OXALIPLATIN TEVA 5 mg/ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

Oxaliplatin Teva 5 mg/ml Concentrate for Solution for Infusion EFG

oxaliplatin

Read all of this leaflet carefully before you are given 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.
• 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 Oxaliplatin Teva 5mg/ml concentrate for solution for infusion is and what it is used for.
2. What you need to know before you are given Oxaliplatin Teva 5mg/ml concentrate for solution for infusion.
3. How Oxaliplatin Teva 5mg/ml concentrate for solution for infusion is administered.
4. Possible side effects.
5. Storage of Oxaliplatin Teva 5mg/ml concentrate for solution for infusion.
6. Contents of the pack and further information

1. What Oxaliplatin Teva 5 mg/ml concentrate for solution for infusion is and what it is used for

The active substance of Oxaliplatin Teva 5 mg/ml is oxaliplatin.

Oxaliplatin Teva 5 mg/ml is used for the treatment of colorectal cancer (treatment of stage III colon cancer after complete resection of the primary tumor, metastatic colon cancer, and rectal cancer). Oxaliplatin is used in combination with other anticancer medicines, such as 5-fluorouracil and folinic acid.

Oxaliplatin is a platinum-based anticancer medicine.

2. What you need to know before you are given Oxaliplatin Teva 5 mg/ml concentrate for solution for infusion

You must not be given Oxaliplatin Teva 5 mg/ml concentrate for solution for infusion:

• if you are allergic to oxaliplatin or any of the other ingredients of this medicine (listed in section 6).
• if you are breast-feeding (see also section “Pregnancy, breast-feeding and fertility”).
• if you already have a low number of blood cells.
• if you already have tingling and numbness in your fingers and/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, pharmacist or nurse before you are given Oxaliplatin Teva 5 mg/ml concentrate for solution for infusion

• If you have ever had an allergic reaction to platinum-based medicines such as carboplatin, cisplatin. Allergic reactions can occur during any infusion of oxaliplatin.
• If you have mild or moderate kidney problems.
• If you have any liver problems or abnormal liver function tests.
• 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 must not be vaccinated with live or attenuated vaccines, such as the yellow fever vaccine.

If any of the following happen to you at any time, tell your doctor immediately. Your doctor may need to treat you for these events. Your doctor may need to reduce the dose of Oxaliplatin Teva 5 mg/ml, or delay or interrupt treatment with Oxaliplatin Teva 5 mg/ml.

• If you have an unpleasant sensation in your throat, particularly when swallowing, and feel short of breath, during treatment.
• If you have nerve problems in your hands or feet such as tingling and numbness, or decreased sensation in your hands or feet.
• If you have headache, altered mental function, seizures and abnormal vision, from blurred vision to loss of vision.
• If you feel unwell (nausea and vomiting).
• If you have severe diarrhea.
• If you have mouth sores or 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 Oxaliplatin Teva 5 mg/ml or postpone your treatment with Oxaliplatin Teva 5 mg/ml.
• If you have unexplained respiratory symptoms such as cough, or difficulty breathing. Your doctor may stop your treatment with Oxaliplatin Teva 5 mg/ml.
• 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 kidney failure).
• If you have a fever (temperature of 38°C or higher), 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 Oxaliplatin Teva 5 mg/ml. 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 coffee ground-like vomit, dark stools which can be signs of a gastrointestinal ulcer (gastrointestinal ulcer with potential bleeding or perforation).
• If you have abdominal pain (around the navel), bloody diarrhea, nausea and/or vomiting which can be caused by a decrease in blood flow to the walls of your intestine (intestinal ischemia).

Using Oxaliplatin Teva 5 mg/ml with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken or might take 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 method of contraception. Female patients must take adequate contraceptive measures during treatment and for 4 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 before receiving any treatment.
• If you become pregnant during treatment, you must inform your doctor immediately.

Breast-feeding

• You must not breast-feed during treatment with oxaliplatin.

Fertility

• Oxaliplatin may have an anti-fertility effect 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 for 6 months after treatment and to take appropriate contraceptive measures during this time.

Talk to your doctor or pharmacist 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 affect walking and balance. If this happens, you should not drive or operate machinery. If you have vision problems while being administered Oxaliplatin Teva 5 mg/ml concentrate for solution for infusion, do not drive, operate heavy machinery or engage in hazardous activities.

3. How Oxaliplatin Teva 5 mg/ml concentrate for solution for infusion is administered

Oxaliplatin Teva 5 mg/ml is only administered to adults.

For single use.

Dose

The dose of Oxaliplatin Teva 5 mg/ml depends on your body surface area. This is calculated from your weight and height. The recommended dose for adults, including the elderly, 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 Teva 5 mg/ml.

Method and route of administration

• Oxaliplatin Teva 5 mg/ml 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 Teva 5 mg/ml.
• Oxaliplatin Teva 5 mg/ml is administered by slow injection into a vein (intravenous infusion) over a period of 2 to 6 hours.
• You will be given Oxaliplatin Teva 5 mg/ml at the same time as folinic acid and before the infusion of 5-fluorouracil.

Frequency of administration

Normally you will receive the 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 removal of the tumor.

If you are given too much Oxaliplatin Teva 5 mg/ml concentrate for solution for infusion:

As 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 exacerbation of side effects. Your doctor may give you appropriate treatment for these side effects.

If you have any further questions about your treatment, ask your doctor, pharmacist or nurse.

If you miss a dose of Oxaliplatin Teva 5 mg/ml concentrate for solution for infusion:

Your doctor will decide when you will receive the medicine. If you think you may have missed a dose, contact your doctor as soon as possible.

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

4. Possible Adverse Effects

Like all medicines, this medicine can have adverse effects, although not all people suffer from them. If you experience any adverse effect, it is essential that you inform your doctor before the next treatment.

The following effects that you may experience are described below.

Inform your doctor immediately ifyou notice any of the following:

• Symptoms of an allergic or anaphylactic reaction with sudden signs such as rash, itching, or hives on the skin, difficulty swallowing, swelling in the face, lips, tongue, or other parts of the body, shortness of breath, wheezing, or breathing problems, extreme fatigue (feeling like fainting). In most cases, these symptoms occurred during or immediately after infusion, 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 elevated temperature,

• Persistent or severe diarrhea or vomiting,

• Presence of blood or dark brown particles in your vomit,

• Pain in the lips or ulcers in the mouth (mucositis/stomatitis),

• Unexplained respiratory symptoms such as dry cough, difficulty breathing, or crackles.

• A group of symptoms such as headache, altered mental function, seizures, and vision changes ranging from blurred vision to loss of vision (symptoms of posterior reversible leukoencephalopathy syndrome, a rare neurological disorder).

• 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 little or not at all (symptoms of hemolytic uremic syndrome).

Other known adverse effects of Oxaliplatino Teva 5 mg/ml are:

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

• Oxaliplatino Teva 5 mg/ml may affect the nerves (peripheral neuropathy). You may feel tingling and/or numbness in your fingers and toes, around the mouth, or in the throat, which may be accompanied by cramps.

Often, these adverse effects can be triggered by exposure to cold, such as opening a refrigerator or holding a cold drink. You may also have difficulty performing fine tasks, such as buttoning a garment. Although in most cases the symptoms disappear completely on their own, there is a possibility that the symptoms of peripheral sensory neuropathy may persist after treatment is completed. Some people have experienced a sudden tingling sensation in their arms or trunk when flexing their neck.

• Oxaliplatino Teva 5 mg/ml may sometimes cause an unpleasant sensation in the throat, particularly when swallowing, and you may feel short of breath. This sensation, if it occurs, usually happens during or in the hours following infusion 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.
• Oxaliplatino Teva 5 mg/ml may cause diarrhea, mild nausea (feeling of dizziness), and vomiting; however, your doctor will usually treat you to prevent this discomfort before starting treatment, and it should be continued after treatment.
• Oxaliplatino Teva 5 mg/ml causes a transient reduction in the number of blood cells.

The decrease in red blood cells may 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 may facilitate the onset of infections.

Before starting treatment and before each session, your doctor will perform a blood test to ensure that you have enough cells in your blood.

• Sensation of discomfort near or at the administration site during infusion.
• Fever, chills (shivering), intense or moderate fatigue, body pain.
• Weight changes, loss of appetite, taste alterations, constipation.
• Headache, back pain.
• Inflammation of the muscle nerves, stiffness of the neck, strange sensation in the tongue that may make speaking difficult, stomatitis/mucositis (sores on the lips and ulcers in the mouth).
• Stomach pain.
• Abnormal bleeding, including nosebleeds.
• Cough, difficulty breathing.
• Allergic reactions, skin rash that may be reddish and itchy, moderate hair loss (alopecia).
• Changes in blood tests that show changes in liver function.

Common(may affect up to 1 in 10 people)

• Infection due to a reduction in white blood cells.
• Severe blood infection, as well as a reduction in white blood cells (septic neutropenia), 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, hiccups, hot flashes, dizziness.
• Increased sweating and nail changes, skin peeling.
• Chest pain.
• Pulmonary changes and runny nose.
• 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, blood clots in the lung.
• 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.
• Obstruction or inflammation of the intestine.
• Nervousness.

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

• Hearing loss.
• Scarring. Thickening of the lungs with difficulty breathing, sometimes fatal (interstitial lung disease).
• Reversible short-term loss of vision.
• Unexpected bleeding or bruising due to an increase in blood clots throughout the small blood vessels of the body (disseminated intravascular coagulation) that 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 cause you to urinate 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).
• Autoimmune reaction that causes a reduction in all blood cell lines (autoimmune pancytopenia).
• Severe blood infection and drop in blood pressure (septic shock) that can be fatal.
• Seizures (uncontrolled body agitation).
• Throat spasm that can cause breathing difficulties.
• 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 little or not at all (symptoms of hemolytic uremic syndrome), which can be fatal.
• Abnormal heart rhythm (QT prolongation) that can be seen on an electrocardiogram (ECG) and can be fatal.
• Muscle pain and swelling along with weakness, fever, or reddish-brown urine (symptoms of muscle damage called rhabdomyolysis) that can be fatal.
• Abdominal pain, nausea, vomiting with blood or coffee-ground-like vomit, dark stools (symptoms of gastrointestinal ulcer with potential bleeding or perforation), which can be fatal.
• Decreased blood flow to the intestine (intestinal ischemia) that can be fatal.
• Myocardial infarction (heart attack), angina pectoris (chest pain or discomfort).

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, 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: http://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Oxaliplatino Teva 5 mg/ml concentrate for solution for infusion

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

Store below 25°C. Keep the vial in the outer packaging to protect it from light.

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

Oxaliplatino Teva 5 mg/ml should not come into contact with the eyes or skin. If it is accidentally spilled, inform your doctor or nurse immediately.

When the infusion is complete, any remaining Oxaliplatino Teva 5 mg/ml concentrate for solution for infusion will be carefully disposed of by your doctor or nurse.

6. Container Content and Additional Information

Composition of Oxaliplatin Teva 5 mg/ml Concentrate for Solution for Infusion

• The active ingredient is oxaliplatin. 1 ml of concentrate for solution for infusion contains 5 mg of oxaliplatin.
• The other components are lactose monohydrate and water for injection.

Appearance of the Product and Container Content

Oxaliplatin Teva 5 mg/ml concentrate for solution for infusion is a clear, colorless or almost colorless solution in a colorless glass vial with a bromobutyl rubber stopper, aluminum seal, and polypropylene snap cap.

4 ml of concentrate for solution for infusion contain 20 mg of oxaliplatin.

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

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

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

The vials are supplied in cartons, each containing one vial. Only certain pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Teva Pharma S.L.U.

c/ Anabel Segura 11. Edificio Albatros B, 1ª planta

28108 Alcobendas, Madrid

Manufacturer

Pharmachemie B.V.

Swensweg 5

PO Box 552

2003 RN Haarlem

Netherlands

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 August 2022

This Information is Intended Only for Healthcare Professionals

GUIDE FOR PREPARATION FOR USE OF OXALIPLATIN TEVA 5 mg/ml CONCENTRATE FOR SOLUTION FOR INFUSION EFG

It is important that you read the entire content of this procedure before preparing Oxaliplatin Teva 5 mg/ml, concentrate for solution for infusion.

1. Formulation

Oxaliplatin Teva 5 mg/ml, concentrate for solution for infusion, is a clear, colorless or almost colorless liquid that contains 5 mg/ml of oxaliplatin and 45 mg/ml of lactose monohydrate in water for injection.

1. Presentation

Oxaliplatin Teva 5 mg/ml, concentrate for solution for infusion, is supplied as single-dose vials.

Oxaliplatin Teva 5 mg/ml concentrate for solution for infusion is a clear, colorless or almost colorless solution in a colorless glass vial with a bromobutyl rubber stopper, aluminum seal, and snap cap.

4 ml of concentrate for solution for infusion contain 20 mg of oxaliplatin.

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

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

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

Each box contains one vial of Oxaliplatin Teva 5 mg/ml concentrate for solution for infusion.

Only certain pack sizes may be marketed.

Oxaliplatin Teva 5 mg/ml concentrate for solution for infusion packaged for sale

Store below 25°C. Keep the vial in the outer packaging to protect it from light.

Infusion Solution

After dilution of the concentrate for solution for infusion in 5% glucose (50 mg/ml), physical and chemical stability has been demonstrated for use within 24 hours at 2°C - 8°C and within 6 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 normally exceed 24 hours at 2°C - 8°C, unless the dilution has taken place in controlled and validated aseptic conditions.

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

The medicinal product is for single use. Any 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 drugs, under conditions that ensure the integrity of the product, environmental protection, and in particular the protection of personnel handling these medications, in accordance with hospital standards. A dedicated and reserved area is required for this purpose. Smoking, eating, or drinking is prohibited in this area.

Personnel should be provided with appropriate materials for handling, including sleeves, masks, caps, glasses, sterile single-use gloves, protective suits for the work area, containers, and bags for collecting waste.

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, labeled containers. See the "Elimination" section below.

If oxaliplatin concentrate for solution for infusion or infusion solution comes into contact with the skin, wash immediately and thoroughly with water.

If oxaliplatin concentrate for solution for infusion or infusion solution comes into contact with mucous membranes, wash immediately and thoroughly with water.

1. Preparation for Intravenous Administration

Special Precautions for Administration

• NEVER use injection devices containing aluminum.
• NEVER administer undiluted.
• Only 5% glucose solution (50 mg/ml) for infusion can be used as a solvent. NEVER use sodium chloride solutions or solutions containing chloride.

-NEVER mix with other medications in the same infusion bag or administer simultaneously in the same infusion line with other medications.

• NEVER mix with alkaline medications or solutions, in particular 5-fluorouracil or folinic acid that contain tromethamine as an excipient and tromethamine salts of other medications. Alkaline medications or solutions will negatively affect the stability of oxaliplatin.

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

Intravenous infusion of oxaliplatin 85 mg/m2 in 250 to 500 ml of 5% glucose solution (50 mg/ml) is administered simultaneously with folinic acid in 5% glucose solution (50 mg/ml) for 2 to 6 hours, using a Y-line placed immediately before the injection point. These two medications cannot be combined 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 (50 mg/ml), and NEVER in alkaline solutions or sodium chloride solutions or solutions containing chloride.

Instructions for Use with 5-Fluorouracil

Oxaliplatin should always be administered before fluoropyrimidines, such as 5-fluorouracil.

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

For additional information on this combined medication with oxaliplatin, see the corresponding Summary of Product Characteristics.

• ONLY USE the recommended solvents (see below).
• Only clear solutions without particles should be used.

4.1 Preparation of the Infusion Solution

Remove the required amount of concentrate from the vial(s) and then dilute with 250 ml to 500 ml of 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 of the concentrate for solution for infusion in 5% glucose solution (50 mg/ml), physical and chemical stability 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 normally exceed 24 hours at +2°C and +8°C, unless the dilution has taken place in controlled and validated aseptic conditions (not exceeding 48 hours).

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

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

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, should be infused either 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

Medicinal product residues as well as materials used for dilution and administration should be destroyed according to hospital procedures for cytotoxic agents, taking into account legal requirements for the elimination of hazardous waste.