Oxaliplatin Sun: detailed information

Package leaflet: Information for the user

Oxaliplatin SUN 5 mg/ml concentrate for solution for infusion

oxaliplatin
Generic medicine
Read this leaflet carefully before using this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as you, because it could be harmful.
If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

What Oxaliplatin SUN is and what it is used for
What you need to know before using Oxaliplatin SUN
How to use Oxaliplatin SUN
Possible side effects
How to store Oxaliplatin SUN
Contents of the pack and other information

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

The active substance of Oxaliplatino SUN is oxaliplatin.
Oxaliplatino SUN is used to treat cancer of the large intestine (treatment both of stage III colon cancer after complete resection of the primary tumour, and of metastatic colon and rectal cancer).
Oxaliplatino SUN is used in combination with other anticancer agents called 5-fluorouracil and folinic acid.
Oxaliplatino SUN is an anticancer medicine that inhibits tumour growth and contains platinum.

2. What you need to know before using Oxaliplatin SUN

Do not use Oxaliplatin SUN

if you are allergic to oxaliplatin or to any of the other ingredients of this medicine (listed in section 6)
if you are breastfeeding
if you already have a low number of blood cells (white blood cells and/or platelets)
if you have previously experienced tingling or numbness in the fingers of your hands and/or feet, and have difficulty performing delicate movements, such as buttoning clothes
if you have severe kidney problems.

Warnings and precautions
Talk to your doctor or pharmacist before using Oxaliplatin SUN if

you have previously had an allergic reaction to medicines containing platinum, such as carboplatin or cisplatin. Reactions may occur during any infusion of oxaliplatin,
you have mild or moderate kidney problems,
you have liver problems or if you notice abnormalities in liver function test results during treatment,
you have or have had heart problems, such as an abnormal electrical signal called QT interval prolongation, irregular heartbeat, or a family history of heart problems,
you have recently received or are planning to receive vaccines. During treatment with oxaliplatin, you should not receive "live" or "attenuated" vaccines, such as the yellow fever vaccine.

Inform your doctor immediately 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 Oxaliplatin SUN, delay, or stop treatment with Oxaliplatin SUN.

Inform your doctor if you have an uncomfortable sensation in your throat, especially when swallowing, or if you feel short of breath during treatment.
Inform your doctor if you have nerve problems in your hands or feet, such as numbness or tingling, or reduced sensitivity in your hands or feet.
Inform your doctor if you have headache, changes in mental function, seizures, or vision problems ranging from blurred vision to loss of vision.
Inform your doctor if you feel unwell (nausea or vomiting).
Inform your doctor if you have severe diarrhoea.
Inform your doctor if you have pain in your lips or mouth ulcers (mucositis/stomatitis/inflammation of the mouth or other mucous membranes).
Inform your doctor if you have diarrhoea, or a decrease in white blood cells or platelets. Your doctor may reduce your dose of Oxaliplatin SUN or delay your treatment with Oxaliplatin SUN.
Inform your doctor if you have unexplained respiratory symptoms such as cough or difficulty breathing. Your doctor may stop treatment with Oxaliplatin SUN.
Inform your doctor if you feel extreme fatigue, shortness of breath, or if you develop kidney disease with reduced or no urine output (symptoms of acute kidney failure).
Inform your doctor if you have fever (temperature greater than or equal to 38°C) or chills, which could be signs of infection. You may be at risk of developing a blood infection.
Inform your doctor if you have a fever above 38°C. Your doctor will determine whether you have a low white blood cell count.
Inform your doctor if you experience unexpected bleeding or bruising (disseminated intravascular coagulation), as these may be signs of blood clots in small blood vessels.
Inform your doctor immediately if you faint (lose consciousness) or have an irregular heartbeat while taking Oxaliplatin SUN, as this may be a sign of a serious heart condition.
Inform your doctor if you experience muscle pain and swelling along with weakness, fever, or brownish-red urine. These may be signs of muscle damage (rhabdomyolysis) and could lead to kidney problems or other complications.
Inform your doctor if you have abdominal pain, nausea, vomiting blood or vomit that looks like "coffee grounds", or dark/tarry stools, as these may be signs of an intestinal ulcer (gastrointestinal ulcer with potential bleeding or perforation).
Inform your doctor if you have abdominal pain (stomach 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 Oxaliplatin SUN
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

Pregnancy, breastfeeding and fertility
Pregnancy

You must not become pregnant during treatment and should therefore use an effective method of contraception during treatment. It is recommended to continue using adequate contraception for up to 9 months after the end of treatment;
Male patients are advised not to father a child during treatment and for 6 months after treatment, and to use adequate contraceptive measures during this time;
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, inform your doctor immediately.

Breastfeeding
Breastfeeding is contraindicated during treatment with oxaliplatin.

Fertility in males and females

Oxaliplatin may affect fertility, which can be irreversible. Male patients may wish to seek advice about sperm preservation before starting therapy. After treatment with oxaliplatin, patients planning a pregnancy are advised to seek genetic counselling. Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines
Oxaliplatin SUN may increase the risk of dizziness, nausea and vomiting, and other neurological symptoms that may affect movement and balance. If this happens to you, you must not drive or operate machinery. If you experience vision problems when receiving Oxaliplatin SUN, do not drive a vehicle, operate heavy machinery, or engage in hazardous activities.

3. How to use Oxaliplatin SUN

Oxaliplatin SUN may only be administered to adults.
This medicinal product is for single use only.

Dosage
The dose of Oxaliplatin SUN is determined based on body surface area, calculated according to the patient's height and weight. The usual dose is 85 mg/m² of body surface area for adults, including elderly patients. The dose you will receive may also depend on the results of your blood tests and whether you have previously experienced side effects with Oxaliplatin SUN.

Method and route of administration

Oxaliplatin SUN will be prescribed for you by a specialist in cancer treatment.
You will be treated by a healthcare professional who will have prepared your required dose of Oxaliplatin SUN.
Oxaliplatin SUN is administered by intravenous injection (intravenous infusion) over a period of 2–6 hours.
Oxaliplatin SUN will be administered simultaneously with folinic acid and prior to the infusion of 5-fluorouracil.

Frequency of administration
You will receive the infusion once every two weeks.

Duration of treatment
The duration of treatment will be determined by your doctor.
The treatment will last up to a maximum of 6 months when used after complete resection of the tumour.

If you use more Oxaliplatin SUN than you should
Since this medicine is administered by a healthcare professional, it is highly unlikely that you will receive too much or too little.
In case of overdose, an increase in undesirable effects may occur. Your doctor will provide appropriate treatment for such adverse effects.
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. It is important that you inform your doctor if you experience any side effects before your next treatment.

Below is a description of all potential side effects.

Serious known side effects
Tell your doctor immediately if you notice any of the following symptoms:

Signs of an allergic or anaphylactic reaction with sudden onset such as rash, itching or hives, difficulty swallowing, swelling of the face, lips, tongue or other body parts, shortness of breath or wheezing, breathing difficulties, extreme tiredness (you may feel you are about to faint). In most cases, these symptoms occurred during or immediately after the infusion, but delayed allergic reactions have also been observed hours or even days after infusion.
Unusual bruising, bleeding, or signs of infection such as sore throat or fever,
Persistent or severe diarrhoea or nausea,
Presence of blood or dark brown-coffee-coloured particles in vomit,
Sores on the lips or mouth ulcers (mucositis/stomatitis),
Respiratory symptoms such as dry cough or cough with sputum, difficulty breathing, shortness of breath or wheezing, as these may indicate a serious lung disease that can be fatal,
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 disorder),
Symptoms of a stroke (including sudden severe headache, confusion, visual disturbances in one or both eyes, numbness or weakness of the face, arm or leg, usually on one side, facial muscle drooping, difficulty walking, dizziness, loss of balance, and speech disturbances).
Severe fatigue with a decrease 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 little or no urine output (all symptoms of haemolytic-uraemic syndrome).

Other known side effects:
Very common: may affect more than 1 in 10 people

Oxaliplatin SUN may affect the nervous system (peripheral neuropathy). You may experience tingling and/or numbness in the fingers, toes, around the mouth or throat, sometimes associated with muscle cramps. These side effects are often triggered by exposure to cold, for example when 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, symptoms related to peripheral sensory neuropathy may persist after treatment has ended. Some individuals have reported a tingling sensation like an electric shock when the neck is bent forward and touched along the arms or trunk (Lhermitte's sign).
Oxaliplatin SUN may cause diarrhoea, mild nausea and vomiting; your doctor will therefore give you medicines to prevent this, which are usually administered before treatment. You may continue taking these medicines after treatment.
Oxaliplatin SUN causes a temporary reduction in blood cell counts. 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 perform blood tests 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 or lack of appetite, taste disturbances, constipation.
Headache, back pain.
Swelling of nerves connected to muscles, neck stiffness, unusual sensations in the tongue with possible speech disturbances, stomatitis/mucositis (irritation of the lips 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

Infections due to reduced white blood cells,
Severe blood infection associated with reduced white blood cells (neutropenic sepsis), which can be fatal,
Reduction in white blood cell count accompanied by fever above 38.3°C or prolonged fever above 38°C for more than one hour (febrile neutropenia),
Indigestion, heartburn, hiccups, hot flushes, dizziness.
Increased sweating, nail changes, skin peeling.
Chest pain,
Lung diseases and rhinitis (runny nose),
Joint pain, bone pain,
Pain during urination and changes in kidney function, changes in frequency of urination, dehydration,
Blood in urine, blood in stools, blood clots in the lung (pulmonary embolism),
High blood pressure,
Depression, insomnia,
Conjunctivitis, vision disturbances,
Low levels of calcium in the blood,
Falls.

Uncommon: may affect up to 1 in 100 people

Severe blood infection (sepsis), which can 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 causing breathing difficulties, sometimes fatal (interstitial lung disease),
Short-term 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 can be fatal.

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

Appearance of blood or dark brown-coffee-coloured particles in vomit.
Kidney diseases causing little or no urine output (symptoms of acute renal failure).
Vascular liver disorders.

Not known: frequency cannot be estimated from available data

Allergic vasculitis (inflammation of blood vessels),
Autoimmune reaction leading to a reduction in all blood cell lines (autoimmune pancytopenia), pancytopenia,
Severe blood infection and low blood pressure (septic shock), which can be fatal,
Seizures (uncontrolled body movements),
Spasm of the throat causing breathing difficulties (laryngospasm),
Severe fatigue with reduced red blood cell count and shortness of breath (haemolytic anaemia), alone or in combination with low platelet count and kidney disease with little or no urine output (symptoms of haemolytic-uraemic syndrome). This has been reported as fatal.
Abnormal heart rhythm (QT interval prolongation), detectable on electrocardiogram (ECG), which can be fatal,
Myocardial infarction (heart attack), angina pectoris (chest pain or discomfort),
Muscle pain and swelling associated with weakness, fever or brown-red urine (symptoms of muscle damage known as rhabdomyolysis), which can be fatal,
Abdominal pain, nausea, vomiting with blood or coffee-ground-like material or dark stools (tarry stools) (symptoms of gastrointestinal ulcer with possible bleeding or perforation), which can be fatal,
Oesophagitis (inflammation of the oesophageal lining – the tube connecting the mouth and stomach), causing pain and difficulty swallowing.
Reduced blood flow to the intestine (intestinal ischaemia), which can be fatal,
Risk of developing a new cancer. Leukaemia, a type of blood cancer, has been reported in patients treated with oxaliplatin in combination with certain other medicines. Discuss with your doctor the possibility of an increased risk of this tumour if you are being treated with Oxaliplatin SUN and certain other medicines.
Unusual benign nodules in the liver (focal nodular hyperplasia).

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

5. How to store Oxaliplatin SUN

Keep this medicine out of the sight and reach of children.
Do not store above 25°C.
Do not use this medicine after the expiry date stated on the label and carton after 'Exp'.
The expiry date refers to the last day of that month.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Oxaliplatin SUN 5 mg/ml concentrate for solution for infusion contains

The active substance is oxaliplatin.
One ml of concentrate contains 5 mg of oxaliplatin.
A 10 ml vial of concentrate contains 50 mg of oxaliplatin.
A 20 ml vial of concentrate contains 100 mg of oxaliplatin.
A 40 ml vial of concentrate contains 200 mg of oxaliplatin.
The other excipients are monohydrate lactose and water for injections.

Description of the appearance of Oxaliplatin SUN 5 mg/ml concentrate for solution for infusion and
pack contents
Concentrate for solution for infusion: a clear, colourless solution in a vial.
Available in 10 ml, 20 ml and 40 ml vials in packs of 1 or 5 vials.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Sun Pharma France
31 Rue Des Poissonniers
92200 Neully Sur Seine
France
Local Representative
Sun Pharma Italia Srl - Viale Giulio Richard, 3 - 20143 Milano
Manufacturer
Sun Pharmaceutical Industries Europe B.V.
Polarisavenue 87
2132 JH Hoofddorp
The Netherlands

This medicinal product is authorised in the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:
Germany Oxaliplatin SUN 5 mg/ml concentrate for solution for infusion
France Oxaliplatine SUN 5 mg/ml solution to be diluted for infusion
Italy Oxaliplatino SUN 5 mg/ml concentrato per soluzione per infusione
Spain Oxaliplatino SUN 5 mg/ml concentrado para solución para perfusión EFG
The Netherlands Oxaliplatine SUN 5 mg/ml concentraat voor oplossing voor infusie
Norway Oksaliplatin SUN 5 mg/ml konsentrat til infusjonsvæske, oppløsning
United Kingdom Oxaliplatin 5 mg/ml concentrate for solution for infusion
(Northern Ireland)

The following information is intended exclusively for physicians or healthcare professionals.

Oxaliplatin SUN 5 mg/ml concentrate for solution for infusion
Instructions for handling and disposal

As with other potentially toxic compounds, caution must be exercised when handling and preparing solutions of Oxaliplatin.

Handling
Handling this cytotoxic agent by healthcare personnel requires all necessary precautions to ensure protection of the handler and the surrounding environment.
Solutions for injection of cytotoxic agents must be prepared by trained personnel familiar with the drugs used, under conditions ensuring the integrity of the medicinal product, protection of the environment, and particularly protection of personnel handling the drugs, in accordance with hospital policies. For this purpose, a dedicated area is required for solution preparation. Smoking, eating or drinking in this area is prohibited.
Personnel must be equipped with appropriate handling materials, i.e. long-sleeved gowns, protective masks, caps, protective goggles, sterile disposable gloves, protective covers for the work area, containers and bags for waste collection.
Secretions and vomit must be handled with caution.
Pregnant women should be advised to avoid contact with cytotoxic agents.
Any broken containers must be handled with the same precautions and considered as contaminated waste. Contaminated waste must be incinerated in rigid, properly labelled containers. See the following section, "Disposal".
In case of contact of concentrated Oxaliplatin or infusion solution with the skin, wash immediately and thoroughly with water.
In case of contact of concentrated Oxaliplatin or infusion solution with mucous membranes, wash immediately and thoroughly with water.

Disposal
Any unused medicinal product and all materials used for dilution and administration must be destroyed in accordance with standard procedures applicable to cytotoxic agents, as required by local regulations for disposal of hazardous waste.

Special precautions for administration
DO NOT use injection systems containing aluminium.
DO NOT administer undiluted oxaliplatin.
Use only 5% glucose (50 mg/ml) infusion solutions as diluent. DO NOT dilute for infusion with solutions containing sodium chloride or chloride.
DO NOT mix with other medicinal products in the same infusion bag, nor administer simultaneously through the same infusion line.
DO NOT mix with alkaline medicinal products or solutions, particularly with 5-fluorouracil and folinic acid preparations containing the excipient trometamol and trometamol salts of other active substances. Alkaline medicinal products or solutions may adversely affect the stability of Oxaliplatin.

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

Administer Oxaliplatin 85 mg/m² as an intravenous infusion in 250–500 ml of 5% glucose solution (50 mg/ml) simultaneously with the intravenous infusion of folinic acid in 5% glucose solution, over 2–6 hours, using a Y-line placed immediately before the infusion site.
These two medicinal products must not be mixed in the same infusion bag. Folinic acid must not contain the excipient trometamol and must be diluted exclusively with isotonic 5% glucose solution, and never in alkaline solutions or those containing sodium chloride.
Instructions for use with 5-fluorouracil

Oxaliplatin must always be administered before fluoropyrimidines – i.e. 5-

fluorouracil.
After administration of Oxaliplatin, flush the catheter and then administer 5-fluorouracil.
For further information on medicinal products associated with Oxaliplatin, refer to their respective
product characteristics summaries.

Incompatibilities
This medicinal product must not be mixed with other medicinal products except those mentioned
in the section “Instructions for dilution”.

Instructions for dilution
Use only 5% glucose solution to dilute the concentrate:
Withdraw the required volume of concentrate from the vial(s) and dilute it with 250 ml - 500 ml of 5% glucose solution to obtain an Oxaliplatin concentration between 0.2 mg/ml and 0.7 mg/ml, which is the concentration range within which the physico-chemical stability of Oxaliplatin has been demonstrated.
Inspect visually before use. Only clear, particle-free solutions should be used.
This medicinal product is for single use only. Any unused infusion solution must be discarded.
NEVER use sodium chloride or chloride-containing solutions to dilute this product.
The compatibility of the Oxaliplatin infusion solution has been evaluated with representative administration sets made of PVC.

Infusion
Prehydration is not required prior to Oxaliplatin administration.
The diluted Oxaliplatin solution in 250–500 ml of 5% glucose solution, with a concentration not less than 0.2 mg/ml, should be infused through a peripheral vein or via a central venous line over 2–6 hours. When Oxaliplatin is administered with 5-fluorouracil, the Oxaliplatin infusion must precede the administration of 5-fluorouracil.

Special precautions for storage
Medicinal product packaged for sale:
Do not store above 25°C.

Preparation of infusion:
After dilution with 5% glucose solution, chemical and physical stability during use has been demonstrated for 24 hours at room temperature (15°C–25°C) or for 48 hours under refrigerated conditions (2°C–8°C). From a microbiological standpoint, the infusion preparation should be used immediately. If not used immediately, the in-use storage duration and storage conditions prior to use are the responsibility of the user and normally should not exceed 24 hours at 2–8°C, provided that dilution has been carried out under controlled and validated aseptic conditions.