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.

Drug interactions with CRESEMBA

CRESEMBA 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

Use with caution when coadministered with CRESEMBA1,2

Concomitant drug(s) Drug monitoring/dose adjustment for concomitant drug Effect on CRESEMBA PK Effect on concomitant drug PK
Cmax AUC
Cyclosporine (300 mg) Monitor drug concentrations and dose adjust as needed NS ↑6% ↑29%
Tacrolimus (5 mg) Monitor drug concentrations and dose adjust as needed NS ↑42% ↑125%
Sirolimus (2 mg) Monitor drug concentrations and dose adjust as needed NS ↑65% ↑84%
Mycophenolate mofetil (1 g) Monitor for MPA-related toxicities NS ↓11% ↑35%
Digoxin (0.5 mg) Monitor and titrate digoxin dose to clinical effect NS ↑33% ↑25%
Midazolam (3 mg) Consider dose reduction NS ↑72% ↑103%
Bupropion (100 mg) Consider dose increase; should not exceed maximum dose NS ↓31% ↓42%
Atorvastatin (20 mg) Monitor for atorvastatin-related AEs NS ↑3% ↑37%
Lopinavir (400 mg) Possible loss of antiviral efficacy Cmax ↑ 74%
AUC ↑ 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
NS ↑6% ↑29%

Tacrolimus (5 mg)

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

Sirolimus (2 mg)

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

Mycophenolate mofetil (1 g)

Monitor for MPA-related toxicities
Effect on CRESEMBA PK Effect on concomitant drug PK
Cmax AUC
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
NS ↑33% ↑25%

Midazolam (3 mg)

Consider dose reduction
Effect on CRESEMBA PK Effect on concomitant drug PK
Cmax AUC
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
NS ↓31% ↓42%

Atorvastatin (20 mg)

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

Lopinavir (400 mg)

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

Ritonavir (100 mg)

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

PK=pharmacokinetics; Cmax=maximum plasma concentration; AUC=area under the curve; NS=not significant; MPA=mycophenolic acid; AEs=adverse events.

No dose adjustment1,2

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

Next: CRESEMBA Support SolutionsSM

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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