Bendeka

>10%

Lymphopenia (68-99%)

Leukopenia (61-94%; grade 3/4, 28-56%)

Anemia (88-89%; grades 3/4 11-13%)

Thrombocytopenia (77-86%; grade 3/4, 11-25%)

Neutropenia (75-86%; grade 3/4, 43-60%)

Nausea (20-75%)

Fatigue (9-57%)

Vomiting (16-40%)

Diarrhea (9-37%)

Bilirubin increased (<34%; grade 3/4, 3%)

Constipation (<29%)

Fever (24-34%)

Pyrexia (24%)

Anorexia (<23%)

Cough (4-22%)

Headache (<21%)

Weight loss (7-18%)

Dehydration (<16%)

Rash (8-16%)

Stomatitis (<15%)

Back pain (<14%)

Dizziness (<14%)

Chills (6-14%)

Peripheral edema (13%)

Abdominal pain (5-13%)

Insomnia (<13%)

Dyspepsia (<11%)

Weakness (8-11%)

1-10%

Upper respiratory infection (10%)

Gastroesophageal reflux disease (<10%)

Urinary tract infection (<10%)

Xerostomia (9%)

Hypokalemia (<9%)

Anxiety (8%)

Hyperuricemia (<7%)

Tachycardia (<7%)

Taste alteration (<7%)

Arthralgia (<6%)

Chest pain (<6%)

Depression (<6%)

Hypotension (<6%)

Injection site pain (<6%)

Pain (<6%)

Pruritus (5-6%)

Febrile neutropenia (3-6%)

Rash (5%)

Postmarketing Reports

Injection or infusion site reactions including phlebitis

Blood and lymphatic systems disorders: Pancytopenia, myelosuppression

Cardiovascular disorders: Atrial fibrillation, congestive heart failure (some fatal), myocardial infarction (some fatal), palpitation

General disorders and administration site conditions: Injection site reactions (including irritation, swelling), infusion site reactions (including pruritus, irritation, swelling)

Immune system disorders: Anaphylaxis Infections and infestations: Pneumocystis jiroveci pneumonia

Respiratory, thoracic and mediastinal disorders: Pneumonitis

Skin and subcutaneous tissue disorders: Stevens-Johnson syndrome (with concomitant allopurinol and other medications known to cause the syndrome), toxic epidermal necrolysis (with concomitant allopurinol and other medications known to cause the condition), drug reaction with eosinophilia and systemic symptoms (DRESS)

Tumor lysis syndrome

Skin reactions

Hepatotoxicity

Other malignancies

Extravasation Injury

Bendeka is part of the drug class:

• Nitrogen mustard analogues

Serious side effects have been reported with Bendeka including the following:

• Mild or serious allergic reactions. Immediately report rash, facial swelling, or difficulty breathing during or soon after infusion.
• A decrease in white blood cells, platelets, and red blood cells. Your doctor will monitor your blood counts. Report shortness of breath, significant fatigue, bleeding, fever, or other signs of infection.
• Bendeka may also cause tiredness. Avoid driving any vehicle or operating any dangerous tools or machinery if they experience this side effect.
• Nausea and Vomiting. Tell your doctor if you experience nausea, vomiting, and diarrhea. Your doctor may prescribe treatment to manage these side effects.
• Rash. Mild rash or itching may occur during treatment with Bendeka. Immediately report severe or worsening rash or itching.
• Harm to your unborn baby. Women should not become pregnant throughout treatment and for 3 months after treatment with Bendeka has stopped.

Do not take Bendeka if you are allergic to Bendeka or to any of its ingredients.

You should not be treated with this medicine if you are allergic to bendamustine or mannitol (Osmitrol).

To make sure bendamustine is safe for you, tell your doctor if you have:

• a weak immune system;

• fever or other signs of infection;

• a metabolic disorder or electrolyte imbalance;

• liver disease;

• kidney disease; or

• if you smoke.

Some people receiving bendamustine have developed certain types of cancers. It is not known whether this medication causes cancer. Talk with your doctor about the risks and benefits of using bendamustine.

Do not receive bendamustine if you are pregnant. It could harm the unborn baby. Use effective birth control while you are using this medicine and for at least 3 months after your treatment ends.

It is not known whether bendamustine passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Bendamustine may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

This medicine can pass into body fluids (urine, feces, vomit). For at least 48 hours after you receive a dose, avoid allowing your body fluids to come into contact with your hands or other surfaces. Caregivers should wear rubber gloves while cleaning up a patient's body fluids, handling contaminated trash or laundry or changing diapers. Wash hands before and after removing gloves. Wash soiled clothing and linens separately from other laundry.

Bendamustine injection is used to treat chronic lymphocytic leukemia (CLL, cancer of white blood cells) and indolent B-cell non-Hodgkin's lymphoma (NHL) in patients who have already received other treatments. It interferes with the growth of cancer cells, which are eventually destroyed by the body. Bendamustine belongs to a group of cancer medicines called alkylating agents.

Before you begin treatment with bendamustine, you and your doctor should talk about the benefits this medicine will have as well as the risks of using it.

This medicine is to be given only by or under the direct supervision of your doctor.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur:

• Black, tarry stools
• bleeding gums
• blood in the urine or stools
• chest pain
• chills
• cough or hoarseness
• diarrhea
• fever
• headache
• joint pain, stiffness, or swelling
• lack or loss of strength
• lower back, side, or stomach pain
• muscle aches
• nausea
• painful or difficult urination
• pale skin
• pinpoint red spots on the skin
• sore throat
• stuffy or runny nose
• swelling of the feet or lower legs
• swollen glands
• troubled breathing with exertion
• ulcers, sores, or white spots in the mouth
• unusual bleeding or bruising
• unusual tiredness or weakness
• vomiting

• Burning or stinging of the skin
• fast heartbeat
• hives, itching, or rash
• irritation
• painful cold sores or blisters on the lips, nose, eyes, or genitals
• redness of the skin
• stiffness or swelling
• swelling of the eyelids, face, lips, hands, or feet
• tightness in the chest
• troubled breathing or swallowing

• Blistering, flaking, or peeling of the skin
• bluish color
• changes in skin color
• dizziness
• pain, tenderness, or swelling of the foot or leg
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• red skin lesions, often with a purple center
• red, irritated eyes
• weakness

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Decreased weight

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of fluid and electrolyte problems like mood changes, confusion, muscle pain or weakness, a heartbeat that does not feel normal, very bad dizziness or passing out, fast heartbeat, more thirst, seizures, feeling very tired or weak, not hungry, unable to pass urine or change in the amount of urine produced, dry mouth, dry eyes, or very bad upset stomach or throwing up.
• Chest pain or pressure.
• Shortness of breath, a big weight gain, or swelling in the arms or legs.
• Low mood (depression).
• Patients with cancer who take this medicine may be at a greater risk of getting a bad health problem called tumor lysis syndrome (TLS). Sometimes, this has been deadly. Call your doctor right away if you have a fast heartbeat or a heartbeat that does not feel normal; any passing out; trouble passing urine; muscle weakness or cramps; upset stomach, throwing up, loose stools, or not able to eat; or feel sluggish.
• A very bad skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) may happen. It can cause very bad health problems that may not go away, and sometimes death. Get medical help right away if you have signs like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in your mouth, throat, nose, or eyes.

Safe Handling and Disposal

Bendeka (bendamustine hydrochloride) injection is a cytotoxic drug. Follow applicable special handling and disposal procedures.1 Care should be exercised in the handling and preparation of solutions prepared from Bendeka (bendamustine hydrochloride) injection. The use of gloves and safety glasses is recommended to avoid exposure in case of breakage of the vial or other accidental spillage. If a solution of Bendeka (bendamustine hydrochloride) injection contacts the skin, wash the skin immediately and thoroughly with soap and water. If Bendeka (bendamustine hydrochloride) injection contacts the mucous membranes, flush thoroughly with water.

How Supplied

Bendeka (bendamustine hydrochloride) injection is supplied in individual cartons of 5 mL clear multiple-dose vials containing 100 mg of bendamustine hydrochloride as a clear, and colorless to yellow ready-to-dilute solution.

• NDC 63459-348-04, 100 mg/4 mL (25 mg/mL)

Storage

Store Bendeka (bendamustine hydrochloride) injection in refrigerator, 2°-8°C (36°-46°F). Retain in original carton until time of use to protect from light.

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Tobacco