CRESEMBA for INJECTION Dosage & Rx Info

Cresemba For Injection Generic Name & Formulations

Legal Class

General Description

Isavuconazonium sulfate 372mg; lyophilized pwd for IV inj after reconstitution; preservative-free.

Pharmacological Class

Azole antifungal.

How Supplied

Blister packs (74.5mg)—35, (186mg)—14; Single-dose vial—1

Manufacturer

Astellas Pharma US, Inc.

Generic Availability

Mechanism of Action

Isavuconazonium sulfate is the prodrug of isavuconazole. Isavuconazole inhibits the synthesis of ergosterol, a key component of the fungal cell membrane, through the inhibition of cytochrome P-450 dependent enzyme lanosterol 14-alpha-demethylase. This enzyme is responsible for the conversion of lanosterol to ergosterol. An accumulation of methylated sterol precursors and a depletion of ergosterol within the fungal cell membrane weakens the membrane structure and function.

Cresemba For Injection Indications

Indications

Invasive aspergillosis. Invasive mucormycosis.

Cresemba For Injection Dosage and Administration

Adult

Infuse over a minimum of 1hr. ≥18yrs: loading dose: 372mg IV every 8hrs for 6 doses (48hrs); maintenance dose: 372mg IV once daily starting 12–24hrs after the last loading dose. Switching between IV and oral formulations of Cresemba is acceptable; loading dose is not required when switching between formulations. NG tube preparation and administration: see full labeling.

Children

For IV formulation (<1yr): not established. For NG tube administration (<6yrs and <16kg): not established. 1–<3yr (<18kg): loading dose: 15mg/kg IV every 8hrs for 6 doses (48hrs); maintenance dose: 15mg/kg IV once daily starting 12–24hrs after the last loading dose. 3–<18yrs (<37kg): loading dose: 10mg/kg IV every 8hrs for 6 doses (48hrs); maintenance dose: 10mg/kg IV once daily starting 12–24hrs after the last loading dose. 3–<18yrs (≥37kg): loading dose: 372mg IV every 8hrs for 6 doses (48hrs); maintenance dose: 372mg IV once daily starting 12–24hrs after the last loading dose. Switching between IV and oral formulations of Cresemba is acceptable; loading dose is not required when switching between formulations. NG tube preparation and administration: see full labeling.

Cresemba For Injection Contraindications

Contraindications

Concomitant strong CYP3A4 inhibitors (eg, ketoconazole, high-dose ritonavir [400mg every 12hrs]). Concomitant strong CYP3A4 inducers (eg, rifampin, carbamazepine, St. John's wort, long-acting barbiturates). Familial short QT syndrome.

Cresemba For Injection Boxed Warnings

Not Applicable

Cresemba For Injection Warnings/Precautions

Warnings/Precautions

Do not administer capsules via NG tube. Perform liver-related lab tests at the start of and during therapy; monitor for more severe hepatic injury if abnormal test results. Discontinue if liver disease, infusion-related reactions (including hypotension, dyspnea, chills, dizziness, paresthesia, hypoesthesia), anaphylactic, or severe cutaneous reactions (eg, Stevens-Johnson syndrome) develop. Azole hypersensitivity (monitor). IV formulation: may form precipitate; administer via an in-line filter. Severe hepatic impairment (Child-Pugh Class C): consider use only if benefits outweigh the risks. Embryo-fetal toxicity. Advise females of reproductive potential to use effective contraception during and for 28 days after the last dose. Pregnancy. Nursing mothers: not recommended.

Cresemba For Injection Pharmacokinetics

Absorption

Maximum plasma concentration: 2 to 3 hours (capsules). Absolute bioavailability: 98% (capsules).

Distribution

Volume of distribution: ~450 L. Plasma protein bound: >99%.

Metabolism

Rapidly hydrolyzed in blood by esterases, predominantly by butylcholinesterase.

Elimination

Oral admin: fecal (46.1%), renal (45.5%). IV admin: renal (95%). Half-life: 130 hours.

Cresemba For Injection Interactions

Interactions

See Contraindications. Avoid concomitant use with vincristine. Caution with concomitant lopinavir/ritonavir, atorvastatin (monitor), midazolam (consider dose reduction), bupropion (consider dose increase), mycophenolate mofetil (monitor for MPA-related toxicities), digoxin (monitor). Concomitant cyclosporine, sirolimus, tacrolimus; monitor and adjust dose as needed.

Cresemba For Injection Adverse Reactions

Adverse Reactions

Nausea, vomiting, diarrhea, headache, elevated liver chemistry tests, hypokalemia, constipation, dyspnea, cough, peripheral edema, back pain; infusion-related reactions, hypersensitivity reactions.

Cresemba For Injection Clinical Trials

See Literature

Cresemba For Injection Note