Overview
11 DESCRIPTION CRESEMBA contains isavuconazonium sulfate, which is the prodrug of isavuconazole, an azole antifungal drug. Isavuconazonium sulfate drug substance is an amorphous, white to yellowish-white powder. The chemical name of isavuconazonium sulfate is glycine, N -methyl-, [2-[[[1-[1-[(2 R ,3 R )-3-[4-(4-cyanophenyl)-2-thiazolyl]-2-(2,5-difluorophenyl)-2-hydroxybutyl]-4 H...
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Isavuconazonium sulfate is the prodrug of isavuconazole, an azole antifungal [see Microbiology ( 12.4 )] . 12.2 Pharmacodynamics Pharmacokinetic/Pharmacodynamic Relationship In patients treated with CRESEMBA for invasive aspergillosis in a controlled trial, there was no significant association between plasma AUC or plasma isavuconazole concentration and efficacy. Cardiac Electrophysiology The effect on QTc interval of multiple doses of CRESEMBA capsules was evaluated. CRESEMBA was administered as 2 capsules (equivalent to 200 mg isavuconazole) three times daily on days 1 and 2 followed by either 2 capsules or 6 capsules (equivalent to 600 mg isavuconazole) once daily for 13 days in a randomized, placebo- and active-controlled (moxifloxacin...
Indications
- 1 INDICATIONS AND USAGE CRESEMBA ® is an azole antifungal indicated for the treatment of: Invasive aspergillosis ( 1.1 ) and Invasive mucormycosis ( 1.2 ) as follows: • CRESEMBA for injection : adults and pediatric patients 1 year of age and older • CRESEMBA capsules : adults and pediatric patients 6 years of age and older who weigh 16 kilograms (kg) and greater 1.1 Invasive Aspergillosis CRESEMBA ® is indicated for the treatment of invasive aspergillosis as follows: CRESEMBA for injection : adults and pediatric patients 1 year of age and older [see Clinical Studies ( 14.
Common Doses
- 372 mg
- 186 mg
- 74.5 mg
- 15 mg
Dosage
2 DOSAGE AND ADMINISTRATION Important Administration Instructions: • CRESEMBA for injection is intended for use in patients who are 1 year of age and older ( 2.1 , 2.3 ). • CRESEMBA for injection via nasogastric (NG) tube administration is intended for use by patients who are 6 years of age and older and weighing 16 kg and greater. ( 2.1 , 2.6 ). • CRESEMBA for injection must be administered through an in-line filter over a minimum of 1 hour. ( 2.1 , 2.5 ). • CRESEMBA capsules are intended for use in patients who are 6 years of age and older and weighing 16 kg and greater ( 2.1 , 2.3 ).
Contraindications
- 4 CONTRAINDICATIONS • 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 )] . • Coadministration of strong CYP3A4 inducers, such as rifampin, carbamazepine, St.
Side Effects
- 6 ADVERSE REACTIONS 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, hypokalemia, constipation, dyspnea, cough, peripheral edema, and back pain. ( 6.
Interactions
- 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 pharmacokinetics of isavuconazole and the effect of isavuconazole on the pharmacokinetics of coadministered drugs [see Clinical Pharmacology ( 12.3 )] . Table 4.