2.5 mg/ml powder for concentrate for solution for infusion bendamustine
hydrochloride
What Ribovact is and what it is used for
Ribovact is a medicine used to treat certain cancers ( cytostatics ).
Ribovact is used alone or in combination with other medicines 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 were short-lived or completely absent
multiple myeloma when high-dose chemotherapy with autologous stem cell transplantation (with own stem cells ) or treatment with thalidomide or bortezomib is not appropriate.
Before using Ribovact
Do not use Ribovact
- if you are allergic to bendamustine hydrochloride or any of the other ingredients of this medicine (listed in section 6).
- if you are breastfeeding. If treatment with Ribovact is necessary while breast-feeding, breast-feeding must be stopped (see “Pregnancy, breast-feeding and fertility”)
- if you have a severe liver failure (liver damage).
- if the skin or whites of the eyes are yellow due to problems with the liver or blood.
- if you have severely impaired bone marrow function (bone marrow depression) and the values for your white blood cells ( leukocytes ) or platelets ( platelets ) are very low
- if you have undergone major surgery within 30 days before starting treatment.
- if you have an infection, especially if it is associated with a low white blood cell count ( leukopenia ).
- in connection with vaccination against yellow fever.
Warnings and cautions
Talk to your doctor, pharmacist, or nurse before using Ribovact
- if the ability to form blood cells in your bone marrow is impaired. The number of white blood cells and platelets should be checked before starting treatment with Ribovact, before each new course, and between courses.
- 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 when you are treated with Ribovact. 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 already 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 amount of urine 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 Ribovact. Your doctor can make sure you get enough fluids (hydrated) and give you other medicines to prevent the problem from occurring.
- if you have a severe allergic reaction or hypersensitivity reaction. Remember if you experience infusion-related reactions (fever, chills, itching, or rash) after the first course.
Pregnancy, breastfeeding, and fertility
If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.
Pregnancy
Ribovact can damage hereditary systems and has caused malformations in experimental animals. Ribovact must not be used during pregnancy unless your doctor has told you to. If you have to take medication during pregnancy, discuss the risk of birth defects with your doctor, and also discuss genetic counseling.
If you are a woman and could become pregnant, you must use an effective method of contraception both before and during treatment with Ribovact. If you become pregnant while being treated with Ribovact, contact your doctor immediately and ask for genetic counseling.
Breast-feeding
Ribovact must not be used during breastfeeding. If Ribovact treatment is necessary while breastfeeding, breastfeeding must be stopped.
Ask your doctor or pharmacist for advice before taking any medicine during pregnancy or breastfeeding.
Fertility
Men treated with Ribovact should avoid having children during treatment and 6 months after stopping treatment. Find out the possibilities of storing sperm before starting treatment – treatment with Ribovact can lead to permanent infertility (sterility).
If you are a man, you should avoid having children when you are treated with Ribovact and for another 6 months after stopping treatment. Ribovact can lead to infertility, so it may be a good idea to find out how to store your sperm before starting treatment.
Driving and using machines
Ribovact 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 ribs act
Always use this medicine exactly as your doctor or pharmacist has told you. Ask your doctor or pharmacist if you are unsure.
Ribovact is given as a drip into a vein for 30-60 minutes. The dosage varies and the drug can be given either as a single treatment or in combination with other drugs.
Treatment should not be initiated if the value of the white blood cells and/or platelets in the blood is too low.
These values are tested regularly.
Chronic lymphocytic leukemia
| 100 mg Ribovact per square meter body area (calculated by weight and height) | Day 1 and 2 |
| The course is repeated at 4-week intervals up to 6 times. |
Non-Hodgkin’s lymphoma
| 120 mg Ribovact per square meter of body surface area (calculated by weight and length) | Day 1 and 2 |
| The course is repeated at 3-week intervals at least 6 times. |
Multiple myeloma
| 120-150 mg Ribovact per square meter body area (calculated by weight and height) | Day 1 and 2 |
| 60 mg prednisone per square meter of body surface area (calculated by weight and height) intravenously or orally. | Day 1-4 |
| The course is repeated at 4-week intervals at least 3 times. |
Treatment must be stopped if the number of white blood cells drops to established levels. Treatment can continue when the number of white blood cells and the number of platelets have increased.
Liver or kidney failure
Dosage may need to be adjusted according to the degree of liver failure (30% in patients with moderate hepatic impairment). No dose adjustment is required in patients with renal impairment. The attending physician decides on any dose adjustments.
Method of administration
Ribovact treatment must be performed under the supervision of a physician experienced in the treatment of cancer. Your doctor will prescribe the dose of Ribovact that is right for you and will take the necessary precautions.
The treating physician gives the prescribed infusion solution as a rapid intravenous infusion for 30-60 minutes.
Duration of treatment
There are no set time limits for how long Ribovact cures should be given. The duration of treatment depends on the disease and the effect of the treatment.
If you have any further questions or if you have any further questions on the use of Ribovact, ask your doctor or nurse.
If you forget to use Ribovact
If a dose of Ribovact is missed, your doctor will usually continue treatment according to the usual dosing schedule.
If you stop using Ribovact
The attending physician decides whether to discontinue treatment or switch to another treatment.
If you have any further questions on the use of this product, ask your doctor or pharmacist.
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.
When assessing side effects, the following definitions of the occurrence of side effects are used:
| Very common | With more than 1 user out of 10 |
| Usual | With 1-10 users out of 100 |
| Less common | With 1-10 users out of 1000 |
| Rare | With 1-10 users out of 10,000 |
| Very rare | With less than 1 user out of 10,000 |
| No known frequency of side effects | The frequency can not be calculated from the available data |
In very rare cases, tissue damage ( necrosis ) has occurred, as the drug has ended up outside the blood vessel (extravasation). If the patient has a burning sensation at the site where the needle was inserted, it may be because the medicine has ended up outside the blood vessel. If the medicine reaches the tissues in this way, pain and skin damage may occur. The skin damage heals poorly.
A side effect that limits the use of Ribovact is weakened bone marrow function. In general, bone marrow function recovers and 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
• Low white blood cell count ( disease-fighting cells in your blood)
Decreased hemoglobin value (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
• Increased creatinine value in the blood (a chemical residue produced by your muscles)
• Increased urea value in the blood (a chemical residue)
• Fever
• Fatigue
Usual
• Bleeding
• Disrupted metabolism due to dying cancer cells that release slag products into the blood
Reduced red blood cell count ( anemia ), which may cause paleness, weakness, or shortness of breath
Low neutrophil count (a common type of white blood cell count important to fight infections )
• Hypersensitivity reaction that causes inflammation in the skin, hives
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 in the blood (a nutrient that is necessary for the function of nerve and muscle cells, including those in your heart)
• Disrupted heart function
• Rhythm disturbances in the heart
• Low or high blood pressure
• Impaired lung function
• Diarrhea
• Constipation
• Pain in the mouth (inflammation of the mouth)
• Loss of appetite
• Hair loss
• Skin changes
• Missed period
• Pain
• Insomnia
• Chills
• Dehydration
• Dizziness
Itchy rash ( urticaria )
Less common
• Accumulation of fluid in the pericardium (which surrounds the heart)
• Inefficient production of blood cells in the bone marrow
• Acute leukemia
• Heart attack, chest pain
• Heart failure
Rare
• Blood poisoning ( sepsis )
• Severe allergic hypersensitivity reactions (anaphylactic reactions)
• Impaired bone marrow function, which can make you feel sick or can be seen on blood tests
• Symptoms reminiscent of anaphylaxis (anaphylactoid reactions)
Drowsiness
• Silent voice
• Acute circulatory failure (decreased blood pressure and blood flow leading to a deterioration in the supply of oxygen and other nutrients to the body)
• Reddening of the skin
• Skin rash ( dermatitis )
Itching _
• Rash in the form of spots and blemishes (maculopapular rash)
• Heavy sweating
Very rare
• Primary atypical pneumonia
Degradation of red blood cells
• Rapid drop in blood pressure with skin reactions or rash (anaphylactic shock )
• Disturbed sense of taste
• Disturbed sensation ( paresthesia )
• Damage to peripheral nerves (discomfort and pain in the extremities )
• Severe conditions that result in blockade of specific receptors in the nervous system
• Disorder of the nervous system
• Disrupted coordination
• Inflammation of the heart
• Fast pulse
Inflammation of veins
Increase in connective tissue in the lungs
• Esophageal inflammation with bleeding
• Bleeding in the stomach or intestines
• Sterility
• Multiple organ damage
No known frequency of side effects
• 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 in combination therapy with rituximab
• Pneumonitis ( pneumonia )
• Bleeding from the lungs
Tumors ( myelodysplastic syndrome, acute myeloid leukemia [AML], tracheal carcinoma) have been reported following treatment with Ribovact. No obvious association with Ribovact 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 Stevens-Johnson syndrome and toxic epidermal necrolysis. These can appear as reddish dot-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).
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor.
How to store Ribovact
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 the outer carton.
The expiration date is the last day of the specified month.
Store the packaging in the outer carton. Sensitive to light.
Shelf life after opening the medicine pack or preparing the infusion solution
Infusion solutions prepared according to the instructions given at the end of this leaflet are durable in polyethylene bags at room temperature and 60% relative humidity for 3.5 hours and at refrigerator temperature for 2 days. Ribovact does not contain any preservatives. Therefore, solutions stored longer than the stated shelf life must not be used.
The user is responsible for the product being handled aseptically.
The medicine 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.
Contents of the package and other information
Content declaration
The active substance is bendamustine hydrochloride.
One vial contains 25 mg bendamustine hydrochloride or 100 mg bendamustine hydrochloride.
After reconstitution, 1 ml of concentrate contains 2.5 mg of bendamustine hydrochloride.
Contains mannitol.
What the medicine looks like and the contents of the pack
Brown glass vial with rubber stopper and removable aluminum lid.
The powder is white and crystalline.
Ribovact is available in packs of
5, 10, or 20 vials of 25 mg bendamustine hydrochloride
and
5 vials of 100 mg bendamustine hydrochloride.
Not all pack sizes may be marketed.
Marketing Authorization Holder and Manufacturer
Marketing Authorisation Holder
Astellas Pharma GmbH
Ridlerstrasse 57
80339 Munich
Germany
Manufacturer
Haupt Pharma Wolfratshausen GmbH
Pfaffenrieder Straβe 5
D-82515 Wolfratshausen
Germany
Information is provided by
Mundipharma AB
Mölndalsvägen 30B
412 63 Gothenburg
Tel .: 031 773 75 30
Fax: 031 773 75 49