OXALIPLATIN KALCEKS 5 mg/ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

Oxaliplatin Kalceks 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 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 or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What Oxaliplatin Kalceks is and what it is used for
2. What you need to know before you are given Oxaliplatin Kalceks
3. How Oxaliplatin Kalceks will be given to you
4. Possible side effects
5. Storage of Oxaliplatin Kalceks
6. Contents of the pack and other information

1. What Oxaliplatin Kalceks is and what it is used for

The active substance in Oxaliplatin Kalceks is oxaliplatin.

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

Oxaliplatin Kalceks is an anti-cancer medicine that contains platinum.

2. What you need to know before you are given Oxaliplatin Kalceks

Oxaliplatin Kalceks must not be given to you:

• 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 hands and/or feet and have difficulty performing delicate tasks, such as buttoning your clothes.
• If you have severe kidney problems.

Warnings and precautions

Talk to your doctor or nurse beforeyou start receiving Oxaliplatin Kalceks:

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

Children and adolescents

Oxaliplatin must not be used in children and adolescents under 18 years.

Other medicines and Oxaliplatin Kalceks

Tell your doctor 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 for advice before receiving this medicine.

• Pregnancy should be avoided during treatment with oxaliplatin and effective contraception must be used. Women must use adequate contraceptive measures during treatment and for up to 9 months after the end of treatment.
• If you are pregnant or planning to become pregnant, it is very important that you discuss this with your doctor beforereceiving any treatment.
• If you become pregnant during treatment, you must inform your doctor immediately.

Breast-feeding

You must notbreast-feed while being treated with oxaliplatin.

Fertility

• Oxaliplatin may affect fertility irreversibly. Male patients should seek advice on sperm conservation before treatment.
• Male patients are advised not to father a child during and for up to 6 months after treatment and to take appropriate contraceptive measures during this time.

Driving and using machines

Treatment with oxaliplatin may increase the risk of dizziness, nausea, and vomiting, as well as other neurological symptoms that can affect walking and balance. If you are affected by any of these symptoms, you should not drive or operate machinery. If you have vision problems while being treated with oxaliplatin, you should not drive, operate heavy machinery, or engage in hazardous activities.

3. How Oxaliplatin Kalceks will be given to you

For intravenous infusion.

Oxaliplatin is only indicated in adults.

Oxaliplatin concentrate for solution for infusion will be administered by a healthcare professional. The medicine must be dissolved and made into a solution before it can be injected into a vein.

Dose

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

The usual dose for 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.

Method and route of administration

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

Frequency of administration

Usually, you will receive an infusion every 2 weeks.

Duration of treatment

Your doctor will decide the duration of your treatment.

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

If you are given too much Oxaliplatin Kalceks

This medicine will be administered by a healthcare professional, so 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 or nurse.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, telephone 91 562 04 20.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

If you experience any side effects, it is important that you tell your doctor before starting the next treatment.

The following effects may be experienced:

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

• Symptoms of an allergic reaction or anaphylaxis, with sudden signs such as rash, itching, or hives, difficulty swallowing, swelling of the face, lips, tongue, or other parts of the body, shortness of breath, wheezing, or breathing problems, extreme tiredness (may feel like you are going to faint). In most cases, these symptoms occurred during the infusion or immediately after, but delayed allergic reactions have also been observed hours or even days after the infusion.
• Unusual bruising, bleeding, or signs of infection, such as sore throat and fever (due to a reduction in platelets or white blood cells).
• Persistent or severe diarrhea or vomiting.
• Blood or dark brown particles in your vomit.
• Stomatitis/mucositis (sores on the lips and ulcers in the mouth).
• Unexplained respiratory symptoms such as dry cough, difficulty breathing.
• A group of symptoms such as headache, altered mental status, 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 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 tiredness, accompanied by a decrease in the number of red blood cells and shortness of breath (hemolytic anemia), alone or accompanied by a decrease in platelets and kidney problems that cause little or no urine production (symptoms of hemolytic uremic syndrome), which can be fatal.

Other side effects of oxaliplatin are:

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

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

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

• Oxaliplatin may cause diarrhea, mild nausea (feeling sick), and vomiting. However, your doctor will usually give you treatment to prevent this discomfort before starting treatment and will continue it after treatment.

• Oxaliplatin causes a temporary reduction in the number of blood cells. A decrease in red blood cells can cause anemia (decrease in the number of red blood cells), abnormal bleeding, or bruising (due to a decrease in the number of platelets). A decrease in the number of white blood cells can make it easier to get 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 near or at the injection site during the infusion.
• Fever, chills, mild or extreme fatigue, body aches.
• Weight changes, loss of appetite, taste changes, constipation.
• Headache, back pain.
• Inflammation of the nerve muscles, 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 may be red and itchy, moderate hair loss (alopecia).
• Abnormal blood test results, including changes in liver function.

Common(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 (septic neutropenia), 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).
• Blood or dark brown particles in your vomit.
• Indigestion and heartburn, hiccups, belching.
• Increased sweating and nail changes, skin peeling.
• Chest pain.
• Lung changes and coughing.
• Joint pain and bone pain.
• Pain when urinating and changes in kidney function, changes in the frequency of urination, dehydration.
• Blood in the urine/stool, inflammation of the veins, blood clots in the lungs.
• 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 people)

• Severe blood infection (sepsis) that can be fatal.
• Decrease in blood pH (metabolic acidosis).
• Hearing difficulties, vertigo, ringing in the ears.
• 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, with difficulty breathing, which can be fatal (interstitial lung disease).
• Reversible and temporary loss of vision.
• Unusual bleeding or bruising due to the spread 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)

• Kidney problems that cause little or no urine production (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 reduction in all blood cell lines (autoimmune pancytopenia), pancytopenia.
• Severe blood infection and low blood pressure (septic shock), which can be fatal.
• Seizures (uncontrolled body movements).
• Throat spasm that can cause difficulty breathing.
• Pneumonia (severe lung infection), which can be fatal.
• Reports of extreme tiredness, accompanied by a decrease in the number of red blood cells and shortness of breath (hemolytic anemia), alone or accompanied by a decrease in platelets, and kidney problems that cause little or no urine production (symptoms of hemolytic uremic syndrome), which can be fatal.
• Abnormal heart rhythm (prolongation of the QT interval), which can be seen on an electrocardiogram (ECG) and can be fatal.
• Heart attack (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 lining of the esophagus - the tube that connects the mouth to the stomach - which can cause pain and difficulty swallowing).
• Abdominal pain, nausea, vomiting with blood or vomiting like "coffee grounds", black/tarry stools (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 medicines. Ask your doctor about the potential increased risk of this type of cancer when using oxaliplatin with certain medicines.
• Abnormal liver nodules, non-cancerous (focal nodular hyperplasia).

Reporting of side effects

If you experience any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Oxaliplatino Kalceks

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

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

This medicine does not require any special storage conditions.

Shelf-life after dilution

Chemical and physical stability has been demonstrated for 24 hours at 25 °C and 4 days at 2-8 °C when diluted with glucose 50 mg/ml (5%) solution in concentrations between 0.2 mg/ml and 2 mg/ml.

From a microbiological point of view, the diluted solution should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user and would normally not be longer than 24 hours at 2-8 °C, unless dilution has been made in controlled and validated aseptic conditions.

Oxaliplatino should not come into contact with the eyes or skin. In case of accidental spillage, inform your doctor or nurse immediately.

After completion of the infusion, the doctor or nurse will dispose of this medicine with the necessary safety measures.

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

6. Package Contents and Additional Information

Composition of Oxaliplatino Kalceks

• The active substance is oxaliplatino.

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

Each 10 ml vial of concentrate contains 50 mg of oxaliplatino.

Each 20 ml vial of concentrate contains 100 mg of oxaliplatino.

Each 40 ml vial of concentrate contains 200 mg of oxaliplatino.

• The other ingredients (excipients) are water for injections.

Appearance and Package Contents of the Product

This medicine is a concentrate for solution for infusion (sterile concentrate). It is a clear, colorless solution, practically free from visible particles.

Colorless glass vial with 10 ml, 20 ml or 40 ml of solution, sealed with a rubber stopper and aluminum flip-off cap. The vials are packaged in cardboard boxes.

Package sizes: 1 vial of 10 ml, 20 ml or 40 ml

Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

AS KALCEKS

Krustpils iela 71E, Riga, LV-1057, Latvia

Tel.: +371 67083320

E-mail: kalceks@kalceks.lv

You can request more information about this medicine from the local representative of the Marketing Authorization Holder

Grindeks Kalceks España, S.L.

c/ José Abascal, 58 2º dcha

28003 Madrid

Spain

This medicine is authorized in the Member States of the European Economic Area under the following names:

Latvia Oxaliplatin Kalceks 5 mg/ml koncentrats infuziju šķiduma pagatavošanai

Czech Republic, Norway, Poland Oxaliplatin Kalceks

Belgium Oxaliplatin Kalceks 5 mg/ml concentraat voor oplossing voor infusie

Oxaliplatin Kalceks 5 mg/ml solution à diluer pour perfusion

Oxaliplatin Kalceks 5 mg/ml Konzentrat zur Herstellung einer Infusionslösung

Croatia Oksaliplatin Kalceks 5 mg/ml koncentrat za otopinu za infuziju

France OXALIPLATINE KALCEKS 5 mg/mL, solution à diluer pour perfusion

Germany Oxaliplatin Kalceks 5 mg/ml Konzentrat zur Herstellung einer Infusionslösung

Spain Oxaliplatino Kalceks 5 mg/ml concentrado para solución para perfusión EFG

Date of last revision of this leaflet: 12/2023

Other sources of information

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

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This information is intended only for healthcare professionals:

SPECIAL PRECAUTIONS FOR DISPOSAL AND OTHER HANDLING

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

Handling instructions

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

Preparation of injectable solutions of cytotoxic agents should be performed by specialized personnel with knowledge of the medications used, under conditions that ensure the integrity of the drug, environmental protection, and, in particular, protection of the personnel handling the drugs, in accordance with hospital policy. 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 medication, 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 rigid containers properly labeled (see the "Disposal" section below).

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

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

Special precautions for administration

• DO NOT use injection equipment containing aluminum.
• DO NOT administer undiluted.
• ONLY use the recommended diluent (50 mg/ml (5%) glucose solution for infusion). DO NOT dilute with solutions for infusion containing sodium chloride or chloride.
• DO NOT mix with other medications in the same infusion bag or administer simultaneously in the same infusion line.
• DO NOT mix with alkaline solutions or medications, in particular, 5-fluorouracil preparations or folinic acid preparations containing tromethamine as an excipient and tromethamine salts of other medications. Alkaline solutions or medications will negatively affect the stability of oxaliplatino.

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

Intravenous infusion of 85 mg/m2 of oxaliplatino in 250-500 ml of glucose 50 mg/ml (5%) solution is administered simultaneously with folinic acid diluted in a glucose 50 mg/ml (5%) solution over 2-6 hours, using a Y-line placed just before the infusion point. These two medications 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 glucose 50 mg/ml (5%) solution, never in alkaline solutions or sodium chloride solutions or those containing chloride.

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

Oxaliplatino should always be administered before fluoropyrimidines, i.e., 5-fluorouracil.

After administration of oxaliplatino, flush the line and then administer 5-fluorouracil.

See the detailed information on the administration of concomitant medications in the corresponding summary of product characteristics.

Concentrate for solution for infusion

Inspect the medicine visually before use. Only clear solutions without particles should be used.

Any concentrate showing signs of precipitation should not be used and should be destroyed in accordance with legal requirements for the disposal of hazardous waste (see the "Disposal" section below).

For single use only. Any unused concentrate should be discarded (see the "Disposal" section below).

Dilution for intravenous infusion

USE ONLY the recommended diluent (50 mg/ml (5%) glucose solution for infusion).

Withdraw the required volume of concentrate from the vials and then dilute with 250-500 ml of glucose 50 mg/ml (5%) solution to obtain an oxaliplatino concentration between 0.2 mg/ml and 0.7 mg/ml. The concentration range in which the physical-chemical stability of oxaliplatino has been demonstrated is 0.2-2.0 mg/ml.

Administer by intravenous infusion.

Chemical and physical stability has been demonstrated for 24 hours at 25 °C and 4 days at 2-8 °C when diluted with glucose 50 mg/ml (5%) solution in concentrations between 0.2 mg/ml and 2 mg/ml.

From a microbiological point of view, the diluted solution should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user and would normally not be longer than 24 hours at 2-8 °C, unless dilution has been made in controlled and validated aseptic conditions.

NEVER use sodium chloride or solutions containing chloride for dilution.

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

Inspect the diluted solution visually before use. Only clear solutions without particles should be used. Any unused infusion solution should be discarded (see the "Disposal" section below).

Infusion

Administration of oxaliplatino does not require prehydration.

Oxaliplatino diluted in 250-500 ml of glucose 50 mg/ml (5%) solution to obtain a concentration of at least 0.2 mg/ml should be infused through a central or peripheral venous line over 2-6 hours.

When oxaliplatino is administered with 5-fluorouracil, the infusion of oxaliplatino should precede that of 5-fluorouracil.

Disposal

Disposal of unused medicinal products and all materials that have come into contact with them during dilution and administration should be carried out in accordance with local regulations on cytotoxic agents, in compliance with local legal requirements for the disposal of hazardous waste.