BAVENCIO Concentrate for solution Ref.[6315] Active ingredients: Avelumab

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

Posology

The recommended dose of Bavencio is 10 mg/kg body weight administered intravenously over 60 minutes every 2 weeks.

Administration of Bavencio should continue according to the recommended schedule until disease progression or unacceptable toxicity. Patients with radiological disease progression not associated with significant clinical deterioration, defined as no new or worsening symptoms, no change in performance status for greater than two weeks, and no need for salvage therapy, could continue treatment.

Premedication

Patients have to be premedicated with an antihistamine and with paracetamol prior to the first 4 infusions of Bavencio. If the fourth infusion is completed without an infusion-related reaction, premedication for subsequent doses should be administered at the discretion of the physician.

Treatment modifications

Dose escalation or reduction is not recommended. Dosing delay or discontinuation may be required based on individual safety and tolerability; see Table 1.

Detailed guidelines for the management of immune-related adverse reactions are described in section 4.4.

Table 1. Guidelines for withholding or discontinuation of Bavencio:

Special populations

Elderly

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

Paediatric population

The safety and efficacy of Bavencio in children and adolescents below 18 years of age have not been established.

Renal impairment

No dose adjustment is needed for patients with mild or moderate renal impairment (see section 5.2). There are insufficient data in patients with severe renal impairment for dosing recommendations.

Hepatic impairment

No dose adjustment is needed for patients with mild hepatic impairment (see section 5.2). There are insufficient data in patients with moderate or severe hepatic impairment for dosing recommendations.

Method of administration

Bavencio is for intravenous infusion only. It must not be administered as an intravenous push or bolus injection.

Bavencio has to be diluted with either sodium chloride 9 mg/mL (0.9%) solution for injection or with sodium chloride 4.5 mg/mL (0.45%) solution for injection. It is administered over 60 minutes as an intravenous infusion using a sterile, non-pyrogenic, low-protein binding 0.2 micrometre in-line or add-on filter.

For instructions on the preparation and administration of the medicinal product, see section 6.6.

Three patients were reported to be overdosed with 5% to 10% above the recommended dose of avelumab. The patients had no symptoms, did not require any treatment for the overdose, and continued on avelumab therapy.

In case of overdose, patients should be closely monitored for signs or symptoms of adverse reactions. The treatment is directed to the management of symptoms.

Shelf life

Unopened vial: 2 years.

After opening: From a microbiological point of view, once opened, the medicinal product should be diluted and infused immediately.

After preparation of infusion: Chemical and physical in-use stability of the diluted solution has been demonstrated for 24 hours at 20°C to 25°C and room light. From a microbiological point of view, unless the method of dilution precludes the risk of microbial contamination, the diluted solution should be infused immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user.

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 vial (Type I glass) with a halobutyl rubber stopper and an aluminium seal fitted with a removable plastic cap.

Pack size of 1 vial.

Bavencio is compatible with polyethylene, polypropylene, and ethylene vinyl acetate infusion bags, glass bottles, polyvinyl chloride infusion sets and in-line filters with polyethersulfone membranes with pore sizes of 0.2 micrometre.

Handling instructions

An aseptic technique for the preparation of the solution for infusion should be used.

• The vial should be visually inspected for particulate matter and discoloration. Bavencio is a clear, colourless to slightly yellow solution. If the solution is cloudy, discoloured, or contains particulate matters, the vial should be discarded.
• An infusion bag of appropriate size (preferably 250 mL) containing either sodium chloride 9 mg/mL (0.9%) solution for injection or with sodium chloride 4.5 mg/mL (0.45%) solution for injection should be used. The required volume of Bavencio should be withdrawn from the vial(s) and transferred to the infusion bag. Any partially used or empty vials have to be discarded.
• The diluted solution should be mixed by gently inverting the bag in order to avoid foaming or excessive shearing of the solution.
• The solution should be inspected to ensure it is clear, colourless, and free of visible particles. The diluted solution should be used immediately once prepared.
• Do not co-administer other medicinal products through the same intravenous line. Administer the solution for infusion using a sterile, non-pyrogenic, low-protein binding 0.2 micrometre in-line or add-on filter as described in section 4.2.

After administration of Bavencio, the line should be flushed with either sodium chloride 9 mg/mL (0.9%) solution for injection or with sodium chloride 4.5 mg/mL (0.45%) solution for injection.

Do not freeze or shake the diluted solution. If refrigerated, allow the diluted solution in the intravenous bags to come to room temperature prior to use.

Disposal

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