CRESEMBA (isavuconazonium sulfate)

General Pharmacokinetics In healthy subjects, the pharmacokinetics of isavuconazole following oral administration of CRESEMBA capsules at isavuconazole equivalent doses up to 600 mg per day (6 capsules) are dose proportional ( Table 6 ). Based on a population pharmacokinetics analysis of healthy subjects and patients, the mean plasma half-life of isavuconazole was 130 hours and the mean volume of distribution (V ss ) was approximately 450 L following intravenous administration. Table 6. Steady S...

14.1 Treatment of Invasive Aspergillosis Trial 1 was a randomized, double-blind, non-inferiority active controlled trial which evaluated the safety and efficacy of CRESEMBA versus voriconazole for primary treatment of invasive fungal disease caused by Aspergillus species or other filamentous fungi. Eligible patients had proven, probable, or possible invasive fungal infections per European Organisation for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria 1 . Patients were stratified by history of allogeneic bone marrow transplant, uncontrolled malignancy at baseline, an...

The following are discussed in more detail in other sections of the labeling:

• Hepatic Adverse Drug Reactions [see Warnings and Precautions ( 5.1 )]
• Infusion-Related Reactions [see Warnings and Precautions ( 5.2 )]
• Hypersensitivity Reactions [see Warnings and Precautions ( 5.3 )]
• Embryo-Fetal Toxicity [see Warnings and Precautions ( 5.4 )]
• Adult Patients: The most frequent adverse reactions in adult patients were nausea, vomiting, diarrhea, headache, elevated liver chemistry tests, hypo...

• CRESEMBA is contraindicated in persons with known hypersensitivity to isavuconazole.
• Coadministration of strong CYP3A4 inhibitors, such as ketoconazole or high-dose ritonavir (400 mg every 12 hours), with CRESEMBA is contraindicated because strong CYP3A4 inhibitors can significantly increase the plasma concentration of isavuconazole [see Drug Interactions ( 7 ) and Clinical Pharmacology ( 12.3...

• Hepatic Adverse Drug Reactions: Serious hepatic reactions have been reported. Evaluate liver-related laboratory tests at the start and during the course of CRESEMBA therapy. ( 5.1 )
• Infusion-related reactions were reported during intravenous administration of CRESEMBA. Discontinue the infusion if these reactions occur. ( 5.2 )
• Hypersensitivity Reactions: Anaphylactic reactions, with fatal outcome, have been reported during treatment with CRESEMBA. Serious skin reactions, such as Stevens-Jo...

7 DRUG INTERACTIONS Isavuconazole is a sensitive substrate of CYP3A4. CYP3A4 inhibitors or inducers may alter the plasma concentrations of isavuconazole. Isavuconazole is a moderate inhibitor of CYP3A4, and a mild inhibitor of P-glycoprotein (P-gp), and organic cation transporter 2 (OCT2). Drug interaction studies were conducted to investigate the effect of coadministered drugs on the pharmacokine...