Source: European Medicines Agency (EU) Revision Year: 2020 Publisher: Basilea Pharmaceutica Deutschland GmbH, Marie-Curie-Strasse 8, 79539, Lörrach, Germany
CRESEMBA is indicated in adults for the treatment of:
Consideration should be given to official guidance on the appropriate use of antifungal agents.
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).
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).
For long-term treatment beyond 6 months, the benefit-risk balance should be carefully considered (see sections 5.1 and 5.3).
CRESEMBA is also available as hard capsules containing 100 mg isavuconazole, equivalent to 186 mg isavuconazonium sulfate. On the basis of the high oral bioavailability (98%, see section 5.2), switching between intravenous and oral administration is appropriate when clinically indicated.
No dose adjustment is necessary for elderly patients; however the clinical experience in elderly patients is limited.
No dose adjustment is necessary in patients with renal impairment, including patients with end-stage renal disease (see section 5.2).
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).
CRESEMBA 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.
The safety and efficacy of CRESEMBA in children aged below 18 years has not yet been established.
No data are available.
Intravenous use.
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 μm to 1.2 μm. 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.
Symptoms reported more frequently at supratherapeutic doses of CRESEMBA (equivalent to isavuconazole 600 mg/day) evaluated in a QT study than in the therapeutic dose group (equivalent to isavuconazole 200 mg/day dose) included: headache, dizziness, paraesthesia, somnolence, disturbance in attention, dysgeusia, dry mouth, diarrhoea, oral hypoaesthesia, vomiting, hot flush, anxiety, restlessness, palpitations, tachycardia, photophobia and arthralgia
Isavuconazole is not removed by haemodialysis. There is no specific antidote for isavuconazole. In the event of an overdose, supportive treatment should be instituted.
Shelf life: 48 months.
Chemical and physical in-use stability after reconstitution and dilution has been demonstrated for 24 hours at 2°C to 8°C, or 6 hours at room temperature.
From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C to 8°C, unless reconstitution and dilution has taken place in controlled and validated aseptic conditions.
Store in a refrigerator (2°C to 8°C).
For storage conditions after reconstitution and dilution of the medicinal product, see section 6.3.
One 10 mL Type I glass vial with rubber stopper and an aluminum cap with plastic seal.
One vial of the powder for concentrate for solution for infusion should be reconstituted by addition of 5 mL water for injections to the vial. The vial should be shaken to dissolve the powder completely. The reconstituted solution should be inspected visually for particulate matter and discoloration. Reconstituted concentrate should be clear and free of visible particulate. It must be further diluted prior to administration.
After reconstitution, the entire content of the reconstituted concentrate should be removed from the vial and added to an infusion bag containing at least 250 mL of either sodium chloride 9 mg/mL (0.9%) solution for injection or 50 mg/mL (5%) dextrose solution. The infusion solution contains approximately 1.5 mg/mL isavuconazonium sulfate (corresponding to approximately 0.8 mg isavuconazole per mL). After the reconstituted concentrate is further diluted, the diluted solution may show fine white-to-translucent particulates of isavuconazole, that do not sediment (but will be removed by in-line filtration). The diluted solution should be mixed gently, or the bag should be rolled to minimise the formation of particulates. Unnecessary vibration or vigorous shaking of the solution should be avoided. The solution for infusion must be administered via an infusion set with an in-line filter (pore size 0.2 μm to 1.2 μm) made of polyether sulfone (PES).
Isavuconazole should not be infused into the same line or cannula concomitantly with other intravenous products.
Storage conditions after reconstitution and dilution are provided in section 6.3.
If possible, the intravenous administration of isavuconazole should be completed within 6 hours after reconstitution and dilution at room temperature. If this is not possible, the infusion solution should be immediately refrigerated after dilution, and infusion should be completed within 24 hours. Further information regarding the storage conditions after reconstitution and dilution of the medicinal product is provided in section 6.3.
An existing intravenous line should be flushed with sodium chloride 9 mg/mL (0.9%) solution for injection or 50 mg/mL (5%) dextrose solution.
This medicinal product is for single use only. Discard partially-used vials.
This medicinal product may pose a risk to the environment (see section 5.3).
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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