OXALIPLATIN QILU 5 mg/ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

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

oxaliplatino

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.
• 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 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 Package Leaflet

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

1. What is Oxaliplatino Qilu and what is it used for

The active substance of Oxaliplatino Qilu is oxaliplatin.

This medicine is used to treat colon cancer (treatment of stage III colon cancer after complete resection of the primary tumor and metastatic colorectal cancer). Oxaliplatino Qilu is used in combination with other anti-cancer medicines called 5-fluorouracil (5-FU) and folinic acid.

Oxaliplatino Qilu is an anti-cancer medicine that contains platinum.

2. What you need to know before you are given Oxaliplatino Qilu

Do not use Oxaliplatino Qilu:

• 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 low number of blood cells.
• if you already have tingling or numbness of the fingers of the hand and feet and have difficulty performing delicate tasks, such as buttoning your clothes.
• if you have severe kidney disease.

Warnings and precautions

Tell your doctor or pharmacist before you start receiving Oxaliplatino Qilu:

• If you have ever had an allergic reaction to platinum-containing medicines, such as carboplatin and cisplatin. Allergic reactions can occur during oxaliplatin infusion.
• If you have moderate or mild kidney impairment.
• If you have liver problems or abnormal liver function test results 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 been given or are planned to be given any vaccine. During treatment with oxaliplatin, you should not be vaccinated with live or attenuated live vaccines, such as the yellow fever vaccine.

If you experience any of the following symptoms at any time, tell your doctor immediately.Your doctor may need to treat these symptoms and reduce the dose of Oxaliplatino Qilu, postpone treatment with this medicine, or stop it:

• If you experience an unpleasant sensation in the throat, especially when swallowing, and feel short of breath during treatment, tell your doctor.
• If you have nerve problems in your hands or feet, such as tingling or numbness, or reduced sensitivity in your hands or feet, tell your doctor.
• If you have a headache, altered mental status, seizures, and vision changes (ranging from blurred vision to loss of vision), tell your doctor.
• If you feel or are nauseous (nausea and vomiting), tell your doctor.
• If you have severe diarrhea, tell your doctor.
• If your lips hurt or you have ulcers in your mouth (mucositis/stomatitis), tell your doctor.
• If you have diarrhea or a decreased white blood cell or platelet count, tell your doctor. Your doctor may reduce the dose of Oxaliplatino Qilu or postpone treatment with this medicine.
• If you experience unexplained respiratory symptoms, such as cough or difficulty breathing, tell your doctor. Your doctor may stop your treatment with Oxaliplatino Qilu.
• If you experience extreme fatigue, shortness of breath, or kidney problems where you urinate little or nothing (symptoms of acute kidney failure), tell your doctor.
• If you have a fever (a temperature above or equal to 38°C) or chills, tell your doctor immediately, as these may be signs of infection. You may be at risk of developing a blood infection.
• If you have a fever with a temperature > 38°C, tell your doctor. He will determine if you also have a decreased white blood cell count.
• If you experience any unexpected bleeding or bruising (disseminated intravascular coagulation), tell your doctor, as these may be signs of blood clot formation in the small veins of the body.
• If you faint (loss of consciousness) or experience an irregular heartbeat while taking Oxaliplatino Qilu, tell your doctor immediately, as this may be a sign of a serious heart condition.
• If you experience muscle pain and swelling, accompanied by weakness, fever, or dark-colored urine, tell 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 blood or vomit that looks like "coffee grounds" or black, tarry stools, which may be signs of a stomach ulcer (gastroduodenal ulcer, with possible bleeding or perforation), tell 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), tell your doctor.

Children and Adolescents

Oxaliplatino Qilu is only indicated in adults.

Other Medicines and Oxaliplatino Qilu

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

Pregnancy, Breast-feeding, and Fertility

Pregnancy

If you are pregnant or breast-feeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.

• It is not recommended to become pregnant during treatment with oxaliplatin; therefore, during treatment, you should use an effective method of contraception. It is recommended to use adequate contraceptive measures during the 15 months following the end of treatment.
• Male patients are advised not to father a child during treatment and for up to 12 months after the end of treatment and to use adequate contraceptive measures during this time.
• If you are pregnant or planning to become pregnant, it is very important that you talk to your doctor beforereceiving any treatment.
• If you become pregnant during treatment, you must tell your doctor immediately.

Breast-feeding

• Breast-feeding should be discontinued during treatment with Oxaliplatino Qilu.

Fertility in Men and Women

• Oxaliplatin may cause infertility, and this may be irreversible. Male patients should seek advice on sperm preservation before treatment.

After treatment with oxaliplatin, patients who wish to become pregnant are advised to seek genetic counseling.

Ask your doctor or pharmacist for advice before taking any medicine.

Driving and Using Machines

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

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

If you experience vision problems while being treated with Oxaliplatino Qilu, you should not drive, operate heavy machinery, or engage in hazardous activities.

3. How to Use Oxaliplatino Qilu

Oxaliplatino Qilu is only indicated in adults.

For single use.

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 your blood test results and whether you have previously experienced side effects with this medicine.

Form and Route of Administration

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

Frequency of Administration

Generally, you will receive an infusion every 2 weeks.

Duration of Treatment

Your doctor will determine the duration of treatment.

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

If you use more Oxaliplatino Qilu than you should

Since this medicine will be administered by a healthcare professional, it is unlikely that you will be given too much or too little medicine. In the event of an overdose, you may experience an increase in side effects. Your doctor may give you the appropriate treatment for these side effects.

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

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 very important that you inform your doctor before starting the next treatment.

The following effects that you may experience are described below.

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

• Symptoms of an allergic or anaphylactic reaction, accompanied by 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, difficult breathing, wheezing or breathing problems, extreme fatigue (you may feel like you are going to faint). These symptoms usually appear in most cases during perfusion or immediately after, 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 fever.
• Persistent or severe diarrhea or vomiting.
• Presence of blood or dark brown particles in the vomit.
• Stomatitis/mucositis (sores on the lips and ulcers in the mouth).
• Respiratory symptoms such as dry or productive cough, breathing difficulties or wheezing, shortness of breath and wheezing, as they could be indicators of a serious lung disease that could be fatal.
• A set of symptoms such as headache, altered mental activity, seizures and abnormal vision (from blurred vision to loss of vision) (symptoms of posterior reversible leukoencephalopathy syndrome, which is a rare neurological disorder).
• Symptoms of stroke (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, drooping face, difficulty walking, dizziness, loss of balance and difficulty speaking).
• Extreme fatigue, accompanied by a decrease in the number of red blood cells and shortness of breath (hemolytic anemia), alone or accompanied by a decrease in platelet count, abnormal bruising (thrombocytopenia) and kidney problems where you urinate little or nothing (symptoms of hemolytic uremic syndrome).

Other adverse effects of Oxaliplatino Qilu are:

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

• Tingling or numbness of the fingers of the hands and feet, around the mouth or throat, which are sometimes accompanied by cramps (peripheral neuropathy).

These adverse effects are usually triggered by exposure to cold, such as opening the refrigerator or holding a cold drink. You may also have difficulty performing fine tasks, such as buttoning your clothes. Although in most cases these symptoms resolve completely on their own, it is possible that the symptoms of peripheral sensory neuropathy may persist after finishing treatment. Some people have experienced a sudden tingling sensation in the arms or trunk when flexing the neck.

• An unpleasant sensation in the throat, specifically when swallowing, which can give the sensation of shortness of breath.
• This sensation, if it occurs, usually happens during perfusion or in the following hours 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 (feeling of dizziness) and vomiting (discomfort). However, your doctor will give you treatment to prevent this discomfort before starting treatment and it should be continued after treatment.
• Transient reduction in the number of blood cells.
• The decrease in red blood cells can cause anemia (decrease in the number of red blood cells), abnormal bleeding or bruising (due to the decrease in the number of platelets). The decrease in the number of white blood cells can 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 the blood.

• Feeling of discomfort around or at the injection site during perfusion.
• Fever, chills (shivering), mild or extreme fatigue, body pain.
• Weight changes, loss of appetite, taste alterations, constipation.
• Headache, back pain.
• Inflammation of the muscle nerves, stiffness of the neck, abnormal sensation in the tongue that can make speaking difficult, stomatitis/mucositis (sores on the lips and ulcers in the mouth).
• Stomach pain.
• Unusual bleeding, including nosebleeds.
• Cough, difficulty breathing.
• Allergic reactions, skin rash that can be red and itchy, moderate hair loss (alopecia).
• Alteration of blood tests, including changes in liver function.

Frequent(may affect up to 1 in 10 people)

• Infection due to a decrease in the number of white blood cells.
• Severe blood infection, in addition to a decrease in the number of white blood cells (neutropenic sepsis), which can be fatal.
• Decrease in the number of white blood cells, accompanied by fever >38.3°C or prolonged fever >38°C for more than one hour (febrile neutropenia).
• Indigestion and heartburn, hiccups, hot flashes, dizziness.
• Increased sweating and nail alterations, skin peeling.
• Chest pain.
• Pulmonary alterations and mucus.
• Joint pain and bone pain.
• Pain when urinating and alterations in kidney function, changes in urination frequency, dehydration.
• Blood in the urine/stool, vein inflammation, blood clots in the lung.
• High blood pressure.
• Depression and insomnia.
• Conjunctivitis and vision problems.
• Decrease in calcium levels in the blood.
• Falls.

Uncommon(may affect up to 1 in 100 people)

• Severe blood infection (sepsis) that can be fatal.
• Obstruction or inflammation of the intestine.
• Nervousness.

Rare(may affect up to 1 in 1,000 people)

• Hearing loss.
• Scarring and thickening of the lungs, accompanied by difficulty breathing, which can be fatal (interstitial lung disease).
• Reversible and temporary loss of vision.
• Unexpected bleeding or bruising due to the dissemination of blood clots in the small blood vessels of 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 particles in the vomit.
• Kidney problems that make you urinate very little or nothing (symptoms of acute renal failure).
• Vascular disorders of the liver.

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

• Allergic vasculitis (inflammation of the blood vessels).
• Autoimmune reaction that causes a decrease in all blood cell lines (autoimmune pancytopenia), pancytopenia.
• Severe blood infection or low blood pressure (septic shock), which can be fatal.
• Seizures (uncontrolled body agitation).
• Throat spasm that can cause difficulty breathing.
• There have been reports of extreme fatigue, accompanied by a decrease in the number of red blood cells and shortness of breath (hemolytic anemia), alone or accompanied by a decrease in platelet count, and kidney problems that make you urinate little or nothing (symptoms of hemolytic uremic syndrome), which can be fatal.
• Abnormal heart rhythm (prolonged QT interval), which can be observed in the electrocardiogram (ECG) and can be fatal.
• Myocardial infarction (heart attack), angina pectoris (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 vomit like "coffee grounds", dark/black stools with blood (symptoms of a gastrointestinal ulcer, with possible bleeding or perforation), which can be fatal.
• Decreased blood flow to the intestine (intestinal ischemia), which can be fatal.
• Risk of new cancers. Leukemia, a type 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.
• Abnormal liver nodules, non-cancerous (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 Oxaliplatino Qilu

Keep this medicine out of sight and reach of children.

Before mixing this medicine, it should be stored in its original packaging to protect it from light and should not be frozen.

Do not use this medicine after the expiration date that appears on the box and on the label of the vial 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 case of accidental spillage, immediately inform your doctor or nurse.

Once the perfusion has been completed, your doctor or nurse will dispose of this medicine with the necessary safety measures.

Medicines should not be thrown away through the sewers or in the trash. Ask your pharmacist how to dispose of the packaging and medicines that you no longer need. This way, you will help protect the environment.

6. Container Content and Additional Information

Composition of Oxaliplatin Qilu

The active ingredient of Oxaliplatin Qilu is oxaliplatin.

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

Each 10 ml vial contains 50 mg of oxaliplatin.

Each 20 ml vial contains 100 mg of oxaliplatin.

Each 40 ml vial contains 200 mg of oxaliplatin.

The other components are water for injectable preparations.

Appearance of the Product and Container Content

The vials of Oxaliplatin Qilu contain a concentrate for solution for infusion (a concentrated solution that is diluted to convert it into a solution that can be administered in the form of slow infusion through a dropper).

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 oxaliplatin.

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

Manufacturer

KYMOS, S.L.

Ronda de Can Fatjó,

7B (Parque Tecnológico del Vallès),

Cerdanyola del Vallès, 08290

Barcelona, Spain

This medicinal product is authorized in the Member States of the European Economic Areaand in the United Kingdom (Northern Ireland)with the following names:

Date of the Last Revision of this Prospectus:August 2024

Detailed and updated information on this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.es/

This information is intended only for healthcare professionals:

PREPARATION GUIDE FOR THE USE OF OXALIPLATIN Qilu 5 MG/ML CONCENTRATE FOR SOLUTION FOR INFUSION EFG

1. FORMULATION

Oxaliplatin Qilu 5 mg/ml concentrate for solution for infusion EFG is a clear and colorless liquid that contains 5 mg/ml of oxaliplatin in water for injectable preparations.

1. Presentation

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

The 10 ml vial of Oxaliplatin Qilu is made of transparent type I glass and contains 50 mg of oxaliplatin concentrate for solution for infusion, with a bromobutyl elastomer stopper.

The 20 ml vial of Oxaliplatin Qilu is made of transparent type I glass and contains 100 mg of oxaliplatin concentrate for solution for infusion, with a bromobutyl elastomer stopper.

The 40 ml vial of Oxaliplatin Qilu is made of transparent type I glass and contains 200 mg of oxaliplatin concentrate for solution for infusion, with a bromobutyl elastomer stopper.

Oxaliplatin Qilu packaged for sale:

This medicinal product should be stored in its original container to protect it from light and should not be frozen.

Solution for infusion:

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

From a microbiological point of view, the infusion preparation should be used immediately. If not used immediately, the time and conditions of storage 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 medicinal product is for single use. Any unused solution should be discarded.

1. RECOMMENDATIONS FOR SAFE HANDLING

As with other medicinal products containing potentially toxic compounds, extreme caution should be exercised during handling and preparation of solutions containing oxaliplatin.

Handling instructions

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

Preparation of injectable solutions of cytotoxic agents should be performed by specialized personnel qualified in this class of medicinal products, under conditions that guarantee the integrity of the product, environmental protection, and, in particular, the protection of personnel handling the medicinal products, in accordance with hospital regulations. A dedicated preparation area is required. Smoking, eating, or drinking is prohibited in this area.

Personnel should be equipped with appropriate materials for handling the medicinal product, such as sleeves, protective mask, cap, protective glasses, sterile disposable gloves, protective suit for the work area, containers, and waste collection 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 properly labeled rigid containers. See the Eliminationsection.

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

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

1. PREPARATION FOR INTRAVENOUS ADMINISTRATION

Special Administration Precautions

• DO NOT use injection material that contains aluminum.
• DO NOT administer undiluted.
• ONLY use a 5% glucose solution (50 mg/ml) as a diluent.

DO NOT dilute with infusion solutions that contain sodium chloride or chloride.

• DO NOT mix with other medicinal products in the same infusion bag or administer simultaneously in the same infusion line.
• DO NOT mix with alkaline solutions or medicinal products, in particular, 5-fluorouracil preparations or folinic acid that contain tromethamine as an excipient and tromethamine salts of other medicinal products. Alkaline solutions or medicinal products will negatively affect the stability of oxaliplatin.

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

The intravenous infusion of 85 mg/m2 of oxaliplatin in 250-500 ml of 5% glucose solution (50 mg/ml) is administered simultaneously with folinic acid diluted in a 5% glucose solution (50 mg/ml) over 2-6 hours, using a Y-line placed just before the injection point. These two medicinal products should not be combined in the same infusion bag. Folinic acid should not contain tromethamine 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 those containing chloride.

Instructions for Use with 5-Fluorouracil

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

See the detailed information on the administration of combined medicinal products in the corresponding summary of product characteristics.

• USE ONLY the recommended solvents (see below).

• Only use solutions that are transparent and do not contain particles in suspension.

1. Preparation of the Solution for Infusion

Extract the necessary volume of concentrate from the vials and then dilute with 250-500 ml of a 5% glucose solution (50 mg/ml) to administer an oxaliplatin concentration 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 0.2-2.0 mg/ml.

Administer by intravenous infusion.

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

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

If not used immediately, the time and conditions of storage 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 medicinal product is for single use. Any unused infusion solution should be discarded (see the Eliminationsection).

NEVER use sodium chloride or solutions containing chloride in the dilution.

The compatibility of the oxaliplatin infusion solution has been verified with administration equipment with PVC components.

1. Infusion of the Solution

Administration of oxaliplatin does not require prehydration.

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

1. Elimination

Elimination of unused medicinal product 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 compliance with local legal requirements for the elimination of hazardous waste.