OXALIPLATIN KABI 5 mg/ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

Oxaliplatino Kabi 5 mg/ml

Concentrate for Solution for Infusion EFG

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, pharmacist, or nurse.
• If you experience any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the Pack

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

1. What Oxaliplatino is and what it is used for

The active substance of Oxaliplatino Kabi 5mg/ml concentrate for solution for infusion is oxaliplatin.

Oxaliplatino is used for the treatment of colorectal cancer (treatment of stage III colon cancer after complete resection of the primary tumor, metastatic colon cancer, and rectal cancer). Oxaliplatino is used in combination with other anticancer medicines called 5-fluorouracil and folinic acid.

Oxaliplatino is a platinum-based anticancer medicine.

2. What you need to know before you use Oxaliplatino

Do not use Oxaliplatino if:

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

Warnings and precautions:

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

• If you have ever had an allergic reaction to platinum-based medicines such as carboplatin or cisplatin. Allergic reactions can 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 called QT interval prolongation, an 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 should not be vaccinated with live or attenuated vaccines, such as the yellow fever vaccine.

If any of the following happen to you at any time, tell your doctor immediately. Your doctor may need to treat you for these events. Your doctor may need to reduce the dose of oxaliplatin, or delay or interrupt treatment with Oxaliplatino.

• If you have an unpleasant sensation in your throat, particularly when swallowing, and have a feeling of shortness of breath, during treatment, tell your doctor.
• If you have nerve problems in your hands or feet, such as numbness or tingling, or decreased sensation in your hands or feet, tell your doctor.
• If you have a headache, changes in mental function, seizures, and abnormal vision from blurred vision to loss of vision, tell your doctor.
• If you do not feel well (nausea or vomiting), tell your doctor.
• If you have severe diarrhea, tell your doctor.
• If you have pain in your lips or ulcers in your mouth (mucositis/stomatitis), tell your doctor.
• If you have diarrhea or a reduction in white blood cells or platelets, tell your doctor. Your doctor may need to reduce the dose of Oxaliplatino or postpone your treatment with Oxaliplatino.
• If you have unexplained respiratory symptoms such as cough or difficulty breathing, tell your doctor. Your doctor may suspend your treatment with oxaliplatin.
• If you experience extreme fatigue, shortness of breath, or kidney problems, which cause you to urinate very little or not at all (symptoms of acute kidney failure), tell your doctor.
• If you have a fever (temperature greater than or equal to 38 ° C) or chills, which could be signs of infection, tell your doctor immediately. You may be at risk of developing a blood infection.
• If you have a temperature > 38 ° C, tell your doctor. Your doctor may determine that you also have a reduction in white blood cells.
• If you unexpectedly experience bleeding or bruising (disseminated intravascular coagulation), tell your doctor, as these can be signs of blood clots in the small blood vessels of your body.
• If you feel dizzy (lose consciousness) or have an irregular heartbeat while taking Oxaliplatino, tell your doctor immediately, as this may be a sign of a serious heart condition.
• If you experience pain and swelling in your muscles, in combination with weakness, fever, or brownish-red urine, tell 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 like coffee grounds, dark stools that may be signs of an intestinal ulcer (gastrointestinal ulcer with potential bleeding or perforation), consult your doctor.
• If you have abdominal pain (belly), diarrhea with blood, and nausea and/or vomiting, which may be caused by a reduction in blood flow to the intestinal wall (intestinal ischemia), tell your doctor.

Using oxaliplatin with other medicines

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

Pregnancy, breastfeeding, and fertility

Pregnancy

• You must not become pregnant during treatment and must use an effective method of contraception during treatment. It is recommended to use an appropriate contraceptive method until 15 months after stopping treatment.
• Male patients are advised not to father a child during treatment and for up to 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

• Oxaliplatino may produce anti-fertility effects that could be irreversible. Men are advised to seek advice on sperm preservation before treatment.
• After treatment with oxaliplatin, female patients who are planning a 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, and vomiting, and other neurological symptoms that affect walking and balance. If this occurs, you should not drive or operate machinery. If you have vision problems while taking oxaliplatin, do not drive, operate heavy machinery, or engage in hazardous activities.

3. How to use Oxaliplatino

For use in adult patients only.

For single use only.

Dose

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 the elderly, is 85 mg/m2 of body surface area.

The dose given will also depend on the results of your blood tests and whether you have previously experienced side effects as a result of oxaliplatin administration.

Method and route of administration

• The prescription of oxaliplatin will be made 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 to you.
• Oxaliplatino is administered by slow injection into a vein (intravenous infusion) over a period of 2 to 6 hours.
• Oxaliplatino will be administered to you at the same time as folinic acid and before 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. The treatment lasts for a maximum of 6 months after surgery to remove your cancer.

If you use more Oxaliplatino than you should

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

If you have any further questions on the use of this product, ask your doctor, pharmacist, or nurse.

4. Possible Adverse Effects

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

The following adverse effects may be experienced.

Inform 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 in the face, lips, tongue, or other parts of the body, shortness of breath, wheezing, or breathing problems, extreme fatigue (feeling like you are going to faint). In most cases, these symptoms occurred during or immediately after infusion, but delayed allergic reactions have also been observed hours or even days after infusion.

• Abnormal 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 particles in your vomit.
• Stomatitis/mucositis (lip pain or mouth ulcers).
• Unexplained respiratory symptoms such as dry or productive cough, difficulty breathing, or breathing noises, shortness of breath, and wheezing, as they may be indicators of a severe lung disease that can cause death.
• A group of symptoms such as headache, altered mental function, seizures, and abnormal vision from blurred vision to loss of vision (symptoms of posterior reversible leukoencephalopathy syndrome, a rare neurological disorder).
• Symptoms of stroke (including sudden and 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 fatigue with a decrease in the number of red blood cells and difficulty breathing (hemolytic anemia), alone or in combination with a low platelet count, abnormal bruising (thrombocytopenia), and kidney problems that cause you to urinate little or not at all (symptoms of hemolytic uremic syndrome).

Other known adverse effects of oxaliplatin are:

Very common: may affect more than 1 in 10 patients

Oxaliplatin may affect the nerves (peripheral neuropathy). You may feel tingling and/or numbness of the fingers of the hands, feet, around the mouth, or in the throat, which may be associated with cramps. These effects may appear often due to exposure to cold, for example, opening a refrigerator or handling a cold drink. You may also experience difficulty in performing delicate tasks, such as buttoning buttons. Although in most cases these symptoms resolve completely on their own, it is possible that the symptoms of peripheral sensory neuropathy may persist after treatment ends. Some people have experienced tingling, a shock-like sensation that passes through the arms or trunk when the neck is flexed.

• Oxaliplatin may cause an unpleasant sensation in the throat, particularly when swallowing, and give the sensation of shortness of breath. This sensation, if it appears, usually occurs during or in the hours following infusion and may be triggered by exposure to cold. Although it is unpleasant, it does not last long and disappears without the need for treatment. Your doctor may decide to alter your treatment as a result of this.

• Oxaliplatin may cause diarrhea, mild nausea (feeling of dizziness), and vomiting (feeling unwell); however, your doctor will generally treat you to prevent this discomfort before starting treatment, and it should be continued after treatment.
• Oxaliplatin causes a transient reduction in the number of blood cells. The reduction of red blood cells may cause anemia (a reduction of red blood cells), abnormal bleeding, or bruising (due to a reduction in platelets). The reduction in the number of white blood cells may make you more prone to infections.
• Your doctor will take blood samples to check that you have enough blood cells before you start treatment and after each subsequent cycle.
• Feeling of discomfort near or at the site of administration during infusion.
• Fever, chills (shivering), moderate or intense fatigue, body pain.
• Weight changes, loss of appetite, taste disorders, constipation.
• Headache, back pain.
• Inflammation of the nerves in the muscles, stiffness in the neck, strange sensation of the tongue that can alter speech, stomatitis/mucositis (lip pain or mouth ulcers).
• Stomach pain.
• Abnormal bleeding, including nosebleeds.
• Cough, difficulty breathing.
• Allergic reactions, skin rash that may be red or itchy, moderate hair loss (alopecia).
• Alteration of blood tests, including those that show changes in liver function.

Common: may affect up to 1 in 10 patients

• Infection due to a reduction in the number of white blood cells.

• Severe blood infection, in addition to a reduction in white blood cells (septic neutropenia), which can be fatal.
• Reduction of 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, belching, dizziness.
• Increased sweating and nail disorders, skin peeling.
• Chest pain.
• Lung disorders and sputum.
• Pain in the joints and bones.
• Pain when urinating and changes in kidney function, changes in the frequency of urination, dehydration.
• Blood in the urine/stool, swelling of the veins, blood clots in the lung.
• High blood pressure.
• Depression and insomnia.
• Conjunctivitis and vision problems.
• Decreased calcium levels in the blood.
• Falls.

Uncommon: may affect up to 1 in 100 patients

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

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

• Hearing loss.

• Scarring or thickening of the lungs that can cause breathing difficulties, sometimes fatal (interstitial lung disease).
• Reversible short-term vision loss.
• Unexpected bleeding or bruising due to an increase in blood clots throughout the small blood vessels of your body (disseminated intravascular coagulation) that can be fatal.

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

• Presence of blood or dark brown particles in your vomit.
• Kidney problems that cause you to urinate little or not at all (symptoms of acute renal failure).
• Vascular disorders of the liver.

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

• Allergic vasculitis (inflammation of blood vessels).
• Autoimmune reaction that causes a reduction in all blood cell lines (autoimmune pancytopenia, pancytopenia).
• Severe blood infection and drop in blood pressure (septic shock) that can be fatal.
• Seizures (uncontrolled body agitation).
• Throat spasm that can cause breathing difficulties.
• Extreme fatigue with a decrease in the number of red blood cells and shortness of breath (hemolytic anemia), alone or in combination with a decrease in platelets and kidney problems that cause you to urinate little or not at all (symptoms of hemolytic uremic syndrome), which can be fatal.
• Abnormal heart rhythm (QT prolongation) that can be seen on an electrocardiogram (ECG) that can be fatal.
• Muscle pain and swelling along with weakness, fever, or reddish-brown urine (symptoms of muscle damage called rhabdomyolysis) that can be fatal.
• Abdominal pain, nausea, vomiting with blood or vomit like "coffee grounds", dark stools (symptoms of gastrointestinal ulcer with potential bleeding or perforation), which can be fatal.
• Decreased blood flow to the intestine (intestinal ischemia) that can be fatal.
• Risk of new cancers. Leukemia, a form of blood cancer, has been reported in patients after using oxaliplatin in combination with certain medications. Consult your doctor about the potential increased risk of this type of cancer when using oxaliplatin with certain medications.
• Myocardial infarction (heart attack), angina pectoris (chest pain or discomfort).
• Esophageal inflammation (inflammation of the inner lining of the esophagus - the tube that connects the mouth to the stomach - which causes pain and difficulty swallowing).

Abnormal liver nodules (focal nodular hyperplasia).

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that is not listed in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

.

5. Conservation of Oxaliplatin

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

Do not use this medicine after the expiration date that appears on the label and box after CAD. The expiration date is the last day of the month indicated.

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

Do not use oxaliplatin if you observe that the solution is not transparent and is not free of particles.

Medicines should not be thrown away through wastewater or household waste. Ask your pharmacist how to dispose of the packaging and medicines that are no longer needed. This will help protect the environment.

6. Container Content and Additional Information

Oxaliplatin Composition

• 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 contain 50 mg of oxaliplatin.

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

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

• The other components are water for injectable preparations.

Product Appearance and Container Content

This medicine is a concentrate for solution for infusion. The concentrate is a clear and colorless infusion solution free of visible particles.

Each vial contains 50mg, 100mg or 200mg of oxaliplatin. The concentrate is presented in type I glass vials of 10 ml, 20 ml and 40 ml with a chlorobutyl or bromobutyl rubber stopper with an aluminum cap with a plastic "flip-off" cap. Each vial may have a retractable sleeve and may or may not be packaged in a plastic container.

The vials are supplied in cardboard boxes of one vial.

Not all pack sizes may be marketed

Marketing Authorization 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 medicine is authorized 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 concentrate for infusion solution

Denmark Oxaliplatin "Fresenius Kabi", concentrate for infusion solution, solution

Germany Oxaliplatin Kabi 5 mg/ml concentrate for the preparation of an infusion solution

Hungary Oxaliplatin Kabi 5 mg/ml concentrate for infusion solution

Italy Oxaliplatino Kabi

Ireland Oxaliplatin 5 mg/ml concentrate for solution for infusion

Netherlands Oxaliplatine Kabi 5 mg/ml concentrate for solution for infusion

Norway Oxaliplatin Kabi 5 mg/ml concentrate for infusion solution

Poland Oxaliplatin Kabi

Portugal Oxaliplatina Kabi 5 mg/ml concentrate for solution for infusion

Slovakia Oxaliplatin Kabi 5 mg/ml infusion concentrate

Spain Oxaliplatino Kabi 5 mg/ml concentrate for solution for infusion EFG

United Kingdom Oxaliplatin 5 mg/ml concentrate for solution for infusion

(Northern Ireland)

Date of last revision of this leaflet: June 2024

-----------------------------------------------------------------------------------------------------------------------

This information is intended only for healthcare professionals:

INSTRUCTIONS FOR USE, HANDLING AND DISPOSAL

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

Handling Instructions

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

The preparation of injectable solutions of cytotoxic agents should be carried out by specialized personnel trained in the handling of this class of medicines, under conditions that guarantee the integrity of the medicine, environmental protection, and in particular the protection of the personnel handling these drugs, in accordance with hospital policy. Preparation in an area reserved for this purpose is required. Smoking, eating, or drinking is prohibited in this area.

Specialized personnel should provide themselves with appropriate materials for handling, long-sleeved gowns, masks, caps, glasses, sterile single-use gloves, protective suits for the work area, containers, and bags for collecting waste.

Feces and vomit should be handled with care.

Pregnant women should avoid handling cytotoxic agents.

Any broken container should be treated with the same precautions and considerations as contaminated waste. Contaminated waste should be incinerated in suitable, rigid, and labeled containers. See the "Waste Disposal" section below.

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

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

Special Administration Precautions

• DO NOT use injection equipment that contains aluminum.
• DO NOT administer undiluted.
• Only glucose 5% (50 mg/ml) solutions should be used as diluents. DO NOT DILUTE for infusion with sodium chloride solution or solutions containing chlorides.
• DO NOT mix other drugs in the same infusion bag or administer simultaneously in the same infusion line.
• DO NOT mix with alkaline drugs or solutions, in particular 5-fluorouracil, folinic acid preparations containing tromethamine as an excipient, and tromethamine salts of other active ingredients. Alkaline medications or solutions may adversely affect the stability of oxaliplatin.

Instructions for Use with Folinic Acid (FA) (as Calcium Folinic or Disodium Folinic)

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

Instructions for Use with 5-Fluorouracil (5-FU)

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

For additional information on the combination of drugs with oxaliplatin, see the corresponding Summary of Product Characteristics.

• USE ONLY the recommended solvents (see below).

• Any concentrate that shows evidence of precipitation should not be used and should be destroyed in accordance with legal requirements for the disposal of hazardous waste (see below).

Concentrate for Solution for Infusion

Inspect visually before use. Only clear solutions without particles should be used. The pharmaceutical product is for single use. Any unused infusion solution should be discarded.

Dilution before Intravenous Infusion

Remove the required amount of concentrate from the vial(s) and then dilute with 250 to 500 ml of a 5% glucose solution to administer a concentration of oxaliplatin between 0.2 mg/ml and 0.7 mg/ml. The concentration range in which the physical-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 24 hours at room temperature (15°C-25°C) and in the refrigerator (2°C - 8°C).

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

Inspect visually before use. Only clear solutions without particles should be used. The medicine is for single use. Any unused solution should be discarded.

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

The compatibility of Oxaliplatin infusion solution has been analyzed with representative administration equipment based on PVC.

Infusion

Administration of oxaliplatin does not require prehydration.

Oxaliplatin diluted in 250 ml or 500 ml of glucose 5% solution to administer a concentration not less than 0.2 mg/ml, will be infused by peripheral or central venous route, over 2 to 6 hours. When oxaliplatin is administered with 5-fluorouracil, the infusion of oxaliplatin should precede the administration of 5-fluorouracil.

Disposal

Any remaining material or unused medication should be disposed of in accordance with local requirements.