For US Healthcare Professionals Only
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:
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
CRESEMBA® (isavuconazonium sulfate) is used for the treatment of invasive aspergillosis and invasive mucormycosis.1
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
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
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
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
CRESEMBA® (isavuconazonium sulfate) is the prodrug of isavuconazole, an azole antifungal drug. Prescribe CRESEMBA using the recommended dosage regimen shown below1:
| Injection and PO dosing regimen in adult patients1 | ||
|---|---|---|
| Loading dose | Maintenance dose§ | |
| CRESEMBA for injection 372 mg* of isavuconazonium sulfate per vial |
1 vial q8h for 6 doses (48 h) |
1 vial once daily |
| CRESEMBA capsules 186 mg† of isavuconazonium sulfate per capsule |
2 capsules q8h for 6 doses (48 h) |
2 capsules once daily |
| CRESEMBA capsules 74.5 mg‡ of isavuconazonium sulfate per capsule |
5 capsules q8h for 6 doses (48 h) |
5 capsules once daily |
*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
| Weight- and age-based dosing with once-daily maintenance | ||||
|---|---|---|---|---|
| Dosage form | Age | Body weight (kg) | Loading dose | Maintenance dose# |
| CRESEMBA for injection 372 mg|| of isavuconazonium sulfate per vial |
1 to <3 years of age | <18 kg | 15 mg/kg q8h for 6 doses |
15 mg/kg once daily |
| 3 to <18 years of age | <37 kg | 10 mg/kg q8h for 6 doses |
10 mg/kg once daily |
|
| ≥37 kg | 1 vial q8h for 6 doses |
1 vial once daily |
||
| CRESEMBA capsules 74.5 mg¶ of isavuconazonium sulfate per capsule |
6 to <18 years of age | 16 kg to <18 kg | 2 capsules q8h for 6 doses |
2 capsules once daily |
| 18 kg to <25 kg | 3 capsules q8h for 6 doses |
3 capsules once daily |
||
| 25 kg to <32 kg | 4 capsules q8h for 6 doses |
4 capsules once daily |
||
| ≥32 kg | 5 capsules** q8h for 6 doses |
5 capsules** once daily |
||
||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
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
CRESEMBA® (isavuconazonium sulfate) has no generic equivalent available.
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
Learn more about the pharmacokinetic profile of isavuconazole
Encourage patients and caretakers to read the FDA-approved patient labeling.
Astellas has also developed a Patient Education Brochure with patient-friendly information about invasive fungal infections, treatment with CRESEMBA® (isavuconazonium sulfate) capsules, and CRESEMBA Support Solutions.
Before starting patients on CRESEMBA, healthcare providers should advise patients and caregivers on the following1:
Indications and Usage
CRESEMBA (isavuconazonium sulfate) is an azole antifungal indicated for the treatment of invasive aspergillosis and invasive mucormycosis as follows:
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).
CONTRAINDICATIONS
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.
Reference: 1. CRESEMBA [package insert]. Northbrook, IL: Astellas Pharma US, Inc. 2. Walsh TJ. Aspergillosis. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine. 26th ed. Philadelphia, PA: Elsevier Saunders, 2020:2052-56.e2. 3. Freifeld AG, Kaul DR. Infection in the patient with cancer. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, eds. Abeloff’s Clinical Oncology. 6th ed. Philadelphia, PA: Elsevier, Inc., 2020:544-64.e6. 4. Kontoyiannis DP. Mucormycosis. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine. 26th ed. Philadelphia, PA: Elsevier, Inc., 2020:2056-60.e2. 5. Cornely OA, Arikan-Akdagli S, Dannaoui E, et al. ESCMID and ECMM joint clinical guidelines for the diagnosis and management of mucormycosis 2013. Clin Microbiol Infect 2014;20(Suppl 3):5-26.
Indications and Usage
CRESEMBA (isavuconazonium sulfate) is an azole antifungal indicated for the treatment of invasive aspergillosis and invasive mucormycosis as follows:
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).
CONTRAINDICATIONS
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.
Reference: 1. CRESEMBA [package insert]. Northbrook, IL: Astellas Pharma US, Inc. 2. Walsh TJ. Aspergillosis. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine. 26th ed. Philadelphia, PA: Elsevier Saunders, 2020:2052-56.e2. 3. Freifeld AG, Kaul DR. Infection in the patient with cancer. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, eds. Abeloff’s Clinical Oncology. 6th ed. Philadelphia, PA: Elsevier, Inc., 2020:544-64.e6. 4. Kontoyiannis DP. Mucormycosis. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine. 26th ed. Philadelphia, PA: Elsevier, Inc., 2020:2056-60.e2. 5. Cornely OA, Arikan-Akdagli S, Dannaoui E, et al. ESCMID and ECMM joint clinical guidelines for the diagnosis and management of mucormycosis 2013. Clin Microbiol Infect 2014;20(Suppl 3):5-26.