting heath care professional. Advise patient to read Patient Information before starting and with each Rx refill in case of changes.
• Advise patient to notify health care professional promptly of signs and symptoms of liver disease (itchy skin, nausea, vomiting, yellowing of eyes, feeling very tired, flu-like symptoms), infusion-related reactions, or rash occur.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
• Rep: May cause fetal harm. Advise females of reproductive potential to use effective contraception during and for 28 days after final dose and to avoid breastfeeding during therapy. Advise patient to notify health care professional if pregnancy is planned or suspected.
• Emphasize the importance of lab tests to monitor for side effects during therapy.

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NDC Code^*

• 0469- Astellas Pharma US, Inc.
  • 0469-0420- CRESEMBA
    • 0469-0420-99- 10 CARTON in 1 CARTON (0469-0420-99) > 1 VIAL, SINGLE-DOSE in 1 CARTON > 5 mL in 1 VIAL, SINGLE-DOSE

• 0469- Astellas Pharma US, Inc.
  • 0469-0520- CRESEMBA
    • 0469-0520-14- 4 CARTON in 1 CARTON (0469-0520-14) > 14 BLISTER PACK in 1 CARTON > 1 CAPSULE in 1 BLISTER PACK