Doxorubicin Hydrochloride 2 Mg/Ml Solution For Infusion
Doxorubicin hydrochloride 2 mg/ml • 82411-VP1GB • BA - 02.14 • Pharma-Code: 93
Format: 592 x 150 mm • HKS 44 • Corrective action: KV01_osc_10.02.14
Doxorubicin hydrochloride 2 mg/ml • 82411-VP1GB • BA - 02.14 • Pharma-Code: 93
Format: 592 x 150 mm • HKS 44 • Corrective action: KV01_osc_10.02.14
Read all of this leaflet carefully before you receive this medicine because it contains important information for you.
• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only.
Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.
Package leaflet: Information for the patient
Doxorubicin hydrochloride 2 mg/ml
solution for infusion
Doxorubicin hydrochloride
What is in this leaflet
1. What Doxorubicin hydrochloride is and what it is used for
2. What you need to know before you receive Doxorubicin hydrochloride
3. How Doxorubicin hydrochloride is administered
4. Possible side effects
5. How to store Doxorubicin hydrochloride
6. Contents of the pack and other information
1. What Doxorubicin hydrochloride is and what it is used for
Doxorubicin is one of a group of medicines known as anthracyclines. It works by killing tumour and blood cancer cells. Your doctor will be able to explain how doxorubicin might help in your particular condition.
This medication is used to treat:
• breast cancer
• ovarian cancer
• uterine cancer
• cancer of the bladder
• lung cancer
• thyroid cancer
• soft tissue and bone cancer (sarcoma)
• neuroblastoma (cancer of the nerve cells)
• Wilms’ tumour
• malignant lymphoma (Hodgkin’s and non-Hodgkin’s)
• leukaemias (cancer cause abnormal production of blood cells)
• cancer of white blood cells (multiple myeloma)
2. Before you receive Doxorubicin hydrochloride
You must not receive Doxorubicin hydrochloride
in the following cases. Please tell your doctor
• if you are allergic to doxorubicin or any of the other ingredients of this medicine (listed in section 6) or to other anthracyclines.
• if you have been told that your blood is thin (your bone marrow is not working well).
• if you have, or ever have had, any heart problems.
• if you have received doxorubicin, other anthracyclines, other anti-tumour medicines or immunosuppressive medicines before.
• if you tend to bleed easily.
• if you suffer from any kind of infection.
• if you suffer from mouth ulcers.
• if your liver is not working well.
• if you suffer from an infection of the bladder or if you have blood in your urine (in case the medicine is given to you by an administration into your bladder)
• if you are breast-feeding.
Take special care with Doxorubicin hydrochloride and tell your doctor
• if you have had any radiotherapy before.
• if you are pregnant, trying to become pregnant, likely to want to try to become pregnant in the future or if you want to father a child.
• if you are on a controlled sodium diet.
If there is a burning sensation in the area of the infusion, this can be a sign of an injection error and the infusion must be stopped immediately.
You should avoid contact to persons recently vaccinated against polio when you are under treatment with Doxorubicin hydrochloride.
Other medicines and Doxorubicin hydrochloride
Tell your doctor if you are taking, have recently taken or might take any other medicines.
The following medications can interact with Doxorubicin hydrochloride:
• Other cytostatics (medication against cancer) e.g. anthracyclines (daunorubicin, epirubicin, idarubicin), cisplatin, cyclophosphamide, cyclosporin, cytarabine, dacarbazine, dactinomycin, fluorouracil, mitomycin C, taxanes (e.g. paclitaxel), mercaptopurine, methotrexate, streptozocin
• Cardioactive medicines (medications for heart diseases), e.g. calcium channel blockers, verapamil, digoxin
• Inhibitors of cytochrome P-450 (medicines that stop the substance cytochrome P-450, which is important for the detoxification of your body, from working; e.g. cimetidine)
• Medicine inducing cytochrome P-450 (e.g. rifampicin, barbiturates)
• Antiepileptic medicines (e.g. carbamazepine, phenytoin, valproate)
• Heparin (prevents the clotting of the blood)
• Amidopyrine derivatives (pain-killers)
• Antiretroviral medicines (medications against special forms of viruses, e.g. ritonavir against AIDS)
• Chloramphenicol
• Sulphonamides (medications against bacteria)
• Progesterone (e.g. at threatening miscarriage)
• Amphotericin (used to treat fungal infections)
• Live vaccines (e.g. against polio myelitis, malaria)
• Trastuzumab (used in the treatment of breast cancer)
• Clozapine (antipsychotic medicine)
• Dose adjustment of uric acid lowering agents may be necessary
Please note that these statements may also apply to products used some time ago or at some time in the future.
Pregnancy, breast-feeding and fertility
If you are a woman, you should not get pregnant during treatment with doxorubicin or up to 6 months after treatment.
If you are a man, you should take adequate precautions to ensure that your partner does not become pregnant during your treatment with doxorubicin or up to 6 months
after treatment. If you are considering becoming parents after the treatment please discuss with your doctor. Because doxorubicin may cause permanent infertility, it is advised to discuss with your doctor the possibility of freezing sperm before treatment start (cryo-preservation or cryo-conservation).
Doxorubicin is not recommended if you are pregnant.
Breast-feeding must be discontinued for the duration of Doxorubicin hydrochloride therapy.
Ask your doctor or pharmacist for advice before taking any medicine.
Driving and using machines
Due to the frequent occurrence of drowsiness, nausea and vomiting, you are not advised to drive cars and operate machinery.
Doxorubicin hydrochloride contains sodium
Please tell your doctor if you are on a low-sodium diet. He/she will take into account that 1 ml of Doxorubicin hydrochloride contains 3.5 mg sodium.
3. How Doxorubicin hydrochloride is administered
Method and routes of administration
Do not administer the medicine yourself. Your medicine will be given to you as part of an intravenous infusion, into a blood vessel, under the direction of specialists. You will be monitored regularly both during and after your treatment.
If you suffer from superficial bladder cancer it is possible that you may receive your medicine into your bladder (intravesical use).
Dosage
The dosage is usually calculated on the basis of your body surface area. 60 - 75 mg per square metre of body surface area may be given every three weeks when used alone. The dosage may need to be reduced to 30 - 40 mg per square metre of body surface area when given in combination with other anti-tumour medicines. The dosage may be given as either a single dose every three weeks or divided over three consecutive days (20 - 25 mg per square metre of body surface area on each day). If given weekly the recommended dose is 20 mg per square metre of body surface area.
Your doctor will advise you of how much you will need.
Patients with reduced liver or kidney function
If your liver or kidney function is reduced, the dosage should be decreased. Your doctor will advise you of how much you need.
Use in children/obese patients/elderly/patients after radiotherapy
The dosage may need to be reduced in children, in obese patients and the elderly or if you have received any radiotherapy. Your doctor will advise you of how much you need.
If you received more Doxorubicin hydrochloride than you should
During and after treatment you will be carefully monitored by your doctor or nurse. The symptoms of an overdose are an extension of doxorubicin's possible side effects, particularly the blood changes and heart problems. Heart disorders may even occur up to six months after you received the overdose.
In case of an overdose your doctor will take appropriate measures, such as a blood transfusion and/or treatment with antibiotics.
The following information is intended for healthcare professionals only:
Incompatibilities
Doxorubicin should not be mixed with heparin as a precipitate may form and it should not be mixed with 5-fluorouracil as degradation may occur. Prolonged contact with any solution of an alkaline pH should be avoided as it will result in hydrolysis of the medicine.
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
Opened vials
The product should be used immediately after opening the vial.
Prepared infusion solutions
Chemical and physical in-use stability at a concentration of 0.5 mg/ml has been demonstrated in sodium chloride 0.9 % and glucose 5 % for up to 7 days at 2 °C to 8 °C or room temperature (20 °C to 25 °C) when prepared in PE-bags and protected from light.
From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 °C to 8 °C, unless dilution has taken place in controlled and validated aseptic conditions.
Special precautions for disposal and other handling
For single use only.
Any unused product or waste material should be disposed of in accordance with local requirements.
Observe guidelines for handling cytotoxic medicines.
The following protective recommendations are given
due to the toxic nature of this substance:
• Personnel should be trained in good technique for handling.
• Pregnant staff should be excluded from working with this medicine.
• Personnel handling doxorubicin should wear protective clothing: goggles, gowns, disposable gloves and masks.
• A designated area should be defined for reconstitution (preferably under a laminar flow system). The work surface should be protected by disposable, plastic-backed and absorbent paper.
• All items used for administration or cleaning, including gloves, should be placed in high risk waste disposal bags for high temperature (700 °C) incineration.
• In case of skin contact, thoroughly wash the affected area with soap and water or sodium bicarbonate solution. However, do not graze the skin by using
a scrubbing brush.
• In case of contact with eye(s), hold back the eyelid(s) and flush the affected eyes with copious amounts
of water for at least 15 minutes. Then seek medical evaluation by a physician.
• Spillage or leakage should be treated with dilute sodium hypochlorite (1 % available chlorine) solution, preferably soaking overnight and then rinse with water.
• All cleaning materials should be disposed of as indicated previously.
• Always wash hands after removing gloves.
Please tell your doctor if any of the symptoms occur.
Effects when treatment with Doxorubicin hydrochloride is interrupted or stopped early
Your doctor will decide on the duration of your treatment with Doxorubicin hydrochloride. If the treatment is stopped before the advised course of treatment is finished, the effects of the doxorubicin therapy might be reduced.
Ask your doctor for advice if you wish to stop the treatment.
4. Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Contact your doctor straight away if you notice any of the following serious side effects:
They have been ranked according to their potential seriousness.
• You may develop hives, fever, chills, severe
hypersensitivity. This type of allergic reaction can be life-threatening.
• Heart problems - for example you may notice your heart beating abnormally quickly, with an increase in pulse rate. In case of heart problems, routine ECG monitoring is commonly applied. If you have suffered from heart problems (even a long time ago) before treatment with Doxorubicin hydrochloride make sure to tell your doctor about this.
• Blood changes - e.g. your vulnerability for infections may increase, you may suffer from unusual bleedings and you may observe signs of anaemia (weakness, tiredness, laboured breathing with a feeling of apprehension).
Your urine may be coloured red, particularly the first time that you pass urine after each injection of Doxorubicin hydrochloride. This is nothing to worry about and your urine will soon return to its normal colour.
Common (may affect up to 1 in 10 people):
• decreased activity in bone marrow leads to reduced blood cells
• cardiomyopathy (heart disease in which your heart muscle does not work properly)
• ECG changes (includes irregular heartbeat)
• deficiency in blood cells causing infection
• nausea and/or vomiting (feeling and /or being sick)
• mucositis (inflammation of membranes in digestive tract, starts with burning sensations in mouth or pharynx)
• anorexia (eating disorder)
• diarrhoea - may result in dehydration
• bladder inflammation sometimes with painful urination, need to urinate more often or during night or blood in urine (following administration into the bladder)
• alopecia (hair loss)
• sepsis (serious infection of the whole body)
• septicaemia (bacterial infection of the blood)
Uncommon (may affect up to 1 in 100 people):
• dehydration
• phlebitis (vein inflammation)
• local hypersensitivity reaction of the field of radiation
• bleeding in stomach or bowel
• abdominal pain
• ulceration and necrosis (death of cells of the tissue) of the digestive tract
• inflammation of voice box and throat
Rare (may affect up to 1 in 1,000 people):
• secondary leukaemia (blood cancer arisen from combined treatment with a special kind of other anti-cancer medicines)
• tumour lysis syndrome (complications of having chemotherapy)
• severe allergic reactions including skin rash, itching, fever, chills and breathing difficulties
• abnormal reduction of white blood cells when given with other cancer medicines
• conjunctivitis (usually causing red watery eyes)
• hives
• rash
• erythematous reactions (rash-like symptoms) along the vein used for the injection
• skin and nails may appear darker than usual.
• separation of nail plates may also occur after being treated with doxorubicin
• shivering
• fever
• dizziness
Not known (cannot be estimated from the available data):
• severe reducing in blood cells may cause spontaneous bleeding or anaemia
• hot flushes
• severe heart failure (loss of cardiac function)
• inflammation of the veins
• clot formation in a blood vessel
• irregular heart beat
• bronchospasm (coughing or difficulty in breathing)
• inflammation of the lung after radiation
• increase of liver enzymes
• hand-foot syndrome
• local death of cells of tissue
• loss of renal function may lead to renal failure
• high uric acid level in blood
• absence of menstruation
• infertility in men, low sperm volume or lack of sperm
Burning, redness and swelling at the administration site may occur. If this is the case during an infusion you should inform the doctor or nurse, because the injection should be stopped immediately and restarted at another site.
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 www.mhra.gov.uk/yellowcard. By reporting side effects you can help provide more information on the safety of this medicine.
5. How to store Doxorubicin hydrochloride
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.
The expiry date refers to the last day of that month. Store the unopened vials in a refrigerator (2-8 °C). Keep the vial in the outer carton in order to protect from light.
The product should be used immediately after opening the vial.
For single dose use only. Any unused solution should be discarded immediately after initial use.
Do not use this medicine if you notice that the solution is not clear, red and free of particles.
Remnants of the medicinal product as well as all materials that have been used for dilution and administration must be destroyed according to hospital standard procedures applicable to cytotoxic agents with due regard to current laws related to the disposal of hazardous waste.
6. Contents of the pack and other information
What Doxorubicin hydrochloride contains
1 ml contains 2 mg doxorubicin hydrochloride.
Each 5 ml vial contains a total content of doxorubicin hydrochloride of 10 mg.
Each 10 ml vial contains a total content of doxorubicin hydrochloride of 20 mg.
Each 25 ml vial contains a total content of doxorubicin hydrochloride of 50 mg.
Each 75 ml vial contains a total content of doxorubicin hydrochloride of 150 mg.
Each 100 ml vial contains a total content of doxorubicin hydrochloride of 200 mg.
The other ingredients are sodium chloride, hydrochloric acid (for pH adjustment) and water for injections.
What Doxorubicin hydrochloride looks like and contents of the pack
Doxorubicin hydrochloride is a clear, red solution which is practically free of particles.
Pack sizes:
The solution is available in packs of 1 or 5 vials containing 5/10/25/75 or 100 ml solution.
This corresponds to 10/20/50/150 or 200 mg of the active substance, doxorubicin hydrochloride, per vial.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
medac
Gesellschaft fur klinische Spezialpraparate mbH Theaterstr. 6 22880 Wedel Germany
This leaflet was last revised in February 2014.
82411-VP1GB
BA