REZZAYO Powder for solution for infusion Ref.[107889] Active ingredients: Rezafungin

Treatment with REZZAYO should be initiated by a physician experienced in the management of invasive fungal infections.

Posology

A single 400 mg loading dose on Day 1, followed by 200 mg on Day 8 and once weekly thereafter.

The duration of treatment should be based upon the patient’s clinical and microbiological response. In general, antifungal therapy should continue for at least 14 days after the last positive culture. During clinical trials patients were treated with rezafungin for up to 28 days. The safety information on rezafungin treatment durations longer than 4 weeks is limited.

If a scheduled dose is missed (not given on the assigned day) the missed dose should be administered as soon as possible.

• If the missed dose is administered within 3 days of the assigned day, the next weekly dose may be given on schedule.
• If the missed dose is administered more than 3 days after the assigned day, the dosing schedule should be revised to ensure there are at least 4 days before the next dose.
• If administration is restarted after at least 2 weeks of missed dosing, the dosing should be started again at the 400 mg loading dose.

Special populations

Elderly

No dose adjustment is required in elderly patients aged 65 years or more (see section 5.2).

Hepatic impairment

No dose adjustment is required for patients with hepatic impairment (see section 5.2).

Renal impairment

No dose adjustment is required for patients with renal impairment. This medicinal product can be given without regard to the timing of haemodialysis (see section 5.2).

Other populations

No dose adjustment is required based on patients' weight (see section 5.2).

Paediatric population

The safety and efficacy of REZZAYO in children below 18 years have not yet been established. No data are available.

Method of administration

For intravenous use only.

After reconstitution and dilution (see section 6.6), the solution should be administered by slow intravenous infusion over approximately 1 hour, infusion time may be increased up to 180 minutes to manage any evolving symptoms of infusion-related reaction (see section 4.4).

For instructions on reconstitution and dilution of the medicinal product before administration, see section 6.6.

In the event of overdose, supportive care and symptomatic treatment is advised with maintenance of homeostasis and vital functions.

In a Phase 1 clinical trial, single doses of 600 mg and 1 400 mg were administered with no reported dose-limiting toxicity. Rezafungin doses of 400 mg once weekly for up to 4 weeks were administered in a Phase 2 clinical trial with no reported dose-limiting toxicity.

Rezafungin is highly protein-bound and not expected to be dialysable (see section 5.2).

Unopened vial:

3 years.

Stability of the reconstituted solution in the vial and the diluted solution for infusion:

Chemical and physical in-use stability, when reconstituted with water for injections, has been demonstrated for up to 24 hours at 25°C and 2 to 8°C.

Chemical and physical in-use stability of the diluted solution for infusion (immediately following reconstitution) has been demonstrated for 48 hours at 25°C and 2 to 8°C.

From a microbiological point of view, the reconstituted solution and the diluted solution for infusion should be used immediately. If not used immediately, in-use storage conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C from first opening, unless reconstitution and dilution have taken place in controlled and validated aseptic conditions.

Do not store above 25°C.

Keep the vial in the outer carton in order to protect from light.

For storage conditions after reconstitution and dilution of the medicinal product, see section 6.3.

Glass vial with chlorobutyl rubber stopper and aluminium seal with plastic flip-off cap.

Pack size: 1 vial.

REZZAYO should be administered as a single agent via intravenous infusion in sodium chloride 9 mg/mL (0.9%) solution for injection, sodium chloride 4.5 mg/mL (0.45%) solution for injection, or 5% glucose.

Instructions for use in adult patients

REZZAYO must be reconstituted and diluted prior to administration.

From a microbiological point of view, the reconstituted solution and the diluted solution for infusion should be used immediately. If not used immediately, in-use storage conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C from first opening, unless reconstitution and dilution have taken place in controlled and validated aseptic conditions.

Using aseptic techniques, reconstitute each vial with 9.5 mL water for injections. The concentration of the reconstituted vial will be 20 mg/mL. Do not use sterile sodium chloride 9 mg/mL (0.9%) solution for injection to reconstitute the vial, only use water for injections.

To minimise foaming, do not shake or mix vigorously. The white to pale yellow powder will dissolve completely. Mix using a gentle swirling motion for up to 5 minutes until the reconstituted solution is a clear, colourless to pale yellow solution. The reconstituted solution should be visually inspected for particulate matter or discolouration. If irregularities are found, do not use the vial.

The vial is for single use only. Therefore, unused reconstituted concentrate must be discarded immediately.

For the 400 mg loading dose, the reconstitution step should be repeated for the additional vial of REZZAYO (refer to dosing table).

The infused total volume should be 250 mL, therefore, the volume of the intravenous infusion bag (or bottle) should be adjusted accordingly, as shown in the dosing table. Aseptically transfer 10 mL from each of the reconstituted vials into an intravenous infusion bag (or bottle) containing either sodium chloride 9 mg/mL (0.9%) solution for injection, sodium chloride 4.5 mg/mL (0.45%) solution for injection, or 5% glucose. The total reconstituted volume to be added to the intravenous bag or bottle is shown in the dosing table. Mix the solution by gentle inversion of the intravenous bag (or bottle). Avoid excessive agitation.

After dilution, the solution is to be discarded if particulate matter or discolouration is identified.

Dosing table – Preparation of the solution for infusion in adults:

^* 10 mL from each of two vials totalling 20 mL.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.