Package Insert: Information for the User

Oxaliplatino Qilu 5 mg/ml Concentrate for Solution for Infusion EFG

oxaliplatino

Read this package insert carefully before starting to use this medication, as it contains important information for you.

• Keep this package insert, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medication has been prescribed only for you, and you should not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this package insert. See section 4.

The active ingredient of Oxaliplatino Qilu is oxaliplatino.

This medication is used in the treatment of colorectal cancer (treatment of colon cancer in stage III after complete resection of the primary tumor and metastatic carcinoma of the colon and rectum). Oxaliplatino Qilu is used in combination with other antineoplastic medications called 5-fluorouracil (5-FU) and folinic acid.

Oxaliplatino Qilu is an antineoplastic or anticancer medication that contains platinum.

Do not use Oxaliplatino Qilu:

• if you are allergic to oxaliplatino or any of the other components of this medication (listed in section 6).
• if you are breastfeeding.
• if you have a reduced number of blood cells.
• if you have numbness or tingling in your hands and feet and have difficulty performing delicate tasks, such as buttoning your clothes.
• if you have a severe kidney disease.

Warnings and precautions

Consult your doctor or pharmacist before starting to receive Oxaliplatino Qilu:

• If you have ever had an allergic reaction to medications containing platinum, such as carboplatino and cisplatino. Allergic reactions can occur during oxaliplatino infusion.
• If you have a moderate or mild kidney disorder.
• If you have a liver problem or have abnormal liver activity test results during your treatment.
• If you have or have had heart problems, such as an abnormal heart signal (called QT interval prolongation), irregular heartbeat, or a family history of heart problems.
• If you have been administered or are planned to be administered any vaccine. During treatment with oxaliplatino, you should not be vaccinated with live or attenuated vaccines, such as the yellow fever vaccine.

If you experience any of the following symptoms at any time, inform your doctor immediately.It may be necessary for your doctor to treat these symptoms and reduce the dose of Oxaliplatino Qilu, postpone treatment with this medication, or discontinue it:

• If you experience an unpleasant sensation in your throat, especially when swallowing, and feel like you are short of breath during treatment, inform your doctor.
• If you experience numbness or tingling in your hands or feet, or reduced sensitivity in your hands or feet, inform your doctor.
• If you experience headaches, altered mental activity, seizures, and vision changes (ranging from blurred vision to loss of vision), inform your doctor.
• If you feel or are dizzy (nausea and vomiting), inform your doctor.
• If you experience severe diarrhea, inform your doctor.
• If you experience painful lips or mouth ulcers (mucositis/stomatitis), inform your doctor.
• If you experience diarrhea or a decrease in white blood cell or platelet count, inform your doctor. Your doctor may reduce the dose of Oxaliplatino Qilu or postpone treatment with this medication.
• If you experience unexplained respiratory symptoms, such as coughing or difficulty breathing, inform your doctor. Your doctor may discontinue treatment with Oxaliplatino Qilu.
• If you experience extreme fatigue, shortness of breath, or kidney problems where you urinate little or not at all (symptoms of acute renal failure), inform your doctor.
• If you experience fever (a temperature of 38°C or higher) or chills, inform your doctor immediately, as they may be signs of infection. You may be at risk of developing blood infection.
• If you experience fever with a temperature of > 38°C, inform your doctor. They will determine if you also have a decrease in white blood cell count.
• If you experience unexpected bleeding or bruising (disseminated intravascular coagulation), inform your doctor, as they may be signs of blood clot formation in small blood vessels throughout the body.
• If you faint (loss of consciousness) or experience irregular heartbeat while taking Oxaliplatino Qilu, inform your doctor immediately, as it may be a sign of severe heart disease.
• If you experience muscle pain and swelling, accompanied by weakness, fever, or dark urine, inform your doctor, as these symptoms may be signs of muscle damage (rhabdomyolysis) and may cause kidney problems or other complications.
• If you experience abdominal pain, nausea, vomiting, or vomiting that appears to be "coffee grounds" or dark or black stools with blood, which may be signs of intestinal ulcer (gastroduodenal ulcer, possibly accompanied by bleeding or perforation), inform your doctor.
• If you experience abdominal pain (stomach pain), bloody diarrhea, and nausea or vomiting, which may be caused by decreased blood flow to the intestinal wall (intestinal ischemia), inform your doctor.

Children and adolescents

Oxaliplatino Qilu is only indicated for adults.

Other medications and Oxaliplatino Qilu

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

Pregnancy, breastfeeding, and fertility

Pregnancy

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medication.

• It is not recommended to become pregnant during treatment with oxaliplatino, therefore, during treatment, you should use an effective contraceptive method. It is recommended to use appropriate contraceptive measures during the 15 months following the end of treatment.
• It is recommended that male patients do not father children during treatment and for 12 months after the end of treatment and use appropriate contraceptive measures during this time..
• If you are pregnant or are planning to become pregnant, it is very important to discuss this with your doctorbeforereceiving any treatment.
• If you become pregnant during treatment, you must inform your doctor immediately.

Breastfeeding

• You should stop breastfeeding during treatment with Oxaliplatino Qilu.

Fertility in men and women

• Oxaliplatino maycause infertility and this may be irreversible. Male patients should seek advice on sperm conservation before treatment.

After treatment with oxaliplatino, it is recommended that patients who wish to become pregnant seek genetic counseling.

Consult your doctor or pharmacist before taking any medication.

Driving and operating machinery

Treatment with oxaliplatino may increase the risk of experiencing dizziness, nausea, and vomiting, as well as other neurological symptoms that may affect your gait and balance.

If you are affected by any of these symptoms, do not drive or operate machinery.

If you experience vision problems while taking Oxaliplatino Qilu, do not drive, operate heavy machinery, or engage in hazardous activities.

Oxaliplatino Qilu is only indicated for adults.

For single use only.

Dose

The dose of Oxaliplatino Qilu depends on your body surface area, which is calculated from your height and weight.

The usual dose in adults (including elderly patients) is 85 mg/m2 of body surface area. The dose you receive will also depend on the results of blood tests and if you have experienced previous adverse effects with this medication.

Form and route of administration

• Oxaliplatino Qilu will be prescribed by a specialist doctor in cancer treatment.
• You will be treated by a healthcare professional, and this person will have calculated the dose of medication you need.
• Oxaliplatino Qilu is administered through a slow injection into a vein (intravenous infusion) over a period of 2-6 hours.
• This medication will be administered at the same time as folinic acid and before the infusion of 5-fluorouracil.

Administration frequency

Generally, you will receive an infusion every 2 weeks.

Treatment duration

Your doctor will determine the duration of treatment.

Your treatment will last a maximum of 6 months when used after complete tumor resection.

If you use more Oxaliplatino Qilu than you should

Since this medication will be administered by a healthcare professional, it is unlikely that you will receive too much or too little medication. In the event of an overdose, you may experience an increase in adverse effects. Your doctor may provide you with the necessary treatment for these adverse effects.

If you have any other questions about the use of this medication, ask your doctor, nurse, or pharmacist.

Like all medications, this medication may cause side effects, although not everyone will experience them.

If you experience any side effect, it is very important that you inform your doctor before starting the next treatment.

The following side effects may occur.

Inform your doctor immediately if you experience any of the following symptoms:

• Allergic or anaphylactic reactions, accompanied by sudden signs such as rash, itching, or hives on the skin, difficulty swallowing, facial swelling, lip, tongue, or other body part swelling, difficulty breathing, wheezing, or breathing problems, extreme fatigue (you may feel like you are going to faint). These symptoms usually occur during infusion or shortly after, but delayed allergic reactions have also been observed hours or even days after infusion.
• Abnormal hematomas, bleeding, or signs of infection, such as sore throat and fever.
• Persistent or severe diarrhea or vomiting.
• Presence of blood or dark brown coffee-colored particles in vomit.
• Stomatitis/mucositis (lips and mouth sores).
• Respiratory symptoms such as dry or productive cough, difficulty breathing, or wheezing, shortness of breath, and sibilance, which may indicate a severe lung disease that can be fatal.
• A set of symptoms such as headache, altered mental activity, seizures, and abnormal vision (from blurry vision to loss of vision) (posterior reversible encephalopathy syndrome, a rare neurological disorder).
• Stroke symptoms (including sudden severe headache, confusion, vision problems in one or both eyes, numbness or weakness in the face, arm, or leg, usually on one side, facial drooping, difficulty walking, dizziness, loss of balance, and difficulty speaking).
• Extreme fatigue, accompanied by a decrease in red blood cell count and shortness of breath (hemolytic anemia), alone or accompanied by a decrease in platelet count, abnormal cardinals (thrombocytopenia), and kidney problems where little or no urine is produced (uric acid syndrome).

Other side effects of Oxaliplatino Qilu are:

Very common(may affect more than 1 in 10 people)

• Numbness or tingling in the fingers of the hands and feet, around the mouth or throat, which may be accompanied by cramps (peripheral neuropathy).

These side effects are usually triggered by exposure to cold, such as opening the refrigerator or holding a cold drink. You may also have difficulty with fine motor tasks, such as buttoning your clothes. Although in most cases these symptoms resolve on their own, there is a possibility that peripheral sensory neuropathy symptoms may persist after treatment is completed. Some people have experienced sudden tingling sensations in the arms or trunk when bending their neck.

• An unpleasant sensation in the throat, specifically when swallowing, and may give the sensation of lack of air.
• This sensation, if it occurs, usually happens during infusion or in the hours that follow 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 modify your treatment as a result of this.
• Diarrhea, mild nausea (sensation of dizziness), and vomiting (discomfort). However, your doctor will give you a treatment to prevent this discomfort before starting treatment and should be continued after it.
• Temporary reduction in the number of blood cells.
• The decrease in red blood cells may cause anemia (decrease in red blood cell count), abnormal bleeding, or appearance of petechiae (due to a decrease in platelet count). The decrease in white blood cell count may facilitate the appearance of infections.

Before starting treatment and before each treatment cycle, your doctor will perform a blood test to check that you have a sufficient number of cells in your blood.

• Discomfort or pain around or at the injection site during infusion.
• Fever, chills (shivering), mild or extreme fatigue, body pain.
• Weight changes, loss of appetite, taste alterations, constipation.
• Headache, back pain.
• Muscle inflammation, neck stiffness, abnormal sensation in the tongue that may make it difficult to speak, stomatitis/mucositis (lips and mouth sores).
• Abdominal pain
• Unusual bleeding, including nosebleeds.
• Cough, difficulty breathing.
• Allergic reactions, red rash with itching, moderate hair loss (alopecia).
• Alterations in blood test results, including changes in liver function.

Common(may affect up to 1 in 10 people)

• Infection due to a decrease in white blood cell count.
• Severe blood infection, in addition to a decrease in white blood cell count (neutropenic sepsis) that can be fatal.
• Decrease in white blood cell count, accompanied by fever >38.3°C or prolonged fever >38°C for more than an hour (febrile neutropenia).
• Indigestion and stomach burning, hiccups, dizziness.
• Increased sweating and nail alterations, skin peeling.
• Chest pain.
• Pulmonary alterations and coughing.
• Joint pain and bone pain.
• Urination pain and kidney function alterations, changes in urination frequency, dehydration.
• Blood in urine/stool, vein inflammation, pulmonary embolism.
• High blood pressure.
• Depression and insomnia.
• Conjunctivitis and vision problems.
• Decrease in calcium levels in the blood.
• Fall.

Rare(may affect up to 1 in 100 people)

• Severe blood infection (sepsis) that can be fatal.
• Intestinal obstruction or inflammation.
• Nervousness.

Very rare(may affect up to 1 in 1,000 people)

• Loss of hearing.
• Formation of scars and lung thickening, accompanied by difficulty breathing, which may be fatal (interstitial lung disease).
• Temporary and reversible loss of vision.
• Unexpected bleeding or bruises due to the dissemination of blood clots in small blood vessels throughout the body (disseminated intravascular coagulation), which can be fatal.

Very rare(may affect up to 1 in 10,000 people)

• Presence of blood or dark brown coffee-colored particles in vomit.
• Kidney problems that cause little or no urine to be produced (acute renal failure symptoms).
• Liver vascular disorders.

Frequency unknown(cannot be estimated from available data)

• Allergic vasculitis (inflammation of blood vessels).
• Autoimmune reaction that causes a decrease in all blood cell lines (pancytopenia autoimmune), pancytopenia.
• Severe blood infection or low blood pressure (septic shock), which can be fatal.
• Seizures (uncontrolled body agitation).
• Throat spasm that may cause difficulty breathing.
• Extreme fatigue, accompanied by a decrease in red blood cell count and shortness of breath (hemolytic anemia), alone or accompanied by a decrease in platelet count, and kidney problems that cause little or no urine to be produced (uric acid syndrome), which can be fatal.
• Abnormal heart rhythm (prolongation of the QT interval), which may be observed on the electrocardiogram (ECG) and may be fatal.
• Myocardial infarction (heart attack), angina (chest pain or discomfort)
• Muscle pain and swelling, accompanied by weakness, fever, or brownish-red urine (symptoms of muscle damage called rhabdomyolysis), which can be fatal.
• 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).
• Abdominal pain, nausea, vomiting with blood or coffee grounds-like vomit, dark/black stools with blood (symptoms of gastrointestinal ulcers, with possible bleeding or perforation), which can be fatal.
• Intestinal blood flow reduction (ischemic intestinal disease), which can be fatal.
• Risk of new cancers. Leukemia, a type of blood cancer, has been reported in patients after using oxaliplatino in combination with certain medications. Consult your doctor about the potential increased risk of this type of cancer when oxaliplatino is used with certain medications.
• Abnormal liver nodules, non-cancerous (focal nodular hyperplasia)

Reporting side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Usewww.notificaram.es. By reporting side effects, you can contribute to providing more information about the safety of this medication.

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

Before mixing this medication, it must be stored in its original container to protect it from light and it should not be frozen.

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

Oxaliplatino Qilu should not come into contact with the eyes or skin. In the event of an accidental spill, inform the doctor or nurse immediately.

Once the infusion has been completed, the doctor or nurse will dispose of this medication with the necessary safety measures.

Medications should not be thrown down the drain or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. This will help protect the environment.

Composition of Oxaliplatino Qilu

The active ingredient of Oxaliplatino Qilu is oxaliplatino.

Each milliliter of concentrate for solution for infusion contains 5 mg of oxaliplatino.

Each vial of 10 ml contains 50 mg of oxaliplatino.

Each vial of 20 ml contains 100 mg of oxaliplatino.

Each vial of 40 ml contains 200 mg of oxaliplatino.

The other components are water for injection.

Appearance of the product and contents of the package

Oxaliplatino Qilu vials contain a concentrate for solution for infusion (a concentrated solution that is diluted to convert it into a solution that can be administered as a slow infusion through a drip).

The solution is transparent, colorless, and free of visible particles in suspension and is contained in glass containers called vials, which contain 50 mg (10 ml), 100 mg (20 ml), and 200 mg (40 ml) of oxaliplatino.

The vials are supplied in boxes with a single vial.

Marketing Authorization Holder

QILU PHARMA SPAIN S.L.

Paseo de la Castellana 40,

8º, Madrid, 28046,

Spain

Responsible for manufacturing

KYMOS, S.L.

Ronda de Can Fatjó,

7B (Parque Tecnológico del Vallès),

Cerdanyola del Vallès, 08290

Barcelona, Spain

This medicine is authorized in the member states of the European Economic Areaand in the United Kingdom (Northern Ireland)with the following names:

Last review date of this leaflet:August 2024

The detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.es/

This information is intended solely for healthcare professionals:

GUIDELINES FOR PREPARATION FOR USE OF OXALIPLATINO Qilu 5 MG/ML CONCENTRATE FOR SOLUTION FOR INFUSION EFG

It is very important that you read all the content of this procedure before preparing Oxaliplatino Qilu solution for infusion EFG.

1. FORMULATION

Oxaliplatino Qilu 5 mg/ml concentrate for solution for infusion EFG is a transparent and colorless liquid that contains 5 mg/ml of oxaliplatino in water for injection.

1. Presentation

Oxaliplatino Qilu is presented in single-dose vials. Each box contains a vial of Oxaliplatino Qilu (50 mg, 100 mg, or 200 mg).

The 10 ml vial of Oxaliplatino Qilu is a transparent type I glass vial and contains 50 mg of oxaliplatino concentrate for solution for infusion, with a bromobutyl elastomeric stopper.

The 20 ml vial of Oxaliplatino Qilu is a transparent type I glass vial and contains 100 mg of oxaliplatino concentrate for solution for infusion, with a bromobutyl elastomeric stopper.

The 40 ml vial of Oxaliplatino Qilu is a transparent type I glass vial and contains 200 mg of oxaliplatino concentrate for solution for infusion, with a bromobutyl elastomeric stopper.

Oxaliplatino Qilu packaged for sale:

This medicine should be stored in its original packaging to protect it from light and should not be frozen.

Infusion solution:

After dilution of the concentrate for solution for infusion in 5% glucose solution (50 mg/ml), the physical and chemical stability during use is 48 hours at a temperature of between 2°C and 8°C and 24 hours at 25°C.

From a microbiological point of view, the infusion solution should be used immediately. If not used immediately, the time and conditions of conservation prior to use are the responsibility of the user and should not exceed 24 hours at 2-8°C, unless the dilution has taken place under controlled and validated aseptic conditions.

Visually inspect the vial before use. Only solutions that are transparent and do not contain particles in suspension should be used. This medicine is for single use only. Any unused solution should be discarded (see the section onDisposal).

1. SAFE HANDLING RECOMMENDATIONS

As with other medicines containing potentially toxic compounds, extreme caution should be taken during the handling and preparation of solutions containing oxaliplatino.

Manipulation instructions

The handling of this cytotoxic agent by healthcare personnel requires taking precautions to ensure the protection of the handler and the work area.

The preparation of injectable solutions of cytotoxic agents should be performed by specialized personnel properly qualified in this type of medication, in conditions that ensure the integrity of the product, the protection of the environment, and, in particular, the protection of the personnel handling the medicines, in accordance with hospital regulations. A reserved preparation area is required for this purpose. Smoking, eating, or drinking is prohibited in this area.

Personnel should be equipped with appropriate materials for handling the medicine, such as gloves, a protective mask, a cap, protective glasses, disposable sterile gloves, a protective suit for the work area, containers, and waste bags.

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 rigid containers properly labeled. See the section onDisposal.

If the oxaliplatino concentrate for solution for infusion or the oxaliplatino infusion solution comes into contact with the skin, wash the affected area immediately with plenty of water.

If the oxaliplatino concentrate for solution for infusion or the oxaliplatino infusion solution comes into contact with mucous membranes, wash the affected area immediately with plenty of water.

1. PREPARATION FOR INTRAVENOUS ADMINISTRATION

Special administration precautions

• DO NOT use equipment containing aluminum.
• DO NOT administer without diluting.
• Only use a 5% glucose solution (50 mg/ml) as a diluent.

DO NOT dilute with sodium chloride solutions or solutions containing chloride.

• DO NOT mix with other medicines in the same infusion bag or administer simultaneously through the same infusion route.
• DO NOT mix with alkaline solutions, specifically 5-fluorouracil preparations or folinic acid preparations containing trometamol as an excipient and trometamol salts of other medicines. Alkaline solutions will negatively affect the stability of oxaliplatino.

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

The intravenous infusion of 85 mg/m2of oxaliplatino in 250-500 ml of 5% glucose solution (50 mg/ml) is administered at the same time as folinic acid diluted in 5% glucose solution (50 mg/ml) over 2-6 hours, using a Y-connector placed just before the injection site. These two medicines should not be combined in the same infusion bag. Folinic acid should not contain trometamol as an excipient and should only be diluted in an isotonic 5% glucose solution (50 mg/ml), and never in alkaline solutions or sodium chloride solutions or solutions containing chloride.

Instructions for use with 5-fluorouracil

Oxaliplatino should always be administered before fluoropyrimidines, i.e., 5-fluorouracil (5-FU). After administering oxaliplatino, rinse the infusion site and then administer 5-fluorouracil (5-FU).

See the detailed information on concurrent administration of medicines in the corresponding technical data sheet.

• USE ONLY the recommended solvents (see below).

• Only solutions that are transparent and do not contain particles in suspension should be used.

Withdraw the required volume of concentrate from the vials and then dilute with 250-500 ml of a 5% glucose solution (50 mg/ml) to administer a concentration of oxaliplatino not less than 0.2 mg/ml. The concentration interval in which the physical and chemical stability of oxaliplatino has been demonstrated is 0.2-2.0 mg/ml.

Administer by intravenous infusion.

After dilution in 5% glucose solution (50 mg/ml), the physical and chemical stability during use is 48 hours at a temperature of between 2°C and 8°C and 24 hours at 25°C.

From a microbiological point of view, the prepared infusion solution should be used immediately.

If not used immediately, the time and conditions of conservation prior to use are the responsibility of the user and should not exceed 24 hours at 2-8°C, unless the dilution has taken place under controlled and validated aseptic conditions.

Visually inspect the vial before use. Only solutions that are transparent and do not contain particles in suspension should be used.

This medicine is for single use only. Any unused solution should be discarded (see the section onDisposal).

Do not useNEVERin dilution sodium chloride or solutions containing chloride.

The compatibility of the oxaliplatino infusion solution has been confirmed with infusion equipment with PVC components.

The administration of oxaliplatino does not require prehydration.

Oxaliplatino diluted in 250-500 ml of a 5% glucose solution (50 mg/ml) to obtain a concentration not less than 0.2 mg/ml should be infused through a peripheral or central venous route over 2-6 hours. When administering oxaliplatino with 5-fluorouracil (5-FU), the infusion of oxaliplatino should precede the infusion of 5-fluorouracil (5-FU).

The disposal of unused medicine and all materials that have come into contact with it during dilution and administration should be carried out in accordance with local regulations for cytotoxic agents, in accordance with local legal requirements for the disposal of hazardous waste.