Oxaliplatin Kabi 5 mg/ml concentrate for solution for infusion EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Oxaliplatin Kabi 5 mg/ml

concentrate for solution for infusion EFG

Read this entire leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet as you may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• If you get any side effects, talk to your doctor, pharmacist, or nurse, even if it is a side effect not listed in this leaflet. See section 4.

Leaflet contents

1. What Oxaliplatin is and what it is used for
2. What you need to know before using Oxaliplatin
3. How to use Oxaliplatin
4. Possible side effects
5. How to store Oxaliplatin
6. Contents of the pack and other information

1. What Oxaliplatin is and what it is used for

The active substance in Oxaliplatin Kabi 5 mg/ml concentrate for solution for infusion is oxaliplatin.

Oxaliplatin is used to treat cancer of the large intestine (treatment of stage III colon cancer after complete resection of the primary tumour, metastatic colon cancer, and rectal cancer). Oxaliplatin is used in combination with other anticancer medicines called 5-fluorouracil and folinic acid.

Oxaliplatin is an antineoplastic or anticancer medicine containing platinum.

2. What you need to know before starting Oxaliplatin

Do not use Oxaliplatin if:

• You are allergic to oxaliplatin or to any of the other ingredients of the medicine (listed in section 6).
• You are breastfeeding.
• You have low levels of red or white blood cells.
• You experience tingling or numbness in the fingers of your hands and/or feet, or have difficulty performing delicate tasks such as buttoning clothes.
• You have severe kidney problems.

Warnings and precautions:

Talk to your doctor, pharmacist, or nurse before starting oxaliplatin:

• If you have ever had an allergic reaction to medicines containing platinum, such as carboplatin or cisplatin. Allergic reactions may occur during any infusion of oxaliplatin.
• If you have mild or moderate kidney problems.
• If you have liver disorders or abnormal liver function tests during treatment.
• If you have or have had heart problems such as an abnormal electrical signal known as QT interval prolongation, irregular heartbeat, or a family history of heart problems.
• If you have recently received or plan to receive any vaccine. During treatment with oxaliplatin, you must not be vaccinated with "live" or "attenuated" vaccines, such as the yellow fever vaccine.

If any of the following occur at any time, inform your doctor immediately. Your doctor may need to treat these events and may need to reduce the dose of oxaliplatin, delay, or stop treatment with Oxaliplatin.

• If you experience an unpleasant sensation in your throat, especially when swallowing, and feel short of breath during treatment, inform your doctor.
• If you have nerve problems in your hands or feet, such as numbness, tingling, or reduced sensation in your hands or feet, inform your doctor.
• If you have headache, mental function changes, seizures, or abnormal vision ranging from blurred vision to vision loss, inform your doctor.
• If you feel unwell (nausea or vomiting), inform your doctor.
• If you have severe diarrhea, inform your doctor.
• If you have lip pain or mouth ulcers (mucositis/stomatitis), inform your doctor.
• If you have diarrhea or a reduction in white blood cells or platelets, inform your doctor. Your doctor may need to reduce the dose of Oxaliplatin or delay your treatment with Oxaliplatin.
• If you have unexplained respiratory symptoms such as cough or difficulty breathing, inform your doctor. Your doctor may stop your treatment with oxaliplatin.
• If you experience extreme fatigue, shortness of breath, or kidney problems causing you to urinate little or not at all (symptoms of acute kidney injury), inform your doctor.
• If you have fever (temperature greater than or equal to 38°C) or chills, which could be signs of infection, inform your doctor immediately. You may be at risk of developing a blood infection.
• If you have a temperature > 38°C, inform your doctor. Your doctor may determine that you also have a low white blood cell count.
• If you unexpectedly experience bleeding or bruising (disseminated intravascular coagulation), inform your doctor, as these may be signs of blood clots forming throughout the small blood vessels in your body.
• If you feel dizzy (lose consciousness) or have an irregular heartbeat while taking Oxaliplatin, inform your doctor immediately, as this may be a sign of a serious heart condition.
• If you experience muscle pain and swelling, together with weakness, fever, or brownish-red urine, inform your doctor. These could be signs of muscle damage (rhabdomyolysis) and could lead to kidney problems or other complications.
• If you have abdominal pain, nausea, vomiting resembling coffee grounds, or dark stools, which may be signs of a gastrointestinal ulcer (gastrointestinal ulcer with potential hemorrhage or perforation), consult your doctor.
• If you have abdominal pain, bloody diarrhea, and nausea and/or vomiting, which may be caused by reduced blood flow to the intestinal wall (intestinal ischemia), inform your doctor.

Use of oxaliplatin with other medicines

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

Pregnancy, breastfeeding, and fertility

Pregnancy

• You must not become pregnant during treatment and should therefore use an effective method of contraception during treatment. It is recommended to continue using an appropriate contraceptive method for up to 15 months after stopping treatment.
• Male patients are advised not to father a child during treatment and for 12 months after treatment, and to use appropriate contraceptive measures during this period.
• If you are pregnant or planning to become pregnant, it is very important that you discuss this with your doctor before receiving any treatment.
• If you become pregnant during treatment, you must inform your doctor immediately.

Breastfeeding

• You must not breastfeed while being treated with oxaliplatin.

Fertility

• Oxaliplatin may cause anti-fertility effects that could be irreversible. Men are advised to seek advice on sperm preservation before treatment.
• After treatment with oxaliplatin, patients planning pregnancy are advised to seek genetic counseling.

Consult your doctor or pharmacist before taking any medicine.

Driving and using machines

Treatment with oxaliplatin may increase the risk of dizziness, nausea, vomiting, and other neurological symptoms affecting gait and balance. If this occurs, you must not drive or operate machinery. If you experience vision problems while taking oxaliplatin, do not drive, operate heavy machinery, or participate in hazardous activities.

3. How to use Oxaliplatin

For use in adult patients only.

For single use only.

Dosage

The dose of oxaliplatin is based on your body surface area. This is calculated from your height and weight.

The normal dose for adults, including elderly patients, is 85 mg/m² of body surface area.

The administered dose may also depend on the results of blood tests and whether you have previously experienced side effects following administration of oxaliplatin.

Method and route of administration

• Oxaliplatin must be prescribed by a specialist in cancer treatment.
• You will be treated under the supervision of a healthcare professional, who will administer the appropriate dose of oxaliplatin.
• Oxaliplatin is given as a slow injection into a vein (intravenous infusion) over a period of 2 to 6 hours.
• Oxaliplatin will be administered together with folinic acid and prior to the infusion of 5-fluorouracil.

Frequency of administration

Normally, you will receive your treatment once every 2 weeks.

Duration of treatment

The duration of treatment will be determined by your doctor. Treatment lasts for a maximum of 6 months after surgery to remove your cancer.

If you use more Oxaliplatin than you should

Since this medicine is administered by a healthcare professional, it is unlikely that you will receive a dose that is higher or lower than intended. In the event of overdose, you may experience an increase in side effects. Your doctor will provide appropriate treatment for these effects.

If you have any further questions about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them. If you experience any adverse effect, it is important that you inform your doctor before starting the next treatment.

The adverse effects you may experience are described below.

Contact your doctor immediately if you experience any of the following:

• Symptoms of an allergic or anaphylactic reaction with sudden signs such as rash, itching or hives on the skin, difficulty swallowing, swelling of the face, lips, tongue or other parts of the body, shortness of breath, wheezing or breathing difficulties, extreme tiredness (feeling faint). In most cases, these symptoms occurred during or immediately after the infusion, but delayed allergic reactions have also been observed hours or even days after the infusion.

• Unusual bruising, bleeding or signs of infection such as sore throat and high temperature.

• Persistent and severe diarrhea and vomiting.

• Presence of blood or dark brown coffee-ground-like particles in your vomit.

• Stomatitis/mucositis (lip pain or mouth ulcers).

• Unexplained respiratory symptoms such as dry or productive cough, difficulty breathing or noisy breathing, shortness of breath and wheezing, as they may indicate a serious lung disease that can be fatal.

• A group of symptoms such as headache, altered mental function, seizures and abnormal vision ranging from blurred vision to vision loss (symptoms of reversible posterior leukoencephalopathy syndrome, a rare neurological disorder).

• Symptoms of stroke (including sudden, severe headache, confusion, difficulty seeing with one or both eyes, numbness or weakness of the face, arm or leg, usually on one side, facial drooping, difficulty walking, dizziness, loss of balance and difficulty speaking).

• Extreme tiredness with reduced number of red blood cells and difficulty breathing (hemolytic anemia), alone or combined with low platelet count, unusual bruising (thrombocytopenia) and kidney problems causing you to pass little or no urine (symptoms of hemolytic uremic syndrome).

Other known adverse effects of oxaliplatin are:

Very common: may affect more than 1 in 10 patients

Oxaliplatin can affect the nerves (peripheral neuropathy). You may experience tingling and/or numbness in the fingers, toes, around the mouth or in the throat, which may sometimes be associated with cramps. These effects often occur upon exposure to cold, for example, opening a refrigerator or handling a cold drink. You may also have difficulty performing delicate tasks, such as buttoning clothes. Although in most cases these symptoms resolve completely on their own, symptoms of sensory peripheral neuropathy may persist after treatment ends. Some people have experienced tingling or electric shock-like sensations passing through the arms or trunk when the neck is bent.

• Oxaliplatin may cause an unpleasant sensation in the throat, particularly when swallowing, and a feeling of breathlessness. If this occurs, it usually happens during or in the hours following the infusion and may be triggered by exposure to cold. Although unpleasant, it does not last long and resolves without treatment. Your doctor may decide to modify your treatment as a result.

• Oxaliplatin may cause diarrhea, mild nausea (feeling sick) and vomiting (feeling unwell); however, your doctor will usually treat you to prevent this discomfort before starting treatment, and this should be continued after treatment.

• Oxaliplatin causes a temporary reduction in blood cell counts. A reduction in red blood cells may cause anemia (a decrease in red blood cells), abnormal bleeding or bruising (due to a reduction in platelets). A reduction in white blood cells may make you more susceptible to infections.

• Your doctor will take blood samples to check that you have sufficient blood cells before starting treatment and after each subsequent cycle.

• Discomfort or pain at or near the site of administration during infusion.

• Fever, chills (shivering), moderate or severe fatigue, body aches.

• Weight changes, loss of appetite or appetite loss, taste disturbances, constipation.

• Headache, back pain.

• Inflammation of nerves in the muscles, neck stiffness, unusual tongue sensation that may affect speech, stomatitis/mucositis (lip pain or mouth ulcers).

• Stomach pain.

• Abnormal bleeding including nosebleeds.

• Cough, difficulty breathing.

• Allergic reactions, skin rash which may be red or itchy, moderate hair loss (alopecia).

• Changes in blood test results including those indicating changes in liver function.

Common: may affect up to 1 in 10 patients

• Infection due to a reduction in white blood cells.

• Severe blood infection in addition to a reduction in white blood cells (septic neutropenia), which may be fatal.

• Reduction in white blood cells accompanied by a temperature > 38.3°C or a prolonged temperature > 38°C for more than one hour (febrile neutropenia).

• Indigestion and heartburn, hiccups, hot flushes, dizziness.

• Increased sweating and nail disorders, skin peeling.

• Chest pain.

• Lung disorders and nasal discharge.

• Joint and bone pain.

• Pain when urinating and changes in kidney function, changes in frequency of urination, dehydration.

• Blood in urine/stool, swelling of veins, blood clots in the lung.

• High blood pressure.

• Depression and insomnia.

• Conjunctivitis and visual disturbances.

• Low levels of calcium in the blood.

• Falls.

Uncommon: may affect up to 1 in 100 patients

• Severe blood infection (sepsis), which may be fatal.
• Blockage or inflammation of the intestine.
• Nervousness.

Rare: may affect up to 1 in 1,000 patients

• Hearing loss.

• Formation of scarring or thickening in the lungs which may cause breathing difficulties, sometimes fatal (interstitial lung disease).

• Short-term reversible vision loss.

• Unexpected bleeding or bruising due to widespread blood clotting throughout the small blood vessels of your body (disseminated intravascular coagulation), which may be fatal.

Very rare: may affect up to 1 in 10,000 patients

• Presence of blood or dark brown coffee-ground-like particles in vomit.
• Kidney problems causing you to pass little or no urine (symptoms of acute renal failure).
• Vascular disorders of the liver.

Frequency not known (frequency cannot be estimated from the available data)

• Allergic vasculitis (inflammation of blood vessels).
• Autoimmune reaction causing reduction in all blood cell lines (autoimmune pancytopenia, pancytopenia).
• Severe blood infection and low blood pressure (septic shock), which may be fatal.
• Seizures (uncontrolled body shaking).
• Throat spasm which may cause breathing difficulties.
• Extreme tiredness with reduced number of red blood cells and shortness of breath (hemolytic anemia), alone or in combination with reduced platelets and kidney problems causing you to pass little or no urine (symptoms of hemolytic uremic syndrome), which may be fatal.
• Abnormal heart rhythm (QT prolongation) visible on an electrocardiogram (ECG), which may be fatal.
• Muscle pain and swelling along with weakness, fever or red-brown colored urine (symptoms of muscle damage called rhabdomyolysis), which may be fatal.
• Abdominal pain, nausea, vomiting with blood or coffee-ground-like vomit, dark stools (symptoms of gastrointestinal ulcer with potential for bleeding or perforation), which may be fatal.
• Reduced blood flow to the intestine (intestinal ischemia), which may be fatal.
• Risk of new cancers. Leukemia, a type of blood cancer, has been reported in patients after using oxaliplatin in combination with certain medicines. Consult your doctor about the potential increased risk of this type of cancer when oxaliplatin is used with certain medicines.
• Myocardial infarction (heart attack), angina pectoris (chest pain or discomfort).
• Esophagitis (inflammation of the inner lining of the esophagus—the tube connecting the mouth to the stomach—causing pain and difficulty swallowing).

Abnormal non-cancerous liver nodules (focal nodular hyperplasia).

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicinal Products: www.notificaRAM.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of oxaliplatin

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the label and the carton after EXP. The expiry date refers to the last day of the month indicated.

Store the vial in the outer packaging to protect it from light. Store below 25°C. Do not freeze.

Do not use oxaliplatin if the solution appears not clear or contains particles.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and containers you no longer need. This will help protect the environment.

6. Contents of the container and other information

Composition of oxaliplatin

• The active substance is oxaliplatin. One ml of concentrate for solution for infusion contains 5 mg of oxaliplatin.

• 10 ml of concentrate for solution for infusion contains 50 mg of oxaliplatin.

• 20 ml of concentrate for solution for infusion contains 100 mg of oxaliplatin.

• 40 ml of concentrate for solution for infusion contains 200 mg of oxaliplatin.

• The other components are water for injections.

Appearance of the product and contents of the container

This medicine is a concentrate for solution for infusion. The concentrate is a clear, colourless solution for infusion free from visible particles.

Each vial contains 50 mg, 100 mg or 200 mg of oxaliplatin. The concentrate is supplied in 10 ml, 20 ml and 40 ml Type I glass vials with a chlorobutyl or bromobutyl rubber stopper and an aluminium seal with a "flip-off" plastic cap. Each vial may be individually wrapped in a shrinkable sleeve and may be packaged or not in a plastic overwrap. The vials are supplied in cardboard boxes containing one vial.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Fresenius Kabi España S.A.U
C/Marina 16-18
08005 – Barcelona
Spain

Manufacturer

Fresenius Kabi Deutschland GmbH
Pfingstweide 53
61169 Friedberg
Germany

This medicinal product is authorised in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

Czech Republic Oxaliplatin Kabi 5 mg/ml koncentrát pro infuzní roztok
Denmark Oxaliplatin “Fresenius Kabi”, koncentrat til infusionsvæske, opløsning
Germany Oxaliplatin Kabi 5 mg/ml Konzentrat zur Herstellung einer Infusionslösung
Hungary Oxaliplatin Kabi 5 mg/ml koncentrátum oldatos infúzióhoz
Italy Oxaliplatino Kabi
Ireland Oxaliplatin 5 mg/ml concentrate for solution for infusion
Netherlands Oxaliplatine Kabi 5 mg/ml concentraat voor oplossing voor infusie
Norway Oxaliplatin Kabi 5 mg/ml konsentrat til infusjonsvæske
Poland Oxaliplatin Kabi
Portugal Oxaliplatina Kabi 5 mg/ml concentrado para solução para perfusão
Slovakia Oxaliplatin Kabi 5 mg/ml infúzny koncentrát
Spain Oxaliplatino Kabi 5 mg/ml concentrado para solución para perfusión EFG
United Kingdom Oxaliplatin 5 mg/ml concentrate for solution for infusion (Northern Ireland)

Date of the most recent review of this leaflet: June 2024

This information is intended for healthcare professionals only:

INSTRUCTIONS FOR USE, HANDLING AND DISPOSAL

As with any potentially toxic compound, precautions must be taken when handling and preparing solutions of oxaliplatin.

Handling instructions

Handling this cytotoxic agent by healthcare personnel requires caution to ensure protection of the handler and the surrounding environment.

Preparation of injectable solutions of cytotoxic agents must be carried out by trained, specialised personnel in conditions that guarantee the integrity of the medicine, environmental protection and, in particular, protection of personnel handling these drugs, in accordance with hospital policy. A designated area must be used for this purpose. Smoking, eating or drinking in this area is prohibited.

Specialised personnel must use appropriate materials for handling, including long-sleeved gowns, masks, caps, goggles, single-use sterile gloves, protective suits for the work area, and containers and bags for collecting waste.

Faeces and vomit must be handled with care.

Pregnant women must avoid handling cytotoxic agents.

Any broken container must be treated with the same precautions and considerations as contaminated waste. Contaminated waste must be incinerated in appropriate, rigid, labelled containers. See the section “Waste disposal” below.

If the oxaliplatin concentrate or the infusion solution comes into contact with the skin, wash immediately and thoroughly with water.

If the oxaliplatin concentrate or the infusion solution comes into contact with mucous membranes, rinse immediately and thoroughly with water.

Special administration precautions

• DO NOT use injection equipment containing aluminium.
• DO NOT administer undiluted.
• Only 5% glucose (50 mg/ml) solutions should be used as diluent. DO NOT DILUTE with sodium chloride solution or solutions containing chlorides.
• DO NOT mix other drugs in the same infusion bag or administer simultaneously via the same infusion line.
• DO NOT mix with alkaline drugs or solutions, in particular 5-fluorouracil, leucovorin preparations containing tromethamine as excipient, or tromethamine salts of other active substances. Alkaline drugs or solutions may adversely affect the stability of oxaliplatin.

Instructions for use with folinic acid (FA) (as calcium folinate or disodium folinate)

Intravenous infusion of oxaliplatin 85 mg/m² in 250–500 ml of 5% glucose is administered simultaneously with an intravenous infusion of folinic acid in 5% glucose, over 2 to 6 hours, using a Y-line placed immediately before the infusion site. These two drugs must not be combined in the same infusion bag. Folinic acid (FA) should not contain tromethamine as excipient and should only be diluted using 5% isotonic glucose solution, never in alkaline solutions, sodium chloride solutions or solutions containing chlorides.

Instructions for use with 5-fluorouracil (5-FU)

Oxaliplatin should always be administered before fluoropyrimidines—e.g., fluorouracil (5-FU). After administration of oxaliplatin, flush the line and then administer 5-fluorouracil (5-FU).

For further information on drug combinations with oxaliplatin, see the corresponding Summary of Product Characteristics.

• USE ONLY the recommended solvents (see below).
• Any concentrate showing evidence of precipitation must not be used and must be destroyed in accordance with legal requirements for disposal of hazardous waste (see below).

Concentrate for solution for infusion

Inspect visually before use. Only clear solutions free from particles should be used. The medicinal product is for single use only. Any unused infusion solution must be discarded.

Dilution prior to intravenous infusion

Withdraw the required amount of concentrate from the vial(s) and dilute with 250 to 500 ml of 5% glucose solution to achieve an oxaliplatin concentration between 0.2 mg/ml and 0.7 mg/ml. The concentration range in which the physico-chemical stability of oxaliplatin has been demonstrated is 0.2 mg/ml to 2.0 mg/ml.

Administer by intravenous infusion.

After dilution in 5% glucose solution, chemical and physical stability has been demonstrated for up to 24 hours at room temperature (15°C–25°C) and in the refrigerator (2°C–8°C).

From a microbiological standpoint, the prepared infusion should be used immediately. If not used immediately, the storage time and conditions prior to use are the responsibility of the user and should normally not exceed 24 hours at a temperature between 2°C and 8°C, unless dilution has taken place under controlled and validated aseptic conditions.

Inspect visually before use. Only clear solutions free from particles should be used. The medicinal product is for single use only. Any unused solution must be discarded.

DO NOT use sodium chloride solutions or solutions containing chlorides for dilution.

Compatibility of oxaliplatin solution for infusion has been evaluated with representative administration sets based on PVC.

Infusion

Administration of oxaliplatin does not require prehydration.

Diluted oxaliplatin in 250 ml or 500 ml of 5% glucose solution to achieve a concentration of at least 0.2 mg/ml, should be administered by peripheral or central venous infusion over 2 to 6 hours. When oxaliplatin is administered with 5-fluorouracil, the oxaliplatin infusion must precede the administration of 5-fluorouracil.

Disposal

Any unused medicinal product or waste material must be disposed of in accordance with local requirements.