Frequently asked questions about CRESEMBA
Frequently asked questions about CRESEMBA
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What is CRESEMBA?
CRESEMBA® (isavuconazonium sulfate) is a prodrug of isavuconazole, an azole antifungal drug. CRESEMBA is indicated for the treatment of invasive aspergillosis and invasive mucormycosis as follows1:
- 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.1
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What is CRESEMBA used for?
CRESEMBA® (isavuconazonium sulfate) is used for the treatment of invasive aspergillosis and invasive mucormycosis.1
About invasive aspergillosis:
Aspergillosis, or infection by Aspergillus mold, typically occurs when the fungi’s conidia are inhaled. Invasive infections most commonly originate in the lungs (pulmonary aspergillosis) but may also manifest in the sinuses, central nervous system, cutaneous system, and internal organs. If left untreated, aspergillosis can cause invasive, chronic, and allergic conditions as well as death.2,3
See CRESEMBA efficacy in treatment of invasive aspergillosis in adult patients
Please see Important Safety Information below
About invasive mucormycosis:
Mucormycosis, or infection by Mucorales mold, typically occurs when the fungi’s conidia are inhaled and deposit into the pulmonary alveoli; however, infection can also occur through cutaneous transmission or ingestion. Consequently, the most common sites of mucormycosis are the sinuses (rhinocerebral mucormycosis), lungs (pulmonary mucormycosis), and skin (cutaneous mucormycosis). An extremely aggressive infection, mucormycosis is characterized by angioinvasion followed by infarction and tissue necrosis; however, clinical manifestations are largely dependent on host immune and medical statuses.4,5
See CRESEMBA efficacy in treatment of invasive mucormycosis in adult patients
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How does CRESEMBA work?
CRESEMBA® (isavuconazonium sulfate) is a prodrug of isavuconazole, an azole antifungal drug.1
Isavuconazole inhibits the synthesis of ergosterol, a key component of the fungal cell membrane, through the inhibition of cytochrome P-450 dependent enzyme lanosterol 14-alpha-demethylase. This enzyme is responsible for the conversion of lanosterol to ergosterol. An accumulation of methylated sterol precursors and a depletion of ergosterol within the fungal cell membrane weakens the membrane structure and function. Mammalian cell demethylation is less sensitive to isavuconazole inhibition.1
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What microorganisms does CRESEMBA cover?
Isavuconazole, the active component of CRESEMBA® (isavuconazonium sulfate), has activity against most strains of the following microoganisms, both in vitro and in clinical infections: Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger, and Mucorales such as Rhizopus oryzae and Mucormycetes species.1
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How is CRESEMBA administered?
CRESEMBA® (isavuconazonium sulfate) for injection is administered by intravenous injection via an infusion set with an in-line filter (pore size 0.2 to 1.2 micron).1
CRESEMBA for injection can also be administered by nasogastric (NG) tube.1
CRESEMBA capsules are administered orally with or without food.1
Swallow whole; do not chew, crush, dissolve, or open the capsules.1
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What is the recommended dosage of CRESEMBA for adult patients?
CRESEMBA® (isavuconazonium sulfate) is the prodrug of isavuconazole, an azole antifungal drug. Prescribe CRESEMBA using the recommended dosage regimen shown below1:
*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.
Switching between the intravenous and oral formulations of CRESEMBA is acceptable as bioequivalence has been demonstrated. Loading dose is not required when switching between formulations.1
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What is the recommended dosage of CRESEMBA for pediatric patients?
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.
Switching between the intravenous and oral formulations of CRESEMBA is acceptable as bioequivalence has been demonstrated. Loading dose is not required when switching between formulations.1
Special considerations
Special considerations
- The maximum of any individual loading or daily maintenance dose to be administered to any pediatric patient is 372 mg of CRESEMBA1
- 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 tube
- The maximum of any individual loading or daily maintenance dose to be administered to any pediatric patient is 372 mg of CRESEMBA1
- 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 tube
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How do I switch between formulations of CRESEMBA?
Switching between the intravenous and oral formulations of CRESEMBA® (isavuconazonium sulfate) is acceptable as bioequivalence has been demonstrated. Loading dose is not required when switching between formulations.1
Learn more about the pharmacokinetic profile of isavuconazole
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What is the generic drug for CRESEMBA?
CRESEMBA® (isavuconazonium sulfate) has no generic equivalent available.
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Are there therapeutic drug monitoring requirements for CRESEMBA?
The prescribing information for CRESEMBA® (isavuconazonium sulfate) does not require therapeutic drug monitoring testing. Please see full Prescribing Information for information on coadministration of drugs with 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
Learn more about the pharmacokinetic profile of isavuconazole
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What do my patients need to know about CRESEMBA?
Encourage patients and caretakers to read the FDA-approved patient labeling.
Before starting patients on CRESEMBA, healthcare providers should advise patients and caregivers on the following1:
- CRESEMBA capsules can be taken with or without food. Each capsule should be swallowed whole. Do not chew, crush, dissolve, or open the capsules
- Patients should inform their physician if they are taking other drugs as certain drugs can decrease or increase the plasma concentrations of CRESEMBA
- CRESEMBA can decrease or increase the plasma concentrations of other drugs
- Patients should inform their physician if they are pregnant, plan to become pregnant, or are nursing
- Advise patients to inform their physician immediately if they have ever had an allergic reaction to isavuconazole or other antifungal medicines such as ketoconazole, fluconazole, itraconazole, posaconazole, or voriconazole. Advise patients to discontinue CRESEMBA and seek immediate medical attention if any signs or symptoms of severe allergic reaction occur
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).