Bendamustine Fresenius Kabi

Chronic Lymphocytic Leukemia (CLL)

Bendamustine Fresenius Kabi (Bendamustine Fresenius Kabi hydrochloride) Injection is indicated for the treatment of patients with chronic lymphocytic leukemia. Efficacy relative to first line therapies other than chlorambucil has not been established.

Non-Hodgkin Lymphoma (NHL)

Bendamustine Fresenius Kabi (Bendamustine Fresenius Kabi hydrochloride) Injection is indicated for the treatment of patients with indolent B-cell non-Hodgkin lymphoma that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen.

Bendamustine Fresenius Kabi injection is used to treat a type of cancer of the white blood cells called chronic lymphocytic leukemia (CLL). It is also used to treat indolent B-cell non-Hodgkin's lymphoma (NHL) in patients who have already been treated with rituximab.

Bendamustine Fresenius Kabi belongs to the group of medicines called alkylating agents. It interferes with the growth of cancer cells, which are eventually destroyed. Since the growth of normal cells may also be affected by the medicine, other effects may also occur. Some of these may be serious and must be reported to your doctor. Other effects may not be serious but may cause concern. Some effects may occur after treatment with Bendamustine Fresenius Kabi has been stopped.

Before you begin treatment with Bendamustine Fresenius Kabi, you and your doctor should talk about the benefits Bendamustine Fresenius Kabi will have as well as the risks of using it.

Bendamustine Fresenius Kabi is to be given only by or under the direct supervision of your doctor.

Once a medicine has been approved for marketing for a certain use, experience may show that it is also useful for other medical problems. Although these uses are not included in product labeling, Bendamustine Fresenius Kabi is used in certain patients with the following medical conditions:

• Breast cancer, metastatic (breast cancer that has already spread).
• Multiple myeloma (a type of cancer in the bone marrow).

Selection Of Bendamustine Fresenius Kabi Formulation To Administer

Bendamustine Fresenius Kabi is available in two formulations, a solution (Bendamustine Fresenius Kabi Injection) and a lyophilized powder (Bendamustine Fresenius Kabi for Injection).

Do not use Bendamustine Fresenius Kabi Injection if you intend to use closed system transfer devices (CSTDs), adapters and syringes containing polycarbonate or acrylonitrile-butadiene-styrene (ABS) prior to dilution in the infusion bag.

If using a syringe to withdraw and transfer Bendamustine Fresenius Kabi Injection from the vial into the infusion bag, only use a polypropylene syringe with a metal needle and polypropylene hub to withdraw and transfer Bendamustine Fresenius Kabi Injection into the infusion bag. Polypropylene syringes are translucent in appearance.

Bendamustine Fresenius Kabi Injection and the reconstituted Bendamustine Fresenius Kabi for Injection have different concentrations of Bendamustine Fresenius Kabi hydrochloride. The concentration of Bendamustine Fresenius Kabi hydrochloride in the solution is 90 mg/mL and the concentration of Bendamustine Fresenius Kabi hydrochloride in the reconstituted solution of lyophilized powder is 5 mg/mL. Do not mix or combine the two formulations.

Bendamustine Fresenius Kabi Injection must be withdrawn and transferred for dilution in a biosafety cabinet (BSC) or containment isolator using a polypropylene syringe with a metal needle and a polypropylene hub.

If a CSTD or adapter that contains polycarbonate or ABS is used as supplemental protection prior to dilution. If a solution of Bendamustine Fresenius Kabi contacts the skin, wash the skin immediately and thoroughly with soap and water. If Bendamustine Fresenius Kabi contacts the mucous membranes, flush thoroughly with water.

How Supplied

Bendamustine Fresenius Kabi (Bendamustine Fresenius Kabi hydrochloride) Injection is supplied as a 90 mg/mL clear colorless to yellow solution in individual cartons as follows:

NDC 63459-395-02: 45 mg/0.5 mL of solution in an amber single-dose vial

NDC 63459-396-02: 180 mg/2 mL of solution in an amber single-dose vial

Bendamustine Fresenius Kabi (Bendamustine Fresenius Kabi hydrochloride) for Injection is supplied in individual cartons as follows:

NDC 63459-390-08: 25 mg white to off-white lyophilized powder in a 8 mL amber single-dose vial

NDC 63459-391-20: 100 mg white to off-white lyophilized powder in a 20 mL amber single-dose vial

Storage

Bendamustine Fresenius Kabi Injection (45 mg/0.5 mL or 180 mg/2 mL solution)

Bendamustine Fresenius Kabi Injection must be stored refrigerated between 2° to 8°C (36° to 46°F). Retain in original package until time of use to protect from light.

Bendamustine Fresenius Kabi for Injection (25 mg/vial or 100 mg/vial lyophilized powder)

Bendamustine Fresenius Kabi for Injection may be stored up to 25°C (77°F) with excursions permitted up to 30°C (86°F). Retain in original package until time of use to protect from light.

Distributed By: Teva Ph carmaceuticals USA, Inc. North Wales, PA 19454. Revised: Oct 2015

See also:
What is the most important information I should know about Bendamustine Fresenius Kabi?

Hypersensitivity to Bendamustine Fresenius Kabi hydrochloride or to any excipients of Bendamustine Fresenius Kabi. During breast-feeding. Severe hepatic impairment (serum bilirubin >3 mg/dL); jaundice; severe bone marrow suppression and severe blood count alterations (leukocyte and/or platelet values dropped to <3,000/μL or <75,000/μL, respectively); major surgery less than 30 days before start of treatment; infections, especially involving leukocytopenia; yellow fever vaccination.

Use in Lactation: It is not known whether Bendamustine Fresenius Kabi passes into the breast milk therefore, Bendamustine Fresenius Kabi is contraindicated during breastfeeding. Breastfeeding must be discontinued during treatment with Bendamustine Fresenius Kabi.

Use Bendamustine Fresenius Kabi as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Bendamustine Fresenius Kabi is given as an injection at your doctor's office, hospital, or clinic. If you will be using Bendamustine Fresenius Kabi at home, a health care provider will teach you how to use it. Be sure you understand how to use Bendamustine Fresenius Kabi. Follow the procedures you are taught when you use a dose. Contact your health care provider if you have any questions.
• Do not use Bendamustine Fresenius Kabi if it contains particles, is cloudy or discolored, or if the vial is cracked or damaged.
• If Bendamustine Fresenius Kabi accidentally spills on your skin, wash it off right away with soap and water.
• Keep this product, as well as syringes and needles, out of the reach of children and away from pets. Do not reuse needles, syringes, or other materials. Ask your health care provider how to dispose of these materials after use. Follow all local rules for disposal.
• If you miss a dose of Bendamustine Fresenius Kabi, contact your doctor right away.

Ask your health care provider any questions you may have about how to use Bendamustine Fresenius Kabi.

Use: Labeled Indications

Chronic lymphocytic leukemia: Treatment of chronic lymphocytic leukemia (CLL)

Non-Hodgkin lymphoma: Treatment of indolent B-cell non-Hodgkin lymphoma (NHL) which has progressed during or within 6 months of rituximab treatment or a rituximab-containing regimen

Off Label Uses

Hodgkin lymphoma (relapsed or refractory)

Data from a phase II study supports the use of Bendamustine Fresenius Kabi in the treatment of relapsed or refractory Hodgkin lymphoma following failure of autologous stem cell transplant as a bridge to allogeneic stem cell transplant.

See also:
What other drugs will affect Bendamustine Fresenius Kabi?

Allopurinol: May enhance the adverse/toxic effect of Bendamustine Fresenius Kabi. Specifically, the risk of severe skin reactions may be enhanced. Monitor therapy

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Monitor therapy

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Avoid combination

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy

CYP1A2 Inducers (Moderate): May decrease the serum concentration of Bendamustine Fresenius Kabi. Concentrations of active metabolites may be increased. Management: Consider alternatives to moderate CYP1A2 inducers during therapy with Bendamustine Fresenius Kabi due to the potential for decreased Bendamustine Fresenius Kabi plasma concentrations and reduced efficacy. Consider therapy modification

CYP1A2 Inhibitors (Moderate): May increase the serum concentration of Bendamustine Fresenius Kabi. Management: Consider alternatives to moderate CYP1A2 inhibitors during therapy with Bendamustine Fresenius Kabi due to the potential for increased Bendamustine Fresenius Kabi plasma concentrations and increased Bendamustine Fresenius Kabi toxicity. Consider therapy modification

CYP1A2 Inhibitors (Strong): May increase the serum concentration of Bendamustine Fresenius Kabi. Concentrations of the active metabolites of Bendamustine Fresenius Kabi may be decreased. Management: Consider alternatives to strong CYP1A2 inhibitors during therapy with Bendamustine Fresenius Kabi due to the potential for increased Bendamustine Fresenius Kabi plasma concentrations and increased Bendamustine Fresenius Kabi toxicity. Consider therapy modification

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Consider therapy modification

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination

Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Consider therapy modification

Lipegfilgrastim: Antineoplastic Agents may diminish the therapeutic effect of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Consider therapy modification

Mesalamine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Palifermin: May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Consider therapy modification

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

See also:
What are the possible side effects of Bendamustine Fresenius Kabi?

The following serious adverse reactions have been associated with Bendamustine Fresenius Kabi hydrochloride in clinical trials and are discussed in greater detail in other sections of the prescribing information.

• Myelosuppression
• Infections
• Anaphylaxis and Infusion Reactions
• Tumor Lysis Syndrome
• Skin Reactions
• Other Malignancies
• Extravasation Injury

Adverse Events In Clinical Trials

The data described below reflect exposure to Bendamustine Fresenius Kabi hydrochloride in 329 patients who participated in an actively controlled trial (N=153) for the treatment of CLL and two single arm studies (N=176) for the treatment of indolent B cell NHL. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of Bendamustine Fresenius Kabi (Bendamustine Fresenius Kabi hydrochloride) Injection administered IV as a 50 mL admixture over a 10-minute infusion is supported by clinical trials using Bendamustine Fresenius Kabi hydrochloride administered IV as a 500 mL admixture over 30-60 minutes infusion time, as well as an open-label, crossover study in 81 'end-of-life' cancer patients treated with Bendamustine Fresenius Kabi. In total, safety data from clinical studies are available from over 400 cancer patients exposed to Bendamustine Fresenius Kabi hydrochloride at doses in the range used in the treatment of CLL and NHL.

No clinically significant differences in the adverse event profile were noted among Bendamustine Fresenius Kabi hydrochloride administered as a 500 mL admixture over standard infusion time (30-60 minutes) and Bendamustine Fresenius Kabi administered as a 50 mL admixture in a 'short-time' infusion over 10 minutes.

The safety and tolerability of Bendamustine Fresenius Kabi was evaluated in an 8-week clinical study of Bendamustine Fresenius Kabi in 81 'end-of-life' cancer patients, diagnosed with solid tumors and hematologic malignancies (excluding CLL). The population was 40-82 years of age, 58% females, 84% white, 12.3% Black, 1.2% Asian and 2.5% were classified as 'other'. Bendamustine Fresenius Kabi was administered IV at a 120 mg/m² dose as a 50 mL admixture over 10 minutes. Patients in the study received Bendamustine Fresenius Kabi(50 mL IV, over 10 minutes) or Bendamustine Fresenius Kabi hydrochloride (500 mL IV, over 60 minutes) on Days 1 and 2 every 28 days for two consecutive 2-day cycles.

Adverse reactions (any grade) that occurred with a frequency greater than 5% during Bendamustine Fresenius Kabi infusion and within one hour post-infusion were nausea (8.2%) and fatigue (5.5%).

Adverse reactions (any grade) that occurred with a frequency greater than 5% within 24 hours of Bendamustine Fresenius Kabi were nausea (10.9%) and fatigue (8.2%).

The adverse reactions leading to study withdrawal in 4 patients receiving Bendamustine Fresenius Kabi were pyrexia (1.2%), nausea (1.2%), vomiting (1.2%), pneumonia (1.2%) and fatigue (1.2%).

Clinical Trials Experience In CLL

The data described below reflect exposure to Bendamustine Fresenius Kabi hydrochloride in 153 patients. Bendamustine Fresenius Kabi hydrochloride was studied in an active-controlled trial. The population was 45-77 years of age, 63% male, 100% white, and had treatment na

Each vial contains Bendamustine HCl 25 or 100 mg equivalent to Bendamustine Fresenius Kabi 22.7 or 90.8 mg, respectively. It also contains mannitol as an excipient.

Bendamustine Fresenius Kabi HCl is an alkylating drug. It is 1H-benzimidazole-2-butanoic acid, 5-[bis(2-chloroethyl)amino]-1 methyl-, monohydrochloride. Its empirical formula is C₁₆H₂₁Cl₂N₃O₂·HCl and the molecular weight is 394.7. Bendamustine Fresenius Kabi HCl contains a mechlorethamine group and a benzimidazole heterocyclic ring with a butyric acid substituent.