Oxaliplatin Teva

Patient Information Leaflet

Oxaliplatin Teva 5 mg/ml concentrate for solution for infusion

Oxaliplatin
Generic medicine
Please read all of this leaflet carefully before you start using this medicine, as it contains important information for you.

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

Contents of this leaflet:

1. What Oxaliplatin Teva 5 mg/ml is and what it is used for
2. What you need to know before using Oxaliplatin Teva 5 mg/ml
3. How to use Oxaliplatin Teva 5 mg/ml
4. Possible side effects
5. How to store Oxaliplatin Teva 5 mg/ml
6. Contents of the pack and other information

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

The active substance of Oxaliplatin Teva 5 mg/ml is oxaliplatin.
Oxaliplatin is used to treat colorectal cancer (treatment of both stage III colon cancer after complete resection of the primary tumour, and metastatic colon and rectal cancer). Oxaliplatin is used in combination with other anticancer medicines called 5-fluorouracil and folinic acid.
Oxaliplatin Teva 5 mg/ml is an antineoplastic agent, i.e. an anticancer drug, and contains platinum.

2. What you need to know before using Oxaliplatino Teva 5 mg/ml

Do not use Oxaliplatino Teva 5 mg/ml:

• if you are allergic to oxaliplatin or to 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 low blood cell counts,
• if you already experience tingling and reduced sensitivity in the fingers of your hands and/or feet, and have difficulty performing delicate tasks, such as buttoning clothes,
• if you suffer from severe kidney problems.

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Oxaliplatino Teva 5 mg/ml:

• if you have previously experienced an allergic reaction to medicines containing platinum, such as carboplatin or cisplatin. Allergic reactions may occur during any infusion of oxaliplatin.
• if you have moderate or mild kidney problems,
• if you have liver problems, or if you have abnormal liver function test results,
• if you have or have had heart problems, such as an abnormal electrical signal known as QT interval prolongation, an irregular heartbeat, or a family history of heart problems.

Immediately inform your doctor if you experience any of the following symptoms. Your doctor
may need to treat you for these events. Your doctor may reduce your dose of Oxaliplatino Teva 5 mg/ml, or
delay or stop treatment with Oxaliplatino Teva 5 mg/ml.

• If, during treatment, you feel discomfort in your throat, especially when swallowing, and have a sensation of breathlessness.
• If you have nerve problems in your hands or feet, such as numbness or tingling, or reduced sensitivity in your hands or feet.
• If you have headache, changes in mental function, seizures, or vision abnormalities ranging from blurred vision to loss of vision.
• If you feel unwell or are unwell (nausea or vomiting).
• If you have severe diarrhoea.
• If you have pain in your lips or mouth ulcers (mucositis/stomatitis).
• If you have diarrhoea, or a decrease in white blood cells or platelets. Your doctor may reduce your dose of Oxaliplatino Teva 5 mg/ml or delay your treatment with Oxaliplatino Teva 5 mg/ml.
• If you experience unexplained respiratory symptoms such as cough or difficulty breathing. Your doctor may stop treatment with Oxaliplatino Teva 5 mg/ml.
• If you feel extreme tiredness, shortness of breath, or develop a kidney condition in which you pass little or no urine (symptoms of acute renal failure).
• If you have a fever (temperature greater than or equal to 38°C) or chills, which may be signs of infection. You may be at risk of developing a blood infection.
• If you have a fever above 38°C. Your doctor will determine whether you have a reduced white blood cell count.
• If you experience unexpected bleeding or bruising (disseminated intravascular coagulation), as these may be signs of blood clots in small blood vessels.
• If you faint (lose consciousness) or have an irregular heartbeat while taking Oxaliplatino Teva 5 mg/ml, as this may be a sign of a serious heart condition.
• If you experience muscle pain and swelling associated with weakness, fever, or brown-red urine. These may 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 vomit resembling "coffee grounds", or dark/tarry stools, as these may be signs of an intestinal ulcer (gastrointestinal ulcer with potential bleeding or perforation).
• If you have abdominal pain, diarrhoea with blood, and nausea and/or vomiting, which may be caused by reduced blood flow to the abdominal wall (intestinal ischemia).

Other medicines and Oxaliplatino Teva 5 mg/ml
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those obtained without a prescription.
Pregnancy, breast-feeding and fertility
Pregnancy

• Pregnancy is not recommended during treatment with oxaliplatin; therefore, an effective method of contraception is required. Female patients must use appropriate contraceptive measures during treatment and for 4 months after stopping treatment.
• If you are pregnant or planning a pregnancy, it is very important to discuss this with your doctor before starting 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 may be irreversible. Male patients may wish to inquire about sperm preservation before starting treatment.
• Male patients are advised not to father a child during treatment and for 6 months after its completion, and to use appropriate contraceptive measures during this period.

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 (feeling unwell), vomiting (being unwell), and other neurological symptoms affecting walking and balance. If you experience these symptoms, do not drive and do not operate machinery. If you develop vision problems while being treated with Oxaliplatino Teva 5 mg/ml, do not drive vehicles, operate heavy machinery, or perform hazardous activities.

3. How to use Oxaliplatin Teva 5 mg/ml

Oxaliplatin Teva 5 mg/ml is used exclusively in adults.
For single use only.
Dose
The dose of Oxaliplatin Teva 5 mg/ml depends on your body surface area. This is calculated based on your weight and height.
For adults, including elderly patients, the recommended dose is 85 mg/m² of body surface area.
The administered dose may also depend on the results of your blood tests and whether you have previously experienced adverse 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 prepare the correct dose of Oxaliplatin Teva 5 mg/ml.
• Oxaliplatin Teva 5 mg/ml is administered by slow injection into one of your veins (an intravenous infusion) over a period of 2 to 6 hours.
• Oxaliplatin Teva 5 mg/ml will be administered together with folinic acid and before the infusion of 5-fluorouracil.

Frequency of administration
Typically, an infusion is scheduled once every 2 weeks.
Duration of treatment
The duration of therapy will be determined by your doctor.
After complete removal of the tumour, treatment will last up to a maximum of 6 months.
If you use more Oxaliplatin Teva 5 mg/ml than you should
Since this medicine is administered by qualified healthcare personnel, it is highly unlikely that you will receive an excessive or insufficient dose.
In case of overdose, you may experience an increase in adverse effects. Your doctor can prescribe appropriate treatment for these side effects.
If you have any doubts regarding your treatment, consult your doctor, pharmacist, or nurse.
If you forget to take Oxaliplatin Teva 5 mg/ml
Your doctor will determine when you should receive the medication. If you think you have missed a dose, you must contact your doctor as soon as possible.
If you have any doubts about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
If you experience any side effect, it is important that you inform your doctor before starting the next
treatment cycle.
Below you will find a description of the side effects you might experience.
If you develop any of the following symptoms, contact your doctor immediately:

• Signs of an allergic or anaphylactic reaction with sudden onset symptoms such as rash, itching or hives on the skin, difficulty swallowing, swelling of the face, lips, tongue or other body parts, shortness of breath or wheezing, or difficulty breathing, extreme tiredness (you may feel like you are about to faint). In most cases, these symptoms occurred during or immediately after the infusion, but delayed allergic reactions have been observed hours or even days after infusion.
• Unusual bruising, bleeding, or signs of infection such as sore throat and high fever.
• Severe or persistent diarrhoea or vomiting (feeling unwell).
• Presence of blood or dark brown coffee-ground-like particles in vomit.
• Sores on the lips or mouth ulcers (mucositis/stomatitis).
• Unexplained respiratory symptoms such as dry cough, difficulty breathing, or crackling sounds.
• A combination 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 condition).
• Severe fatigue with a reduction in red blood cells and shortness of breath (haemolytic anaemia), alone or in combination with low platelet count, unusual bruising (thrombocytopenia), and kidney disease causing reduced or no urine output (all symptoms of haemolytic-uremic syndrome).

Other known side effects of Oxaliplatin 5 mg/ml are:
Very common (may affect more than 1 in 10 people)

• Oxaliplatin Teva 5 mg/ml may affect the nervous system (peripheral neuropathy). You may experience tingling and/or numbness in the fingers, toes, around the mouth, or in the throat; these disturbances may sometimes occur together with muscle cramps. These side effects are often triggered by exposure to cold, for example, opening a refrigerator or holding a cold drink. You may also have difficulty performing precise tasks, such as buttoning clothes. Although in most cases these symptoms resolve completely on their own, persistent symptoms related to peripheral sensory neuropathy may be observed after treatment ends. Some individuals may experience a tingling sensation similar to an electric shock when the neck is flexed and touched along the arms or trunk.

• Oxaliplatin Teva 5 mg/ml may occasionally cause discomfort in the throat, particularly during swallowing, and may give a sensation of shortness of breath. If this occurs, it typically happens during or within a few hours after infusion and may be triggered by exposure to cold; although unpleasant, it does not last long and resolves without requiring additional treatment. In such cases, your doctor may decide to adjust your treatment.

• Oxaliplatin Teva 5 mg/ml may cause diarrhoea, mild nausea (feeling unwell), and vomiting (feeling unwell); however, to prevent these symptoms, your doctor usually administers a medicine before treatment, which may also be given after treatment ends.

• Oxaliplatin Teva 5 mg/ml causes a temporary reduction in blood cells. A reduction in red blood cells may lead to anaemia (a decrease in red blood cells), abnormal bleeding or bruising (due to a decrease in platelets). A decrease in white blood cells may make you more susceptible to infections. Your doctor will take blood samples to monitor your blood cell counts before starting treatment and before each subsequent cycle.

• Discomfort at or near the injection site during infusion.

• Fever, chills (shivering), mild or severe fatigue, body aches.

• Changes in body weight, loss of appetite or lack of appetite, altered taste, constipation.

• Headache, back pain.

• Swelling of nerves connected to muscles, neck stiffness, unusual sensations in the tongue, possible speech disturbances, stomatitis/mucositis (lip irritation or mouth ulcers).

• Stomach pain.

• Abnormal bleeding, including nosebleeds.

• Cough, difficulty breathing, allergic reactions, skin rashes which may include red, itchy skin, mild hair loss (alopecia).

• Changes in blood tests, including those indicating abnormal liver function.

Common (may affect up to 1 in 10 people)

• Infection due to a reduction in white blood cells.
• Severe blood infection associated with a reduction in white blood cells (neutropenic sepsis), which may be fatal.
• Reduction in white blood cells with fever > 38.3°C or prolonged fever > 38°C for more than 1 hour (febrile neutropenia).
• Indigestion and heartburn, hiccups, flushing, dizziness.
• Increased sweating, nail changes, skin peeling.
• Chest pain.
• Lung changes and runny nose.
• Joint and bone pain.
• Pain during urination and altered kidney function, changes in urinary frequency, dehydration.
• Blood in urine or stools, swelling of veins, blood clots in the lungs.
• High blood pressure.
• Depression and insomnia.
• Conjunctivitis and vision problems.
• Low levels of calcium in the blood.
• Falls.

Uncommon (may affect up to 1 in 100 people)

• Severe blood infection (sepsis), which may be fatal.
• Blockage or swelling 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).
• Temporary and reversible loss of vision.
• Unexpected bleeding or bruising due to widespread blood clots in small blood vessels throughout the body (disseminated intravascular coagulation), which may be fatal.

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

• Presence of blood or dark brown coffee-ground-like particles in vomit.
• Kidney diseases with reduced or no urine output (symptoms of acute renal failure).
• Vascular liver diseases.

Frequency not known (frequency cannot be estimated from the available data)

• Allergic vasculitis (inflammation of blood vessels).
• Autoimmune reaction leading to a reduction in blood cell lines (autoimmune pancytopenia).
• Severe blood infection and low blood pressure (septic shock), which may be fatal.
• Seizures (uncontrolled body movements).
• Throat spasms causing breathing difficulties.
• Severe fatigue with a reduction in red blood cells and shortness of breath (haemolytic anaemia), alone or in combination with low platelet count and kidney disease with reduced or no urine output (symptoms of haemolytic-uremic syndrome), which may be fatal.
• Abnormal heart rhythm (QT prolongation), detectable by electrocardiogram (ECG), which may be fatal.
• Muscle pain and swelling associated with weakness, fever, or brown-red urine (symptoms of muscle damage known as rhabdomyolysis), which may be fatal.
• Abdominal pain, nausea, vomiting blood or coffee-ground-like vomit, or dark/tarry stools (symptoms of gastrointestinal ulcer with potential bleeding or perforation), which may be fatal.
• Reduced blood flow to the intestine (intestinal ischemia), which may be fatal.
• Myocardial infarction (heart attack), angina pectoris (chest pain or discomfort).
• Inflammation of the oesophagus (inflammation of the oesophageal lining – the tube connecting the mouth to the stomach – resulting in pain and difficulty swallowing).
• Blood cancer after treatment ends (secondary leukaemia).
• Reduction in all types of blood cells (pancytopenia).
• Disorder/disturbance in blood flow to the brain (ischaemic and haemorrhagic cerebrovascular disorder).
• Infection affecting the lungs (pneumonia) with possible breathing difficulties (bronchopneumonia), which may be fatal.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please tell your doctor, pharmacist, or nurse. You may also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Oxaliplatin Teva 5 mg/ml

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 expiry date stated on the packaging and vial after EXP. The expiry date refers to the last day of that month.
Oxaliplatin Teva 5 mg/ml must not come into contact with eyes or skin. In case of accidental spillage, inform the doctor or nurse immediately.
After completion of the infusion, any remaining Oxaliplatin Teva 5 mg/ml must be carefully disposed of by the doctor or a nurse.

6. Contents of the pack and other information

What Oxaliplatin Teva 5 mg/ml contains

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

Description of the appearance of Oxaliplatin Teva 5 mg/ml and contents of the pack
Oxaliplatin Teva 5 mg/ml is a clear, colourless, almost transparent solution contained in a transparent glass vial with a bromobutyl rubber stopper, aluminium seal and a pull-off polipropylene cap.
4 ml of concentrate for solution for infusion contains 20 mg of oxaliplatin
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.
Each vial is individually packaged in a box.
It is possible that not all pack sizes are marketed.

Marketing Authorisation Holder
Teva Italia S.r.l. - Piazzale Luigi Cadorna, 4 - 20123 Milano, Italy

Manufacturer
Pharmachemie B.V. - Swensweg 5 - PO Box 552 - 2003 RN Haarlem (The Netherlands)
Teva Pharmaceutical Works Private Limited Company - Tàncsics Mihàly st. 82 – H-2100 Gödöllő (Hungary)

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

The following information is intended for healthcare professionals only
PREPARATION GUIDE TO BE USED WITH OXALIPLATIN TEVA 5 MG/ML
CONCENTRATE FOR INFUSION SOLUTION
It is important to read the entire content of this procedure before preparing Oxaliplatin Teva 5 mg/ml,
concentrate for infusion solution.

1. Composition

Oxaliplatin Teva 5 mg/ml concentrate for solution for infusion is a clear, colourless or almost colourless liquid containing 5 mg/ml of oxaliplatin and 45 mg/ml of monohydrate lactose in water for injections.

2. Presentation

Oxaliplatin Teva 5 mg/ml is supplied in a single-dose vial.
Oxaliplatin Teva 5 mg/ml is a clear, colourless or almost colourless solution contained in a transparent glass vial with a bromobutyl rubber stopper, aluminium seal and tamper-evident cap.
4 ml concentrate for infusion solution contains 20 mg of oxaliplatin.
10 ml concentrate for infusion solution contains 50 mg of oxaliplatin.
20 ml concentrate for infusion solution contains 100 mg of oxaliplatin.
40 ml concentrate for infusion solution contains 200 mg of oxaliplatin.
Each pack contains one vial of Oxaliplatin Teva 5 mg/ml.
Not all pack sizes may be marketed.
Oxaliplatin Teva 5 mg/ml as marketed pack
Store below 25°C.
Keep the vial in the outer packaging to protect from light.
Infusion solution
After dilution of the concentrate for infusion solution in 5% glucose (50 mg/ml), chemical and physical in-use stability has been demonstrated for 24 hours at 2°C–8°C and for 6 hours at 25°C.
From a microbiological standpoint, the infusion preparation should be used immediately.
If the medicinal product is not used immediately, the user is responsible for the storage times and conditions prior to use, which should not exceed 24 hours at 2°C–8°C, unless dilution occurred under controlled and aseptic conditions.
Visually inspect before use. Only use solutions that are clear and free from particles.
The medicinal product is for single use only. Any unused solution must be discarded.

3. Recommendations for safe handling

As with any other potentially toxic agent, the preparation and handling of oxaliplatin solutions must be carried out with caution.

Instructions for handling
Handling this cytotoxic medicinal product by healthcare personnel requires a set of precautions to ensure the protection of the operator and the working environment.
The preparation of injectable solutions of cytotoxic agents should only be performed by specialized and specifically trained personnel who are familiar with the drugs used, and who work under conditions ensuring product integrity, environmental protection, and, in particular, the protection of personnel handling the medicinal product, in accordance with hospital procedures. This requires a dedicated preparation area where eating, drinking, and smoking are strictly prohibited.

Personnel must have access to appropriate materials, in particular: long-sleeved gowns, protective masks, head covers, protective eyewear, sterile disposable gloves, protective absorbent pads for the work area, and containers and bags for waste collection.

Excreta and vomit must be handled with care.

Pregnant women should avoid handling cytotoxic drugs.

All broken containers must be treated with the same precautions and considered as contaminated waste. Contaminated waste must be incinerated in rigid, designated containers. See section "Disposal" below.

If concentrated oxaliplatin for infusion solution or the diluted oxaliplatin infusion solution comes into contact with the skin, mucous membranes, or eyes, immediately and thoroughly wash the affected area with water.

If concentrated oxaliplatin for infusion solution or the diluted oxaliplatin infusion solution comes into contact with mucous membranes, immediately and thoroughly wash the affected area with water.

4. Preparation for Intravenous Administration

Special Precautions for Administration

• DO NOT use injection materials containing aluminium.
• DO NOT administer the product undiluted.
• Use ONLY 5% glucose solution (50 mg/ml) as diluent. DO NOT dilute for infusion with sodium chloride or any other solution containing chlorides.
• DO NOT mix with other medicinal products in the same infusion bag and do not administer through the same infusion line.
• DO NOT mix with alkaline medicinal products or alkaline solutions, in particular with 5-fluorouracil, with folinic acid preparations containing tromethamine as excipient, or with tromethamine salts of other active substances. Alkaline medicinal products or alkaline solutions may adversely affect the stability of oxaliplatin.

Instructions for Use with Folinic Acid (as calcium folinate or disodium folinate)
The intravenous infusion of oxaliplatin 85 mg/m² in 250–500 ml of 5% glucose solution (50 mg/ml) may be administered simultaneously with the intravenous infusion of folinic acid over 2–6 hours, using a Y-line connected immediately before the infusion site. These two medicinal products must not be mixed in the same infusion bag. Folinic acid must not contain tromethamine as excipient and must be diluted using only 5% isotonic glucose solution (50 mg/ml), never alkaline solutions, sodium chloride, or chloride-containing solutions.

Instructions for Use with 5-Fluorouracil
Oxaliplatin must always be administered before fluoropyrimidines (i.e., 5-fluorouracil).
After administration of oxaliplatin, flush the infusion line and then administer 5-fluorouracil.
For further information regarding medicinal products to be used with oxaliplatin, refer to the corresponding Summary of Product Characteristics.

• USE ONLY the recommended solvents (see below).
• Only clear solutions free from particles should be used.

4.1 Preparation of the Infusion Solution
Withdraw the required volume from the vial(s) and dilute in 250 ml up to 500 ml of 5% glucose solution (50 mg/ml) to obtain an oxaliplatin concentration between at least 0.2 mg/ml and 0.7 mg/ml. The physico-chemical stability of oxaliplatin has been demonstrated within a concentration range of 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 in use has been demonstrated for 24 hours at 2°C–8°C and for 6 hours at 25°C.
From a microbiological standpoint, the infusion preparation should be used immediately. If not used immediately, the user is responsible for storage duration and conditions prior to use, which should not exceed 24 hours at 2°C–8°C, unless dilution occurred under controlled and aseptic conditions.
Inspect visually before use. Only clear, particle-free solutions should be used.
This medicinal product is for single use only. Any unused solution must be discarded (see section “Disposal” below).
NEVER use solutions containing sodium chloride or chloride-containing solutions for dilution.
The compatibility of oxaliplatin in infusion solution has been tested with samples of PVC administration sets.

4.2 Infusion Solution
Administration of oxaliplatin does not require prehydration.
The infusion of oxaliplatin diluted in 250–500 ml of 5% glucose solution (50 mg/ml) to achieve a concentration of not less than 0.2 mg/ml must be administered through a central or peripheral venous line over 2–6 hours. When oxaliplatin is administered in combination with 5-fluorouracil, the oxaliplatin infusion must precede the administration of 5-fluorouracil.

4.3 Disposal
Residues of the medicinal product and any materials used for reconstitution, dilution, and administration must be destroyed in accordance with standard hospital procedures for disposal of cytotoxic waste, in compliance with current regulations on hazardous waste disposal.