Package Leaflet: Information for the user

Oxaliplatino Teva 5 mg/ml Concentrate for solution for infusion EFG

oxaliplatino

Read this leaflet carefully before you receive the medicine, because it contains important information for you.

- Keep this leaflet, as you may need to read it again.

- If you have any questions, ask your doctor, pharmacist or nurse.

-If you experience any side effects, consult your doctor, pharmacist or nurse,evenif they do not appear in this leaflet.See section 4.

The active ingredient of Oxaliplatino Teva 5 mg/ml is oxaliplatino.

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

Oxaliplatino is an antineoplastic or anticancer medication that contains platinum.

You should not receive OxaliplatinoTeva 5mg/ml concentrated solution for infusion:

- if you areallergicto oxaliplatino or to any of the other components of this medication(listed in section 6).

- if you arebreastfeeding(also see section “Pregnancy, breastfeeding and fertility”).

- if you already havea reduced number of blood cells.

- if you already havetingling and numbnessin your fingers of the hands and/or fingers of the feet, and have difficulty performing delicate tasks, such as dressing.

- if you havesevere kidney problems.

Warnings and precautions

Consult your doctor, pharmacist or nurse before you receive Oxaliplatino Teva 5 mg/ml concentrated solution for infusion

• If you have ever had an allergic reaction to medications containing platinum such as carboplatin, cisplatin. You may experience allergic reactions during any infusion of oxaliplatino.
• 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 heart signal, called prolonged QT interval, irregular heartbeat or a family history of heart problems.
• If you have recently received or plan to receive any vaccine. During treatment with oxaliplatino, you should not receive live or attenuated vaccines, such as the yellow fever vaccine.

If any of the following happens, tell your doctor immediately. Your doctor may need to treat you for these events. Your doctor may need to reduce the dose of Oxaliplatino Teva 5 mg/ml, or delay or stop treatment with Oxaliplatino Teva 5 mg/ml.

• If you have an unpleasant sensation in your throat, particularly when swallowing, and feel like you are 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 headaches, altered mental function, convulsions and abnormal vision, from blurry vision to loss of vision.
• If you do not feel well (nausea and vomiting).
• If you have severe diarrhea.
• If you have pain in your lips or ulcers in your mouth (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 Teva 5 mg/ml or postpone treatment with Oxaliplatino Teva 5 mg/ml.
• If you have unexplained respiratory symptoms such as coughing, or difficulty breathing. Your doctor may stop treatment with Oxaliplatino Teva 5 mg/ml.
• If you develop extreme fatigue, shortness of breath, or kidney problems that cause you to urinate little or not at all (symptoms of acute kidney failure).
• If you have a fever (temperature of 38°C or higher), or chills, which may 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 a bruise (disseminated intravascular coagulation). This may be a sign of blood clots throughout the small blood vessels in your body.
• If you feel dizzy (loss of consciousness) or have an irregular heartbeat while taking Oxaliplatino Teva 5 mg/ml. This may be a sign of a serious heart problem.
• If you develop muscle pain and swelling, along with weakness, fever and reddish-brown urine. These may be signs of muscle damage (rhabdomyolysis) and may lead to kidney problems or other complications.
• If you have abdominal pain, nausea, vomiting with blood or vomiting like coffee grounds, dark stools that may be signs of a gastrointestinal ulcer (gastrointestinal ulcer with potential for bleeding or perforation).
• If you have abdominal pain (around the navel), diarrhea with blood, nausea and/or vomiting that may be caused by a decrease in blood flow to the walls of your intestine (intestinal ischemia).

Use of Oxaliplatino Teva 5 mg/ml with other medications

Inform your doctor or pharmacist if you are taking/using, have taken/used recently or may need to take/use other medications.

Pregnancy, breastfeeding and fertility

Pregnancy

• It is not recommended to become pregnant during treatment with oxaliplatino and you should use effective contraception. Patients should take appropriate contraceptive measures during treatment and for 4 months after treatment is completed.
• If you are pregnant or planning to become pregnant, it is very important to discuss this with your doctor before receiving any treatment.
• If you become pregnant during treatment, you should inform your doctor immediately.

Breastfeeding

• During treatment with oxaliplatino, you should not breastfeed.

Fertility

• Oxaliplatino may have an antifertility effect that could be irreversible. Male patients should seek advice on sperm conservation before treatment.
• It is advised that male patients do not have children during treatment and for 6 months after treatment and take appropriate contraceptive measures during this time.

Consult your doctor or pharmacist before using any medication.

Driving and operating machinery

Treatment with oxaliplatino may increase the risk of dizziness, nausea and vomiting and other neurological symptoms that affect walking and balance. If this occurs, you should not drive or operate machinery. If you experience vision problems while receiving Oxaliplatino Teva 5 mg/ml concentrated solution for infusion, do not drive, operate heavy machinery or engage in hazardous activities

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

For single use only.

Dose

The dose of Oxaliplatino Teva 5 mg/ml depends on your body surface area, which is calculated from your weight and height. The recommended dose for adults, including the elderly, is 85 mg/m 2 of body surface area. The dose you receive will also depend on blood test results and whether you have previously experienced adverse effects with Oxaliplatino Teva 5 mg/ml.

Method and Route of Administration

• Oxaliplatino Teva 5 mg/ml will be prescribed by a specialist in cancer treatment.
• You will be treated by a healthcare professional who has prepared the appropriate dose of Oxaliplatino Teva 5 mg/ml.
• Oxaliplatino 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 Oxaliplatino Teva 5 mg/ml at the same time as folinic acid and before the infusion of 5-fluorouracil.

Administration Frequency

You will normally receive the infusion every 2 weeks.

Treatment Duration

Your doctor will determine the duration of treatment.

Treatment will last a maximum of 6 months when used after complete tumor removal.

If you are given more Oxaliplatino Teva 5 mg/ml Concentrate for Solution for Infusion than recommended:

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

In the event of an overdose, you may experience an exacerbation of adverse reactions. Your doctor may provide appropriate treatment for these adverse effects.

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

If you forget to administer Oxaliplatino Teva 5 mg/ml Concentrate for Solution for Infusion:

Your doctor will decide when you will receive the medication. If you think you may not have received a dose, contact your doctor as soon as possible.

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

Like all medicines, this medicine can have side effects, although not everyone will experience them.This medicine may cause side effects, although not everyone will experience them.

It is important to report any side effects to your doctor before the next treatment.

Inform your doctor immediately if you notice any of the following:

• Abnormal cardinals, bleeding, or signs of infection, such as sore throat and elevated temperature,

• Persistent or severe diarrhea or vomiting,

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

• Mouth pain or ulcers (mucositis/stomatitis),

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

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

• Extreme fatigue with a decrease in red blood cell count 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 acute kidney injury).

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

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

• Oxaliplatino Teva 5 mg/ml can 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 side effects can often be triggered by exposure to cold, such as opening a refrigerator or holding a cold drink. You may also have difficulty with fine motor tasks, such as buttoning a shirt. Although in most cases, symptoms disappear completely on their own, there is a possibility that peripheral sensory neuropathy symptoms 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 can cause an unpleasant sensation in the throat, particularly when swallowing, and you may feel a lack of air. 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 treatment. Your doctor may decide to modify your treatment as a result of this.
• Oxaliplatino Teva 5 mg/ml can cause diarrhea, mild nausea (feeling of dizziness), and vomiting (feeling unwell); 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 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 the appearance of bruises (due to a reduction in platelet count). The decrease in white blood cells can facilitate the appearance of infections.

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

• Sensation of discomfort near or at the site of administration during infusion.
• Fever, chills, intense or moderate fatigue, body aches.
• Weight changes, loss of appetite, altered taste, constipation.
• Headache, back pain.
• Muscle inflammation, stiffness, and weakness, fever, or reddish-brown urine (symptoms of muscle damage called rhabdomyolysis) that can be fatal.
• Abdominal pain, nausea, vomiting with blood or coffee grounds-like vomit, dark stools (symptoms of gastrointestinal ulcer with potential hemorrhage or perforation) that can be fatal.
• Decreased blood flow to the intestine (intestinal ischemia) that can be fatal.

Frequent (may affect up to 1 in 10 people)(may affect up to 1 in 10 people)

• Infection due to a decrease in white blood cells.
• Severe blood infection, as well as a decrease in white blood cells (septic neutropenia) that can be fatal.
• Decrease in white blood cells accompanied by fever > 38.3°C or prolonged fever > 38°C for more than an hour (febrile neutropenia).
• Indigestion and stomach burning, hiccups, dizziness.
• Increased sweating and nail changes, skin peeling.
• Chest pain.
• Pulmonary changes and nasal discharge.
• Joint pain and bone pain.
• Urinary pain and kidney function changes, changes in urination frequency, dehydration.
• Blood in urine/deposits, vein inflammation, pulmonary embolism.
• High blood pressure.
• Depression and insomnia.
• Conjunctivitis and vision problems.
• Decreased calcium levels in the blood.
• Fall.

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

• Severe blood infection (sepsis) that can be fatal.
• Intestinal obstruction or inflammation.
• Nervousness.

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

• Presence of blood or dark brown coffee-colored particles in the vomit.
• Kidney problems that cause you to urinate little or not at all (symptoms of acute kidney injury).
• Liver vascular disorders.

Frequency unknown (cannot be estimated from available data)(cannot be estimated from available data)

• Allergic vasculitis (inflammation of blood vessels).
• Autoimmune reaction that causes a reduction in all blood cell lines (autoimmune pancytopenia).
• Severe blood infection and low blood pressure (septic shock) that can be fatal.
• Seizures (uncontrolled body agitation).
• Throat spasm that can cause difficulty breathing.
• Extreme fatigue with a decrease in red blood cell count 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 acute kidney injury), which can be fatal.
• Abnormal heart rhythm (prolonged QT) that can be seen on an electrocardiogram (ECG) that 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 grounds-like vomit, dark stools (symptoms of gastrointestinal ulcer with potential hemorrhage or perforation) that can be fatal.
• Decreased blood flow to the intestine (intestinal ischemia) that can be fatal.
• Heart attack (myocardial infarction), angina (chest pain or discomfort).

Intestinal inflammation (inflammation of the inner lining of the esophagus - the tube that connects the mouth to the stomach - causing pain and difficulty swallowing).

• Secondary leukemia (blood cancer) at the end of treatment.
• Reduction in the number of all types of blood cells (pancytopenia).
• Cerebral blood flow disorder (ischemic and hemorrhagic stroke).
• Pulmonary infection (pneumonia) with possible difficulty breathing (bronchopneumonia), which can be fatal.
• Abnormal non-cancerous liver nodules (focal nodular hyperplasia)

Reporting side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the Spanish System for the Vigilance of Medicines for Human Use: http://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Store below 25 °C..Store the vial in the outer packagingto protect it from light.

Do not use this medication 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, report it immediately to the doctor or nurse.

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

Composition of Oxaliplatino Teva 5 mg/ml concentratefor infusion solution

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

Aspect of the product and content of the package

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

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

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

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

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

The vials are supplied in cartons each containing one vial. Some package sizes may only be marketed.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

Teva Pharma S.L.U.

c/ Anabel Segura 11. Edificio Albatros B, 1st floor

28108 Alcobendas, Madrid

Responsible for manufacturing

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 with the following names

Last review date of this leaflet August 2022

This information is intended solely for doctors or healthcare professionals

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

1. Formulation

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

2. Presentation

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

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

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

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

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

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

Each carton contains one vial of Oxaliplatino Teva 5 mg/ml concentrate for infusion solution.

Some package sizes may only be marketed.

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

Store below 25 ºC. Store the vial in the outer packaging to protect it from light.

Infusion solution

After dilution of the concentrate for infusion solution in glucose 5% (50 mg/ml), physical and chemical stability has been demonstrated for use for 24 hours at 2 ºC -8ºCand for 6 hours at25ºC.

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

Unless otherwise specified, the time and conditions of storage prior to use are the responsibility of the user and should not normally exceed 24hours at 2 ºC -8ºCunless the dilution has taken place in controlled and validated aseptic conditions (not exceeding 48 hours).

Visually inspect before use. Only clear solutions without particles should be used.

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

3. Safe handling recommendations

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

Handling instructions

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

The preparation of injectable solutions of cytotoxic agents should be performed by specialized personnel in this class of drugs, in conditions that ensure the integrity of the product, environmental protection, and in particular the protection of personnel handling these medicines, in accordance with hospital standards. A prepared 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, gloves, mask, cap, glasses, sterile disposable gloves, protective clothing 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 containers suitable for the purpose, properly labeled. See the "Disposal" section below.

If the oxaliplatino concentrate for infusion solution or the infusion solution come into contact with the skin, wash immediately and abundantly with water.

If the oxaliplatino concentrate for infusion solution or the infusion solution come into contact with mucous membranes, wash immediately and abundantly with water.

4. Preparation for intravenous administration

Special precautions for administration

- NEVER use injection devices containing aluminum.

- NEVER administer without dilution.

- Only glucose 5% (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 vein with other medications.

- NEVER mix with alkaline medications, particularly 5-fluorouracil or folic acid containing trometamol as an excipient and trometamol salts of other medications. Alkaline medications will negatively affect the stability of oxaliplatino.

Instructions for use with folic acid (such as calcium folinate or sodium folinate)

The intravenous infusion of oxaliplatino 85 mg/m2in250 to500 ml of glucose 5% (50 mg/ml) solution, is administered at the same time as folic acid in glucose 5% (50 mg/ml) solution, over2 to6 hours, using a Y-connector placed immediately before the injection site. These two medications cannot be combined in the same infusion bag. Folic acid should not contain trometamol as an excipient and should only be diluted using an isotonic glucose 5% (50 mg/ml) solution, and NEVER in alkaline solutions or sodium chloride solutions or solutions containing chloride.

Instructions for use with 5-fluorouracil

Oxaliplatino must always be administered before fluoropyrimidines, such as 5-fluorouracil.

After administration of oxaliplatino, wash the vein and then administer 5-fluorouracil.

For additional information on this medication combined with oxaliplatino, see the corresponding Technical Dossier.

- 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 from the vial(s) and then dilute with 250 ml to 500 ml of a glucose 5% (50 mg/ml) solution to administer a concentration of oxaliplatino between 0.2 mg/ml and 0.7 mg/ml. The concentration interval for which physical and chemical stability has been demonstrated is 0.2 mg/ml to 2.0mg/ml.

Administer by intravenous infusion.

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

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

Unless otherwise specified, the time and conditions of storage prior to use are the responsibility of the user and should not normally exceed 24hours at +2 ºC and +8ºCunless the dilution has taken place in controlled and validated aseptic conditions (not exceeding 48 hours).

Visually inspect before use. Only clear solutions without particles should be used.

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

NEVERuse sodium chloride or solutions containing chloride for dilution.

The compatibility of the oxaliplatino solution has been verified for infusion systems with PVC components.

4.2 Infusion of the solution

Oxaliplatino does not require prehydration.

Oxaliplatino, diluted in 250 ml to 500 ml of glucose 5% (50 mg/ml) solution to administer a concentration not less than 0.2 mg/ml, will infuse well by central or peripheral vein, over2 to6 hours. When oxaliplatino is administered with 5-fluorouracil, the infusion of oxaliplatino should precede that of 5-fluorouracil.

4.3 Disposal

The remains of the medicinal product as well as the materials used for dilution and administration must be destroyed in accordance with the procedures established in the hospital for cytotoxic agents, taking into account the legal requirements for the disposal of hazardous waste.