IMREPLYS Powder for solution for injection Ref.[116016] Active ingredients: Sargramostim

Treatment with Imreplys should be started as soon as possible in any adult, adolescent, child, or infant who has been acutely exposed to myelosuppressive doses (greater than 2 gray [Gy]) of radiation with suspected H-ARS based on clinical signs and symptoms or confirmed H-ARS based on laboratory tests. If possible, a baseline complete blood count (CBC) with differential should be obtained.

If possible, estimate a patient's absorbed radiation dose (i.e., level of radiation exposure) based on information from public health authorities, biodosimetry if available, or clinical features and laboratory findings such as lymphocyte depletion kinetics.

Treatment should not be withheld if H-ARS is suspected or diagnosed even if the absorbed radiation dose is estimated as lower than 2 Gy. Imreplys should not be delayed if a CBC is not readily available or absorbed radiation dose cannot be estimated.

Posology

Imreplys should be administered once daily as a subcutaneous injection and dosing is based on body weight as follows:

• 7 micrograms/kg in children and adolescents weighing greater than 40 kg and in adults
• 10 micrograms/kg in children and adolescents weighing 15 kg to 40 kg
• 12 micrograms/kg in neonates, infants or children weighing less than 15 kg

See Treatment Response for guidance regarding Imreplys duration of treatment.

Dose modification

For grade 3 or 4 adverse reactions (see section 4.8), Imreplys dose should be reduced to 50%, or interrupted until the adverse reaction abates and then resumed at 50% of the dose. Other measures to manage the adverse reaction should be instituted and continued as necessary. If a grade 3 or 4 adverse reaction persists or recurs following dose adjustment/resumption, Imreplys should be permanently discontinued.

For grade 1 or 2 adverse reactions (see section 4.8), sargramostim should be continued with close patient monitoring and management of the adverse reaction.

Special populations

Elderly

No dose adjustment is required in elderly individuals ≥65 years of age.

Treatment response

A baseline CBC with differential and then serial CBCs should be obtained approximately every third day (when possible) until the absolute neutrophil count (ANC) remains greater than 1 000/mm³ for 3 consecutive CBCs. After the first achievement of ANC greater than 1 000/mm³, then serial CBCs should be collected daily (when possible) to avoid unnecessary treatment and minimise any risk of leucocytosis (see section 4.4). The start or continuation of administration of Imreplys should not be delayed if a CBC is not available.

Administration of Imreplys should continue until the ANC remains greater than 1 000/mm³ for 3 consecutive CBCs or exceeds 10 000/mm³ after a radiation-induced nadir. If CBCs are not available or in absence of treatment response, Imreplys may be discontinued after 23 consecutive days of dosing.

Method of administration

Imreplys should be administered subcutaneously in the abdomen, thigh, or upper arm.

Imreplys may be self-administered or administered by a caregiver.

Imreplys must be reconstituted in 1 mL of water for injections. Instructions for the preparation and administration of the reconstituted Imreplys powder are given in the package leaflet, section 3, "How to use Imreplys".

Doses up to 100 mcg/kg/day (4 000 mcg/m²/day or about 16 times the recommended dose) were administered to 4 patients with solid tumours in a Phase 1 uncontrolled study by continuous intravenous infusion for 7 to 18 days. Increases in WBC up to 200 000 cells/mm 3 were observed.

Dyspnoea, malaise, nausea, fever, rash, tachycardia, respiratory disorder, thrombocytopenia, headache, and chills were reported and were reversible after discontinuation of sargramostim.

In case of overdose, discontinue Imreplys therapy and monitor the patient for WBC increase and respiratory symptoms.

Unopened vial:

4 years.

Additional information:

• If unopened vials reach temperatures up to 25°C, they are stable up to 1 year when protected from light.
• If unopened vials reach temperatures up to 40°C, they are stable up to 1 month when protected from light.
• Do not expose to more than 1 Gy of ionising radiation. If unopened vials are exposed to up to 1 Gy of ionising radiation, they are stable up to 2 weeks at temperatures up to 40°C when protected from light.

After reconstitution:

After reconstitution with water for injections (not co-packaged with Imreplys), chemical and physical in-use stability has been demonstrated for 24 hours at 2°C–8°C.

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–8°C, unless reconstitution has taken place in controlled and validated aseptic conditions.

Store in a refrigerator (2°C–8°C).

Do not freeze.

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

Pack size of five 8 mL (Type I clear glass) vials.

Do not shake.

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