Equiben Solution

EQUIBEN is a medicinal product which is used for the treatment of certain types of cancer (cytostatic medicine). EQUIBEN 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.

EQUIBEN should not be administered to you:

• if you are hypersensitive (allergic) to bendamustine hydrochloride or any of the other ingredients of EQUIBEN (listed in section 6).
• during pregnancy, or if you are breastfeeding your baby
• 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 (white blood cells and/or thrombocyte values drop to < 3 x 109/L or < 75 x 109/L, respectively);
• 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 or other live attenuated vaccines.
• if you have a condition called congenital QT prolongation where your heart has an abnormal rhythm
• if you are taking medicines that can cause abnormal heart rhythms such as medicines for mental disorders (e.g., citalopram, chlorpromazine, lithium, haloperidol, venlafaxine), antibiotics (e.g., clarithromycin, efavirenz, moxifloxacin), antifungals (e.g., fluconazole, voriconazole), medicines for heart conditions (e.g., amiodarone, flecainide, sotalol), medicines for malaria (e.g., quinine), cancer medicines (e.g., dasatinib, lapatinib, pazopanib)

Warnings and precautions

Tell your doctor or healthcare provider before being given the injection:

• if you have a 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 EQUIBEN, before each subsequent course of treatment and in the intervals between courses of treatment.
• if you have any infections which may include TB (tuberculosis). You should contact your doctor if you have signs of infection, including fever or lung symptoms.
• 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).
• if you get reactions on your skin during treatment with EQUIBEN. The skin reactions may increase in severity.
• 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.
• if you have 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.
• if you have an existing heart disease (e.g., heart attack, chest pain, severely disturbed heart rhythms).
• if 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 EQUIBEN. Your doctor may ensure you are adequately hydrated and give you other medicines to help prevent it.
• if you get severe allergic or hypersensitivity reactions. You should pay attention to infusion reactions after your first cycle of therapy.
• If you are a man receiving treatment with EQUIBEN you should not father a child during your treatment and for up to 6 months afterwards. Before starting treatment, you should seek advice on storing your sperm cells because of the possibility of permanent infertility.
• Unintentional injection into the tissue outside blood vessels (extravasal injection) may cause local tissue damage. Your doctor will treat this.

You will not be expected to give yourself EQUIBEN. It will be given to you by a person who is qualified to do so. Treatment with EQUIBEN should be undertaken only by doctors experienced in cancer therapy. Your doctor will give you the exact dose of EQUIBEN 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 EQUIBEN. Duration of treatment depends on your disease and your response to treatment.

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

If you receive more EQUIBEN than you should

Since a healthcare provider will administer EQUIBEN, he / she will control the dosage. However, in the event of overdosage your doctor will manage the overdosage.

If you forget to use EQUIBEN

Since a healthcare provider will administer EQUIBEN, it is unlikely that the dose will be missed.

EQUIBEN can have side effects. Not all side effects reported for EQUIBEN are included in this leaflet. Should your general health worsen or if you experience any untoward effects while taking EQUIBEN, please consult your healthcare provider for advice.

Tell your doctor immediately if experience any of the following side effects, you may need urgent medical attention or hospitalisation:

• severe allergic hypersensitivity reactions (anaphylactic reactions)
• swelling of the hands, feet, ankles, face, lips and mouth or throat, which may cause difficulty in swallowing or breathing,
• rash or itching,
• fainting.
• rapid decrease in blood pressure sometimes with skin reactions or rash (anaphylactic shock)

These are all very serious side effects. If you have them, you may have had a serious reaction to EQUIBEN. You may need urgent medical attention or hospitalisation.

Tell your doctor immediately or go to the casualty department at your nearest hospital if you notice any of the following:

Frequent side effects:

• infections including Herpes zoster (viral infection of the nerves causing painful rash occurring in a strip), cytomegalovirus (a kind of herpesvirus which usually produces very mild symptoms in an infected person but may cause severe neurological damage in people with weakened immune systems and in the new-born), hepatitis B (liver infection).
• disturbed metabolism caused by dying cancer cells releasing their contents into the blood stream (tumour lysis syndrome)
• low counts of white blood cells (disease-fighting cells in your blood)
• blood platelet count is low (thrombocytopenia)
• a condition in which there is a lower-than-normal number of lymphocytes (a type of white blood cell) in the blood (lymphopenia)
• reduction in red blood cells which can make the skin pale and cause weakness or breathlessness (anaemia)
• your body does not have enough neutrophils, an important white blood cell that fights infections (neutropenia)
• bleeding (haemorrhage)
• increased heart rate (tachycardia)
• rapid, strong, or irregular heartbeat (palpitations)
• a condition marked by severe pain in the chest, often also spreading to the shoulders, arms, and neck, owing to an inadequate blood supply to the heart (angina pectoris)
• disturbed function (dysfunction) of the heart
• disturbed heart rhythms (dysrhythmia, QT prolongation)
• impaired lung function
• decrease in the red pigment of the blood (haemoglobin: a protein in red blood cells that carries oxygen throughout the body)
• increased blood level of creatinine (a chemical waste product that is produced by your muscle)
• increased blood level of urea (a chemical waste product)
• 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)

Less frequent side effects:

• serious fungal infection of the lungs that causes inflammation and fluid build-up in your lungs
• infection of the blood (septicaemia)
• a life-threatening immune system reaction to an infection (sepsis)
• primary atypical inflammation of the lungs (pneumonia)
• bacterial infection which is spread through the air and usually affects the lungs (tuberculosis)
• ineffective production of all blood cells in the bone marrow (the spongy material inside your bones where blood cells are made) (myelodysplastic syndrome)
• acute leukaemia
• a condition in which there is a lower-than-normal number of red and white blood cells and platelets in the blood (pancytopenia)
• reduction in your bone marrow function, which may make you feel unwell or show up in your blood tests
• break-down of red blood cell (haemolysis)
• inflammation of the brain (encephalitis)
• accumulation of fluid in the heart sac (escape of fluid into the pericardial space)
• heart attack, chest pain (myocardial infarct)
• heart failure
• 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)

Frequency of side effects not known:

• irregular and often rapid heart rate (atrial fibrillation)
• inflammation of the walls of the alveoli (air sacs) in the lungs (pneumonitis)
• bleeding from the lungs
• liver failure
• renal failure
• 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.
• drug rash in combination therapy with rituximab 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).

These are all serious side effects. You may need urgent medical attention.

Tell your doctor if you notice any of the following:

Frequent side effects:

• headache
• sleeplessness (insomnia)
• dizziness
• low or high blood pressure (hypotension or hypertension)
• feeling sick (nausea)
• vomiting
• diarrhoea
• constipation
• sore mouth (stomatitis)
• hair loss (alopecia)
• skin disorders
• itchy rash (urticaria)
• missed periods (amenorrhoea)
• mucosal inflammation
• fatigue
• fever (pyrexia)
• pain
• chills
• dehydration
• anorexia

Less frequent side effects:

• drowsiness
• loss of voice (aphonia)
• disturbed sense of taste
• altered sensations (paraesthesia)
• malaise and pain in the limbs (peripheral neuropathy)
• disease of the nervous system (anticholinergic syndrome)
• disorders that affect the brain as well as the nerves found throughout the human body and the spinal cord (neurological disorders)
• lack of coordination (ataxia)
• inflammation of the veins (phlebitis)
• formation of scar tissue in the lungs (fibrosis of the lungs)
• inflammation and bleeding of the gullet (haemorrhagic oesophagitis)
• bleeding of stomach or gut
• reddening of the skin (erythema)
• inflammation of the skin (dermatitis)
• itching (pruritus)
• skin rash (macular exanthema)
• excessive sweating (hyperhidrosis)
• infertility
• multiple organ failure

If you notice any side effects not mentioned in this leaflet, please inform your doctor or pharmacist.

Reporting of side effects

If you get side effects, talk to your doctor, pharmacist, or nurse. You can also report side effects to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on the SAHPRA website. By reporting side effects, you can help provide more information on the safety of EQUIBEN.

Store all medicines out of reach of children.

Store at or below 25 °C.

There are no special storage instructions for EQUIBEN. Do not use after the expiry date stated on the label.

Note on shelf-life after opening or preparing the solution

Solutions for infusions prepared according to the directions are stable in polyethylene bags 25 °C for 3,5 hours, and in a refrigerator, they are stable for 2 days. EQUIBEN contains no preservatives. The solutions should not therefore be used after these lengths of time.

Do not dispose of unused medicine in drains or sewerage systems (e.g., toilets).