isavuconazonium sulfate (Rx)

Brand and Other Names:Cresemba, isavuconazole
  • Print

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

capsule

  • 186mg isavuconazonium sulfate (equivalent to 100mg isavuconazole)

injection, lyophilized powder for reconstitution

  • 372mg isavuconazonium sulfate (equivalent to 200mg isavuconazole)

Invasive Aspergillosis

Indicated for invasive aspergillosis

Has activity against most strains of the following microorganisms, both in vitro and in clinical infection: Aspergillus flavus, Aspergillus fumigatus, and Aspergillus niger

Initial: 372 mg PO/IV q8hr x6 doses (48 hr)

Maintenance: 372 mg PO/IV qDay

Invasive Mucormycosis

Indicated for invasive mucormycosis caused by Mucorales fungi such as Rhizopus oryzae and Mucormycetes species

Initial: 372 mg PO/IV q8hr x6 doses (48 hr)

Maintenance: 372 mg PO/IV qDay

Dosage Modifications

Renal impairment

  • Mild, moderate, or severe (including ESRD): No dose adjustment required

Hepatic impairment

  • Mild or moderate: No dose adjustment required
  • Severe: Not studied

<18 years: Safety and efficacy not established

Next:

Interactions

Interaction Checker

and isavuconazonium sulfate

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            All Interactions Sort By:
             activity indicator 
            Previous
            Next:

            Adverse Effects

            >10%

            Nausea (27.6%)

            Vomiting (24.9%)

            Diarrhea (23.7%)

            Hypokalemia (19.1%)

            Elevated liver tests (17.1%)

            Dyspnea (17.1%)

            Abdominal pain (16.7%)

            Headache (16.7%)

            Peripheral edema (15.2%)

            Constipation (14%)

            Fatigue (10.5%)

            Insomnia (10.5%)

            Back pain (10.1%)

            Renal failure (10.1%)

            1-10%

            Chest pain (8.9%)

            Decreased appetite (8.6%)

            Delirium (8.6%)

            Rash (8.6%)

            Pruritus (8.2%)

            Hypotension (8.2%)

            Anxiety (8.2%)

            Acute respiratory failure (7.4%)

            Injection site reaction (6.2%)

            Dyspepsia (6.2%)

            Hypomagnesemia (5.4%)

            Cardiac disorders: Atrial fibrillation, atrial flutter, bradycardia, reduced QT interval on electrocardiogram, palpitations, supraventricular extrasystoles, supraventricular tachycardia, ventricular extrasystoles, cardiac arrest (<5%)

            Nervous system disorders: Convulsion, dysgeusia, encephalopathy, hypoesthesia, migraine, peripheral neuropathy, paraesthesia, somnolence, stupor, syncope, tremor (<5%)

            Psychiatric disorders: Confusion, hallucination, depression (<5%)

            Renal and urinary disorders: Hematuria, proteinuria (<5%)

            Respiratory, thoracic, and mediastinal disorders: Bronchospasm, tachypnea (<5%)

            Previous
            Next:

            Warnings

            Contraindications

            Known hypersensitivity

            Strong CYP3A4 inhibitors; coadministration with strong CYP3A4 inhibitors can significantly increase the plasma concentration of isavuconazole

            Strong CYP3A4 inducers; coadministration with strong CYP3A4 inducers can significantly decrease the plasma concentration of isavuconazole

            Familial short QT syndrome; isavuconazole shortens the QTc interval in a concentration-related manner

            Cautions

            Hepatic adverse drug reactions (eg, elevated ALT, AST, alkaline phosphatase, total bilirubin) reported; the elevations in liver-related laboratory tests were generally reversible and did not require discontinuation of drug; 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 (eg, hematologic malignancy) during treatment with azole antifungal agents

            Infusion-related reactions, including hypotension, dyspnea, chills, dizziness, paresthesia, and hypoesthesia, were reported; discontinue the infusion if these reaction occur

            Serious hypersensitivity and severe skin reactions (eg, anaphylaxis, Stevens-Johnson syndrome) have been reported during treatment with other azole antifungal agents

            May cause fetal harm when administered to a pregnant woman; should be used during pregnancy only if the potential benefit to the patient outweighs the risk to the fetus

            Previous
            Next:

            Pregnancy & Lactation

            Pregnancy

            Pregnancy Category: C

            Based on animal data, predicted to have the potential for increasing the risk of adverse developmental outcomes above background risk

            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

            Lactation

            Do not breast-feed

            Isavuconazole is excreted in the milk of lactating rats following intravenous administration

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

            Previous
            Next:

            Pharmacology

            Mechanism of Action

            Triazole antifungal agent; isavuconazole is the active moiety of the prodrug isavuconazonium sulfate

            Absorption

            Absolute bioavailability: 98%

            Peak plasma concentration: 7,499 ng/mL (2 capsules); 20,028 (6 capsules)

            Peak plasma time: 3 hr (2 capsules); 4 hr (6 capsules)

            AUC: 121,402 hr ng/mL (2 capsules); 352,805 hr•ng/mL (6 capsules)

            Distribution

            Protein bound: >99%

            Vd: 450 L

            Metabolism

            Isavuconazonium sulfate is rapidly hydrolyzed in blood to isavuconazole by esterases, predominately by butylcholinesterase to isavuconazole

            Isavuconazole is a substrate of cytochrome P450 enzymes 3A4 and 3A5

            Except for the active moiety isavuconazole, no individual metabolite observed with an AUC >10% of drug-related material

            In vivo studies indicate that CYP3A4, CYP3A5, and subsequently uridine diphosphate-glucuronosyltransferases (UGTs) are involved in the metabolism of isavuconazole

            Elimination

            Half-life: 130 hr

            Excretion: 46.1% feces; 45.5% urine

            Previous
            Next:

            Administration

            IV Compatibilities

            0.9% NaCl injection

            D5W injection

            IV Preparation

            Reconstitute lyophilized powder in vial

            • Reconstitute 1 vial by adding 5 mL sterile water for injection
            • Gently shake to dissolve the powder completely
            • Visually inspect the reconstituted solution for particulate matter and discoloration; reconstituted solution should be clear and free of visible particulate

            Further dilution

            • Remove 5 mL of the reconstituted solution from the vial and add it to an infusion bag containing 250 mL (approximately 1.5 mg/mL isavuconazonium sulfate) 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 - 1.2 micron and in-line filter reminder sticker to the infusion bag

            IV Administration

            Do not use a pneumatic transport system

            Complete IV administration within 6 hr of dilution at room temperature (or immediately store refrigerated, see Storage)

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

            Infuse over a minimum of 1 hr 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 with other intravenous medications

            Flush IV lines with 0.9% NaCl injection or D5W prior to and after infusion

            Oral Administration

            Switching between IV and oral formulations is acceptable as bioequivalence has been demonstrated

            Loading dose is not required when switching between formulations

            Swallow oral capsules whole; do not chew, crush, dissolve, or open the capsules

            Can be taken with or without food

            Storage

            Reconstituted solution: May be stored below 25°C for maximum 1 hr prior to preparation of the patient infusion solution

            Diluted IV solution

            • If unable to administer IV diluted solution within 6 hr of preparation, immediately refrigerate (2-8°C [36-46°F]) the infusion solution after dilution and complete the infusion within 24 hr
            • Do not freeze the infusion solution
            Previous
            Next:

            Images

            Previous
            Next:

            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
            Additional Offers
            Email to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Email Forms to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Previous
            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.