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

Bendamustine hydrochloride

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

Bendamustine Hydrochloride 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.

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

Bendamustine Hydrochloride 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

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

Repeat the cycle after 4 weeks up to 6 times

Non-Hodgkin lymphomas

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

Repeat the cycle after 3 weeks at least 6 times

Multiple myeloma

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

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

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

Like all medicines, Bendamustine Hydrochloride 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:

Very common: affects more than 1 user in 10

Common: affects 1 to 10 users in 100

Uncommon: affects 1 to 10 users in 1,000

Rare: affects 1 to 10 users in 10,000

Very rare: affects less than 1 user in 10,000

Not known: frequency cannot be estimated from the available data

Tissue decay (necrosis) has been observed very rarely following leakage of Bendamustine Hydrochloride 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 Bendamustine Hydrochloride 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:

• Bleeding (haemorrhage)
• Disturbed metabolism caused by dying cancer cells releasing their contents into the blood stream
• Reduction in red blood cells which can make the skin pale and cause weakness or breathlessness (anaemia)
• Low counts of neutrophils (a common type of white blood cell important to fighting off infections)
• Hypersensitivity reactions such as allergic inflammation of the skin (dermatitis), nettle rash (urticaria)
• A rise in liver enzymes AST/ALT (which may indicate inflammation or damage to cells in the liver)
• A rise in the enzyme alkaline phosphatase (an enzyme made mostly in the liver and bones)
• A rise in bile pigment (a substance made during the normal breakdown of red blood cells)
• Low potassium blood levels (a nutrient that is necessary for the function of nerve and muscle cells, including those in your heart)
• Disturbed function (dysfunction) of the heart
• Disturbed heart rhythms (arrhythmia)
• Low or high blood pressure (hypotension or hypertension)
• Disturbed lung function
• Diarrhoea
• Constipation
• Sore mouth (Stomatitis)
• Loss of appetite
• Hair loss
• Skin changes
• Missed periods (amenorrhoea)
• Pain
• Insomnia
• Chills
• Dehydration
• Dizziness
• Itchy rash (urticaria)

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:

• Primary atypical inflammation of the lungs (pneumonia)
• Break-down of red blood cell
• Rapid decrease in blood pressure sometimes with skin reactions or rash (anaphylactic shock)
• Disturbed sense of taste
• Altered sensations (paraesthesia)
• Malaise and pain in the limbs (peripheral neuropathy)
• Serious condition resulting in the blockade of specific receptor in the nervous systems
• Disorders of the nervous system
• Lack of coordination (ataxia)
• Inflammation of the brain (encephalitis)
• Increased heart rate (tachycardia)
• Inflammation of the veins (phlebitis)
• Formation of tissue in the lungs (fibrosis of the lungs)
• Bleeding inflammation of the gullet (haemorrhagic oesophagitis)
• Bleeding of stomach or gut
• Infertility
• Multiple organ failure

Not known:

• 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
• Excessive urination, including at night, and excessive thirst even after drinking fluids (nephrogenic diabetes insipidus)

There have been reports of tumours (myelodysplastic syndrome, AML, bronchial carcinoma) following treatment with Bendamustine Hydrochloride. No clear relationship with Bendamustine Hydrochloride 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.

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

Do not use Bendamustine Hydrochloride after the expiry date which is stated on the carton & label.

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 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.