CRESEMBA POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION 200MG

4.1 Therapeutic indications

CRESEMBA is indicated in adults for the treatment of

• invasive aspergillosis
• mucormycosis in patients for whom amphotericin B is inappropriate (see sections 4.4 and 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information)

Consideration should be given to official guidance on the appropriate use of antifungal agents.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.

Co-administration with ketoconazole (see section 4.5 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Co-administration with high-dose ritonavir (>200 mg every 12 hours) (see section 4.5 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Co-administration with strong CYP3A4/5 inducers such as rifampicin, rifabutin, carbamazepine, long-acting barbiturates (e.g., phenobarbital), phenytoin and St. John’s wort or with moderate CYP3A4/5 inducers such as efavirenz, nafcillin and etravirine (see section 4.5 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Patients with familial short QT syndrome (see section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

4.2 Posology and method of administration

Posology

Early targeted therapy (pre-emptive or diagnostic-driven therapy) may be instituted pending confirmation of the disease from specific diagnostic tests. However, once these results become available, antifungal therapy should be adjusted accordingly.

Loading dose

The recommended loading dose is one vial after reconstitution and dilution (equivalent to 200 mg of isavuconazole) every 8 hours for the first 48 hours (6 administrations in total).

Maintenance dose

The recommended maintenance dose is one vial after reconstitution and dilution (equivalent to 200 mg of isavuconazole) once daily, starting 12 to 24 hours after the last loading dose.

Duration of therapy should be determined by the clinical response (see section 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

For long-term treatment beyond 6 months, the benefit-risk balance should be carefully considered (see sections 5.1 and 5.3 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Switch to oral isavuconazole

CRESEMBA is also available as hard capsules containing 100 mg isavuconazole.

On the basis of the high oral bioavailability (98%, see section 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information), switching between intravenous and oral administration is appropriate when clinically indicated.

Elderly

No dose adjustment is necessary for elderly patients; however the clinical experience in elderly patients is limited.

Renal impairment

No dose adjustment is necessary in patients with renal impairment, including patients with end-stage renal disease (see section 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Hepatic impairment

No dose adjustment is necessary in patients with mild or moderate hepatic impairment (Child-Pugh Classes A and B) (see sections 4.4 and 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Isavuconazole has not been studied in patients with severe hepatic impairment (Child-Pugh Class C). Use in these patients is not recommended unless the potential benefit is considered to outweigh the risks (see sections 4.4, 4.8 and 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Paediatric population

The safety and efficacy of CRESEMBA in children aged below 18 years has not yet been established. No data are available.

Method of administration

Intravenous use.

Precautions to be taken before handling or administering the medicinal product

CRESEMBA must be reconstituted and then further diluted to a concentration corresponding to approximately 0.8 mg/mL isavuconazole prior to administration by intravenous infusion over a minimum of 1 hour to reduce the risk of infusion-related reactions. The infusion must be administered via an infusion set with an in-line filter with a microporous membrane made of polyethersulfone (PES) and with a pore size of 0.2 micrometre to 1.2 micrometre. CRESEMBA must only be given as an intravenous infusion.

For detailed instructions on the reconstitution and dilution of CRESEMBA before administration, see section 6.6 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.