Bendamustine Hydrochloride 2.5mg/ml powder for concentrate for solution for infusion

• 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 symptoms are the same as yours.
• If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

1. What Bendamustine Hydrochloride is and what it is used for
2. What you need to know before you use Bendamustine Hydrochloride
3. How to use Bendamustine Hydrochloride
4. Possible side effects
5. How to store Bendamustine Hydrochloride
6. Contents of the pack and other information

• if you are allergic to bendamustine hydrochloride or any of the other ingredients of this medicine (listed in section 6);
• while breast-feeding, if treatment with Bendamustine hydrochloride is necessary during lactation you must discontinue breast-feeding (see section warnings and precautions on breastfeeding);
• if you have severe liver dysfunction (damage to the functional cells of the liver);
• if you have yellowing of the skin or whites of the eyes caused by liver or blood problems (jaundice);
• if you have severely disturbed bone marrow function (bone marrow depression) and serious changes in your number of white blood cells and platelets in the blood;
• if you have had major surgical operations less than 30 days before starting treatment;
• if you have an infection, especially one accompanied by a reduction in white blood cells (leucocytopenia);
• in combination with yellow fever vaccines.

Talk to your doctor, pharmacist or nurse before using Bendamustine Hydrochloride.

• in case of reduced capability of the bone marrow to replace blood cells. You should have your number of white blood cells and platelets in the blood checked before starting treatment with Bendamustine Hydrochloride, before each subsequent course of treatment and in the intervals between courses of treatment.
• in case of infections. You should contact your doctor if you have signs of infection, including fever or lung symptoms.
• At any time during or after your treatment, tell your doctor immediately if you notice or someone notices in you: memory loss, trouble thinking, difficulty walking or sight loss – these may be due to a very rare but serious brain infection which can be fatal (progressive multifocal leukoencephalopathy or PML).
• in case of reactions on your skin during treatment with Bendamustine Hydrochloride. The skin reactions may increase in severity.
• Contact your doctor if you notice any suspicious skin changes because there may be an increased risk of certain types of skin cancer (non-melanoma skin cancer) with the use of this medicine.
• in case of painful red or purplish rash that spreads and blisters and/or other lesions begin to appear in the mucous membrane (e.g. mouth and lips), in particular if you had before light sensitivity, infections of the respiratory system (e.g. bronchitis) and/or fever.
• in cases of existing heart disease (e.g. heart attack, chest pain, severely disturbed heart rhythms).
• in case you notice any pain in your side, blood in your urine or reduced amount of urine. When your disease is very severe, your body may not be able to clear all the waste products from the dying cancer cells. This is called tumour lysis syndrome and can cause kidney failure and heart problems within 48 hours of the first dose of Bendamustine Hydrochloride. Your doctor may ensure you are adequately hydrated and give you other medicines to help prevent it.
• in case of severe allergic or hypersensitivity reactions. You should pay attention to infusion reactions after your first cycle of therapy.

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

If Bendamustine Hydrochloride is used in combination with medicines which inhibit the formation of blood in the bone marrow, the effect on the bone marrow may be intensified.

If Bendamustine Hydrochloride is used in combination with medicines which alter your immune response, this effect may be intensified.

Cytostatic medicines may diminish the effectiveness of live-virus vaccination. Additionally cytostatic medicines increase the risk of an infection after vaccination with live vaccines (e.g. viral vaccination).

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.

Pregnancy

Bendamustine Hydrochloride can cause genetic damage and has caused malformations in animal studies. You should not use Bendamustine Hydrochloride during pregnancy unless certainly indicated by your doctor. In case of treatment you should use medical consultation about the risk of potential adverse effects of your therapy for the unborn child and genetic consultation is recommended.

If you are a woman of childbearing potential, you must use an effective method of contraception both before and during treatment with Bendamustine Hydrochloride. If pregnancy occurs during your treatment with Bendamustine Hydrochloride you must immediately inform your doctor and should use genetic consultation.

Breast-feeding

Bendamustine Hydrochloride must not be administered during breast feeding. If treatment with Bendamustine Hydrochloride is necessary during lactation you must discontinue breast-feeding.

Ask your doctor or pharmacist for advice before taking any medicine.

Fertility

Men receiving treatment with Bendamustine hydrochloride are advised not to father a child during treatment and for up to 6 months afterwards. Before starting treatment, you should seek advice on storing sperm because of the possibility of permanent infertility.

If you are a man, you should avoid fathering a child during treatment with Bendamustine hydrochloride and for up to 6 months after treatment has stopped. There is a risk that treatment with Bendamustine hydrochloride will lead to infertility and you may wish to seek advice on conservation of sperm before treatment starts.

Bendamustine hydrochloride has major influence on the ability to drive and to use machines. Do not drive or operate machines if you experience side effects, such as dizziness or lack of coordination.

Bendamustine Hydrochloride 100 mg per square meter of your body surface area (based on your height and weight) on Days 1+2

Repeat the cycle after 4 weeks up to 6 times

Bendamustine Hydrochloride 120 mg per square meter of your body surface area (based on your height and weight) on Days 1 + 2

Repeat the cycle after 3 weeks at least 6 times

Bendamustine Hydrochloride 120 - 150 mg per square meter of your body surface area (based on your height and weight) on Days 1 + 2

Prednisone 60 mg per square meter of your body surface area (based on your height and weight) by injection or orally. on Days 1 - 4

Repeat the cycle after 4 weeks at least 3 times

Treatment should be terminated if white blood cell (leukocyte) and/or platelet values dropped to determined levels. Treatment can be continued after white blood cell and platelet values have increased.

Impaired liver or kidney function

Dependent on the degree of impairment of your liver function it may be necessary to adjust your dose (by 30% in case of moderate liver dysfunction). No dose adjustment is necessary in case of impairment of kidney function. Your attending doctor will decide whether a dosage adjustment is necessary.

How it is administered

Treatment with Bendamustine Hydrochloride should be undertaken only by doctors experienced in tumour therapy. Your doctor will give you the exact dose of Bendamustine Hydrochloride and use the necessary precautions.

Your attending doctor will administer the solution for infusion after preparation as prescribed. The solution is administered into a vein as a short-term infusion over 30 - 60 minutes.

Duration of use

There is no time limit laid down as a general rule for treatment with Bendamustine Hydrochloride. Duration of treatment depends on disease and response to treatment.

If you are at all worried or have any questions regarding treatment with Bendamustine Hydrochloride, please speak to your doctor or nurse.

If a dose of Bendamustine Hydrochloride has been forgotten, your doctor will usually retain the normal dosage schedule.

The doctor treating you will decide whether to interrupt the treatment or to change over to a different preparation.

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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.

Solutions for infusions prepared according to the directions listed at the end of this leaflet are stable in polypropylene bags at room temperature / 60% relative humidity for 3.5 hours, and in a refrigerator they are stable for 2 days. Bendamustine Hydrochloride contains no preservatives. The solutions should not therefore be used after these lengths of time.

It is the responsibility of the user to maintain 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 to protect the environment.

• The active substance is Bendamustine Hydrochloride.
  • Each vial contains 25 milligrams of Bendamustine Hydrochloride (as bendamustine hydrochloride monohydrate).
  • Each vial contains 100 milligrams of Bendamustine Hydrochloride (as bendamustine hydrochloride monohydrate).
  • After reconstitution 1 ml of the concentrate contains 2.5 mg bendamustine hydrochloride (as bendamustine hydrochloride monohydrate).
• The other ingredients are mannitol and hydrochloric acid (for pH adjustment).

Brown glass vials with rubber stopper and an aluminium flip-off cap.

It appears white to off-white cake or powder.

Bendamustine Hydrochloride is available in packs containing 5 vials with 25 mg of bendamustine hydrochloride (as bendamustine hydrochloride monohydrate) and 1 vial with 100 mg of bendamustine hydrochloride (as bendamustine hydrochloride monohydrate).

Not all pack sizes may be available.