Source: European Medicines Agency (EU) Revision Year: 2024 Publisher: Merck Europe B.V., Gustav Mahlerplein 102, 1082 MA Amsterdam, The Netherlands
Bavencio is indicated as monotherapy for the treatment of adult patients with metastatic Merkel cell carcinoma (MCC).
Bavencio is indicated as monotherapy for the first-line maintenance treatment of adult patients with locally advanced or metastatic urothelial carcinoma (UC) who are progression-free following platinum-based chemotherapy.
Bavencio in combination with axitinib is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC) (see section 5.1).
Treatment should be initiated and supervised by a physician experienced in the treatment of cancer.
The recommended dose of Bavencio as monotherapy is 800 mg administered intravenously over 60 minutes every 2 weeks.
Administration of Bavencio should continue according to the recommended schedule until disease progression or unacceptable toxicity.
The recommended dose of Bavencio in combination with axitinib is 800 mg administered intravenously over 60 minutes every 2 weeks and axitinib 5 mg orally taken twice daily (12 hours apart) with or without food until disease progression or unacceptable toxicity.
For information on the posology of axitinib, please refer to the axitinib product information.
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.
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:
| Treatment-related adverse reaction | Severity* | Treatment modification |
|---|---|---|
| Infusion-related reactions | Grade 1 infusion-related reaction | Reduce infusion rate by 50% |
| Grade 2 infusion-related reaction | Withhold until adverse reactions recover to Grade 0-1; restart infusion with a 50% slower rate | |
| Grade 3 or Grade 4 infusion-related reaction | Permanently discontinue | |
| Pneumonitis | Grade 2 pneumonitis | Withhold until adverse reactions recover to Grade 0-1 |
| Grade 3 or Grade 4 pneumonitis or recurrent Grade 2 pneumonitis | Permanently discontinue | |
| Hepatitis For Bavencio in combination with axitinib, see below | Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 3 and up to 5 times upper limit of normal (ULN) or total bilirubin greater than 1.5 and up to 3 times ULN | Withhold until adverse reactions recover to Grade 0-1 |
| AST or ALT greater than 5 times ULN or total bilirubin greater than 3 times ULN | Permanently discontinue | |
| Colitis | Grade 2 or Grade 3 colitis or diarrhoea | Withhold until adverse reactions recover to Grade 0-1 |
| Grade 4 colitis or diarrhoea or recurrent Grade 3 colitis | Permanently discontinue | |
| Pancreatitis | Suspected pancreatitis | Withhold |
| Confirmed pancreatitis | Permanently discontinue | |
| Myocarditis | Suspected myocarditis | Withhold |
| Confirmed myocarditis | Permanently discontinue | |
| Endocrinopathies (hypothyroidism, hyperthyroidism, adrenal insufficiency, hyperglycaemia) | Grade 3 or Grade 4 endocrinopathies | Withhold until adverse reactions recover to Grade 0-1 |
| Nephritis and renal dysfunction | Serum creatinine more than 1.5 and up to 6 times ULN | Withhold until adverse reactions recover to Grade 0-1 |
| Serum creatinine more than 6 times ULN | Permanently discontinue | |
| Skin reactions | Grade 3 rash | Withhold until adverse reactions recover to Grade 0-1 |
| Grade 4 or recurrent Grade 3 rash or confirmed Stevens–Johnson syndrome (SJS) or Toxic epidermal necrolysis (TEN) | Permanently discontinue | |
| Other immune-related adverse reactions (including myositis, hypopituitarism, uveitis, myasthenia gravis, myasthenic syndrome, Guillain-Barré syndrome) | For any of the following: • Grade 2 or Grade 3 clinical signs or symptoms of an immune-related adverse reaction not described above | Withhold until adverse reactions recover to Grade 0-1 |
| For any of the following: • Life threatening or Grade 4 adverse reaction (excluding endocrinopathies controlled with hormone replacement therapy) • Recurrent Grade 3 immune-related adverse reaction • Requirement for 10 mg per day or greater prednisone or equivalent for more than 12 weeks • Persistent Grade 2 or Grade 3 immune-mediate adverse reactions lasting 12 weeks or longer | Permanently discontinue |
* Toxicity was graded per National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE v4.03)
If ALT or AST ≥3 times ULN but <5 times ULN or total bilirubin ≥1.5 times ULN but <3 times ULN, both Bavencio and axitinib should be withheld until these adverse reactions recover to Grades 0-1. If persistent (greater than 5 days), corticosteroid therapy with prednisone or equivalent followed by a taper should be considered. Rechallenge with Bavencio or axitinib or sequential rechallenge with both Bavencio and axitinib after recovery should be considered. Dose reduction according to the axitinib product information should be considered if rechallenging with axitinib.
If ALT or AST ≥5 times ULN or >3 times ULN with concurrent total bilirubin ≥2 times ULN or total bilirubin ≥3 times ULN, both Bavencio and axitinib should be permanently discontinued and corticosteroid therapy should be considered.
When Bavencio is administered in combination with axitinib, please refer to the axitinib product R/9608 | R/9609information for recommended dose modifications for axitinib.
No dose adjustment is needed for elderly patients (≥ 65 years) (see sections 5.1 and 5.2).
The safety and efficacy of Bavencio in children and adolescents below 18 years of age have not been established. Currently available data of Bavencio are described in section 5.1 but no recommendation on a posology can be made.
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.
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.
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.
Unopened vial:
3 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 as follows:
| Infusion solution | Storage at 2°C to 8°C protected from light | Storage at 20°C to 25°C and room light |
|---|---|---|
| Sodium chloride 9 mg/mL (0.9%) solution for injection | 96 hours | 72 hours |
| Sodium chloride 4.5 mg/mL (0.45%) solution for injection | 24 hours | 24 hours |
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.
An aseptic technique for the preparation of the solution for infusion should be used.
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.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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