OXALIPLATIN AUROVIT 5 mg/ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

Oxaliplatin Aurovit 5 mg/ml concentrate for solution for infusion EFG

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• 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 get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

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

Oxaliplatin Aurovit contains the active substance oxaliplatin, which belongs to a group of medicines called platinum-based medicines, used to treat cancer.

Oxaliplatin is used to treat advanced colorectal cancer (especially after complete resection of the primary tumor, metastatic cancer (cancer cells that have spread to other parts of the body) of the colon and rectum). Oxaliplatin is used in combination with other anticancer medicines called 5-fluorouracil and folinic acid.

2. What you need to know before you use Oxaliplatin Aurovit

Do not useOxaliplatin Aurovit if

• you are allergic to oxaliplatin.
• you are breast-feeding.
• you already have a low number of blood cells.
• you already have tingling and numbness in your fingers and/or toes and have difficulty performing delicate tasks, such as buttoning your clothes.
• you have severe kidney problems.

Warnings and precautions

Tell your doctor or pharmacist before starting oxaliplatin:

• If you have ever had an allergic reaction to platinum-containing medicines, such as carboplatin or cisplatin. Allergic reactions may occur during any oxaliplatin infusion.
• If you have mild or moderate kidney problems.
• If you have low blood counts after previous treatment with oxaliplatin. Your doctor will need to perform tests to check if you have enough blood cells before starting treatment.
• If you have symptoms of nerve damage, such as weakness, numbness, altered taste, or abnormal sensations after previous treatment with oxaliplatin. These symptoms may be caused by a cold. Tell your doctor if you notice any of these symptoms, especially if they are uncomfortable and/or last more than 7 days. Your doctor will perform neurological examinations before and during treatment, especially if you are receiving other medicines that may cause nerve damage. Symptoms of nerve damage may persist after treatment is completed.
• If you are also receiving 5-fluorouracil, due to the increased risk of diarrhea, vomiting, mouth ulcers, and abnormal blood parameters.
• If you have liver problems.
• If you have or have had heart problems, such as an abnormal electrical signal called QT interval prolongation, an irregular heartbeat, or a family history of heart problems.
• If you have recently received or plan to receive any vaccine. During treatment with oxaliplatin, you should not be vaccinated with live or attenuated vaccines, such as the yellow fever vaccine.
• If you are pregnant or plan to become pregnant (see Pregnancy, breast-feeding, and fertility).
• Read the section on fertility even if you are a man.

Other medicines and Oxaliplatin Aurovit

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

Pregnancy, breast-feeding, and fertility

Pregnancy

• It is not recommended to become pregnant during treatment with oxaliplatin and you must use an effective contraceptive method. Patients must take adequate contraceptive measures during treatment and up to 4 months after its completion.
• If you are pregnant or plan to become pregnant, it is very important that you discuss this with your doctor before receiving any treatment.
• If you become pregnant during treatment, you must inform your doctor immediately.

Breast-feeding

• You must not breast-feed while being treated with oxaliplatin.

Fertility

• Oxaliplatin may cause infertility, which could be irreversible. Male patients should seek advice on sperm preservation before treatment.
• Male patients are advised not to father a child during treatment and up to 6 months after treatment, and to take appropriate contraceptive measures during this time.

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

Driving and using machines

Treatment with oxaliplatin may increase the risk of dizziness, nausea, and vomiting, and other neurological symptoms that may affect walking and balance. If this happens, you should not drive or operate machinery. If you have vision problems while using oxaliplatin, do not drive or operate heavy machinery, or engage in hazardous activities.

3. How to use Oxaliplatin Aurovit

Oxaliplatin is only indicated for adults.

Dose

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

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 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 appropriate dose of oxaliplatin.
• Oxaliplatin is administered by slow injection into a vein (intravenous infusion) over a period of 2 to 6 hours.
• This medicine will be administered at the same time as folinic acid and before the infusion of 5-fluorouracil.

Frequency of administration

You will usually 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 are given too much Oxaliplatin Aurovit

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

In case of overdose, you may experience an increase in side effects. Your doctor may give you appropriate treatment for these side effects.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone 91 562 04 20, indicating the medicine and the amount administered.

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

4. Possible side effects

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

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

Seek medical attention immediatelyif you notice any of the following symptoms:

• Symptoms of an allergic 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, shortness of breath, wheezing, or breathing problems, extreme fatigue (you may feel like you are going to faint). In most cases, these symptoms occurred during or immediately after the infusion, but allergic reactions have also been observed hours or even days after the infusion. Very common (may affect more than 1 in 10 people).
• Abnormal bruising or bleeding. Very common (may affect more than 1 in 10 people).
• Signs of infection, such as sore throat and high temperature. Common (may affect up to 1 in 10 people).
• Persistent or severe diarrhea or vomiting. Very common (may affect more than 1 in 10 people).
• Blood or dark brown particles in your vomit. Very rare (may affect up to 1 in 10,000 people).
• Pain in the lips or mouth ulcers. Very common (may affect more than 1 in 10 people).
• Unexplained respiratory symptoms, such as dry or productive cough, breathing difficulties, or wheezing, shortness of breath, and wheezing. Very common (may affect more than 1 in 10 people).
• A group of symptoms such as headache, altered mental function, seizures, and abnormal vision, which can range from blurred vision to loss of vision (symptoms of reversible posterior leukoencephalopathy syndrome, a rare neurological disorder). Rare (may affect up to 1 in 1,000 people).
• Extreme fatigue with a decrease in the number of red blood cells and shortness of breath (hemolytic anemia), alone or in combination with a decrease in platelets, abnormal bruising (thrombocytopenia), and kidney problems that cause you to urinate very little or not at all (symptoms of hemolytic uremic syndrome). Frequency not known (cannot be estimated from the available data).

Other known side effects of oxaliplatin

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

• Oxaliplatin may affect the nerves (peripheral neuropathy). You may feel tingling and/or numbness in your fingers and toes, around your mouth, or in your throat, which may be accompanied by cramps.

These effects are usually triggered by exposure to cold, for example, when opening the 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 resolve completely on their own, it is possible that the symptoms of peripheral sensory neuropathy may persist after treatment is completed.

• Some people have experienced a tingling sensation in their arms or trunk when flexing their neck.
• Oxaliplatin can sometimes cause an unpleasant sensation in the throat, particularly when swallowing, and give the sensation of difficulty breathing. This sensation, if it occurs, usually appears during or in the hours following the infusion and can be triggered by exposure to cold. Although it is unpleasant, it will not last long and will disappear without the need for treatment. As a result, your doctor may decide to modify your treatment.
• Oxaliplatin may cause diarrhea, mild nausea, and vomiting; however, your doctor will usually give you medicines to prevent nausea before treatment and may continue to use them after treatment.
• Oxaliplatin causes a temporary reduction in the number of blood cells. The decrease in red blood cells can cause anemia (reduction in the number of red blood cells), abnormal bleeding, or bruising (due to a reduction in the number of platelets). The reduction 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 enough blood cells.
• Feeling unwell near or at the site of administration during the infusion.
• Chills (shivering), fatigue from mild to severe, body pain.
• Weight changes, loss or lack of appetite, taste alterations, constipation.
• Headache, back pain.
• Inflammation of the nerve muscles, stiffness of the neck, abnormal sensation in the tongue that can make it difficult to speak.
• Stomach pain.
• Moderate hair loss (alopecia).
• Changes in blood tests that show changes in liver function.

Common(may affect up to 1 in 10 people)

• Indigestion and heartburn, hiccups, hot flashes.
• Increased sweating and nail changes, skin peeling.
• Chest pain.
• Nasal congestion.
• Pain in the joints and bones.
• Pain when urinating and changes in kidney function, changes in the frequency of urination, dehydration.
• Blood in the urine/stool, inflammation of the veins, blood clots in the lungs.
• High blood pressure.
• Depression and insomnia.
• Conjunctivitis, vision problems.
• Decreased calcium levels in the blood.
• Falls.

Uncommon(may affect up to 1 in 100 people)

• 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.

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

• Kidney problems that cause you to urinate very little or not at all (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).
• Seizures (uncontrolled body movements).
• Throat spasm that can cause breathing difficulties.
• Abnormal heart rhythm (QT prolongation), which can be seen on an electrocardiogram (ECG) and can be fatal.
• Heart attack (heart attack), angina pectoris (chest pain or discomfort).
• 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).
• 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 other medicines. Ask your doctor about the possible increased risk of this type of cancer when using oxaliplatin with certain medicines.
• 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. This includes any possible side effects not listed in this leaflet. You can also report side effects directly to the Spanish Medicines Agency's Pharmacovigilance System for Human Use: www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Oxaliplatin Aurovit

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

Oxaliplatin should not come into contact with the eyes or skin. If any accidental spill occurs, inform your doctor or nurse immediately.

After the infusion is completed, oxaliplatin should be disposed of with caution by your doctor or nurse.

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

This medicine does not require any special storage conditions.

After dilution in 5% glucose, chemical and physical stability has been demonstrated for 48 hours at 2-8°C and for 24 hours at 25°C. From a microbiological point of view, the infusion solution should be used immediately. If not used immediately, the storage times and conditions before use are the responsibility of the user and normally should not exceed 24 hours at 2-8°C, unless the dilution has been made in validated and controlled aseptic conditions.

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

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 protect the environment.

6. Container Content and Additional Information

Composition ofOxaliplatin Aurovit

• The active ingredient is oxaliplatin. Each vial contains 50 mg, 100 mg, or 200 mg of oxaliplatin.
• The other component is water for injectable preparations.

Appearance ofthe Productand Container Content

Concentrate for solution for infusion.

Clear and colorless solution, essentially free of visible particles. Each vial contains 50 mg, 100 mg, or 200 mg of oxaliplatin in water for injectable preparations. The vials are supplied in boxes with one vial.

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

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

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

Only some pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Eugia Pharma (Malta) Limited

Vault 14, Level 2, Valletta Waterfront

Floriana, FRN 1914

Malta

Manufacturer

APL Swift Services (Malta) Limited

HF26, Hal Far Industrial Estate, Hal Far

Birzebbugia, BBG 3000

Malta

Or

Generis Farmacêutica, S.A.

Rua João de Deus, nº 19, Venda Nova

2700-487 Amadora

Portugal

Or

Arrow Génériques

26 Avenue Tony Garnier

69007 Lyon

France

For further information on this medicinal product, please contact the local representative of the marketing authorization holder:

Aurovitas Spain, S.A.U.

Avda. de Burgos, 16-D

28036 Madrid

Spain

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

Germany: Oxaliplatin PUREN 5 mg/ml Konzentrat zur Herstellung einer Infusionslösung

Belgium: Oxaliplatin Eugia 5 mg/ml concentraat voor oplossing voor infusie / solution à diluer pour perfusion / Konzentrat zur Herstellung einer Infusionslösung

Spain: Oxaliplatino Aurovit 5 mg/ml concentrado para solución para perfusión EFG

France: OXALIPLATINE ARROW LAB 5mg/ml, solution à diluer pour perfusion

Italy: Oxaliplatino Aurobindo Italia

Poland: Oxaliplatin Eugia

Portugal: Oxaliplatina Generis

Sweden: Oxaliplatin Eugia

Date of last revision of this leaflet: January 2023

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

This information is intended only for healthcare professionals.

PREPARATION GUIDE FOR THE USE OF OXALIPLATINO AUROVIT 5 mg/ml CONCENTRATE FOR SOLUTION FOR INFUSION EFG

It is essential to read the entire content of this procedure before preparing the oxaliplatin infusion solution.

1. FORMULATION

Oxaliplatino Aurovit 5 mg/ml concentrate for solution for infusion is a clear and colorless liquid containing 5 mg/ml of oxaliplatin in water for injectable preparations.

1. Presentation

Oxaliplatino Aurovit is supplied as single-dose vials. Each box contains 1 vial of oxaliplatino (50 mg, 100 mg, or 200 mg).

The 10 ml vial of Oxaliplatino Aurovit is made of transparent type I glass with 50 mg of oxaliplatino concentrate for solution for infusion, with a bromobutyl rubber stopper.

The 20 ml vial of Oxaliplatino Aurovit is made of transparent type I glass with 100 mg of oxaliplatino concentrate for solution for infusion, with a bromobutyl rubber stopper.

The 40 ml vial of Oxaliplatino Aurovit is made of transparent type I glass with 200 mg of oxaliplatino concentrate for solution for infusion, with a bromobutyl rubber stopper.

Oxaliplatino Aurovit packaged for sale

This medicinal product does not require special storage conditions.

Infusion solution

After dilution in 5% glucose, chemical and physical stability has been demonstrated for 48 hours at 2-8°C and for 24 hours at 25°C. From a microbiological point of view, the infusion solution should be used immediately. If not used immediately, the storage times and conditions before use are the responsibility of the user and should not normally exceed 24 hours at 2-8°C, unless the dilution has been performed under validated and controlled aseptic conditions (not exceeding 48 hours).

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

The medicinal product is for single use. Unused solution should be discarded.

1. RECOMMENDATIONS FOR SAFE HANDLING

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

Handling instructions

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

Preparation of injectable solutions of cytotoxic agents should be performed by specialized personnel in this class of medicinal products, under conditions that ensure the integrity of the product, environmental protection, and, above all, the protection of the personnel handling these medicinal products, in accordance with hospital regulations. A dedicated and reserved area is required for this purpose. Smoking, eating, or drinking is prohibited in this area.

Personnel should be provided with adequate materials for handling, especially long-sleeved gowns, masks, caps, protective glasses, sterile single-use gloves, protective suits for the work area, containers, and collection bags for waste materials.

Feces and vomit should be handled with care.

Pregnant women should be warned to avoid handling cytotoxic agents.

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

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

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

1. PREPARATION FOR INTRAVENOUS ADMINISTRATION

Special precautions for administration

• DO NOT use injection devices containing aluminum.
• DO NOT administer undiluted.
• Only a 5% glucose solution (50 mg/ml) can be used as a solvent. DO NOT dilute for infusion with sodium chloride or solutions containing chloride.
• DO NOT mix with other medicinal products in the same infusion bag or administer simultaneously in the same infusion line with other medicinal products.
• DO NOT mix with alkaline solutions or medicinal products, in particular 5-fluorouracil, folinic acid preparations containing tromethamine as an excipient, and tromethamine salts of other medicinal products. Alkaline solutions or medicinal products may negatively affect the stability of oxaliplatin.

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

Intravenous infusion of 85 mg/m2 of oxaliplatin in 250 to 500 ml of 5% glucose solution (50 mg/ml) is administered simultaneously with an intravenous infusion of folinic acid in 5% glucose solution (50 mg/ml) for 2 to 6 hours, using a Y-connector placed immediately 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 with isotonic 5% glucose solutions, never in alkaline or sodium chloride solutions or solutions containing chlorides.

Instructions for use with 5-fluorouracil

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

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

• USE ONLY the recommended solvents (see below).

• Only clear solutions without particles should be used.

4.1 Preparation of the Infusion Solution

Extract the necessary amount of concentrate from the vial or vials and dilute with 250 to 500 ml of a 5% glucose solution (50 mg/ml) to administer a concentration of oxaliplatin between 0.2 mg/ml and 0.7 mg/ml. The concentration range 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 solution (50 mg/ml), chemical and physical stability has been demonstrated for 48 hours at 2-8°C and for 24 hours at 25°C.

From a microbiological point of view, the infusion solution should be used immediately. If not used immediately, the storage times and conditions before use are the responsibility of the user and should not normally exceed 24 hours at 2-8°C, unless the dilution has been performed under validated and controlled aseptic conditions (not exceeding 48 hours).

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

The medicinal product is for single use. Unused solution should be discarded (see the "Elimination" section below).

NEVERuse sodium chloride or solutions containing chloride for dilution.

The compatibility of the oxaliplatin solution has been verified for administration systems with PVC components.

4.2 Infusion of the Solution

Administration of oxaliplatin does not require prehydration.

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

4.3 Elimination

Elimination of unused medicinal product and materials used for dilution and administration will be carried out in accordance with hospital procedures for cytotoxic agents, taking into account local regulations for the elimination of hazardous waste.