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IV Dilution -  CRESEMBA ® (isavuconazonium sulfate)

IV Dilution - CRESEMBA ® (isavuconazonium sulfate)

[ Usual Diluents ] [ Standard Dilution ] [ Storage and Stability ]
DESCRIPTION CLINICAL PHARMACOLOGY INDICATIONS AND USAGE
CONTRAINDICATIONS PRECAUTIONS ADVERSE REACTIONS
DOSAGE AND ADMINISTRATION HOW SUPPLIED WARNINGS
PRESCRIBING HIGHLIGHTS:  Please see package insert for additional information and possible updates to ensure safe and effective use of this medication. The authors make no claims of the accuracy of the information contained herein; and these suggested doses are not a substitute for clinical judgment. Neither GlobalRPh Inc. nor any other party involved in the preparation of this program shall be liable for any special, consequential, or exemplary damages resulting in whole or part from any user's use of or reliance upon this material. Please read the disclaimer carefully BEFORE accessing or using this site. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER.  

Drug UPDATES:   [Drug information  /  PDF]  
PACKAGE INSERT -Dosing:  Click (+) next to Dosage and Administration section (drug info link)
 

Usual Diluents top of page

NS,  D5W

Standard Dilutions   [Amount of drug] [Infusion volume] [Infusion rate] top of page

[Prescribed dose ]
[372 mg]  [250 ml]  [60 minutes]

Use filter: Intravenous formulation must be administered via an infusion set with an in-line filter (pore size 0.2 to 1.2 micron). 

Infuse the intravenous formulation over a minimum of 1 hour in 250 mL of a compatible diluent, to reduce the risk for infusion-related reactions. Do not administer as an intravenous bolus injection.

Reconstitute one vial of CRESEMBA by adding 5 mL water for injection, USP to the vial.
Gently shake to dissolve the powder completely.
Visually inspect the reconstituted solution for particulate matter and discoloration. Reconstituted CRESEMBA should be clear and free of visible particulate.
The reconstituted solution may be stored below 25°C for maximum 1 hour prior to preparation of the patient infusion solution.


Stability data:

Stability
Refrigerated
Stability
Room Temp.
Reconstituted
Vial/Powder
Notes P-Insert
Updated
Vial: Store CRESEMBA for injection unreconstituted vials at 2° to 8°C (36° to 46°F) in a refrigerator.

The prepared infusion solution should be kept for not more than 24 hours at 2° to 8°C (36° to 46°F) prior to use. CRESEMBA for injection vials are for single-dose use only.
The prepared infusion solution should be kept for not more than 6 hours at room temperature [20°C to 25°C (68°F to 77°F)] CRESEMBA is a single-dose vial of unpreserved sterile lyophile. Following reconstitution of the lyophile with water for injection USP, the reconstituted solution should be used immediately, or stored below 25°C for a maximum of 1 hour prior to preparation of the patient infusion solution August 5, 2016

WARNINGS  top of page

See warnings and precautions below.


DESCRIPTION  top of page

Description:
CRESEMBA contains isavuconazonium sulfate, which is the prodrug of isavuconazole, an azole antifungal drug.

CLINICAL PHARMACOLOGY: top of page

Mechanism of Action:
Isavuconazonium sulfate is the prodrug of isavuconazole, an azole antifungal

INDICATIONS AND USAGE  top of page


1.1 Invasive Aspergillosis

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

[see Clinical Studies (14.1) and Clinical Pharmacology (12.4)].

1.2 Invasive Mucormycosis

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

[see Clinical Studies (14.2) and Clinical Pharmacology (12.4)].

1.3 Usage

SSpecimens 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 top of page

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 [see Drug Interactions (7) and Clinical Pharmacology (12.3)].
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 [see Drug Interactions (7) and Clinical Pharmacology (12.3)].
CRESEMBA shortened the QTc interval in a concentration-related manner. CRESEMBA is contraindicated in patients with familial short QT syndrome [see Clinical Pharmacology (12.2)].

PRECAUTIONS top of page

5.1 Hepatic Adverse Drug Reactions

Hepatic adverse drug reactions (e.g., elevations in alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, total bilirubin) have been reported in clinical trials. The elevations in liver-related laboratory tests were generally reversible and did not require discontinuation of CRESEMBA. Cases of more 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-related laboratory tests at the start and during the course of CRESEMBA therapy. Monitor patients who develop abnormal liver-related laboratory tests during CRESEMBA therapy for the development of more severe hepatic injury. Discontinue CRESEMBA if clinical signs and symptoms consistent with liver disease develop that may be attributable to CRESEMBA [see Adverse Reactions (6.1)].

5.2 Infusion-Related Reactions

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 [see Adverse Reactions (6.1)].

5.3 Hypersensitivity Reactions

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. There is no information regarding cross-sensitivity between CRESEMBA and other azole antifungal agents. Caution should be used when prescribing CRESEMBA to patients with hypersensitivity to other azoles.

5.4 Embryo-Fetal Toxicity

CRESEMBA may cause fetal harm when administered to a pregnant woman. CRESEMBA should be used during pregnancy only 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 [see Use in Specific Populations (8.1)].

Perinatal mortality was significantly increased in the offspring of pregnant rats dosed orally with isavuconazonium sulfate at 90 mg/kg/day (less than half the maintenance human dose based on AUC comparisons) during pregnancy through the weaning period.

Isavuconazonium chloride administration was associated with dose-related increases in the incidences of rudimentary cervical ribs in rats and rabbits at 30 and 45 mg/kg, respectively, doses equivalent to about one fifth and one tenth of the clinical exposures based on AUC comparisons. In rats, dose-related increases in the incidences of zygomatic arch fusion and supernumerary ribs/rudimentary supernumerary ribs were also noted at 30 mg/kg and above, equivalent to one fifth the clinical dose based on AUC comparisons [see Nonclinical Toxicology (13.1)].

5.5 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 [see Contraindications (4) and Drug Interactions (7)].

5.6 Drug Particulates

Following dilution, CRESEMBA intravenous formulation may form precipitate from the insoluble isavuconazole. Administer CRESEMBA through an in-line filter [see Dosage and Administration (2.4)].

ADVERSE REACTIONS top of page

ADVERSE REACTIONS:

The following are discussed in more detail in other sections of the labeling:

Hepatic Adverse Drug Reactions [see Warnings and Precautions (5.1)]
Infusion-Related Reactions [see Warnings and Precautions (5.2)]
Hypersensitivity Reactions [see Warnings and Precautions (5.3)]
Embryo-Fetal Toxicity [see Warnings and Precautions (5.4)]

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of CRESEMBA cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in prac




See PACKAGE INSERT for PATIENT COUNSELING INFORMATION and Medication Guide.

DOSAGE AND ADMINISTRATION  top of page

DOSAGE AND ADMINISTRATION:

2.1 2.1 Important Instructions for Intravenous Administration

Intravenous formulation must be administered via an infusion set with an in-line filter (pore size 0.2 to 1.2 micron).

Infuse the intravenous formulation over a minimum of 1 hour in 250 mL of a compatible diluent, to reduce the risk for infusion-related reactions. Do not administer as an intravenous bolus injection.

Do not infuse CRESEMBA with other intravenous medications.

Flush intravenous lines with 0.9% sodium chloride injection, USP or 5% dextrose injection, USP prior to and after infusion of CRESEMBA.

After dilution of the intravenous formulation, avoid unnecessary vibration or vigorous shaking of the solution. Do not use a pneumatic transport system.

2.2 Dosage Regimen

CRESEMBA (isavuconazonium sulfate) is the prodrug of isavuconazole, an azole antifungal drug. Prescribe CRESEMBA as shown in Table 1 below.

Table 1. Dosage Regimen for CRESEMBA

Loading Dose

Maintenance Dosec

CRESEMBA for Injection

372 mga of isavuconazonium sulfate per vial

1 reconstituted vial (372 mga)

intravenously

every 8 hours for 6 doses (48 hours)

1 reconstituted vial (372 mga)

intravenously

once daily

CRESEMBA Capsules

186 mgb of isavuconazonium sulfate per capsule

2 capsules (372 mga)

orally

every 8 hours for 6 doses (48 hours)

2 capsules (372 mga)

orally

once daily

a 372 mg of isavuconazonium sulfate is equivalent to 200 mg of isavuconazole
b 186 mg of isavuconazonium sulfate is equivalent to 100 mg of isavuconazole
c Start maintenance doses 12 to 24 hours after the last loading dose

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.

With oral administration, swallow capsules whole. Do not chew, crush, dissolve, or open the capsules. CRESEMBA capsules can be taken with or without food.

2.3 Reconstitution Instructions for the Injection Formulation

Aseptic technique must be strictly observed in all handling since no preservative or bacteriostatic agent is present in CRESEMBA or in the materials specified for reconstitution. CRESEMBA is water soluble, preservative-free, sterile, and nonpyrogenic.

Reconstitute one vial of CRESEMBA by adding 5 mL water for injection, USP to the vial.
Gently shake to dissolve the powder completely.
Visually inspect the reconstituted solution for particulate matter and discoloration. Reconstituted CRESEMBA should be clear and free of visible particulate.
The reconstituted solution may be stored below 25°C for maximum 1 hour prior to preparation of the patient infusion solution.

2.4 Dilution and Preparation Instructions for the Injection Formulation

Remove 5 mL of the reconstituted solution from the vial and add it to an infusion bag containing 250 mL (approximately 1.5 mg isavuconazonium sulfate per mL) of compatible diluent. The diluted solution may show visible translucent to white particulates of isavuconazole (which will be removed by in-line filtration).
Use gentle mixing or roll bag to minimize the formation of particulates. Avoid unnecessary vibration or vigorous shaking of the solution.
Apply in-line filter with a microporous membrane pore size of 0.2 to 1.2 micron and in-line filter reminder sticker to the infusion bag.
Do not use a pneumatic transport system.
The intravenous administration should be completed within 6 hours of dilution at room temperature. If this is not possible, immediately refrigerate (2° to 8°C / 36° to 46°F) the infusion solution after dilution and complete the infusion within 24 hours. Do not freeze the infusion solution.

2.5 Compatibility for the Injection Formulation

CRESEMBA for injection should only be administered with the following diluents:

0.9% sodium chloride injection, USP
5% dextrose injection, USP

HOW SUPPLIED  top of page

DOSAGE FORMS AND STRENGTHS:
Injection
CRESEMBA (isavuconazonium sulfate) for injection is supplied in a single-dose vial as white to yellow sterile lyophilized powder containing 372 mg isavuconazonium sulfate (equivalent to 200 mg isavuconazole).

Individually packaged vials are available for intravenous administration. (NDC 0469-0420-99)

Storage and Stability top of page


Store CRESEMBA for injection unreconstituted vials at 2° to 8°C (36° to 46°F) in a refrigerator. CRESEMBA is a single-dose vial of unpreserved sterile lyophile. Following reconstitution of the lyophile with water for injection USP, the reconstituted solution should be used immediately, or stored below 25°C for a maximum of 1 hour prior to preparation of the patient infusion solution. The prepared infusion solution should be kept for not more than 6 hours at room temperature [20°C to 25°C (68°F to 77°F)] or 24 hours at 2° to 8°C (36° to 46°F) prior to use. CRESEMBA for injection vials are for single-dose use only.



Disclaimer
The authors make no claims of the accuracy of the information contained herein; and these suggested doses are not a substitute for clinical judgment. Neither GlobalRPh Inc. nor any other party involved in the preparation of this program shall be liable for any special, consequential, or exemplary damages resulting in whole or part from any user's use of or reliance upon this material.  PLEASE READ THE DISCLAIMER CAREFULLY BEFORE ACCESSING OR USING THIS SITE. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER.
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Lab Values - A thru Z