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. It contains information that is important to you.

  • Save this information, you may need to read it again.
  • If you have any further questions, ask your doctor or pharmacist.
  • If you get any side effects, talk to your doctor or pharmacist. This also applies to any side effects not mentioned in this information. See section 4

In this leaflet: 
1. What Bendamustin Actavis is and what it is used for 
2. What you need to know before you use Bendamustin Actavis 
3. How to use Bendamustin Actavis 
4. Possible side effects 
5. How to store Bendamustin Actavis 6. Contents of the pack 
and other information 

What Bendamustin Actavis is and what it is used for

Bendamustine Actavis is a medicine used to treat certain cancers ( cytostatics ).

Bendamustine Actavis is used as the sole drug or in combination with other drugs to treat the following cancers:

  • chronic lymphocytic leukemia if combination chemotherapy with fludarabine is not appropriate.
  • non-Hodgkin’s lymphoma when the results of previous rituximab treatment have been short-lived or absent altogether.
  • multiple myeloma when treatment with thalidomide or bortezomib is not appropriate.

Bendamustine hydrochloride contained in Bendamustine Actavis may also be approved for the treatment of other conditions not mentioned in this product information. Ask your doctor, pharmacist, or another healthcare professional if you have any further questions, and always follow their instructions.

What you need to know before you use Bendamustin Actavis

Do not use Bendamustin Actavis

  • if you are allergic to bendamustine hydrochloride or any of the other ingredients of this medicine (listed in section 6)
  • while breastfeeding: if treatment with Bendamustine Actavis is necessary while breast-feeding, breast-feeding must be stopped (see “Pregnancy, breast-feeding and fertility”)
  • if you have severe hepatic impairment (damage to the functional cells of the liver)
  • if you have yellow skin or whites of the eyes due to liver or blood disease (jaundice)
  • if you have severe bone marrow function (bone marrow depression) and severe changes in the number of white blood cells and platelets in the blood
  • if you have undergone major surgery less than 30 days before starting treatment
  • if you have an infection, especially if it is accompanied by a decrease in the number of white blood cells ( leukopenia )
  • in connection with vaccination against yellow fever.

Warnings and cautions

Talk to your doctor, pharmacist, or nurse before or during treatment with Bendamustine Actavis:

  • if the ability to form blood cells in your bone marrow is impaired. The number of white blood cells and platelets in the blood should be checked before starting treatment with Bendamustine Actavis, before each subsequent treatment cycle, and during treatment-free intervals.
  • if you have an infection. Contact a doctor if you have signs of infection, e.g. fever or lung problems.
  • if you get any skin reaction during treatment with Bendamustine Actavis. These skin reactions can be exacerbated.
  • if you get painful red or purple rashes that spread and blisters and/or other injuries begin to appear on the mucous membranes (eg mouth and lips), especially if you have previously had photosensitivity, infection of the respiratory tract (e.g. bronchitis ), and/or fever.
  • if you have any heart disease (eg heart attack, chest pain, severe heart rhythm disturbances).
  • if you feel pain in the side, have blood in the urine, or if your urine volume decreases. If your disease is very severe, your body may not be able to get rid of all the slag from the dying cancer cells. This condition is called tumor lysis syndrome and can lead to kidney failure or heart problems within 48 hours of the first dose of Bendamustin Actavis. Your doctor can make sure you get enough fluids (hydrated) and give you other medicines to prevent the problem from occurring.
  • if you get a severe allergic reaction or hypersensitivity reaction. You should be aware of infusion-related reactions after the first treatment cycle.

Other medicines and Bendamustin Actavis

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

If Bendamustin Actavis is used in combination with other medicines that inhibit the formation of blood in the bone marrow, it may lead to an increase in the effect on the bone marrow.

If Bendamustin Actavis is used in combination with medicines that alter your immune response, e.g. ciclosporin and tacrolimus, the effect on the immune response may be enhanced.

Drugs such as bendamustine ( cytostatics ) may weaken the effect of vaccination with live viruses. Cytostatics also increase the risk of infection when vaccinated with live vaccines (eg vaccines against viral diseases).

If Bendamustin Actavis is used with medicines that inhibit a specific liver enzyme (CYP1A2), such as fluvoxamine (antidepressant), ciprofloxacin (used to treat bacterial infections ), aciclovir (used to treat viral infections), and cimetidine (used to treat heartburn and stomach ulcers ) these drugs can affect each other’s effect.

Pregnancy, breastfeeding, 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 taking this medicine.

Pregnancy

Bendamustine Actavis can cause genetic damage and has caused malformations in experimental animals. Bendamustine Actavis should not be used during pregnancy unless your doctor has told you to. If you need to be treated during pregnancy, consult your doctor about the risk of potential birth defects that the treatment may cause. Genetic counseling is also recommended.

Fertility

If you are a woman of childbearing potential, you must use some effective contraceptive method both before and during treatment with Bendamustine Actavis. If you become pregnant during treatment with Bendamustine Actavis, you must immediately inform your doctor and ask for genetic counseling.

If you are a man, you should avoid having children during the treatment of Bendamustin Actavis and 6 months after the end of treatment. There is also a risk that treatment with Bendamustine Actavis will lead to infertility. You should therefore investigate the possibilities of sperm storage before starting treatment.

Breast-feeding

Bendamustine Actavis must not be used during breast-feeding. If treatment with Bendamustine Actavis is necessary during the breastfeeding period, breast-feeding must be stopped.

Driving and using machines

Bendamustine Actavis has a major impact on the ability to drive and use machines. Do not drive or use machines if you experience side effects, e.g. dizziness or impaired coordination. 

You are responsible for assessing whether you are fit to drive a motor vehicle or perform work that requires sharpened attention. One of the factors that can affect your ability in these respects is the use of drugs due to their effects and/or side effects. Descriptions of these effects and side effects can be found in other sections. Read all the information in this leaflet for guidance. If you are not sure, talk to your doctor or pharmacist.

How to use Bendamustin Actavis

Bendamustine Actavis is given in a vein for 30-60 minutes in different doses, either alone ( monotherapy ) or in combination with other medicines.

Treatment should not be started if you have a low number of white blood cells ( leukocytes ) and/or platelets. This is checked regularly by your doctor.

Chronic lymphocytic leukemia

100 mg Bendamustin Actavis per square meter of body surface area (based on your height and weight) on day 1 + 2
Repeat the cycle after 4 weeks up to 6 times

Non-Hodgkin’s lymphoma

120 mg Bendamustin Actavis per square meter body area (based on your height and weight) on day 1 + 2
Repeat the cycle after 3 weeks at least 6 times

Multiple myeloma

120-150 mg Bendamustin Actavis per square meter body area (based on your height and weight) on day1 + 2
60 mg prednisone per square meter of body surface area (based on your height and weight) intravenously or orally on day1 – 4
Repeat the cycle after 4 weeks at least 3 times

Treatment should be discontinued if the number of white blood cells ( leukocytes ) and/or platelets drops to established levels. Treatment can be continued when the number of white blood cells and platelets has increased.

Hepatic or renal impairment

Depending on how severely impaired your liver function is, it may be necessary to adjust dose one. hepatic impairment). No dose adjustment is necessary for renal impairment. Your treating physician will decide if a dose adjustment is necessary or not.

How it is administered

Treatment with Bendamustin Actavis should only be performed by a physician experienced in the treatment of cancer. Your doctor will prescribe the dose of Bendamustine Actavis that is right for you and will take the necessary precautions.

Your treating physician will give the infusion solution after the prescribed preparations. The solution is given into a vein in the form of a short-term infusion over 30-60 minutes.

Length of treatment

There are no set time limits for how long treatment with Bendamustine Actavis should be given. The duration of treatment depends on the disease and the effect of the treatment.

If you have any further questions on the use of Bendamustine Actavis, ask your doctor or nurse.

If you forget to use Bendamustin Actavis

If a dose of Bendamustin Actavis is missed, your doctor will usually continue treatment according to the usual dosing schedule.

If you stop using Bendamustin Actavis

The attending physician decides whether to discontinue treatment or whether to switch to another treatment.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. Some of the side effects listed below may be detected by tests performed by your doctor.

In very rare cases, tissue damage ( necrosis ) has occurred, as the drug has inadvertently ended up outside the blood vessel (extravasation). A burning sensation in which the infusion needle is inserted may be a sign that administration is taking place outside the blood vessels. The consequence of such administration may be pain and difficult-to-heal skin lesions.

A dose-limiting side effect of Bendamustin Actavis is impaired bone marrow function, which usually returns to normal after treatment. Impaired bone marrow function can lead to a decrease in the number of blood cells, which in turn can lead to an increased risk of infection, anemia, or an increased risk of bleeding.

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

Low white blood cell count ( disease-fighting cells in your blood)

Reduction of the red pigment in the blood (hemoglobin: (a protein in red blood cells that carries oxygen throughout the body))

Low platelet count (colorless blood cells that help the blood to coagulate)

  • Infection is
  • Nausea
  • Vomiting
  • Mucositis
  • Headache
  • Elevated creatinine levels in the blood (a chemical residue produced by your muscles)
  • Elevated urea levels in the blood (a chemical residue)
  • Fever
  • Fatigue

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

  • Bleeding
  • Disrupted metabolism is due to the content of dying cancer cells being released into the blood
  • Decreased number of red blood cells, which can make the skin paler and cause weakness or shortness of breath ( anemia )
  • Low neutrophil count (a common type of white blood cell important for fighting infections )
  • Hypersensitivity reactions, e.g. allergic dermatitis ( dermatitis ), hives ( urticaria )
  • Elevated values ​​of liver enzymes AST / ALT (which may indicate inflammation or damage to cells in the liver)
  • An increase in alkaline phosphatases (an enzyme made mainly in the liver and skeleton)
  • Elevated bilirubin levels (a substance formed during the normal breakdown of red blood cells )
  • Low potassium levels in the blood (a nutrient that is essential for the function of nerve and muscle cells, including those in your heart.)
  • Disorders of heart function
  • Cardiac arrhythmias ( arrhythmia )
  • Low or high blood pressure ( hypotension or hypertension )
  • Impaired lung function
  • Diarrhea
  • Constipation
  • Pain in the mouth ( stomatitis )
  • Reduced appetite
  • Hair loss
  • Skin changes
  • Absence of menstruation ( amenorrhea )
  • Pain
  • Insomnia
  • Overindulge
  • Dehydration
  • Dizziness
  • Itchy rash ( urticaria )

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

  • Pneumonia (pneumocystis jirovecii pneumonia )
  • Accumulation of fluid in the pericardium (which surrounds the heart)
  • Impaired formation of all types of blood cells in the bone marrow (the fungus-like material on the inside of your bones where blood cells are formed)
  • Acute leukemia
  • Myocardial infarction, chest pain
  • Heart failure

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

  • Infection in the blood ( sepsis )
  • Impaired bone marrow function, which can mean that you feel sick or can be seen on blood tests
  • Severe allergic hypersensitivity reactions (anaphylactic reactions)
  • Symptoms reminiscent of anaphylactic reactions (anaphylactoid reactions)
  • Drowsiness
  • Inability to speak (aphonia)
  • Acute circulatory failure (decreased blood pressure and blood flow leading to a deterioration in the supply of oxygen and other nutrients in the body)
  • Redness ( erythema )
  • Inflammation of the skin ( dermatitis )
  • Itching ( pruritus )
  • Skin rash (macular exanthema)
  • Excessive sweating ( hyperhidrosis )

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

  • Primary atypical pneumonia ( pneumonia )
  • Degradation of red blood cells
  • Rapidly decreasing blood pressure, sometimes accompanied by skin reactions or rash (anaphylactic shock )
  • Decreased sense of taste
  • Emotional disorders ( paresthesia )
  • Feelings of discomfort and pain in the joints ( peripheral neuropathy )
  • Severe conditions result in the blockade of specific receptors in the nervous system.
  • Disorder of the nervous system
  • Coordination difficulties ( ataxia )
  • Brain inflammation ( encephalitis )
  • Increased heart rate ( tachycardia )
  • Inflammation of the veins ( phlebitis )
  • Connective tissue formation in the lungs ( pulmonary fibrosis )
  • Bleeding and inflammation of the esophagus (hemorrhagic esophagitis )
  • Bleeding in the stomach or intestines
  • Infertility
  • Multiple organ failure

Has been reported  (occurs in an unknown number of users) :

  • Liver failure
  • Kidney failure
  • Irregular and often fast heart rate ( atrial fibrillation )
  • Painful red or purple rash that spreads and blisters and/or other damage that begins to appear on the mucous membranes (eg mouth and lips), especially if you have previously had photosensitivity, infection of the respiratory tract (eg bronchitis ), and/or fever.
  • Rash with combination therapy with rituximab
  • Pneumonitis
  • Bleeding from the lungs

Tumors ( myelodysplastic syndrome, acute myeloid leukemia (AML), bronchial cancer) have been reported after treatment with bendamustine. No clear association with bendamustine could be established.

Contact a doctor or seek medical attention immediately if you notice any of the following side effects (no known frequency):

  • Severe rash, including Steven Johnson’s syndrome and toxic epidermal necrolysis . These can appear as reddish spot-like spots or circular plaques, often with blisters in the middle of the torso, flaky skin, sores in the mouth, nose, eyes, and genitals and can be followed by fever and flu-like symptoms.
  • Widespread rash, high body temperature, enlarged lymph nodes, and involvement of other body organs (drug side effect with eosinophilia and systemic symptoms also known as DRESS or drug hypersensitivity syndrome).

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 to the Medical Products Agency, www.lakemedelsverket.se. By reporting side effects, you can help increase drug safety information

5. How to store Bendamustin Actavis

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 label and carton after “EXP”. The expiration date is the last day of the specified month.

Unopened

No special storage instructions.

Ready-made concentrate

The powder should be reconstituted immediately after opening the vial.

The reconstituted concentrate should be diluted immediately with 0.9% sodium chloride solution (see instructions at the end of this leaflet).

Infusion solution

After reconstitution and dilution, chemical and physical in-use stability has been demonstrated for 3.5 hours at 25 ° C / 60% RH under normal lighting conditions, and for 2 days at 2 ° C to 8 ° C when protected from light in polyethylene bags.

From a microbiological point of view, the solution should be used immediately. If the solution is not used immediately, the responsibility for shelf life and storage before use lies with the user. This storage should normally not be longer than 24 hours at 2 ° C to 8 ° C unless reconstitution/dilution has been performed under controlled and validated aseptic conditions.

6. Contents of the packaging and other information

Content declaration

  • The active substance is bendamustine hydrochloride. After reconstitution, 1 ml of concentrate contains 2.5 mg of bendamustine hydrochloride. One 26 ml vial contains 25 mg bendamustine hydrochloride. One 60 ml vial contains 100 mg bendamustine hydrochloride.
  • The other ingredient is mannitol. 

What the medicine looks like and the contents of the pack

White to off-white freeze-dried powder.

Amber vials (type I) of 26 ml or 60 ml with freeze-drying caps of type I rubber (bromobutyl) and an aluminum lid with polypropylene disc. The vials are enclosed in a protective cover.

26 ml vials contain 25 mg bendamustine hydrochloride and are supplied in packs of 1, 5, 10, or 20 vials.

60 ml vials contain 100 mg bendamustine hydrochloride and are supplied in packs of 1 or 5 vials.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Actavis Group PTC EHF.

Reykjavikurvegur 76-78 Hafnarfjordur

Iceland

Manufacturer

SC SINDEN-PHARMA SRL

Ion Mihalache Boulevard No.11

Sector 1, 011171, Bucharest

Romania

Muhammad Nadeem

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