Bendamustina medac

Leaflet accompanying the packaging: information for the user

Bendamustine medac, 2.5 mg/ml, powder for concentrate for solution for infusion

Bendamustine hydrochloride

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, so you can read it again if you need to.
• If you have any doubts, consult your doctor or pharmacist.
• If the patient experiences any side effects, including those not listed in this leaflet, they should inform their doctor or pharmacist. See section 4.

Table of contents of the leaflet

• 1. What is Bendamustine medac and what is it used for
• 2. Important information before using Bendamustine medac
• 3. How to use Bendamustine medac
• 4. Possible side effects
• 5. How to store Bendamustine medac
• 6. Contents of the packaging and other information

1. What is Bendamustine medac and what is it used for

Bendamustine medac is a medicine that contains the active substance bendamustine hydrochloride (hereinafter referred to as bendamustine).
Bendamustine is a medicine used to treat certain types of cancer (cytotoxic medicine).
Bendamustine is used alone (as monotherapy) or in combination with other medicines to treat the following types of cancer:

• Chronic lymphocytic leukemia when fludarabine-containing chemotherapy is not indicated,
• Non-Hodgkin's lymphoma that has not responded or has responded too briefly to previous rituximab treatment,
• Multiple myeloma when high-dose chemotherapy with autologous stem cell transplantation or treatment with a regimen containing thalidomide or bortezomib is not indicated.

2. Important information before using Bendamustine medac

When not to use Bendamustine medac:

• If the patient is allergic to bendamustine hydrochloride or any of the other ingredients of this medicine (listed in section 6),
• During breastfeeding; if treatment with Bendamustine medac is necessary during lactation, breastfeeding should be discontinued (see section Pregnancy, breastfeeding and fertility).
• If the patient has severe liver damage (damage to liver cells),
• If the patient has jaundice or yellowing of the skin and eyes due to liver or blood disorders,
• If the patient has severe bone marrow disorders (bone marrow depression) and significant changes in white blood cell and platelet counts,
• If the patient has undergone major surgery within 30 days before starting treatment,
• If the patient has an infection, especially with a decrease in white blood cell count (leukopenia),
• If the patient has been vaccinated against yellow fever.

Warnings and precautions

Before starting treatment with Bendamustine medac, the patient should discuss it with their doctor or nurse:

• In case of reduced bone marrow function. The doctor will check the white blood cell and platelet count before starting treatment with Bendamustine medac, before each subsequent cycle of administration, and during breaks between administrations.
• In case of infection. The patient should contact their doctor if symptoms of infection occur, including fever and respiratory symptoms,
• In case of concomitant heart disease(e.g., heart attack, chest pain, severe arrhythmias).

The patient should immediately inform their doctor if they 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 suspicious skin changes are observed, the patient should contact their doctor due to the increased risk of certain types of skin cancer (non-melanoma skin cancer) that may occur during treatment with this medicine.
During treatment with Bendamustine medac, the patient should discuss the following with their doctor or nurse:

• In case of nausea and vomiting. The doctor may prescribe a medicine to alleviate nausea (antiemetic).
• In case of pain in the side, blood in the urine, or decreased urine output. When the patient is in an advanced stage of the disease, their body may not be able to remove all the unnecessary products of dying cancer tissue. This phenomenon is called tumor lysis syndrome and can lead to kidney failure and heart problems within 48 hours of administering the first dose of Bendamustine medac. The doctor should ensure that the patient is properly hydrated and may prescribe other medicines to prevent this phenomenon.
• In case of skin reactionsduring treatment with Bendamustine medac. These changes may worsen.
• If a painful, red, or purple, spreading rash with blisters and (or) other changes in the mucous membrane (e.g., in the mouth and on the lips) occurs, especially if the patient has previously experienced sensitivity to light, respiratory infection (e.g., bronchitis), and (or) fever.
• In case of severe allergic reactions or hypersensitivity reactions. The patient should pay attention to symptoms related to infusion reactions after the first cycle of treatment.

Men taking Bendamustine medac are advised not to plan to conceive a child during treatment and for 6 months after its completion. Before starting treatment, the patient should consult about the possibility of storing sperm due to the risk of permanent infertility (see section Pregnancy, breastfeeding and fertility).

Children and adolescents

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

Bendamustine medac and other medicines

The patient should inform their doctor or pharmacist about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take.
Bendamustine hydrochloride may affect the action of other medicines. Other medicines may also affect the action of bendamustine hydrochloride. Interactions with bendamustine hydrochloride may occur:
When using Bendamustine medac in combination with other medicines that suppress bone marrow function, the effect on bone marrow function may be enhanced.
Bendamustine medac used in combination with medicines that affect the immune response may enhance this effect.
Cytostatic medicines may reduce the effectiveness of live virus vaccines.
Cytostatic medicines also increase the risk of infection after vaccination with live vaccines (e.g., antiviral vaccines).

Pregnancy, breastfeeding and fertility

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a child, they should consult their doctor or pharmacist before using this medicine.
Women of childbearing age should use effective contraceptionduring treatment with bendamustine and for 6 months after treatment completion.

Men should use effective contraception and not attempt to

conceive a childduring treatment with bendamustine and for 3 months after treatment completion.
Pregnancy
Bendamustine may cause damage to genetic material and birth defects in animals. This medicine should not be used during pregnancy unless the doctor considers it absolutely necessary. If treatment is necessary, the patient should discuss possible adverse effects on the unborn child with their doctor. Genetic counseling is recommended.
Breastfeeding
Bendamustine should not be used during breastfeeding. If treatment with this medicine is necessary, the patient should discontinue breastfeeding.
Fertility
There is a risk that treatment with bendamustine may cause infertility in men; therefore, before starting treatment, the patient should consult about the possibility of storing sperm.

Driving and using machines

Bendamustine hydrochloride has a significant impact on the ability to drive and use machines. The patient should not drive or operate machines if they experience side effects such as dizziness or lack of coordination.

3. How to use Bendamustine medac

Bendamustine medac is administered intravenously, over 30-60 minutes, in different doses, alone or in combination with other medicines.
Treatment should not be started if the white blood cell count and (or) platelet count falls below a certain level.
The doctor will check these parameters at regular intervals.
Chronic lymphocytic leukemia

• Bendamustine medac 100 mg/m² body surface area (determined based on height and weight): on days 1 and 2.
• Repeat the cycle every 4 weeks for up to 6 times.

Non-Hodgkin's lymphoma

• Bendamustine medac 120 mg/m² body surface area (determined based on height and weight): on days 1 and 2.
• Repeat the cycle every 3 weeks for at least 6 times.

Multiple myeloma

• Bendamustine medac 120-150 mg/m² body surface area (determined based on height and weight): on days 1 and 2.
• Prednisone 60 mg/m² body surface area (determined based on height and weight) intravenously or orally: on days 1-4.
• Repeat the cycle every 4 weeks for at least 3 times.

Treatment should be discontinued if the white blood cell count and (or) platelet count falls below a certain level. Treatment can be continued when the white blood cell and platelet count increase.
Impaired liver or kidney function
Depending on the degree of liver function impairment, it may be necessary to adjust the dose (by 30% in case of moderate liver function impairment). In case of severe liver function impairment, Bendamustine medac should not be used. It is not necessary to adjust the dose if the patient has kidney failure. The treating doctor will decide whether a dose adjustment is necessary.
How the medicine is administered
Treatment with Bendamustine medac should only be initiated by doctors experienced in the treatment of cancer. The doctor will administer the appropriate dose of Bendamustine medac and take necessary precautions.
The doctor will administer the solution for infusion after preparation according to the recommendations.
The solution is administered intravenously as a short-term infusion over 30-60 minutes.
Duration of treatment
There is no generally applicable time limit for treatment with Bendamustine medac.
The duration of treatment depends on the disease and how the patient responds to treatment.
In case of doubts or questions about treatment with Bendamustine medac, the patient should consult their doctor or nurse.

Missing a dose of Bendamustine medac

If a dose of Bendamustine medac is missed, the doctor will usually continue treatment according to the adopted dosing schedule.

Discontinuing treatment with Bendamustine medac

The treating doctor will decide whether to discontinue treatment or change the medicine to another one.
In case of any further doubts related to the use of this medicine, the patient should consult their doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The patient should immediately contact their doctor if they experience any of the following side effects (frequency not known):
Severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis. These can occur as red or round patches on the skin, often with central blisters on the torso, skin peeling, 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).
Very rarely, after accidental injection of the medicine outside the blood vessel (extravasation), tissue changes (necrosis) have been observed. A symptom of extravasation may be a burning sensation at the injection site. The consequence of administering the medicine in this way may be pain and poor healing of skin changes.
The side effect of Bendamustine medac that limits the dose is bone marrow dysfunction, which usually returns to normal after treatment. Bone marrow suppression can lead to a decrease in blood cell count, which can increase the risk of infection, anemia, or bleeding.

Very common (may affect more than 1 in 10 patients):

• Decreased white blood cell count (leukopenia)
• Decreased hemoglobin level in the blood
• Decreased platelet count (thrombocytopenia)
• Infections
• Nausea
• Vomiting
• Mucositis
• Increased creatinine level in the blood
• Increased urea level in the blood
• Fever
• Fatigue
• Headache

Common (may affect up to 1 in 10 patients):

• Bleeding (hemorrhage)
• Metabolic disorders related to the release of cancer cell contents into the bloodstream (tumor lysis syndrome)
• Decreased red blood cell count, which can cause pale skin and weakness or shortness of breath (anemia, anemia)
• Decreased neutrophil count (neutropenia)
• Hypersensitivity reactions, such as allergic skin inflammation, hives
• Increased activity of liver enzymes AspAT/AlAT
• Increased activity of the enzyme alkaline phosphatase
• Increased bilirubin level
• Decreased potassium level in the blood
• Heart rhythm disorders (arrhythmia)
• Low or high blood pressure (hypotension or hypertension)
• Lung function disorders
• Diarrhea
• Constipation
• Mouth ulcers
• Loss of appetite
• Hair loss
• Skin changes
• Amenorrhea (absence of menstruation)
• Pain
• Insomnia
• Chills
• Dehydration
• Dizziness
• Itchy rash (hives)

Uncommon (may affect up to 1 in 100 patients):

• Fluid accumulation in the pericardial sac (pericardial effusion)
• Ineffective production of all types of blood cells (myelodysplastic syndrome)
• Acute leukemia
• Heart attack, chest pain
• Heart failure

Rare (may affect up to 1 in 1,000 patients):

• Blood infection (sepsis)
• Severe hypersensitivity reactions (anaphylactic reactions)
• Symptoms similar to anaphylactic reactions (pseudoanaphylactic reactions)
• Drowsiness
• Voice loss (aphonia)
• Cardiac arrest
• Redness of the skin (erythema)
• Skin inflammation
• Itching (pruritus)
• Rash (maculopapular rash)
• Excessive sweating
• Bone marrow suppression, which can cause poor well-being or be visible in blood test results

Very rare (may affect up to 1 in 10,000 patients)

• Primary atypical pneumonia
• Red blood cell destruction
• Sudden drop in blood pressure, sometimes with skin reactions (anaphylactic shock)
• Taste disturbance
• Change in sensation (paresthesia)
• Poor well-being and limb pain (peripheral neuropathy)
• Nervous system disease (anticholinergic syndrome)
• Neurological disorders
• Lack of coordination (ataxia)
• Brain inflammation
• Increased heart rate (tachycardia)
• Vein inflammation
• Lung tissue formation (pulmonary fibrosis)
• Bleeding from the esophagus
• Bleeding from the stomach or intestines
• Infertility
• Multi-organ failure

Frequency not known (frequency cannot be estimated from available data)

• Liver failure
• Kidney failure
• Irregular or rapid heartbeat (atrial fibrillation)
• Painful red or purple spreading rash with blisters and (or) other changes in the mucous membrane (e.g., in the mouth and on the lips), especially if the patient has previously experienced sensitivity to light, respiratory infection (e.g., bronchitis), and (or) fever
• Drug rash (combination therapy with rituximab)
• Lung inflammation
• Bleeding from the lungs
• Excessive urination, including at night, and excessive thirst even after drinking fluids (nephrogenic diabetes insipidus)

Reporting side effects

If any side effects occur, including those not listed in this leaflet, the patient should inform their doctor or nurse. Side effects can be reported directly to the Department of Monitoring of Adverse Reactions to Medicinal Products of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products:
Al. Jerozolimskie 181C, PL-02-222 Warsaw, tel.: +48 22 49-21-301, fax: +48 22 49-21-309,
website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
Reporting side effects will help gather more information on the safety of the medicine.

5. How to store Bendamustine medac

The medicine should be stored out of sight and reach of children.
Do not use this medicine after the expiry date stated on the label and carton after "Expiry date". The first two digits indicate the month, and the last four digits indicate the year.
The expiry date refers to the last day of the stated month.
Store the vial in the outer packaging to protect it from light.

Notice regarding the shelf life of the medicine after opening the packaging or preparing the solution

The physical and chemical stability of the medicinal product after reconstitution and dilution has been demonstrated for 3.5 hours at 25°C and 60% relative humidity and for 2 days at 2°C - 8°C in polyethylene bags.
From a microbiological point of view, the medicine should be used immediately. If the medicine is not used immediately, the user is responsible for the storage conditions and time. The storage time should not normally exceed 24 hours at a temperature of 2°C to 8°C, unless reconstitution/dilution was performed under controlled and validated aseptic conditions.
Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Bendamustine medac contains

• The active substance is bendamustine hydrochloride.

One vial contains 25 mg of bendamustine hydrochloride.
One vial contains 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 medac looks like and contents of the pack

White or off-white lyophilized powder in a vial with a rubber stopper and aluminum flip-top cap.
Vial with a capacity of 25 ml made of type I glass.
Vial with a capacity of 50 ml made of type I glass.
Bendamustine medac is available in packs containing 1, 5, or 10 vials with 25 mg of bendamustine hydrochloride and 1 or 5 vials with 100 mg of bendamustine hydrochloride.
Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

medac Gesellschaft für klinische Spezialpräparate mbH
Theaterstr. 6
22880 Wedel
Germany
Phone:
+48 22 43000-30
Fax:
+48 22 43000-31
e-mail: kontakt@medac.pl

This medicine is authorized in the Member States of the European Economic Area under the following names:

Denmark
Bendamustine hydrochloride medac 2.5 mg/ml
Estonia
Bendamustine medac
Finland
Bendamustine medac 2.5 mg/ml
Latvia
Bendamustine medac 2.5 mg/ml powder for concentrate for solution for infusion

Poland
Bendamustyna medac
Portugal
Bendamustina medac

Date of last revision of the leaflet: 09/2023

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Information intended for healthcare professionals only:

Similarly to all similar cytotoxic substances, due to the potential for the medicine to cause genetic damage and cancer, nursing staff and doctors are required to take more rigorous precautions than usual.
When handling bendamustine, the patient should avoid inhaling the medicine and its contact with the skin and mucous membranes (wear gloves, protective clothing, and, if possible, a face mask!).
In case of contamination of any part of the body with the product, it should be thoroughly washed with water and soap, and the eyes should be rinsed with 0.9% (isotonic) sodium chloride solution. If possible, work on special, protected workstations (under a laminar flow) with a covering of the work surface with a single-use, fluid-impermeable absorbent sheet. Contaminated items are cytostatic waste. Please follow national guidelines for the disposal of materials with cytostatic properties. Pregnant women should not be allowed to work with cytostatic products.
The ready-to-use solution should be prepared by dissolving the contents of the Bendamustine medac vial in water for injections only, as follows:

• 1. Preparation of the concentrate
• One vial of Bendamustine medac containing 25 mg of bendamustine hydrochloride is first dissolved in 10 ml of water for injections by shaking
• One vial of Bendamustine medac containing 100 mg of bendamustine hydrochloride is first dissolved in 40 ml of water for injections by shaking
• 2. Preparation of the infusion solution

As soon as a clear solution is obtained (usually after 5-10 minutes), the recommended dose of Bendamustine medac is immediately dissolved in 0.9% (isotonic) sodium chloride solution to achieve a final volume of approximately 500 ml. Bendamustine medac should not be dissolved in other infusion or injection solutions. Bendamustine medac should not be mixed in an infusion with other substances.