LEVACT 2.5 MG / ML POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION - patient leaflet, side effects, dosage

What is in this leaflet

• 1. What Levact is and what it is used for

• 2. What you need to know before you use Levact

• 3. How to use Levact

• 4. Possible side effects

• 5. How to store Levact

• 6. Contents of the pack and other information

1. WHAT

Levact is a medicine which is used for the treatment of certain types of cancer (cytotoxic medicine).

Levact is used alone (monotherapy) or in combination with other medicines for the treatment of the following forms of cancer:

• – chronic lymphocytic leukaemia in cases where fludarabine combination chemotherapy is not appropriate for you,

• – non-Hodgkin lymphomas, which had not, or only shortly, responded to prior rituximab treatment,

• – multiple myeloma in cases where thalidomide or bortezomib containing therapy is not appropriate for you.

2. what you need to know before you use levact

Do not use

• – 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 Levact 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.

Warnings and precautions

– 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 Levact , 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 Levact. 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 Levact. 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.

Other medicines and

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

If Levact 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 Levact 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).

Pregnancy, breast-feeding and fertility

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

Levact can cause genetic damage and has caused malformations in animal studies. You should not use Levact 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 Levact. If pregnancy occurs during your treatment with Levact you must immediately inform your doctor and should use genetic consultation.

Breast-feeding

Levact must not be administered during breast feeding. If treatment with Levact 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 Levact 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 Levact and for up to 6 months after treatment has stopped. There is a risk that treatment with Levact will lead to infertility and you may wish to seek advice on conservation of sperm before treatment starts.

Driving and using machines

Levact 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.

3. how to use

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Levact is administered into a vein over 30–60 minutes in various dosages, either alone (monotherapy) or in combination with other medicines.

Treatment should not be started if your white blood cells (leukocytes) and/or your blood platelets have fallen to counts below determined levels.

Your doctor will determine these values at regular intervals.

Chronic lymphocytic leukaemia _____________­________________________­_____________________

Non-Hodgkin lymphomas

Multiple myeloma

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 Levact should be undertaken only by doctors experienced in tumour therapy. Your doctor will give you the exact dose of Levact 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 Levact. Duration of treatment depends on disease and response to treatment.

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

If you forget to use

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

If you stop using

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

If you have any further questions on the use of this product, ask your doctor or pharmacist.

4. possible side effects

Like all medicines, Levact can cause side-effects, although not everybody will experience these effects. Some of the findings listed below may be found after tests are performed by your doctor.

The following definitions of frequency are used when assessing side-effects:

Tissue decay (necrosis) has been observed very rarely following leakage of Levact into the tissue outside the blood vessels (extravascular). A burning sensation where the infusion needle is inserted may be a sign of leakage outside the blood vessels. The consequence can be pain and poorly healing skin defects.

The dose-limiting side-effect of Levact is impaired bone-marrow function, which usually returns to normal after treatment. Suppressed bone marrow function may lead to low counts of blood cells, which in turn may lead to an increased risk of infection, anemia or a heightened risk of bleeding.

Very common

• Low counts of white blood cells (disease-fighting cells in your blood)
• Decrease in the red pigment of the blood (haemoglobin: a protein in red blood cells that carries oxygen throughout the body)
• Low counts of platelets (colorless blood cells that help blood clot)
• Infections
• Feeling sick (nausea)
• Vomiting
• Mucosal inflammation
• Headache
• Increased blood level of creatinine (a chemical waste product that is produced by your muscle)
• Increased blood level of urea (a chemical waste product)
• Fever
• Fatigue

Common:

Uncommon:

• Accumulation of fluid in the heart sac (escape of fluid into the pericardial space)
• Ineffective production of all blood cells in the bone marrow (the spongy material inside your bones where blood cells are made)
• Acute leukemia
• Heart attack, chest pain (myocardial infarct)
• Heart failure

Rare:

• Infection of the blood (sepsis)
• Severe allergic hypersensitivity reactions (anaphylactic reactions)
• Reduction in your bone marrow function, which may make you feel unwell or show up in your blood tests
• Signs similar to anaphylactic reactions (anaphylactoid reactions)
• Drowsiness
• Loss of voice (aphonia)
• Acute circulatory collapse (failure of blood circulation mainly from a cardiac origin with failure to maintain the supply of oxygen and other nutrients to the tissues and removing toxins)

• Reddening of the skin (erythema)
• Inflammation of the skin (dermatitis)
• Itching (pruritus)
• Skin rash (macular exanthema)
• Excessive sweating

(hyperhidrosis)

Very rare:

• Liver failure
• Renal failure
• Irregular and often rapid heart rate (atrial fibrillation)
• 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.
• Drug rash in combination therapy with rituximab
• Pneumonitis
• Bleeding from the lungs

There have been reports of tumours (myelodysplastic syndrome, AML, bronchial carcinoma) following treatment with Levact. No clear relationship with Levact could be determined.

Contact your doctor or seek medical attention immediately if you notice any of the following side effects (frequency not known):

Serious skin rashes including Stevens-Johnson syndrome and toxic epidermal necrolysis. These can appear as reddish target-like macules or circular patches often with central blisters on the trunk, skin peeling, ulcers of mouth, throat, nose, genitals and eyes and can be preceded by fever and flu-like symptoms.

Widespread rash, high body temperature, enlarged lymph nodes and other body organs involvement (Drug Reaction with Eosinophilia and Systemic Symptoms which is also known as DRESS or drug hypersensitivity syndrome).

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor.

Reporting of 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 Yellow Card scheme at:. By reporting side effects you can help provide more information on the safety of this medicine.

5. how to store

Keep this medicine out of the sight and reach of children.

Do not use Levact after the expiry date which is stated on the label and the carton. The expiry date refers to the last day of that month.

Keep the container in the outer carton to protect the content from light.

Note on shelf-life after opening or preparing the solution

Solutions for infusions prepared according to the directions listed at the end of this leaflet are stable in polyethylene bags at room temperature / 60% relative humidity for 3.5 hours, and in a refrigerator they are stable for 2 days. Levact 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.

6. contents of the pack and other information

What

The active substance is bendamustine hydrochloride.

• 1 vial contains 25 mg of bendamustine hydrochloride

1 vial contains 100 mg of bendamustine hydrochloride

After reconstitution 1 ml of the concentrate contains 2.5 mg bendamustine hydrochloride.

The other ingredient is Mannitol.

What

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

The powder appears white and crystalline.

Levact is available in packs containing

5, 10 and 20 vials with 25 mg of bendamustine hydrochloride and 5 vials with 100 mg of bendamustine hydrochloride.

Not all pack sizes may be available.

Marketing Authorisation Holder

Astellas Pharma GmbH

RidlerstraBe 57

80339 Munchen

Local representative

Napp Pharmaceuticals Ltd

Cambridge Science Park

Milton Road

Cambridge, CB4 0GW

Telephone: +44 (0) 1223 424444

Manufacturer

Haupt Pharma Wolfratshausen GmbH

Pfaffenrieder Strasse 5

82515 Wolfrat­shausen

This leaflet was last revised in December 2020

This leaflet is also available in large print, Braille or as an audio CD. To request a copy, please call the RNIB Medicine Information line (free of charge) on:

0800 198 5000

You will need to give details of the product name and reference number.

These are as follows:

Product name: Levact 2.5 mg/ml

Reference number: 14427/0026

The following information is intended for medical or healthcare professionals only:

As with all similar cytotoxic substances, stricter safety precautions apply as far as nursing staff and doctors are concerned, due to the potentially genome-damaging and cancer-causing effect of the preparation. Avoid inhalation (breathing in) and contact with the skin and mucous membranes when handling Levact (wear gloves, protective clothing, and possibly a face mask!). If any parts of the body become contaminated, clean them carefully with soap and water, and flush the eyes with 0.9% (isotonic) saline solution. If possible, it is advisable to work on a special safety work bench (laminar flow) with a disposable absorbing sheet that is impermeable to liquids. Contaminated articles are cytostatic waste. Please comply with national guidelines on the disposal of cytostatic material! Pregnant staff must be excluded from working with cytostatics.

The solution ready for use must be prepared by dissolving the contents of a vial of Levact exclusively in water for Injections, as follows:

• 1. Preparation of the concentrate

• One vial of Levact containing 25 mg of bendamustine hydrochloride is first dissolved in 10 ml by shaking
• One vial of Levact containing 100 mg of bendamustine hydrochloride is first dissolved in 40 ml by shaking

• 2. Preparation of the solution for infusion

As soon as a clear solution is obtained (generally after 5 – 10 minutes), the total recommended dose of Levact is immediately diluted with 0.9% (isotonic) saline solution to obtain a final volume of approximately 500 ml. Levact must not be diluted with other solutions for infusion or injection. Levact must not be mixed in an infusion with other substances.

• 3. Administration