Oxaliplatin Evepacks 5mglml Concentrate For Solution For Infusion
Version 03/2016 Var011
PACKAGE LEAFLET: INFORMATION FOR THE USER Oxaliplatin EVEpacks 5 mg/ml concentrate for solution for infusion
Oxaliplatin
Read all of this leaflet carefully before you start using 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.
What is in this leaflet
1. What Oxaliplatin EVEpacks is and what it is used for
2. What you need to know before you use Oxaliplatin EVEpacks
3. How to use Oxaliplatin EVEpacks
4. Possible side effects
5. How to store Oxaliplatin EVEpacks
6. Contents of the pack and other information
1. WHAT OXALIPLATIN EVEPACKS IS AND WHAT IT IS USED FOR
Oxaliplatin EVEpacks is used to treat metastatic (advanced) cancer of the colon (large bowel) or rectum (back passage), or as additional treatment following surgery to remove a tumour (growth) in the colon.
It is used in combination with other anticancer agents, 5-fluorouracil (5-FU) and folinic acid (FS).
2. WHAT YOU NEED TO KNOW BEFORE YOU USE OXALIPLATIN EVEPACKS Do not use Oxaliplatin EVEpacks
- if you are allergic to oxaliplatin or any of the other ingredients of this medicine (listed in section 6).
- if you are breast-feeding
- if you already have a reduced number of blood cells (white blood cells and/or platelets).
- if you already have tingling and numbness in the fingers and/or toes, and have difficulty performing delicate tasks, such as buttoning clothes
- if you have severe kidney problems
Even if you are male, please ensure that you read the section of this leaflet that concerns pregnancy and breast-feeding.
Warnings and precautions
Talk to your doctor or pharmacist before using Oxaliplatin EVEpacks.
Take special care with Oxaliplatin EVEpacks
- if you have ever suffered an allergic reaction to platinum-containing medicines such as carboplatin or cisplatin. Allergic reactions can occur during any oxaliplatin infusion.
- if you have moderate or mild kidney problems,
- if you have any liver problems or abnormal liver function test results during your treatment.
If any of the following applies to you at any time, tell your doctor immediately. Your doctor may need to treat you for these events, and may need to potentially reduce the dose of Oxaliplatin EVEpacks, or delay or stop Oxaliplatin EVEpacks treatment.
- If you have an unpleasant sensation in the throat, in particular when swallowing, and have a sensation of shortness of breath, during the treatment, tell your doctor.
- If you have nerve problems in your hands or feet, such as numbness or tingling, or decreased sensations in your hands or feet, tell your doctor.
- If you have headache, altered mental functioning, seizures and abnormal vision from blurriness to vision loss, tell your doctor.
- If you feel or are sick (nausea or vomiting), tell your doctor.
- If you have severe diarrhea, tell your doctor.
- If you have sore lips or mouth ulcers (mucositis/ stomatitis), tell your doctor.
- If you have diarrhea, or a reduction in white blood cells or platelets, tell your doctor. Your doctor may reduce the dose of Oxaliplatin EVEpacks or postpone your treatment with Oxaliplatin EVEpacks.
- If you have unexplained respiratory symptoms such as cough, or any difficulties in breathing, tell your doctor. Your doctor may stop your treatment with Oxaliplatin EVEpacks.
- If you develop an extreme tiredness, shortness of breath, or kidney disease where you pass little or no urine (symptoms of acute renal failure), tell your doctor.
Other medicines and Oxaliplatin EVEpacks
Please tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. Pregnancy, breast-feeding and fertility
Pregnancy
- It is not recommended that you become pregnant during treatment with oxaliplatin and must use an effective method of contraception. Female patients should take appropriate contraceptive measures during and after cessation of therapy continuing for 4 months.
If you are pregnant or planning a pregnancy it is very important that you discuss this with your doctor before you receive any treatment.
If you get pregnant during your treatment, you must immediately inform your doctor.
Breast-feeding
- You must not breast-feed while you are treated with oxaliplatin.
Fertility
- Oxaliplatin may have an anti-fertility effect, which could be irreversible. Male patients should seek advice on conservation of sperm prior to treatment.
- Male patients are advised not to father a child during treatment and until 6 months after treatment, and to take appropriate contraceptive measures during this time.
Driving and using machines
Oxaliplatin treatment may result in an increased risk of dizziness, nausea and vomiting, and other neurological symptoms that affect walking and balance.
If this happens you should not drive or operate machinery. If you have vision problems while using Oxaliplatin EVEpacks, do not drive, operate heavy machines or engage in dangerous activities.
Oxaliplatin EVEpacks contains lactose.
3. HOW TO USE OXALIPLATIN EVEPACKS
For adults only.
Oxaliplatin EVEpacks will be prescribed for you by a specialist in cancer treatment.
Oxaliplatin EVEpacks is given by injection into a vein (an intravenous infusion) over a 2 to 6 hour period.
The dose of Oxaliplatin EVEpacks is based on your body surface area (calculated from your height and weight). The dose will also depend on results of blood tests and whether you have previously experienced side effects with Oxaliplatin. The usual dose for adults including the elderly is 85 mg/m2 of body surface area once every 2 weeks at the same time as folinic acid and before the infusion of 5-fluorouracil. The duration of the treatment will be determined by your doctor. Your treatment will last a maximum of 6 months when used after complete resection of your tumour.
The needle must remain in the vein while the drug is being given. If the needle comes out or becomes loose, or the solution is going into the tissue outside the vein (you may feel discomfort or pain) - tell the doctor or nurse immediately.
If you use more Oxaliplatin EVEpacks than you should
As this medicine is administered by a healthcare professional it is highly unlikely that you will be given too much or too little.
In case of overdose, you may experience increased side effects. Your doctor may give you appropriate treatment for these side effects. If you have any questions about your treatment, ask your doctor, nurse or pharmacist.
If you forget to use Oxaliplatin EVEpacks
Oxaliplatin needs to be given on a fixed schedule. Be sure to keep all appointments. If you miss a dose, you should discuss this with your doctor. Your doctor will decide when you should be given your next dose of oxaliplatin.
If you stop using Oxaliplatin EVEpacks
Stopping your treatment with oxaliplatin may stop the effect on tumour growth. Do not stop treatment with oxaliplatin unless you have discussed this with your doctor.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
4. POSSIBLE SIDE EFFECTS
Like all medicines, this medicine can cause side effects, although not everybody gets them. If you
experience any side effect it is important that you inform your doctor before your next treatment.
You will find described below the side effects that you could experience.
Tell your doctor immediately if you notice any of the following
- Symptoms of an allergic or anaphylactic reaction with sudden signs such as rash, itching or hives on the skin, difficulties in swallowing, swelling of the face, lips, tongue or other parts of the body, shortness of breath, wheezing or trouble breathing, extreme tiredness (you may feel you are going to faint). In the majority of cases, these symptoms occurred during the infusion or immediately after but delayed allergic reactions have also been observed hours or even days after the infusion.
- Abnormal bruising, bleeding, or signs of infection such as a sore throat and high temperature,
- Persistent or severe diarrhoea or vomiting,
- Presence of blood or dark brown coffee-coloured particles in your vomit,
- Stomatitis/mucositis (sore lips or mouth ulcers),
- Unexplained respiratory symptoms such as dry cough, difficulties in breathing or crackles,
- A group of symptoms such as headache, altered mental functioning, seizures and abnormal vision from blurriness to vision loss (symptoms of reversible posterior leukoencephalopathy syndrome, a rare neurological disorder).
- Extreme tiredness with decreased number of red blood cells, and shortness of breath (haemolytic anaemia), alone or combined with low platelet count, abnormal bruising (thrombocytopenia) and kidney disease where you pass little or no urine (symptoms of Haemolytic-uraemic syndrome).
Other known side effects of Oxaliplatin are:
Very common (may affect more than 1 in 10people):
- Oxaliplatin EVEpacks can affect the nerves (peripheral neuropathy). You may feel a tingling and/or numbness in the fingers, toes, around the mouth or in the throat, which may sometimes occur in association with cramps.
These effects are often triggered by exposure to cold e.g. opening a refrigerator or holding a cold drink. You may also have difficulty in performing delicate tasks, such as buttoning clothes. Although in the majority of cases these symptoms resolve themselves completely there is a possibility of persistent symptoms of peripheral sensory neuropathy after the end of the treatment.
Some people have experienced a tingling, shock-like sensation passing down the arms or trunk when the neck is flexed.
- Oxaliplatin EVEpacks can sometimes cause an unpleasant sensation in the throat, in particular when swallowing, and give the sensation of shortness of breath.
This sensation, if it happens, usually occurs during or within hours of the infusion and may be triggered by exposure to the cold.
Although unpleasant, it will not last long and goes away without the need for any treatment.
Your doctor may decide to alter your treatment as a result.
- Oxaliplatin EVEpacks may cause diarrhoea, mild nausea (feeling sick) and vomiting (being sick); however medication to prevent the sickness is usually given to you by your doctor before treatment and may be continued after treatment.
- Oxaliplatin EVEpacks causes temporary reduction in the number of blood cells.
The reduction of red cells may cause anaemia (a reduction of red cells), abnormal bleeding or bruising (due to a reduction in platelets).
The reduction in white blood cells may make you prone to infections.
Your doctor will take blood to check that you have sufficient blood cells before you start treatment and before each subsequent course.
- Sensation of discomfort close to or at the injection site during the infusion,
- Fever, rigors (tremors), mild or severe tiredness, body pain,
- Weight changes, loss or lack of appetite, taste disorders, constipation,
- Headache, back pain,
- Swelling of the nerves to your muscles, neck stiffness, abnormal tongue sensation possibly altering speech, stomatitis/mucositis (sore lips or mouth ulcers),
- Stomach pain,
- Abnormal bleeding including nose bleeds,
- Coughing, difficulty in breathing,
- Allergic reactions, skin rash which may be red and itchy, mild hair loss (alopecia),
- Alteration in blood tests including those relating to abnormalities in liver function.
Common (may affect up to 1 in 10people):
- Infection due to a reduction in white blood cells,
- Indigestion and heart burn, hiccups, flushing, dizziness,
- Increased sweating and nail disorders, flaking skin,
- Chest pain,
- Lung disorders and runny nose,
- Joint pain and bone pain,
- Pain on passing urine and changes in kidney function, changes of frequency of urination, dehydration,
- Blood in the urine/stools, swelling of the veins, clots in the lung,
- High blood pressure,
- Depression and insomnia,
- Conjunctivitis and visual problems.
Uncommon (may affect up to 1 in 100people):
- Blockage or swelling of the bowel,
- Nervousness.
Rare (may affect up to 1 in 1,000people):
- Loss of hearing,
- Scarring and thickening in the lungs with difficulties in breathing, sometimes fatal (interstitial lung disease),
- Reversible short-term loss of vision.
Very rare (may affect up to 1 in 10,000people):
- Presence of blood or dark brown coffee-coloured particles in your vomit.
- Kidney disease where you pass little or no urine (symptoms of acute renal failure)
- Vascular disorders of liver.
Frequency not known (frequency cannot be estimated from the available data)
- Convulsion (uncontrolled shaking of the body),
- Spasm of the throat causing difficulty in breathing,
- Extreme tiredness with decreased number of red blood cells, and shortness of breath (haemolytic anaemia), alone or combined with low platelet count and kidney disease where you pass little or no urine (symptoms of Haemolytic-uraemic syndrome), which may be fatal, have been reported.
- Allergic vasculitis (inflammation of blood vessels)
- Auto-immune reaction leading to reduction of all blood cell lines (autoimmune pancytopenia).
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 the Yellow Card Scheme at: 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 OXALIPLATIN EVEPACKS
Keep this medicine out of the sight and reach of children
Store below 25°C. Do not refrigerate or freeze. Store in the original package in order to protect from light. Do not use this medicine after the expiry date which is stated on the carton and label after “EXP”. The expiry date refers to the last day of that month.
Do not use this medicine if you notice that the solution is not clear and free of particles.
When the infusion has finished, any remaining Oxaliplatin EVEpacks will be disposed of carefully by the doctor or nurse.
Oxaliplatin should not come into contact with the eyes or skin. If there is any accidental spillage, tell the doctor or nurse immediately.
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.
6. CONTENTS OF THE PACK AND OTHER INFORMATION
What Oxaliplatin EVEpacks contains
- The active substance is oxaliplatin. One ml of the concentrate for solution for infusion contains 5 mg oxaliplatin.
- The other ingredients are lactose monohydrate and water for injection.
What Oxaliplatin EVEpacks looks like and contents of the pack
Oxaliplatin EVEpacks concentrate for solution for infusion is a clear, colourless to pale yellow solution, free from visible particles.
Pack sizes:
1 x 10 ml vial containing 50 mg of oxaliplatin 1 x 20 ml vial containing 100 mg of oxaliplatin
I x 40 ml vial containing 200 mg of oxaliplatin
Not all pack sizes may be marketed.
Marketing Authorisation Holder
EVEpacks B.V.
Irene Vorrinkplein 40 i 1506 WR ZAANDAM The Netherlands
Manufacturer
S.C. Sindan-Pharma S.R.L
II Ion Mihalache Blvd 011171 Bucharest Romania
Or
Actavis Italy S.p.A.
Via Pasteur 10 20014 Nerviano (Milan)
Italy
This medicinal product is authorised in the Member States of the EEA under the following names:
United Kingdom: Oxaliplatin EVEpacks 5 mg/ml concentrate for solution for infusion Germany: Oxaliplatin EVEpacks 5 mg/ml Konzentrat zur Herstellung einer Infusionslosung
This leaflet was last revised in March 2016.
The following information is intended for healthcare professionals only:
Oxaliplatin EVEpacks 5 mg/ml concentrate for solution for infusion
Instructions for use
ANTINEOPLASTIC AGENT
Incompatibilities
This medicinal product should not be mixed with other medicinal products except for those mentioned below in section “Dilution for intravenous infusion”.
Oxaliplatin can be co-administered with folinic acid (FA) via a Y-line.
Do not mix with alkaline medicinal products or solutions, in particular 5-fluorouracil, folinic acid preparations containing trometamol as an excipient and trometamol salts of other active substances. Alkaline medicinal products or solutions will adversely affect the stability of oxaliplatin (see below in section “Dilution for intravenous infusion”).
Do not dilute for infusion with saline or other solutions containing chloride ions (including calcium, potassium or sodium chloride).
Do not mix with other medicinal products in the same infusion bag or infusion line.
Do not use injection equipment containing aluminium.
Storage conditions
Medicinal product as packaged for sale:
Store below 25°C. Do not refrigerate or freeze. Store in the original package in order to protect from light.
Infusion preparation:
After dilution in 5% glucose solution, chemical and physical in-use stability has been demonstrated for 24 hours at 2°C to 8°C and for 6 hours at 25°C. From a microbiological point of view, the infusion preparation 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 to 8°C, unless dilution has taken place in controlled and validated aseptic conditions.
Instructions for handling, use and disposal
As with other potentially toxic compounds, caution should be exercised when handling and preparing oxaliplatin solutions.
Instructions for Handling
The handling of this cytotoxic agent by healthcare personnel requires every precaution to guarantee the protection of the handler and his surroundings.
The preparation of injectable solutions of cytotoxic agents must be carried out by trained specialist personnel with knowledge of the medicines used, in conditions that guarantee the integrity of the medicinal product, the protection of the environment and in particular the protection of the personnel handling the medicines, in accordance with the hospital policy. It requires a preparation area reserved for this purpose. It is forbidden to smoke, eat or drink in this area.
Personnel must be provided with appropriate handling materials, notably long sleeved gowns, protection masks, caps, protective goggles, sterile single-use gloves, protective covers for the work area, containers and collection bags for waste.
Excreta and vomit must be handled with care.
Pregnant women must be warned to avoid handling cytotoxic agents.
Any broken container must be treated with the same precautions and considered as contaminated waste. Contaminated waste should be incinerated in suitably labelled rigid containers. See below section “Disposal”.
If oxaliplatin concentrate or solution for infusion should come into contact with skin, wash immediately and thoroughly with water.
If oxaliplatin concentrate or solution for infusion should come into contact with mucous membranes, wash immediately and thoroughly with water.
Special precautions for administration
- DO NOT use injection equipment containing aluminium.
- DO NOT administer undiluted.
- Only glucose 5 % (50 mg/ml) infusion solution is to be used as a diluent. DO NOT dilute for infusion with sodium chloride or chloride containing solutions.
- DO NOT mix with any other medicinal products in the same infusion bag or administer simultaneously by the same infusion line.
- DO NOT mix with alkaline medicinal products or solutions, in particular 5 fluorouracil, folinic acid preparations containing trometamol as an excipient and trometamol salts of others active substances.
Alkaline medicinal products or solutions will adversely affect the stability of oxaliplatin.
Instruction for use with folinic acid (FA) (as calcium folinate or disodium folinate)
Oxaliplatin 85 mg/m2 intravenous infusion in 250 to 500 ml of glucose 5 % (50 mg/ml) solution is given at the same time as folinic acid (FA) intravenous infusion in glucose 5 % solution, over 2 to 6 hours, using a Y-line placed immediately before the site of infusion.
These two medicinal products should not be combined in the same infusion bag. Folinic acid (FA) must not contain trometamol as an excipient and must only be diluted using isotonic glucose 5 % solution, never in alkaline solutions or sodium chloride or chloride containing solutions.
Instruction for use with 5 fluorouracil (5 FU)
Oxaliplatin should always be administered before fluoropyrimidines - i.e. 5 fluorouracil (5 FU).
After oxaliplatin administration, flush the line and then administer 5 fluorouracil (5 FU).
For additional information on medicinal products combined with oxaliplatin, see the corresponding manufacturer's summary of product characteristics.
Dilution for intravenous infusion
Withdraw the required amount of concentrate from the vial(s) and then dilute with 250 ml to 500 ml of a 5% glucose solution to give an oxaliplatin concentration between not less than 0.2 mg/ml and 0.7 mg/ml. The physico-chemical stability of oxaliplatin has been demonstrated for this concentration range.
Administer by intravenous infusion.
After dilution in 5% glucose solution, chemical and physical in-use stability has been demonstrated for 24 hours at 2°C to 8°C and for 6 hours at 25°C. From a microbiological point of view, this infusion preparation should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user.
Inspect visually prior to use. Only clear solutions without particles should be used.
The medicinal product is for single use only. Any unused infusion solution should be discarded.
NEVER use sodium chloride solution or chloride containing solutions for either reconstitution or dilution.
The compatibility of Oxaliplatin solution for infusion has been tested with representative, PVC-based, administrative sets.
Infusion
The administration of oxaliplatin does not require prehydration.
Oxaliplatin diluted in 250 to 500 ml of a 5% glucose solution to give a concentration not less than 0.2 mg/ml must be infused either by peripheral vein or central venous line over 2 to 6 hours. When oxaliplatin is administered with 5-fluorouracil, the oxaliplatin infusion must precede the administration of 5-fluorouracil.
Disposal
Remnants of the medicinal product as well as all materials that have been used for dilution and administration must be destroyed according to standard procedures applicable to cytotoxic agents in accordance with local requirements related to the disposal of hazardous waste.
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