Bendamustine Glenmark

Package Leaflet: Information for the User

Bendamustine Glenmark, 2.5 mg/ml, Powder for Concentrate for Solution for Infusion

Bendamustine Hydrochloride

Read All of This Leaflet Carefully Before You Start Using This Medicine Because It Contains Important Information for You.

• You should keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the Pack

• 1. What is Bendamustine Glenmark and What is it Used For
• 2. Before You Use Bendamustine Glenmark
• 3. How to Use Bendamustine Glenmark
• 4. Possible Side Effects
• 5. How to Store Bendamustine Glenmark
• 6. Contents of the Pack and Other Information

1. What is Bendamustine Glenmark and What is it Used For

Bendamustine Glenmark is a medicine used to treat certain types of cancer (cytostatic medicine). Bendamustine Glenmark is used alone (monotherapy) or in combination with other medicines to treat the following types of cancer:

• Chronic lymphocytic leukemia when fludarabine combination chemotherapy is not appropriate,
• Non-Hodgkin's lymphoma that has not responded or has responded poorly to previous rituximab treatment,
• Multiple myeloma when chemotherapy containing thalidomide or bortezomib is not appropriate.

2. Before You Use Bendamustine Glenmark

When Not to Use Bendamustine Glenmark:

• If you are allergic to bendamustine hydrochloride or any of the other ingredients of this medicine (listed in section 6);
• During breastfeeding, if the use of Bendamustine Glenmark is necessary during this period, you should stop breastfeeding (see section on warnings and precautions during breastfeeding);
• If you have severe liver damage (liver cell function impairment);
• If you have jaundice or yellowing of the skin and whites of the eyes due to liver function disorders or blood disease (jaundice);
• If you have severe bone marrow disorders (bone marrow suppression) and significant changes in white blood cell and platelet counts;
• If you have had extensive surgery within 30 days before starting treatment;
• If you have an infection, especially with a low white blood cell count (leukopenia);
• If you have been vaccinated against yellow fever.

Warnings and Precautions

Before starting treatment with Bendamustine Glenmark, you should discuss this with your doctor, pharmacist, or nurse.

• In case of reduced bone marrow function. Your doctor will check your white blood cell and platelet counts before starting treatment with Bendamustine Glenmark, before each subsequent treatment cycle, and during treatment breaks.
• In case of infection. You should contact your doctor if you experience symptoms of infection, including fever and respiratory symptoms.
• In case of skin reactionsduring treatment with Bendamustine Glenmark. Skin reactions may worsen.
• In case of painful red or purple rash that spreads and blisters and/or other skin changes that start to appear on the mucous membranes (e.g., in the mouth or on the lips), especially if you have previously experienced sensitivity to light, respiratory infections (e.g., bronchitis), and/or fever.
• In case of heart disease(e.g., heart attack, chest pain, severe heart rhythm disorders).
• In case of pain in the side, blood in the urine, or decreased urine output. If you have advanced disease, your body may not be able to remove the products that result from the death of cancer tissue. This is called tumor lysis syndrome, which can cause kidney function disorders and heart disease within 48 hours of the first dose of Bendamustine Glenmark. Your doctor may ensure that you are properly hydrated and may give you other medicines to prevent this.
• In case of severe allergic reactions or hypersensitivity reactions.You should be aware of reactions related to the administration of the medicine after the first treatment cycle.

You should tell your doctor immediately if you experience any of the following symptoms at any time during or after treatment: memory loss, thinking problems, difficulty walking, or vision loss — these may be caused by a very rare but serious brain infection (progressive multifocal leukoencephalopathy, PML), which can be fatal. If you notice any suspicious skin changes, you should contact your doctor, as there is an increased risk of certain types of skin cancer (non-melanoma skin cancer) during treatment with this medicine.

Children and Adolescents

There is no clinical experience with the use of bendamustine hydrochloride in children and adolescents.

Bendamustine Glenmark and Other Medicines

You should tell your doctor or pharmacist about all medicines you are taking or have recently taken, as well as any medicines you plan to take. If Bendamustine Glenmark is used in combination with medicines that suppress bone marrow function, the effect on the bone marrow may be increased. If Bendamustine Glenmark is used in combination with medicines that affect the immune system, it may enhance this effect. Cytostatic medicines may reduce the effectiveness of vaccinations using live viruses. Cytostatic medicines also increase the risk of infection after vaccination with live vaccines (e.g., live virus vaccines).

Pregnancy, Breastfeeding, and Fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, ask your doctor or pharmacist for advice before using this medicine. Pregnancy Bendamustine Glenmark may cause genetic damage and birth defects in animals. You should not use Bendamustine Glenmark during pregnancy unless your doctor considers it absolutely necessary. If treatment is necessary, you should discuss the possible risks to the unborn child and the possibility of genetic testing with your doctor. Women of childbearing age should use effective contraception before, during, and after treatment with Bendamustine Glenmark. If you become pregnant during treatment with Bendamustine Glenmark, you should inform your doctor immediately and undergo genetic testing. Breastfeeding You should not use Bendamustine Glenmark during breastfeeding. If the use of Bendamustine Glenmark is necessary, you should stop breastfeeding. You should consult your doctor or pharmacist before using any medicine. Fertility Men taking Bendamustine Glenmark are advised not to father a child during treatment and for 6 months after treatment. Before starting treatment, you should consult your doctor about the possibility of sperm preservation due to the risk of permanent infertility. Men should not plan to father a child during treatment with Bendamustine Glenmark or for 6 months after treatment. There is a risk that Bendamustine Glenmark may cause infertility, so before starting treatment, men should consult their doctor about the possibility of sperm preservation.

Driving and Using Machines

Bendamustine Glenmark can significantly affect your ability to drive and use machines. You should not drive or operate machinery if you experience side effects such as dizziness or coordination problems.

3. How to Use Bendamustine Glenmark

You should always use Bendamustine Glenmark exactly as your doctor or pharmacist has told you. If you are not sure, ask your doctor or pharmacist. Bendamustine Glenmark is given by infusion into a vein, in different doses over 30-60 minutes, either alone (monotherapy) or in combination with other anticancer medicines. Treatment should not be started if your white blood cell and/or platelet count is lower than the level determined by your doctor. Your doctor will check these parameters at regular intervals. Chronic Lymphocytic Leukemia

Repeat the cycle every 4 weeks, up to 6 times Non-Hodgkin's Lymphoma Multiple Myeloma

Treatment should be stopped if your white blood cell and/or platelet count decreases below the level determined by your doctor. Treatment can be continued if your white blood cell and platelet counts increase. Liver or Kidney Function Disorders Depending on the severity of liver function disorders, it may be necessary to adjust the dose (by 30% in case of moderate liver function disorders). It is not necessary to adjust the dose if you have kidney function disorders. Your doctor will decide whether a dose adjustment is necessary. Method of AdministrationTreatment with Bendamustine Glenmark should only be initiated by doctors experienced in the use of anticancer medicines. Your doctor will give you the appropriate dose of Bendamustine Glenmark and take the necessary precautions. Your doctor will administer the infusion solution after it has been prepared according to the instructions. The solution is administered intravenously as a short infusion over 30-60 minutes. Duration of TreatmentThere are no general guidelines for the duration of treatment with Bendamustine Glenmark. The length of treatment depends on the disease and your response to treatment. If you have any doubts or questions about treatment with Bendamustine Glenmark, you should ask your doctor or nurse.

Missing a Dose of Bendamustine Glenmark

If you miss a dose of Bendamustine Glenmark, your doctor will usually continue treatment according to the planned dosing schedule.

Stopping Treatment with Bendamustine Glenmark

Your doctor will decide whether to stop treatment or change to a different medicine. If you have any further questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible Side Effects

Like all medicines, Bendamustine Glenmark can cause side effects, although not everybody gets them. Some of the side effects listed below may only be recognized by your doctor. The following definitions of frequency are used: Very Common: affects more than 1 in 10 people Common: affects less than 1 in 10 people Uncommon: affects less than 1 in 100 people Rare: affects less than 1 in 1,000 people Very Rare: affects less than 1 in 10,000 people Not Known: frequency cannot be estimated from the available data Very Rare: After accidental leakage of the medicine outside the blood vessel (extravasation), tissue necrosis (necrosis) has been observed. A sign of medicine leakage outside the blood vessel may be a burning sensation at the injection site. Consequences of medicine leakage may include pain and a poorly healing wound. A side effect of Bendamustine Glenmark that requires a dose reduction is bone marrow suppression, which usually returns to normal after treatment. Bone marrow suppression can lead to a decrease in blood cell counts, which can increase the risk of infection, anemia, or bleeding. Very Common: may affect more than 1 in 10 people

• decrease in white blood cell count (cells that help fight infections),
• decrease in red blood cell count (cells that carry oxygen to the body's tissues),
• decrease in platelet count (cells that help the blood to clot),
• infections,
• nausea (feeling sick),
• vomiting,
• mucositis (inflammation of the mucous membranes),
• headache,
• increased creatinine levels in the blood (a waste product that is normally removed by the kidneys),
• increased urea levels in the blood (a waste product that is normally removed by the kidneys),
• fever,
• fatigue.

Common: may affect less than 1 in 10 people

• bleeding (hemorrhage),
• metabolic disorders related to the release of cancer cell contents into the blood,
• decrease in red blood cell count (anemia),
• decrease in neutrophil count (a type of white blood cell that helps fight infections),
• hypersensitivity reactions, such as allergic skin reactions, hives,
• increased liver enzyme levels (which can indicate liver damage or disease),
• increased alkaline phosphatase levels (an enzyme that can indicate bone or liver disease),
• increased bilirubin levels (a waste product that can indicate liver or blood disorders),
• decreased potassium levels in the blood (which can affect the heart and nervous system),
• heart disorders,
• heart rhythm disorders (arrhythmias),
• low or high blood pressure,
• lung disorders,
• diarrhea,
• constipation,
• mouth pain (stomatitis),
• loss of appetite,
• hair loss,
• skin changes,
• absence of menstruation (amenorrhea),
• pain,
• insomnia,
• tremors,
• dehydration,
• dizziness,
• itching (pruritus).

Uncommon: may affect less than 1 in 100 people

• fluid accumulation in the sac surrounding the heart (pericardial effusion),
• failure of the bone marrow to produce all types of blood cells (bone marrow failure),
• acute leukemia,
• heart attack, chest pain,
• heart failure.

Rare: may affect less than 1 in 1,000 people

• blood infection (sepsis),
• severe hypersensitivity reactions (anaphylactic reactions),
• bone marrow suppression leading to poor health and changes in blood test results,
• reactions similar to anaphylaxis (anaphylactoid reactions),
• drowsiness,
• loss of voice (aphonia),
• sudden cardiac collapse (cardiac arrest),
• redness of the skin (erythema),
• skin inflammation (dermatitis),
• itching (pruritus),
• skin rash (exanthema),
• excessive sweating.

Very Rare: may affect less than 1 in 10,000 people

• primary atypical pneumonia,
• red blood cell destruction (hemolysis),
• sudden drop in blood pressure, sometimes with skin reactions or rash (anaphylactic shock),
• taste disturbance,
• numbness or tingling (paresthesia),
• peripheral neuropathy (nerve damage),
• severe condition resulting from blockage of certain receptors in the nervous system,
• nervous system disorders,
• loss of coordination (ataxia),
• brain inflammation (encephalitis),
• rapid heart rate (tachycardia),
• vein inflammation (phlebitis),
• scarring of lung tissue (pulmonary fibrosis),
• bleeding and inflammation of the esophagus (hemorrhagic esophagitis),
• bleeding from the stomach or intestines,
• infertility,
• multi-organ failure.

Not Known: frequency cannot be estimated from the available data

• liver failure,
• kidney failure,
• irregular and rapid heart rhythm (atrial fibrillation),
• painful red or purple rash that spreads with blisters and/or other skin changes on the mucous membranes (e.g., in the mouth or on the lips), especially if you have previously experienced sensitivity to light, respiratory infections (e.g., bronchitis), and/or fever,
• drug rash in combination therapy with rituximab,
• lung inflammation (pneumonitis),
• bleeding from the lungs,
• excessive urination, including at night, and excessive thirst even after drinking fluids (nephrogenic diabetes insipidus).

There have been reports of the development of secondary tumors (myelodysplastic syndrome, acute myeloid leukemia, lung cancer) in patients treated with Bendamustine Glenmark. However, a link between their occurrence and the use of the medicine has not been established. You should contact your doctor immediately if you experience any of the following side effects (frequency not known): Severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis. These can appear as red or circular patches on the skin, often with central blisters on the torso, peeling of the skin, ulcers in the mouth, throat, nose, genitals, and eyes, and may be preceded by fever and flu-like symptoms. Widespread rash, high body temperature, swollen lymph nodes, and symptoms affecting various organs (drug rash with eosinophilia and systemic symptoms, also known as DRESS or hypersensitivity syndrome). If any of your side effects get worse or if you experience any side effects not listed in this leaflet, you should tell your doctor.

Reporting Side Effects

If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in the "Further information" section. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to Store Bendamustine Glenmark

Keep this medicine out of the sight and reach of children. Do not use this medicine after the expiry date which is stated on the carton after EXP. The expiry date refers to the last day of that month. The vial should be stored in the outer carton to protect it from light.

Special Precautions for Storage After Reconstitution and Preparation of the Solution

The reconstituted solution is stable in polyethylene bags at room temperature and relative humidity of 60% for 3.5 hours and in the refrigerator for 2 days. Bendamustine Glenmark does not contain preservatives. Therefore, the solution should not be used after the specified time. The user is responsible for maintaining aseptic conditions. Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the Pack and Other Information

What Bendamustine Glenmark Contains

• The active substance is bendamustine hydrochloride. One vial contains 25 mg or 100 mg of bendamustine hydrochloride. After reconstitution, 1 ml of the concentrate contains 2.5 mg of bendamustine hydrochloride.
• The other ingredient is mannitol.

What Bendamustine Glenmark Looks Like and Contents of the Pack

White or almost white lyophilized powder in a vial made of orange glass with a bromobutyl rubber stopper and an aluminum flip-off seal. Vials made of type I orange glass with a capacity of 25 ml or 50 ml. Vials with a capacity of 25 ml contain 25 mg of bendamustine hydrochloride and are available in cartons of 5 vials. Vials with a capacity of 50 ml contain 100 mg of bendamustine hydrochloride and are available in cartons of 5 vials.

Marketing Authorization Holder

Glenmark Pharmaceuticals s.r.o. Hvězdova 1716/2b 140 78 Prague 4 Czech Republic

Manufacturer

Synthon Hispania SL C/ Castelló n 1, Pol. Las Salinas Sant Boi de Llobregat 08830 Barcelona Spain Synthon, s.r.o. Brněnská 32/čp. 597 678 01 Blansko Czech Republic

For Further Information on This Medicinal Product, Please Contact the Local Representative of the Marketing Authorization Holder:

Glenmark Pharmaceuticals Sp. z o.o. ul. Osmańska 14 02-823 Warsaw Date of Last Revision of the Leaflet:January 2024 ------------------------------------------------------------------------------------------------------------------------------

Information Intended for Healthcare Professionals Only:

As with all cytotoxic agents, due to the potential for genetic damage and the risk of cancer, more stringent than usual precautions should be taken when handling Bendamustine Glenmark. When preparing bendamustine hydrochloride, you should avoid inhaling the medicine and contact with the skin and mucous membranes (wear gloves, protective clothing, and, if possible, a face mask). Any parts of the body contaminated with the medicine should be washed thoroughly with water and soap, and the eyes should be rinsed with 0.9% (isotonic) sodium chloride solution. If possible, work on a specially protected bench (under a laminar flow hood) covered with a single-use, absorbent, non-permeable sheet. Contaminated items are cytostatic waste. Please follow national guidelines for the disposal of materials with cytostatic properties. Pregnant personnel should not be allowed to work with cytostatic products. The infusion solution should be prepared by dissolving the contents of the vial with bendamustine in water for injections only, as follows:

• 1. Preparation of the Concentrate
  • Dissolve one vial of bendamustine containing 25 mg of bendamustine hydrochloride in 10 ml by shaking
  • Dissolve one vial of bendamustine containing 100 mg of bendamustine hydrochloride in 40 ml by shaking
• 2. Preparation of the Infusion Solution Once a clear solution is obtained (usually within 5-10 minutes), the total dose of bendamustine should be immediately dissolved in 0.9% (isotonic) sodium chloride solution to achieve a final volume of approximately 500 ml. Bendamustine should not be dissolved in other infusion or injection solutions. The infusion solution with bendamustine should not be mixed with other substances.
• 3. Administration The solution is administered intravenously as a short infusion over 30-60 minutes. Vials are for single use only. Any unused product or waste material should be disposed of in accordance with local requirements. In case of accidental leakage of the medicine outside the blood vessel (extravasation), the infusion should be stopped immediately. After brief aspiration of the injected fluid, the needle should be removed. The injection site should be cooled and the arm elevated. It is not established whether the administration of additional medicines, such as corticosteroids, may have a positive effect (see section 4).