ALYMSYS Concentrate for solution for infusion Ref.[27839] Active ingredients: Bevacizumab

Do not shake the vial.

Alymsys must be administered under the supervision of a physician experienced in the use of antineoplastic medicinal products.

Posology

Metastatic carcinoma of the colon or rectum (mCRC)

The recommended dose of Alymsys, administered as an intravenous infusion, is either 5 mg/kg or 10 mg/kg of body weight given once every 2 weeks or 7.5 mg/kg or 15 mg/kg of body weight given once every 3 weeks.

It is recommended that treatment be continued until progression of the underlying disease or until unacceptable toxicity.

Metastatic breast cancer (mBC)

The recommended dose of Alymsys is 10 mg/kg of body weight given once every 2 weeks or 15 mg/kg of body weight given once every 3 weeks as an intravenous infusion.

It is recommended that treatment be continued until progression of the underlying disease or until unacceptable toxicity.

Non-small cell lung cancer (NSCLC)

First-line treatment of non-squamous NSCLC in combination with platinum-based chemotherapy

Alymsys is administered in addition to platinum-based chemotherapy for up to 6 cycles of treatment followed by Alymsys as a single agent until disease progression.

The recommended dose of Alymsys is 7.5 mg/kg or 15 mg/kg of body weight given once every 3 weeks as an intravenous infusion.

Clinical benefit in NSCLC patients has been demonstrated with both 7.5 mg/kg and 15 mg/kg doses (see section 5.1).

It is recommended that treatment be continued until progression of the underlying disease or until unacceptable toxicity.

First-line treatment of non-squamous NSCLC with EGFR activating mutations in combination with erlotinib

EGFR mutation testing should be performed prior to initiation of treatment with the combination of Alymsys and erlotinib. It is important that a well-validated and robust methodology is chosen to avoid false negative or false positive determinations.

The recommended dose of Alymsys when used in addition to erlotinib is 15 mg/kg of body weight given once every 3 weeks as an intravenous infusion.

It is recommended that the treatment with Alymsys in addition to erlotinib is continued until disease progression.

For the posology and method of administration of erlotinib, please refer to the full erlotinib prescribing information.

Advanced and/or metastatic renal cell cancer (mRCC)

The recommended dose of Alymsys is 10 mg/kg of body weight given once every 2 weeks as an intravenous infusion.

It is recommended that treatment be continued until progression of the underlying disease or until unacceptable toxicity.

Epithelial ovarian, fallopian tube and primary peritoneal cancer

Front-line treatment

Alymsys is administered in addition to carboplatin and paclitaxel for up to 6 cycles of treatment followed by continued use of Alymsys as single agent until disease progression or for a maximum of 15 months or until unacceptable toxicity, whichever occurs earlier.

The recommended dose of Alymsys is 15 mg/kg of body weight given once every 3 weeks as an intravenous infusion.

Treatment of platinum-sensitive recurrent disease

Alymsys is administered in combination with either carboplatin and gemcitabine for 6 cycles and up to 10 cycles or in combination with carboplatin and paclitaxel for 6 cycles and up to 8 cycles, followed by continued use of Alymsys as single agent until disease progression. The recommended dose of Alymsys is 15 mg/kg of body weight given once every 3 weeks as an intravenous infusion.

Treatment of platinum-resistant recurrent disease

Alymsys is administered in combination with one of the following agents – topotecan (given weekly) or pegylated liposomal doxorubicin. The recommended dose of Alymsys is 10 mg/kg of body weight given once every 2 weeks as an intravenous infusion. When Alymsys is administered in combination with topotecan (given on days 1-5, every 3 weeks), the recommended dose of Alymsys is 15 mg/kg of body weight given once every 3 weeks as an intravenous infusion. It is recommended that treatment be continued until disease progression or unacceptable toxicity (see section 5.1, study MO22224).

Cervical cancer

Alymsys is administered in combination with one of the following chemotherapy regimens: paclitaxel and cisplatin or paclitaxel and topotecan.

The recommended dose of Alymsys is 15 mg/kg of body weight given once every 3 weeks as an intravenous infusion.

It is recommended that treatment be continued until progression of the underlying disease or until unacceptable toxicity (see section 5.1).

Special populations

Elderly

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

Renal impairment

The safety and efficacy have not been studied in patients with renal impairment (see section 5.2).

Hepatic impairment

The safety and efficacy have not been studied in patients with hepatic impairment (see section 5.2).

Paediatric population

The safety and efficacy of bevacizumab in children aged less than 18 years old have not been established. Currently available data are described in sections 4.8, 5.1 and 5.2 but no recommendation on a posology can be made.

There is no relevant use of bevacizumab in the paediatric population in the indications for treatment of cancers of the colon, rectum, breast, lung, ovary, fallopian tube, peritoneum, cervix and kidney.

Method of administration

Alymsys is for intravenous use. The initial dose should be delivered over 90 minutes as an intravenous infusion. If the first infusion is well tolerated, the second infusion may be administered over 60 minutes. If the 60-minute infusion is well tolerated, all subsequent infusions may be administered over 30 minutes.

It should not be administered as an intravenous push or bolus. Dose reduction for adverse reactions is not recommended. If indicated, therapy should either be permanently discontinued or temporarily suspended as described in section 4.4.

Precautions to be taken before handling or administering the medicinal product

For instructions on dilution of the medicinal product before administration, see section 6.6. Alymsys infusions should not be administered or mixed with glucose solutions. It must not be mixed with other medicinal products except those mentioned in section 6.6.

The highest dose tested in humans (20 mg/kg of body weight, intravenous every 2 weeks) was associated with severe migraine in several patients.

Unopened vial:

30 months.

Diluted medicinal product:

Chemical and physical in-use stability has been demonstrated for 30 days at 2ºC to 8ºC plus an additional 48 hours at temperature not exceeding 30°C in sodium chloride 9 mg/mL (0.9%) solution for injection. From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user and would normally not be longer than 24 hours at 2°C to 8°C, unless dilution has taken place in controlled and validated aseptic conditions.

Store in a refrigerator (2°C-8°C).

Do not freeze.

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

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

4 mL solution in a vial (Type I glass) with a stopper (chlorobutyl rubber) containing 100 mg of bevacizumab.

16 mL solution in a vial (Type I glass) with a stopper (chlorobutyl rubber) containing 400 mg of bevacizumab.

Pack of 1 vial.

Alymsys should be prepared by a healthcare professional using aseptic technique to ensure the sterility of the prepared solution. A sterile needle and syringe should be used to prepare Alymsys.

The necessary amount of bevacizumab should be withdrawn and diluted to the required administration volume with sodium chloride 9 mg/mL (0.9%) solution for injection. The concentration of the final bevacizumab solution should be kept within the range of 1.4 mg/mL to 16.5 mg/mL. In the majority of the occasions the necessary amount of Alymsys can be diluted with sodium chloride 9 mg/mL (0.9%) solution for injection to a total volume of 100 mL.

No incompatibilities between Alymsys and polyvinyl chloride or polyolefin bags or infusion sets have been observed.

Parenteral medicinal products should be inspected visually for particulate matter and discolouration prior to administration.

Alymsys is for single-use only, as the product contains no preservatives. Any unused medicinal product or waste material should be disposed in accordance with local requirements.