CRESEMBA (isavuconazonium sulfate) Lighthouse
CRESEMBA (isavuconazonium sulfate) Lighthouse

CRESEMBA® (isavuconazonium sulfate) is indicated for the treatment of invasive aspergillosis and invasive mucormycosis in adults. Usage 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 efficacy in the treatment of invasive aspergillosis

CRESEMBA demonstrated noninferiority to voriconazole in the treatment of invasive aspergillosis1

CRESEMBA Invasive Aspergillosis All-Cause Mortality Through Day 42 Chart

*Intent-to-treat (ITT) population includes all randomized patients who received at least 1 dose of study drug. 372 mg of isavuconazonium sulfate is equivalent to 200 mg of isavuconazole.

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

A 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. Adjusted treatment difference (CRESEMBA–voriconazole) by Cochran-Mantel-Haenszel method stratified by randomization factors.1

  • CRESEMBA demonstrated noninferiority to voriconazole in all-cause mortality through Day 42 in the ITT population (18.6% and 20.2%, respectively, adjusted treatment difference –1.0 [95% CI: –8.0, 5.9])1
  • Similar results were seen in patients with proven or probable invasive aspergillosis confirmed by serology, culture, or histology1
  • Mean treatment duration was 47 days for both treatment groups, of which 8–9 days were by an IV route of administration1

About Trial 1: A noninferiority trial of CRESEMBA vs voriconazole1

  • A Phase 3, randomized, double-blind, noninferiority trial to evaluate the safety and efficacy of CRESEMBA vs voriconazole for primary treatment of invasive fungal disease caused by Aspergillus species or other filamentous fungi1
  • Eligible patients had proven, probable, or possible invasive fungal disease caused by Aspergillus species or other filamentous fungi based on EORTC/MSG criteria1
  • Patients were randomized 1:1 to receive antifungal treatment with CRESEMBA or voriconazole and stratified by history of allogeneic bone marrow transplant, uncontrolled malignancy at baseline, and by geographic region1

Patient demographics and baseline characteristics in Trial 1

  • Mean patient age was 51 years old (range 17–87)1
  • The majority of patients were Caucasian (78%) and male (60%)1
  • 95% of patients presented with a fungal lung infection1
  • Patients with moderate to severe renal impairment (creatinine clearance <50 mL/min, or currently on or likely to require dialysis) were excluded per labeling restrictions associated with the active comparator2
Baseline risk factors in ITT population1 CRESEMBA
N=258
n (%)
Voriconazole
N=258
n (%)
Hematologic malignancy 211 (82) 222 (86)
Allogeneic hematopoietic stem cell transplant (HSCT) 54 (21) 51 (20)
Neutropenia 163 (63) 175 (68)
Corticosteroid use 48 (19) 39 (15)
T-cell immunosuppressant use 111 (43) 109 (42)

Neutropenia defined as neutrophil count <500 cells/mm3.

  • At least 1 Aspergillus species was identified in 30% of the subjects1
    • A. fumigatus and A. flavus were the most common pathogens identified
    • Other Aspergillus species identified include A. niger, A. sydowii, A. terreus, and A. westerdijkiae

Next: Efficacy in the treatment of invasive mucormycosis

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.

Serious Hypersensitivity and Severe Skin Reactions, such as anaphylaxis or Stevens Johnson syndrome, have been reported during treatment with other azole antifungal agents. Discontinue CRESEMBA if a patient develops a severe cutaneous adverse reaction. Caution should be used when prescribing CRESEMBA to patients with hypersensitivity to other azoles.

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

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%).

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%).

INDICATIONS AND USAGE

CRESEMBA is an azole antifungal indicated for patients 18 years of age and older for the treatment of invasive aspergillosis and invasive mucormycosis.

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.

Important Safety Information and Use of Cresemba

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