OYAVAS Concentrate for solution for infusion Ref.[27639] Active ingredients: Bevacizumab

Source: European Medicines Agency (EU)  Revision Year: 2021  Publisher: STADA Arzneimittel AG, Stadastrasse 2-18, 61118 Bad Vilbel, Germany

4.1. Therapeutic indications

Oyavas in combination with fluoropyrimidine based chemotherapy is indicated for treatment of adult patients with metastatic carcinoma of the colon or rectum.

Oyavas in combination with paclitaxel is indicated for first line treatment of adult patients with metastatic breast cancer. For further information as to human epidermal growth factor receptor 2 (HER2) status, please refer to section 5.1.

Oyavas in combination with capecitabine is indicated for first line treatment of adult patients with metastatic breast cancer in whom treatment with other chemotherapy options including taxanes or anthracyclines is not considered appropriate. Patients who have received taxane and anthracycline containing regimens in the adjuvant setting within the last 12 months should be excluded from treatment with Oyavas in combination with capecitabine. For further information as to HER2 status, please refer to section 5.1.

Oyavas, in addition to platinum-based chemotherapy, is indicated for first line treatment of adult patients with unresectable advanced, metastatic or recurrent non-small cell lung cancer other than predominantly squamous cell histology.

Oyavas, in combination with erlotinib, is indicated for first line treatment of adult patients with unresectable advanced, metastatic or recurrent non-squamous non-small cell lung cancer with Epidermal Growth Factor Receptor (EGFR) activating mutations (see section 5.1).

Oyavas in combination with interferon alfa 2a is indicated for first line treatment of adult patients with advanced and/or metastatic renal cell cancer.

Oyavas, in combination with carboplatin and paclitaxel is indicated for the front-line treatment of adult patients with advanced (International Federation of Gynecology and Obstetrics (FIGO) stages III B, III C and IV) epithelial ovarian, fallopian tube, or primary peritoneal cancer (see section 5.1).

Oyavas, in combination with carboplatin and gemcitabine or in combination with carboplatin and paclitaxel, is indicated for treatment of adult patients with first recurrence of platinum sensitive epithelial ovarian, fallopian tube or primary peritoneal cancer who have not received prior therapy with bevacizumab or other VEGF inhibitors or VEGF receptor–targeted agents.

Oyavas, in combination with topotecan, or pegylated liposomal doxorubicin is indicated for the treatment of adult patients with platinum resistant recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who received no more than two prior chemotherapy regimens and who have not received prior therapy with bevacizumab or other VEGF inhibitors or VEGF receptor targeted agents (see Section 5.1).

Oyavas, in combination with paclitaxel and cisplatin or, alternatively, paclitaxel and topotecan in patients who cannot receive platinum therapy, is indicated for the treatment of adult patients with persistent, recurrent, or metastatic carcinoma of the cervix (see section 5.1).

4.2. Posology and method of administration

Oyavas 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 Oyavas, 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 Oyavas 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

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

The recommended dose of Oyavas 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 Oyavas 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 Oyavas 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 Oyavas 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 Oyavas 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

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

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

Treatment of platinum sensitive recurrent disease

Oyavas 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 Oyavas as single agent until disease progression. The recommended dose of Oyavas is 15 mg/kg of body weight given once every 3 weeks as an intravenous infusion.

Treatment of platinum resistant recurrent disease

Oyavas is administered in combination with one of the following agents – topotecan (given weekly) or pegylated liposomal doxorubicin. The recommended dose of Oyavas is 10 mg/kg of body weight given once every 2 weeks as an intravenous infusion. When Oyavas is administered in combination with topotecan (given on days 1 5, every 3 weeks), the recommended dose of Oyavas 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

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

The recommended dose of Oyavas 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

Oyavas 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. Oyavas 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.

4.9. Overdose

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

6.3. Shelf life

Unopened vial: 30 months.

Diluted medicinal product: Chemical and physical in use stability has been demonstrated for 30 days at 2°C to 8°C 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.

6.4. Special precautions for storage

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.

6.5. Nature and contents of container

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.

6.6. Special precautions for disposal and other handling

Oyavas should be prepared by a healthcare professional using aseptic technique to ensure the sterility of the prepared solution.

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 Oyavas can be diluted with sodium chloride 9 mg/mL (0.9%) solution for injection to a total volume of 100 mL.

No incompatibilities between Oyavas 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.

Oyavas 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.

© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.