CRESEMBA

What it is

CRESEMBA contains isavuconazole (as isavuconazonium sulfate). Isavuconazonium sulfate is the prodrug of isavuconazole, an azole antifungal drug. 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, which 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 is available as a powder for injection containing 200 mg isavuconazole per vial, and as capsules containing either 100 mg or 40 mg isavuconazole per capsule. The powder for concentrate for solution for infusion is available for adults and paediatric patients from 1 year of age, and hard capsules in 40 mg and 100 mg strengths are also available.

Approved indications

CRESEMBA is indicated in adults and paediatric patients from 1 year of age for the treatment of invasive aspergillosis and mucormycosis in patients for whom amphotericin B is inappropriate. — Invasive aspergillosis — Mucormycosis in patients for whom amphotericin B is inappropriate

Dosing overview

For adult patients, the recommended loading dose is one reconstituted vial (200 mg) of powder for injection intravenously every 8 hours for 6 doses over 48 hours, or two 100 mg capsules orally every 8 hours for 6 doses over 48 hours. The recommended maintenance dose is one reconstituted vial (200 mg) intravenously once daily or two 100 mg capsules orally once daily, starting 12 to 24 hours after the last loading dose. For paediatric patients, dosing is weight-based. Patients weighing less than 37 kg receive a loading dose of 5.4 mg/kg isavuconazole intravenously every 8 hours for 6 doses, followed by a maintenance dose of 5.4 mg/kg intravenously once daily. Paediatric patients weighing 37 kg or more receive the same loading and maintenance doses as adults. Oral capsule dosing for paediatric patients from 6 years of age is weight-based, ranging from 80 mg to 200 mg per dose, with loading doses given every 8 hours for 6 doses and maintenance doses given once daily. Switching between intravenous and oral administration is appropriate when clinically indicated due to high oral bioavailability of 98%.

Key safety warnings

Hypersensitivity to isavuconazole may result in adverse reactions including anaphylactic reaction, hypotension, respiratory failure, dyspnoea, drug eruption, pruritus, and rash. In case of anaphylactic reaction, CRESEMBA should be discontinued immediately and appropriate medical treatment should be initiated. During intravenous administration of CRESEMBA, infusion-related reactions including hypotension, dyspnoea, dizziness, paraesthesia, nausea, and headache have been reported. The infusion should be stopped if these reactions occur. Severe cutaneous adverse reactions, such as Stevens-Johnson syndrome, have been reported during treatment with azole antifungal agents. If a patient develops a severe cutaneous adverse reaction, CRESEMBA should be discontinued. In a QT study in healthy human subjects, isavuconazole shortened the QTc interval in a concentration-related manner. For the 200 mg dosing regimen, the least squares mean difference from placebo was 13.1 ms at 2 hours post dose. Increasing the dose to 600 mg resulted in an LSM difference from placebo of 24.6 ms at 2 hours post dose. Caution is warranted when prescribing CRESEMBA to patients taking other medicinal products known to decrease the QT interval, such as rufinamide. Elevated liver transaminases have been reported in clinical studies, and while elevations rarely required discontinuation of CRESEMBA, serious hepatic reactions have been reported. Monitoring of hepatic enzymes should be considered as clinically indicated, and liver-related laboratory tests should be evaluated at the start and during the course of CRESEMBA therapy.

Contraindications

CRESEMBA is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients. Co-administration with ketoconazole is contraindicated. Co-administration with high dose ritonavir (greater than 200 mg every 12 hours) is contraindicated. Co-administration with strong CYP3A4/5 inducers such as rifampicin, rifabutin, carbamazepine, long-acting barbiturates (for example phenobarbital), phenytoin and St. John's wort or with moderate CYP3A4/5 inducers such as efavirenz, nafcillin and etravirine is contraindicated. CRESEMBA is contraindicated in patients with familial short QT syndrome.

PBS listing

No information regarding PBS listing for CRESEMBA has been provided in the source documents.

Regulatory history

CRESEMBA 200 mg powder for injection (ARTG 305480) and 100 mg capsules (ARTG 305452) were first listed on the ARTG on 17 May 2019. CRESEMBA 40 mg capsules (ARTG 437390) were first listed on the ARTG on 25 March 2025. The medicinal product is subject to additional monitoring in Australia due to approval of an extension of indications.