OXALIPLATIN ACCORD 5 mg/ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

Oxaliplatino Accord 5 mg/ml concentrate for solution for infusion EFG

Read all of this leaflet carefully before you start using this medicine.

• 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, even if they are not listed in this leaflet. See section 4.

Contents of the pack:

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

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

Oxaliplatino Accord contains the active substance oxaliplatin.

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

Oxaliplatin must be dissolved in a solution before it can be injected into a vein.

Oxaliplatin is an anticancer or antitumor medication and contains platinum.

2. What you need to know before you use Oxaliplatino Accord

Do not use Oxaliplatino Accord

• if you are allergic to oxaliplatin or any of the other ingredients of Oxaliplatino Accord.
• if you are breastfeeding.
• if you already have a reduced blood cell count.
• if you already have a sensation of tingling or numbness in your fingers or toes 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 pharmacist before starting Oxaliplatino Accord

• if you have ever had an allergic reaction to platinum-containing medications, such as carboplatin or cisplatin. Allergic reactions can occur during the infusion of any platinum medication.

• if you have moderate or mild kidney problems.
• if you have any liver problems or abnormal liver function tests during treatment.
• If you have or have had cardiac disorders such as an abnormal electrical signal called QT interval prolongation, an irregular heartbeat, or a family history of heart problems.
• If you have been or are scheduled to be vaccinated. During treatment with oxaliplatin, you should not be vaccinated with live or attenuated live vaccines, such as the yellow fever vaccine.

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

• If you have an unpleasant sensation in your throat, particularly when swallowing, and have a feeling of shortness of breath during treatment.
• If you have nerve problems in your hands or feet, such as tingling and numbness, or decreased sensations in your hands or feet.
• If you have a headache, altered mental function, seizures, and abnormal vision, from blurred vision to loss of vision.
• If you do not feel well (nausea and vomiting).
• If you have severe diarrhea.
• If you have lip pain or mouth ulcers (mucositis/stomatitis).
• If you have diarrhea or a decrease in white blood cells or platelets. Your doctor may need to reduce the dose of Oxaliplatino Accord or postpone your treatment with Oxaliplatino Accord.
• If you have unexplained respiratory symptoms such as cough, or difficulty breathing. Your doctor may stop your treatment with Oxaliplatino Accord.
• If you develop extreme fatigue, shortness of breath, or kidney problems, which cause you to urinate very little or not at all (symptoms of acute renal failure).
• If you have a fever (temperature greater than or equal to 38°C), or chills, which can be signs of infection. You may be at risk of developing a blood infection.
• If you have a fever > 38°C. Your doctor may determine if you also have a decrease in white blood cells.
• If you unexpectedly experience bleeding or bruising (disseminated intravascular coagulation). These can be signs of blood clots throughout the small blood vessels of your body.
• If you feel dizzy (loss of consciousness) or have an irregular heartbeat while taking Oxaliplatino Accord. This can be a sign of a serious heart disorder.
• If you develop muscle pain and swelling, along with weakness, fever, and brownish-red urine. These could be signs of muscle damage (rhabdomyolysis) and could lead to kidney problems or other complications.
• If you have abdominal pain, nausea, vomiting with blood, or vomiting like coffee grounds, dark stools, which can be signs of a gastrointestinal ulcer (gastrointestinal ulcer with potential bleeding or perforation).
• If you have abdominal pain (at the navel level), bloody diarrhea, nausea, and/or vomiting, which can be caused by a decrease in blood flow to the walls of your intestine (intestinal ischemia).

Children and adolescents

Oxaliplatino Accord should not be used in children and adolescents under 18 years of age.

Use of other medications

Tell your doctor or pharmacist if you are using or have recently used any other medications, including those obtained without a prescription.

• 5-fluorouracil (cancer medication)
• Erythromycin (an antibiotic)
• Salicylates (pain-relieving medications)
• Granisetron (a medication to prevent vomiting)
• Paclitaxel (a cancer medication)
• Sodium valproate (a medication for epilepsy)

Pregnancy, breastfeeding, and fertility

Pregnancy

• You are advised not to become pregnant during treatment with oxaliplatin and must use an effective contraceptive method. Female patients must adopt adequate contraceptive measures during treatment and continue them for 4 months after the end of treatment.
• If you are pregnant or planning to become pregnant, it is very important that you talk to your doctor before receiving any treatment.
• If you become pregnant during treatment, you must inform your doctor immediately.

Breastfeeding

• You must not breastfeed your child while being treated with oxaliplatin.

Fertility

• Oxaliplatin may have an anti-fertility effect that can be irreversible. Male patients should seek advice regarding sperm preservation before treatment.
• Male patients are advised not to father children during treatment and up to 6 months after the end of treatment and must take appropriate contraceptive measures during this period.

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

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 happens to you, do not drive or operate machinery. If you experience vision problems while receiving Oxaliplatino Accord, do not drive, use heavy machinery, or engage in hazardous activities.

3. How to use Oxaliplatino Accord

Oxaliplatin is for adults only.

For single use.

Posology

The dose of oxaliplatin is based on body surface area. It 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 the results of your blood tests and whether you have previously experienced side effects with oxaliplatin.

Method and route of administration

• Oxaliplatin will be prescribed by a specialist in cancer treatment.
• You will be treated by a healthcare professional who will have prepared the necessary dose of oxaliplatin.
• Oxaliplatin is administered by slow injection into a vein (intravenous infusion) over a period of 2 to 6 hours.

Oxaliplatin will be administered at the same time as folinic acid and before the infusion of 5-fluorouracil.

Frequency of administration

You will normally receive the infusion every two 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 Accord than you should

Since this medication will be administered by a healthcare professional, it is very unlikely that you will receive too much or too little.

In case of overdose, you may experience more side effects. Your doctor will provide you with the appropriate treatment for these side effects.

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

4. Possible side effects

Like all medications, this medication can cause side effects, although not everyone gets them.

If you experience any side effects, it is important that you inform your doctor about them before the next treatment.

The following side effects may be experienced.

Tell your doctor immediately if younotice any of the following:

• Allergic or anaphylactic reaction with sudden signs such as rash, itching, or hives on the skin, difficulty swallowing, swelling of the face, lips, tongue, or other parts of the body, difficulty breathing, wheezing, or shortness of breath, extreme fatigue (you may feel like you are going to faint).
• Abnormal bruising, bleeding, or signs of infection such as sore throat and high fever.
• Persistent or severe diarrhea or vomiting.
• Presence of blood or dark brown particles in the vomit.
• Stomatitis/mucositis (sore lips or mouth ulcers).
• Respiratory symptoms such as dry or wet cough, difficulty breathing, or wheezing.
• A group of symptoms with or without high blood pressure.
• Symptoms of stroke (such as sudden severe headache, confusion, vision problems in one or both eyes, numbness or weakness of the face, arm, or leg, usually on one side, drooping face, difficulty walking, dizziness, loss of balance, and difficulty speaking).
• Extreme fatigue with a decrease in the number of red blood cells (hemolytic anemia), alone or in combination with a low platelet count, abnormal bruising (thrombocytopenia), and kidney disease in which you urinate very little or not at all (symptoms of hemolytic-uremic syndrome).

Other known side effects of Oxaliplatino Accord are:

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

• Tingling or numbness in the fingers of the hand or foot, around the mouth, or in the throat, which may be accompanied by cramps.
• Feeling of discomfort near or at the injection site during the infusion.
• Fever, chills (shivering), mild or severe fatigue, body aches.
• Weight changes, loss of appetite, taste disturbances, constipation.

• Stomach pain.
• Abnormal bleeding, with nosebleeds.
• Mild hair loss (alopecia).

Common(may affect up to 1 in 10 people)

• Infection due to a decrease in white blood cells.
• Severe blood infection, in addition to a decrease in white blood cells (neutropenic sepsis), which can be fatal.
• Decrease in white blood cells accompanied by fever > 38.3°C or prolonged fever > 38°C for more than one hour (febrile neutropenia).
• Indigestion and heartburn, belching, flushing, dizziness.
• Increased sweating and nail changes, skin peeling.
• Chest pain.
• Lung disorders and nasal congestion.
• Pain in the joints and bones.
• Pain when urinating and changes in kidney function, changes in urination frequency, dehydration.
• Blood in the urine/stool, vein inflammation.
• Increased blood pressure.
• Depression and insomnia.
• Conjunctivitis and vision problems.
• Decreased calcium levels in the blood.
• Falling.

Uncommon(may affect up to 1 in 100 people)

• Severe blood infection (septicemia), which 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 with breathing difficulties, sometimes fatal (interstitial lung disease).
• Reversible short-term vision loss.
• Unexpected bleeding or bruising due to blood clots throughout 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)

• Vascular disorders of the liver (symptoms include abdominal pain and swelling, weight gain, and swelling of the feet, ankles, or other parts of the body).

Not known(cannot be estimated from the available data)

• Allergic vasculitis (inflammation of the blood vessels).
• Autoimmune reaction leading to a decrease in all blood cell lines (autoimmune pancytopenia), pancytopenia.
• Seizures (uncontrolled body agitation).
• Throat spasm causing difficulty breathing.
• Abnormal heart rhythm (QT prolongation), which can be seen on an electrocardiogram (ECG), and can be fatal.
• Muscle pain and swelling, along with weakness, fever, or brownish-red urine (symptoms of muscle damage called rhabdomyolysis), which can be fatal.
• Dark or tarry stools (symptoms of gastrointestinal ulcer, with possible bleeding or perforation), which can be fatal.
• Decreased blood flow to the intestine/intestine (intestinal ischemia), which can be fatal.
• Myocardial infarction (heart attack), angina pectoris (chest pain or discomfort).
• Esophageal inflammation (inflammation of the esophagus, the tube that connects your mouth to your stomach, leading to pain and difficulty swallowing).
• Risk of new cancers such as leukemia, when taken in combination with certain other medications.
• Abnormal non-cancerous liver nodules (focal nodular hyperplasia).

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. You can also report side effects directly through the Spanish Medicines Monitoring System for Human Use: https://www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medication.

5. Storage of Oxaliplatino Accord

Keep out of the sight and reach of children.

Keep the vial in the outer packaging to protect it from light. Do not freeze.

Do not use this medication after the expiration date stated on the packaging after CAD. The expiration date is the last day of the month indicated.

Chemical and physical stability has been demonstrated for 48 hours between 2°C and 8°C and for 24 hours at 25°C. From a microbiological point of view, this preparation for infusion should be used immediately. If not used immediately, the conditions and times of storage before use are the responsibility of the user and normally should not exceed 24 hours between 2°C and 8°C, unless the dilution has taken place under controlled and validated aseptic conditions.

Do not use this medication if you notice that the solution is not transparent and particle-free.

Medications should not be disposed of through wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any unused medication. This will help protect the environment.

Oxaliplatino Accord should not come into contact with the eyes or skin. If accidental spillage occurs, inform your doctor or nurse immediately.

When the infusion is finished, your doctor or nurse will carefully dispose of Oxaliplatino Accord.

6. Container Contents and Additional Information

Composition of Oxaliplatin Accord

The active ingredient is oxaliplatin.

The other ingredients are water for injectable preparations.

Appearance of the Product and Container Contents

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

Oxaliplatin Accord is a colorless and transparent solution without visible particles.

Each glass vial contains 50 mg, 100 mg, or 200 mg of oxaliplatin and is packaged in an individual box.

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

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

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

Only some package sizes may be marketed.

Marketing Authorization Holder

Accord Healthcare S.L.U.

World Trade Center

Moll de Barcelona, s/n

Edifici Est, 6ª planta

08039 Barcelona

Spain

Manufacturer

Accord Healthcare Polska Sp.z o.o.,

ul. Lutomierska 50,95-200

Pabianice,

Poland

or

Accord Healthcare B.V.,

Winthontlaan 200,

3526 KV Utrecht,

Netherlands

or

Accord Healthcare Single Member S.A.

64th Km National Road Athens,

Lamia, 32009,

Greece

This medicinal product is authorized in the Member States of the European Economic Area under the following names

Date of Last Revision of this Leaflet:March 2024

This information is intended solely for healthcare professionals.

PREPARATION GUIDE FOR THE USE OF OXALIPLATIN ACCORD 5 mg/ml CONCENTRATE FOR SOLUTION FOR INFUSION

It is essential to read the entire content of this procedure before preparing OXALIPLATIN ACCORD 5 mg/ml CONCENTRATE FOR SOLUTION FOR INFUSION

1. FORMULATION

Oxaliplatin Accord 5 mg/ml concentrate for solution for infusion is a colorless and transparent solution containing 5 mg/ml of oxaliplatin.

1. Presentation

It is presented in single-dose vials. 1 vial per box.

For 10 ml,

The concentrate for solution for infusion is packaged in a 10 ml capacity transparent type 1 tubular glass vial with a 20 mm chlorobutyl rubber stopper and a 20 mm lavender-colored aluminum flip-off seal.

For 20 ml,

The concentrate for solution for infusion is packaged in a 20 ml capacity transparent type 1 molded glass vial with a 20 mm chlorobutyl rubber stopper and a 20 mm lavender-colored aluminum flip-off seal.

For 40 ml,

The concentrate for solution for infusion is packaged in a 50 ml capacity transparent type 1 molded glass vial with either a 20 mm chlorobutyl rubber stopper or a siliconized rubber stopper with a Teflon coating on the contact surface and a 20 mm lavender-colored aluminum flip-off seal.

Expiry date and storage:

Two years.

After dilution of the solution in 5% glucose, chemical and physical stability has been demonstrated for up to 48 hours between 2°C and 8°C and for 24 hours at 25°C.

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

If not used immediately, the conditions and storage times before use are the responsibility of the user and would normally not exceed 24 hours between 2°C and 8°C unless the dilution has taken place under controlled and validated aseptic conditions.

Store the vial in the outer packaging to protect it from light. Do not freeze.

Inspect visually before use. Only particle-free transparent solutions should be used.

This medicinal product is for single use only. Any unused solution should be discarded.

1. RECOMMENDATIONS FOR SAFE HANDLING

As with other potentially toxic compounds, caution should be exercised when handling and preparing oxaliplatin solutions.

Handling instructions

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

Preparation of injectable cytotoxic solutions should be performed by trained specialist personnel who are familiar with the medications used, under conditions that guarantee the integrity of the medication, environmental protection, and especially the protection of personnel handling the medications, in accordance with hospital policy. This requires a dedicated preparation area. Eating, drinking, and smoking are prohibited in this area.

Appropriate handling materials should be provided to personnel, especially long-sleeved gowns, protective masks, caps, protective glasses, sterile disposable gloves, protective covers for the work area, containers, and bags for waste collection.

Excreta and vomit should be handled with care.

Pregnant women should be advised to avoid handling cytotoxic products.

Broken containers should be treated with the same precautions and considered as contaminated waste. Contaminated waste should be incinerated in properly labeled rigid containers. See the "Elimination" section below.

If Oxaliplatin Accord 5 mg/ml concentrate for solution for infusion comes into contact with the skin, wash immediately and thoroughly with water.

If Oxaliplatin Accord 5 mg/ml concentrate for solution for infusion comes into contact with the mucous membranes, wash immediately and thoroughly with water.

1. PREPARATION FOR INTRAVENOUS ADMINISTRATION

Special Administration Precautions

• DO NOT use injection equipment containing aluminum.
• DO NOT administer undiluted.

• ONLY 5% glucose solution should be used as a diluent. DO NOT dilute the infusion with solutions containing sodium chloride or chlorine.

• DO NOT mix with any other medicinal product in the same infusion bag or administer simultaneously through the same infusion line.

• DO NOT mix with alkaline drugs or solutions, especially 5-fluorouracil, folinic acid preparations containing tromethamine as an excipient, and tromethamine salts of other active substances. Alkaline drugs or solutions will negatively affect the stability of oxaliplatin.

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

Oxaliplatin 85 mg/m² in i.v. infusion in 250 to 500 ml of 5% glucose solution is administered simultaneously with the i.v. infusion of folinic acid in 5% glucose solution, over 2 to 6 hours, using a Y-line placed immediately before the infusion point.

These two medicinal products should not be mixed in the same infusion bag. Folinic acid should not contain tromethamine as an excipient and should only be diluted using an isotonic 5% glucose solution, never in alkaline solutions or solutions containing sodium chloride or chlorine.

Instructions for Use with 5-Fluorouracil

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

After administration of oxaliplatin, the line should be flushed and then 5-fluorouracil should be administered.

For more information on the medicinal product combined with oxaliplatin, see the corresponding summary of product characteristics of the manufacturer.

• USE ONLY the recommended solvents (see below).
• Only particle-free transparent solutions should be used.

4.1Preparation of the Infusion Solution

The required amount of concentrate solution is withdrawn from the vial(s) and diluted with 250 ml to 500 ml of a 5% glucose solution to obtain an oxaliplatin concentration between no less than 0.2 mg/ml and 0.7 mg/ml. The concentration interval for which physical-chemical stability has been demonstrated is 0.2 mg/ml to 2.0 mg/ml.

Administer by intravenous infusion.

After dilution in 5% glucose, chemical and physical stability has been demonstrated for up to 48 hours between 2°C and 8°C and for 24 hours at 25°C.

From a microbiological point of view, this infusion preparation should be used immediately.

If not used immediately, the conditions and storage times before use are the responsibility of the user and would normally not exceed 24 hours between 2°C and 8°C unless the dilution has taken place under controlled and validated aseptic conditions.

Inspect visually before use. Only particle-free transparent solutions should be used.

This medicinal product is for single use only. Any unused infusion solution should be discarded (see the "Elimination" section below).

NEVERuse solutions containing sodium chloride or chlorine for dilution.

The compatibility of the oxaliplatin infusion solution with representative PVC administration equipment has been studied.

4.2Infusion of the Solution

Administration of oxaliplatin does not require prior hydration.

Oxaliplatin diluted in 250 to 500 ml of 5% glucose solution to obtain a concentration of no less than 0.2 mg/ml should be administered by infusion in a peripheral vein or a central venous access over 2 to 6 hours. When oxaliplatin is administered with 5-fluorouracil, the oxaliplatin infusion should precede the administration of 5-fluorouracil.

4.3Elimination

Medicinal product residues as well as all materials used for dilution and administration should be destroyed according to the standard hospital procedures applicable to cytotoxics, in accordance with local requirements for the disposal of hazardous waste.