CRESEMBA® (isavuconazonium sulfate) is indicated for the treatment of invasive aspergillosis and invasive mucormycosis in adults. Usage
Dosing and administration of CRESEMBA
CRESEMBA (isavuconazonium sulfate) is a prodrug containing the active moiety isavuconazole, an azole antifungal drug.1
Dosing regimen for CRESEMBA1
*372 mg of isavuconazonium sulfate is equivalent to 200 mg of isavuconazole. †186 mg of isavuconazonium sulfate is equivalent to 100 mg of isavuconazole. ‡Start maintenance doses 12–24 hours after the last loading dose.
IV=intravenous; PO=by mouth.
Watch the CRESEMBA dosing and administration video
A step-by-step tutorial on dosing, preparing, and administering CRESEMBA IV and PO formulations.
Dosing Regimen – CRESEMBA Dosing & Administration
View information regarding the dosing & administration of CRESEMBA, which is indicated for the treatment of invasive aspergillosis and invasive mucormycosis in adults.
CRESEMBA for injection: a water-soluble formulation1
- IV formulation does not contain cyclodextrin and requires no dose adjustment for renal impairment1
- CRESEMBA can be administered through a peripheral or central venous line4
- IV formulation must be administered via an infusion set with an in-line filter (pore size 0.2–1.2 micron)1
- Infuse the IV formulation over a minimum of 1 hour in 250 mL of a compatible diluent, to reduce the risk for infusion-related reactions. Do not administer as an IV bolus injection1
- Do not infuse CRESEMBA with other IV medications1
- Flush IV lines with 0.9% sodium chloride injection, USP, or 5% dextrose injection, USP, prior to and after infusion of CRESEMBA1
- After dilution of the IV formulation, avoid unnecessary vibration or vigorous shaking of the solution. Do not use pneumatic transport system1
- Infusion-related reactions including hypotension, dyspnea, chills, dizziness, paresthesia, and hypoesthesia were reported during IV administration of CRESEMBA. Discontinue the infusion if these reactions occur1
Switching between the IV and PO formulations of CRESEMBA is acceptable as bioequivalence has been demonstrated. Loading dose is not required when switching between formulations.1
CRESEMBA capsules: an option throughout the care continuum1
- 98% absolute bioavailability1
- CRESEMBA can be taken with or without food1
- CRESEMBA capsules should be swallowed whole; do not chew, crush, dissolve, or open1
No dose adjustments required in specific populations based on1:
Mild, moderate, or severe renal impairment, including end-stage renal disease
- Of the 403 patients who received CRESEMBA in the Phase 3 trials, 79 (20%) patients had an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2
- CRESEMBA is not removed by hemodialysis
Mild to moderate hepatic impairment
- CRESEMBA has not been studied in patients with severe hepatic impairment (Child-Pugh Class C). Monitoring for CRESEMBA-related adverse reactions is recommended when treating these patients
- Age or gender
IMPORTANT SAFETY INFORMATION AND USE OF CRESEMBA
- 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
- Coadministration of strong CYP3A4 inducers, such as rifampin, carbamazepine, St. John's wort, or long acting barbiturates with CRESEMBA is contraindicated because strong CYP3A4 inducers can significantly decrease the plasma concentration of isavuconazole
- CRESEMBA shortened the QTc interval in a concentration-related manner. CRESEMBA is contraindicated in patients with familial short QT syndrome
WARNINGS AND PRECAUTIONS
Hepatic Adverse Drug Reactions (e.g., elevations in ALT, AST, alkaline phosphatase, total bilirubin) have been reported in clinical trials and were generally reversible and did not require discontinuation of CRESEMBA. Cases of severe hepatic adverse drug reactions including hepatitis, cholestasis or hepatic failure including death have been reported in patients with serious underlying medical conditions (e.g., hematologic malignancy) during treatment with azole antifungal agents, including CRESEMBA. Evaluate liver tests at the start and during therapy. Monitor patients who develop liver abnormalities during CRESEMBA therapy for severe hepatic injury. Discontinue if clinical signs and symptoms consistent with liver disease develop that may be attributable to CRESEMBA.
Infusion-Related Reactions including hypotension, dyspnea, chills, dizziness, paresthesia, and hypoesthesia were reported during intravenous administration of CRESEMBA. Discontinue the infusion if these reactions occur.
Serious Hypersensitivity and Severe Skin Reactions, such as anaphylaxis or Stevens Johnson syndrome, have been reported during treatment with other azole antifungal agents. Discontinue CRESEMBA if a patient develops a severe cutaneous adverse reaction. Caution should be used when prescribing CRESEMBA to patients with hypersensitivity to other azoles.
Embryo-Fetal Toxicity: During pregnancy, CRESEMBA may cause fetal harm when administered, and CRESEMBA should only be used if the potential benefit to the patient outweighs the risk to the fetus. Women who become pregnant while receiving CRESEMBA are encouraged to contact their physician.
Drug Interactions: Coadministration of CRESEMBA with strong CYP3A4 inhibitors such as ketoconazole or high-dose ritonavir and strong CYP3A4 inducers such as rifampin, carbamazepine, St. John's Wort, or long-acting barbiturates is contraindicated.
Drug Particulates: Following dilution, CRESEMBA intravenous formulation may form precipitate from the insoluble isavuconazole. Administer CRESEMBA through an in-line filter.
The most frequently reported adverse reactions among CRESEMBA-treated patients were nausea (26%), vomiting (25%), diarrhea (22%), headache (17%), elevated liver chemistry tests (16%), hypokalemia (14%), constipation (13%), dyspnea (12%), cough (12%), peripheral edema (11%), and back pain (10%).
The adverse reactions which most often led to permanent discontinuation of CRESEMBA therapy during the clinical trials were: confusional state (0.7%), acute renal failure (0.7%), increased blood bilirubin (0.5%), convulsion (0.5%), dyspnea (0.5%), epilepsy (0.5%), respiratory failure (0.5%), and vomiting (0.5%).
INDICATIONS AND USAGE
CRESEMBA is an azole antifungal indicated for patients 18 years of age and older for the treatment of invasive aspergillosis and invasive mucormycosis.
Specimens for fungal culture and other relevant laboratory studies (including histopathology) to isolate and identify causative organism(s) should be obtained prior to initiating antifungal therapy. Therapy may be instituted before the results of the cultures and other laboratory studies are known. However, once these results become available, antifungal therapy should be adjusted accordingly.
Please see full Prescribing Information.