CRESEMBA Dosage & Rx Info | Uses, Side Effects

Cresemba Generic Name & Formulations

Legal Class

General Description

Isavuconazonium sulfate 74.5mg, 186mg; caps.

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 Indications

Indications

Invasive aspergillosis. Invasive mucormycosis.

Cresemba Dosage and Administration

Adult

Swallow whole. ≥18yrs: loading dose: 372mg every 8hrs for 6 doses (48hrs); maintenance dose: 372mg 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.

Children

<6yrs (<16kg): not established. Swallow whole. 6–<18yrs (16–<18kg): loading dose: 149mg every 8hrs for 6 doses (48hrs); maintenance dose: 149mg once daily starting 12–24hrs after the last loading dose. (18–<25kg): loading dose: 223.5mg every 8hrs for 6 doses (48hrs); maintenance dose: 223.5mg once daily starting 12–24hrs after the last loading dose. (25–<32kg): loading dose: 298mg every 8hrs for 6 doses (48hrs); maintenance dose: 298mg once daily starting 12–24hrs after the last loading dose. (≥32kg): loading dose: 372mg every 8hrs for 6 doses (48hrs); maintenance dose: 372mg 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.

Cresemba 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 Boxed Warnings

Not Applicable

Cresemba 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 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 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 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 Clinical Trials

See Literature

Cresemba Note