HETRONIFLY Concentrate for solution for infusion Ref.[114653] Active ingredients: Serplulimab

Treatment must be initiated and supervised by a physician experienced in the treatment of cancer.

Posology

The recommended dose is 4.5 mg/kg serplulimab every 3 weeks until disease progression or unacceptable toxicity.

Dose delay or discontinuation (see also section 4.4)

Dose escalation or reduction of HETRONIFLY is not recommended. Dose withholding or discontinuation may be required based on individual safety and tolerability. Dose withholding for up to 12 weeks for tolerability is acceptable (see section 4.4).

Serplulimab should be withheld or discontinued to manage adverse reactions as described in Table 1.

Table 1. Recommended treatment modifications:

Note: Toxicity grades are in accordance with National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v5.0).
ALT: alanine aminotransferase; AST: aspartate aminotransferase; ULN: upper limit of normal.
^# Serplulimab must be permanently discontinued for any Grade 3 immune-related adverse reaction that recurs and for any Grade 4 immune-mediated adverse reactions, except for endocrinopathies that are controlled with replacement hormones (see sections 4.4 and 4.8).
^* The safety of retreatment with serplulimab in patients who experienced immune-related myocarditis is not clear.

Special populations

Elderly

No dose adjustment is needed for elderly patients (≥65 years) (see section 5.1 and section 5.2).

Renal impairment

No dose adjustment is needed for patients with mild (CRCL=60-89 ml/min) or moderate (CRCL=30-59 ml/min) renal impairment. There are insufficient data and no dose recommendation can be made in patients with severe (CRCL=15-29 ml/min) renal impairment (see section 5.2).

Hepatic impairment

No dose adjustment is needed for patients with mild (BIL ≤ ULN and AST > ULN or BIL > 1 to 1.5 × ULN and any AST) hepatic impairment. There are insufficient data in patients with moderate (BIL > 1.5 to 3 × ULN and any AST) hepatic impairments and no data are available in severe (BIL > 3 × ULN and any AST) hepatic impairments. No dose recommendation can be made for patients with moderate or severe hepatic impairment (see section 5.2).

Paediatric population

There is no relevant use of serplulimab in the paediatric population in the indication of small cell lung cancer.

Method of administration

HETRONIFLY is for intravenous use.

The initial infusion rate should be set up to 100 ml per hour. If the first infusion is well tolerated, all subsequent infusions may be shortened to 30 minutes (± 10 minutes).

When administered in combination with chemotherapy, HETRONIFLY should be given first followed by chemotherapy on the same day. Use separate infusion bags for each infusion.

HETRONIFLY must not be administered as an intravenous push or bolus injection.

The total dose of HETRONIFLY required should be diluted with sodium chloride 9 mg/ml (0.9%) solution for injection (see section 6.6).

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

In case of overdose, patients must be closely monitored for signs or symptoms of adverse reactions, and appropriate symptomatic treatment instituted immediately.

Unopened vial:

3 years.

Diluted solution:

From a microbiological point of view, the product, once diluted, should be used immediately. The diluted solution must not be frozen. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and should not be longer than 24 hours at 2°C to 8°C. This 24-hour hold may include up to 6 hours at room temperature (≤25°C). If refrigerated, the vials and/or intravenous bags must be allowed to come to room temperature prior to use.

Store in a refrigerator (2°C-8°C).

Do not freeze.

Store in the original package in order to protect from light.

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

10 ml of concentrate in a 10 ml Type I clear glass vial with chlorobutyl rubber stopper and aluminium-plastic combination caps containing 100 mg of serplulimab.

Pack of 1 vial.

Preparation and administration:

• Aseptic handling should be ensured during the preparation of infusion.
• Do not shake the vial.
• Equilibrate the vial to room temperature (at or below 25°C).
• The product should be inspected visually for the particulate matters and discoloration prior to administration. The concentrate is a colourless to slightly yellow, clear to slightly opalescent solution. Discard the vial if visible particles are observed.
• Confirm the dose of the product and calculate the required volume of HETRONIFLY.
• Withdraw a volume of sodium chloride 9 mg/ml (0.9%) solution for injection corresponding to the volume of infused product from the target intravenous bag using a sterile syringe and discard.
• Use a syringe to withdraw the required volume of HETRONIFLY from the vial and inject it into the sodium chloride 9 mg/ml (0.9%) solution for injection to prepare a diluted solution with a final concentration range from 1.0 to 8.0 mg/ml. Mix the diluted solution by gentle inversion.
• Administer the infusion solution intravenously using a sterile, non-pyrogenic, low-protein binding 0.2 to 5.0 μm in-line or add-on filter.
• Set the initial infusion rate to 100 ml per hour (25 drops per minute is recommended). The infusion rate can be adjusted if infusion-related reactions occur (see section 4.2). If there is no infusion-related adverse reaction in the first infusion, the duration of subsequent administration can be shortened to 30 minutes (± 10 minutes).
• From a microbiological point of view, the product, once diluted, should be used immediately. The diluted solution must not be frozen. If not used immediately, the diluted solution can be stored for 24 hours at 2°C to 8°C. This 24-hour hold may include up to 6 hours at room temperature (≤25°C). If refrigerated, the vials and/or intravenous bags must be allowed to come to room temperature prior to use (see section 6.3).
• At the end of infusion, the infusion tube is flushed with sodium chloride 9 mg/ml (0.9%) solution according to the routine operation procedure of the hospital.
• Do not co-administer other medical products through the same infusion line.
• In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded in the patient file.

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