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.

CRESEMBA clinical safety profile

See safety profile in pediatric patients   

CRESEMBA clinical safety profile

   See safety profile in
   pediatric patients

Adverse reactions observed in Trials 1 and 2 in adult patients1

  • The most frequently reported adverse reactions among CRESEMBA® (isavuconazonium sulfate)-treated patients in Trials 1 and 2 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%)1
  • The frequencies and types of adverse reactions observed in CRESEMBA-treated patients were similar between Trial 1 and Trial 21

Trial 1: Most frequent treatment-emergent adverse reactions¹

(≥14% for CRESEMBA-treated patients)
Constipation
14.0%
20.8%
Peripheral edema
15.2%
17.8%
Abdominal pain
16.7%
22.8%
Headache
16.7%
14.7%
Dyspnea
17.1%
13.5%
Elevated liver laboratory tests*
17.1%
24.3%
Hypokalemia
19.1%
22.4%
Diarrhea
23.7%
23.2%
Vomiting
24.9%
28.2%
Nausea
27.6%
30.1%
% of patients

*Liver laboratory elevations included alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood alkaline phosphatase, blood bilirubin, and gamma-glutamyltransferase.

  • CRESEMBA has no warning for visual disturbances1
  • In Trial 1, the observed rates of adverse reactions by system organ classes for CRESEMBA and voriconazole were: skin (33.5% and 42.5%), eye (15.2% and 26.6%), and hepatobiliary disorders (8.9% and 16.2%)2

Elevated liver transaminases in Trial 11

  • ALT or AST >3 times upper limit of normal (ULN) was reported at the end of study treatment in 4.4% of patients who received CRESEMBA
  • ALT or AST >10 times ULN developed in 1.2% of patients who received CRESEMBA

Discontinuation rates for CRESEMBA and voriconazole1

Trial 1: Permanent discontinuation due to treatment-emergent adverse reactions

Discontinuation rates for CRESEMBA and voriconazole chart
  • CRESEMBA: LD: IV 372 mg* q8h for 48 hours; MD: IV or PO 372 mg* q24h (Day 3 onward)
  • Voriconazole LD: IV 6 mg/kg q12h for 24 hours; MD: IV 4 mg/kg q12h for 24 hours, then can switch to PO 200 mg q12h

*372 mg of isavuconazonium sulfate is equivalent to 200 mg of isavuconazole.

IV=intravenous; LD=loading dose; MD=maintenance dose; PO=by mouth.

Phase 3, randomized, double-blind, noninferiority trial was designed to evaluate the safety and efficacy of CRESEMBA vs voriconazole for primary treatment of invasive fungal disease caused by Aspergillus species or other filamentous fungi. Eligible patients had proven, probable, or possible invasive fungal infections based on European Organisation for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria.1,3

  • In Trial 2, adverse reactions resulting in permanent discontinuation were reported in 19 (13%) CRESEMBA-treated patients1
  • In Trials 1 and 2, adverse reactions that most often led to permanent discontinuation of CRESEMBA therapy 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%)1

Safety profile in pediatric patients

  • The clinical safety of CRESEMBA was assessed in 77 pediatric patients who received at least one dose of intravenous or oral CRESEMBA in two uncontrolled studies1
  • The duration of treatment ranged from 1 to 181 days with a median duration of treatment of 15 days1
  • 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%)1
  • In general, adverse reactions (including serious adverse reactions and adverse reactions leading to permanent discontinuation of CRESEMBA) were similar to those reported in adults1

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