Dosing and administration of CRESEMBA
Dosing and administration of CRESEMBA
CRESEMBA® (isavuconazonium sulfate) is a prodrug containing the active moiety isavuconazole, an azole antifungal drug.1
Dosing regimen for CRESEMBA in adult patients1
*372 mg of isavuconazonium sulfate is equivalent to 200 mg of isavuconazole. †186 mg of isavuconazonium sulfate is equivalent to 100 mg of isavuconazole. ‡74.5 mg of isavuconazonium sulfate is equivalent to 40 mg of isavuconazole. §Start maintenance doses 12–24 hours after the last loading dose. PO=by mouth.
Dosing regimen for pediatric patients1
Dosage regimen for pediatric patients1
Weight- and age-based dosing with once-daily maintenance
||372 mg of isavuconazonium sulfate is equivalent to 200 mg of isavuconazole. ¶74.5 mg of isavuconazonium sulfate is equivalent to 40 mg of isavuconazole. #Start maintenance doses 12–24 hours after the last loading dose. **Five 74.5 mg CRESEMBA capsules are equivalent to two 186 mg CRESEMBA capsules. PO=by mouth.
Special considerations
- The maximum of any individual loading or daily maintenance dose to be administered to any pediatric patient is 372 mg of CRESEMBA1
- Capsules can be taken with or without food1
- Swallow whole; do not chew, crush, dissolve, or open the capsules1
- CRESEMBA for injection via nasogastric tube administration is intended for use by patients ≥6 years of age and weighing ≥16 kg1
- Do not administer CRESEMBA capsules through a nasogastric tube1
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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.
Injection Preparation - CRESEMBA Dosing & Administration
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Injection Administration - CRESEMBA Dosing & Administration
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CRESEMBA Capsules - CRESEMBA Dosing & Administration
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Indications, Usage, and Important Safety Information - CRESEMBA Dosing & Administration
Please see Important Safety Information for CRESEMBA.
Dosing & Administration Brochure
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CRESEMBA for injection: a water-soluble formulation1
- CRESEMBA for injection is intended for use in patients who are 1 year of age and older1
- Injection formulation does not contain cyclodextrin and requires no dose adjustment for renal impairment1
- Intravenous (IV) administration can be through a peripheral or central venous line2
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Injection formulation for IV use must be administered via an infusion set with an in-line filter (pore size 0.2–1.2 micron)1
- Infuse the injection 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
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CRESEMBA injection formulation can be administered via nasogastric (NG) tube1
- CRESEMBA for injection administered via NG tube is intended for use by patients who are ≥6 years of age and weighing ≥16 kg1
- Flush NG tube with three rinses of 5 mL of water for injection, USP, after NG tube administration of CRESEMBA1
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
- CRESEMBA capsules are intended for use in patients who are ≥6 years of age and weighing ≥16 kg1
- 98% absolute bioavailability1
- CRESEMBA can be taken with or without food1
- CRESEMBA capsules should be swallowed whole; do not chew, crush, dissolve, or open1
CRESEMBA Formulation
& Pharmacology
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& Pharmacology
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No dose adjustments required in specific populations based on1:
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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 (GFR) <60 mL/min/1.73 m2
- CRESEMBA is not removed by hemodialysis
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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
- Gender
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CRESEMBA Patient Education
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IMPORTANT SAFETY INFORMATION AND USE OF CRESEMBA
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
- 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.
Hypersensitivity Reactions: Anaphylactic reactions, with fatal outcome, have been reported during treatment with CRESEMBA. Serious skin reactions, such as Stevens Johnson syndrome, have been reported during treatment with other azole antifungal agents. Discontinue CRESEMBA if anaphylactic or serious skin reactions occur, and initiate supportive treatment as needed.
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.
ADVERSE REACTIONS
In adult patients, 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%).
In adult patients, 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%).
In pediatric patients, the most frequently reported adverse reactions were diarrhea (26%), abdominal pain (23%), vomiting (21%), elevated liver chemistry tests (18%), rash (14%), nausea (13%), pruritus (13%), and headache (12%).
In general, adverse reactions in pediatric patients (including serious adverse reactions and adverse reactions leading to permanent discontinuation of CRESEMBA) were similar to those reported in adults.
INDICATIONS AND USAGE
CRESEMBA (isavuconazonium sulfate) is an azole antifungal indicated for the treatment of invasive aspergillosis and invasive mucormycosis 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 kg and greater
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.
INDICATIONS AND USAGE
CRESEMBA (isavuconazonium sulfate) is an azole antifungal indicated for the treatment of invasive aspergillosis and invasive mucormycosis 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 kg and greater
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 for CRESEMBA (isavuconazonium sulfate).