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.

Drug interactions with CRESEMBA

Drug interactions with CRESEMBA

CRESEMBA® (isavuconazonium sulfate) is a sensitive substrate of CYP3A4, a moderate inhibitor of CYP3A4, and a mild inhibitor of
P-glycoprotein (P-gp) and organic cation transporter 2 (OCT2).1

Contraindicated with CRESEMBA1

Concomitant drug(s) Effect on CRESEMBA Comments on concomitant use
Ketoconazole >5-fold increase in exposure Contraindicated with all potent CYP3A4 inhibitors
Rifampin 97% decrease in exposure Contraindicated with all potent CYP3A4 inducers
Concomitant drug(s)
Ketoconazole
Effect on CRESEMBA Comments on concomitant use
>5-fold increase in exposure Contraindicated with all potent CYP3A4 inhibitors
Rifampin
Effect on CRESEMBA Comments on concomitant use
97% decrease in exposure Contraindicated with all potent CYP3A4 inducers

Drug-drug interaction for vincristine1

  • Avoid concomitant use with CRESEMBA in pediatric and adult patients. CRESEMBA is predicted to have a less than 2-fold increase in vincristine exposure in pediatric and adult patients, which may increase the risk of vincristine-related adverse reactions1

Use with caution when coadministered with CRESEMBA1-6

Concomitant
drug(s)		 Drug monitoring/dose
adjustment for
concomitant drug		 Effect on CRESEMBA PK Effect on concomitant drug PK
Cmax AUC Cmax AUC
Cyclosporine
(300 mg)		 Monitor drug concentrations and dose adjust as needed 30% 3% 6% 29%
Tacrolimus
(5 mg)		 Monitor drug concentrations and dose adjust as needed 26% 12% 42% 125%
Sirolimus
(2 mg)		 Monitor drug concentrations and dose adjust as needed 4% 11% 65% 84%
Mycophenolate
mofetil
(1000 mg)		 Monitor for mycophenolic acid–related toxicities 4% NS 11% 35%
Digoxin
(0.5 mg)		 Monitor and titrate digoxin dose to clinical effect NS NS 33% 25%
Midazolam
(3 mg)		 Consider dose reduction NS NS 72% 103%
Bupropion
(100 mg)		 Consider dose increase; should not exceed maximum dose NS NS 31% 42%
Atorvastatin
(20 mg)		 Monitor for atorvastatin-related adverse events NS NS 3% 37%
Lopinavir
(400 mg)		 Possible loss of antiviral efficacy 74% 96% 23% 27%
Ritonavir
(100 mg)		 33% 31%
Concomitant drug(s)

Cyclosporine (300 mg)

Monitor drug concentrations and dose adjust as needed
Effect on CRESEMBA PK Effect on concomitant drug PK
Cmax AUC Cmax AUC
30% 3% 6% 29%

Tacrolimus (5 mg)

Monitor drug concentrations and dose adjust as needed
Effect on CRESEMBA PK Effect on concomitant drug PK
Cmax AUC Cmax AUC
26% 12% 42% 125%

Sirolimus (2 mg)

Monitor drug concentrations and dose adjust as needed
Effect on CRESEMBA PK Effect on concomitant drug PK
Cmax AUC Cmax AUC
4% 11% 65% 84%

Mycophenolate mofetil (1000 mg)

Monitor for mycophenolic acid–related toxicities
Effect on CRESEMBA PK Effect on concomitant drug PK
Cmax AUC Cmax AUC
4% NS 11% 35%

Digoxin (0.5 mg)

Monitor and titrate digoxin dose to clinical effect
Effect on CRESEMBA PK Effect on concomitant drug PK
Cmax AUC Cmax AUC
NS NS 33% 25%

Midazolam (3 mg)

Consider dose reduction
Effect on CRESEMBA PK Effect on concomitant drug PK
Cmax AUC Cmax AUC
NS NS 72% 103%

Bupropion (100 mg)

Consider dose increase; should not exceed maximum dose
Effect on CRESEMBA PK Effect on concomitant drug PK
Cmax AUC Cmax AUC
NS NS 31% 42%

Atorvastatin (20 mg)

Monitor for atorvastatin-related adverse events
Effect on CRESEMBA PK Effect on concomitant drug PK
Cmax AUC Cmax AUC
NS NS 3% 37%

Lopinavir (400 mg)

Possible loss of antiviral efficacy
Effect on CRESEMBA PK Effect on concomitant drug PK
Cmax AUC Cmax AUC
74% 96% 23% 27%

Ritonavir (100 mg)

Possible loss of antiviral efficacy
Effect on CRESEMBA PK Effect on concomitant drug PK
Cmax AUC Cmax AUC
74% 96% 33% 31%

AUC=area under the curve; Cmax=maximum plasma concentration; NS=not significant; PK=pharmacokinetics.

No dose adjustment2-5,7,8

Esomeprazole Omeprazole Norethindrone Methadone
Warfarin Dextromethorphan Ethinyl estradiol Prednisone
Caffeine Repaglinide Methotrexate Metformin
Esomeprazole Omeprazole
Norethindrone Methadone
Warfarin Dextromethorphan
Ethinyl estradiol Prednisone
Caffeine Repaglinide
Methotrexate Metformin

Recommended Dosing for CRESEMBA

Review recommended dosing regimen for CRESEMBA injection and PO formulations.

Recommended dosing for CRESEMBA
Review dosing recommendations and resources

CRESEMBA Pharmacokinetics

Watch a presentation of CRESEMBA pharmacokinetic information, including dosing and drug interaction considerations.

CRESEMBA Pharmacokinetics
Review pharmacokinetic properties of isavuconazole

IMPORTANT SAFETY INFORMATION AND USE OF CRESEMBA

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.

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).

Indications and Usage and Important Safety Information

Indications and Usage and Important Safety Information

Indications and Usage and Important Safety Information