Oxaliplatin Fosun Pharma: detailed information

PACKAGE LEAFLET

Package leaflet: information for the user

Oxaliplatino Fosun Pharma 5 mg/mL concentrate for solution for infusion

oxaliplatin
Generic medicine
Please read this leaflet carefully before 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 experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

What Oxaliplatino Fosun Pharma is and what it is used for
What you need to know before using Oxaliplatino Fosun Pharma
How to use Oxaliplatino Fosun Pharma
Possible side effects
How to store Oxaliplatino Fosun Pharma
Package contents and other information

1. What Oxaliplatin Fosun Pharma is and what it is used for

The active substance of Oxaliplatin Fosun Pharma concentrate for solution for infusion is oxaliplatin.
Oxaliplatin Fosun Pharma 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).
Oxaliplatin Fosun Pharma is used in combination with other anticancer medicines such as 5-fluorouracil
and folinic acid.
Oxaliplatin Fosun Pharma is an antineoplastic, i.e. an anticancer medicine, and contains platinum.

2. What you should know before receiving Oxaliplatino Fosun Pharma

Do not use Oxaliplatino Fosun Pharma:

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.
if you have previously experienced tingling or numbness in the fingers of your hands and/or feet, or if you have difficulty performing precise tasks such as buttoning clothes.
if you have severe kidney problems.

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking Oxaliplatino Fosun Pharma:

if you have previously had an allergic reaction to platinum-containing medicines, 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 liver function tests have shown abnormal results during treatment.
if you have or have had heart disorders characterized by an abnormal electrical signal known as QT interval prolongation, 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 and may consider it necessary to reduce the dose of Oxaliplatino Fosun Pharma, or delay or discontinue treatment with Oxaliplatino Fosun Pharma.

Inform your doctor if you have a bothersome sensation in your throat, especially when swallowing, and if you feel shortness of breath during treatment;
inform your doctor if you have nerve problems in the hands or feet, such as numbness or tingling, or if you have reduced sensitivity in the hands or feet;
inform your doctor if you have headache, changes in mental function, seizures, or vision disturbances including blurred vision or loss of vision;
inform your doctor if you feel unwell, nauseous, or if you vomit;
inform your doctor if you have severe diarrhoea;
inform your doctor if you have pain in the lips or mouth ulcers (mucositis/stomatitis); inform your doctor if you have diarrhoea, or if a reduction in white blood cells or platelets is observed. Your doctor may reduce the dose of Oxaliplatino Fosun Pharma or delay treatment with Oxaliplatino Fosun Pharma;
inform your doctor if you experience unexplained respiratory symptoms such as cough or difficulty breathing. Your doctor may instruct you to stop treatment with Oxaliplatino Fosun Pharma;
inform your doctor if you experience extreme fatigue, shortness of breath, or develop a kidney disorder causing reduced or no urine output (symptoms of acute renal failure);
inform your doctor immediately if you have fever (with 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;
inform your doctor if you have a fever above 38°C. Your doctor will assess whether there is also a reduction in white blood cells;
inform your doctor if you experience unexpected bleeding or notice the appearance of bruises (disseminated intravascular coagulation), as these symptoms may indicate blood clots in small blood vessels;
inform your doctor immediately if you faint (lose consciousness) or have an irregular heartbeat while taking Oxaliplatino Fosun Pharma, as this may be a sign of a serious heart condition;
inform your doctor if you experience muscle pain and swelling associated with weakness, fever, or brown-red coloured 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 resembling "coffee grounds", or black, 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, bloody diarrhoea, nausea and/or vomiting, which may be caused by reduced blood flow to the intestinal wall (intestinal ischemia).

Other medicines and Oxaliplatino Fosun Pharma
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Pregnancy, breastfeeding and fertility
Pregnancy
If you are pregnant, suspect you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.

Pregnancy during oxaliplatin therapy is not recommended; you should use an effective method of contraception. Female patients must use appropriate contraceptive measures during treatment and for 15 months after the end of 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.

Breastfeeding

You must not breastfeed during treatment with oxaliplatin.

Fertility

Oxaliplatin may have an anti-fertility effect, which may be irreversible. Male patients may wish to seek advice regarding sperm preservation before starting treatment.
Male patients are advised not to father a child during treatment and for 12 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
Oxaliplatin may increase the risk of dizziness, nausea and vomiting, and other neurological symptoms affecting walking and balance. If this occurs, you must not drive or operate machinery. If you experience vision problems while taking Oxaliplatino Fosun Pharma, do not drive, operate heavy machinery, or engage in hazardous activities.

3. How to use Oxaliplatin Fosun Pharma

Oxaliplatin Fosun Pharma must be administered only to adult patients. This
medicinal product is for single use only.
Dose
The dose of Oxaliplatin Fosun Pharma depends on the body surface area. This is
calculated from body 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 blood test results and any previously experienced
adverse reactions during prior treatments with Oxaliplatin Fosun Pharma.
Method and route of administration

Oxaliplatin Fosun Pharma will be prescribed by an oncologist, i.e. a doctor specialized in cancer treatment.
You will be treated by a healthcare professional who will prepare the correct dose of Oxaliplatin Fosun Pharma.
Oxaliplatin Fosun Pharma is administered as a slow intravenous injection (intravenous infusion) over a period of 2–6 hours.
Oxaliplatin Fosun Pharma 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 surgical removal of the tumour, treatment will last up to a maximum of 6 months.
If you use more Oxaliplatin Fosun Pharma than you should
Since this medicine will be administered by healthcare professionals, it is highly unlikely that you will receive too much or too little.
In case of overdose, adverse reactions may increase in intensity. Your doctor can provide appropriate treatment to manage these side effects.
If you have any questions about your treatment, please consult your doctor, nurse, or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
If you experience any side effect, it is important that you inform your doctor before receiving the next treatment.

Below are described the side effects you may encounter.

Immediately inform your doctor if you notice any of the following symptoms:

Signs of an allergic or anaphylactic reaction such as sudden rash, itching, skin hives, difficulty swallowing, swelling of the face, lips, tongue or other parts of the body, shortness of breath, wheezing or breathing difficulties, severe fatigue (or feeling faint). In most cases, these symptoms occurred during or immediately after infusion, but delayed allergic reactions have been observed several hours or days after infusion. Very common (may affect more than 1 in 10 people).
Unusual bruising, bleeding or signs of infection such as sore throat or high temperature. Very common (may affect more than 1 in 10 people).
Persistent or severe diarrhoea or vomiting. Very common (may affect more than 1 in 10 people).
Blood or dark brown coffee-ground-like particles in vomit. Very rare (may affect 1 in 10,000 people).
Stomatitis/mucositis (irritation of the lips or mouth ulcers). Very common (may affect more than 1 in 10 people).
Respiratory symptoms such as dry or productive cough, difficulty breathing or crackling sounds, shortness of breath and wheezing, which may indicate a life-threatening lung disease that can lead to death. Very common (may affect more than 1 in 10 people).
A group of symptoms including headache, changes in mental function, seizures and visual disturbances ranging from blurred vision to loss of vision (symptoms of reversible posterior leukoencephalopathy syndrome, a rare neurological disorder). Rare (may affect 1 in 1,000 people).
Symptoms of stroke (including sudden severe headache, confusion, difficulty seeing from one or both eyes, numbness or weakness of facial muscles, arm or leg, usually on one side, facial drooping, difficulty walking, dizziness, loss of balance and difficulty speaking). Frequency not known (cannot be estimated from available data).
Severe fatigue with a decrease in red blood cells and shortness of breath (haemolytic anaemia) – rare (may affect 1 in 1,000 people), alone or in combination with a low platelet count, unusual bruising (thrombocytopenia), and kidney disease with reduced or no urine output (symptoms of haemolytic-uremic syndrome) – frequency not known (cannot be estimated from available data).

Other known side effects of Oxaliplatin are:

Very common: may affect more than 1 in 10 people

Oxaliplatin Fosun Pharma 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 increased 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 experienced a tingling sensation similar to an electric shock that moves down the arms or trunk when bending the neck forward.
Oxaliplatin Fosun Pharma may occasionally cause discomfort in the throat, particularly during swallowing, and a sensation of shortness of breath. If this occurs, it is usually observed during or within a few hours after infusion and may be worsened by exposure to cold. Although unpleasant, this sensation is usually short-lived and resolves without requiring further treatment. As a result, your doctor may decide to adjust your treatment.
Oxaliplatin Fosun Pharma 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.
Oxaliplatin Fosun Pharma causes a temporary reduction in blood cell counts. A reduction in red blood cells may lead to anaemia, abnormal bleeding or bruising (due to a decrease in platelets). A decrease in white blood cells may increase susceptibility 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 pain.
Changes in body weight, loss of appetite or no appetite, taste changes, constipation.
Headache, back pain.
Swelling of nerves connected to muscles, neck stiffness, unusual tongue sensations with 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 above 38.3°C or prolonged fever above 38°C for more than 1 hour (febrile neutropenia).
Indigestion and heartburn, hiccups, flushing, dizziness.
Increased sweating, nail changes, skin peeling.
Chest pain.
Lung disorders and runny nose.
Joint and bone pain.
Pain during urination and altered kidney function, changes in urination frequency, dehydration.
Blood in urine/stool, swelling of veins, blood clots in the lungs.
High blood pressure.
Depression and insomnia.
Conjunctivitis and visual disturbances.
Low calcium levels 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 vision loss.
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

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 disorders.

Frequency not known: cannot be estimated from available data

Allergic vasculitis (inflammation of blood vessels).
Autoimmune reaction causing a reduction in all blood cell lines (autoimmune pancytopenia), 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 decrease 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 (altered urination) (symptoms of haemolytic-uremic syndrome), which may be fatal.
Abnormal heart rhythm (QT prolongation), detectable on electrocardiogram (ECG), which may be fatal.
Muscle pain and swelling associated with weakness, fever, or brown-red urine (symptoms of muscle damage called rhabdomyolysis), which may be fatal.
Abdominal pain, nausea, vomiting blood or vomit resembling "coffee grounds", or dark/tarry stools (symptoms of gastrointestinal ulcer with potential bleeding or perforation), which may be fatal.
Reduced blood flow to the intestine (intestinal ischaemia), which may be fatal.
Risk of a new tumour. Cases of leukaemia, a type of blood cancer, have been reported in patients after treatment with Oxaliplatin Fosun Pharma in combination with other specific medicines. Discuss with your doctor the potential increased risk of this type of cancer when taking Oxaliplatin Fosun Pharma with other specific medicines.
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).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please contact your doctor, pharmacist or nurse. You can 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 Fosun Pharma

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging and on the vial label. The expiry date refers to the last day of that month.
Keep the medicine in its outer packaging to protect it from light. Store below 30 °C.

In-use stability after dilution
After dilution in 5% glucose solution, chemical and physical stability has been demonstrated for 96 hours at 2–8 °C and for 24 hours at 25 °C.
For microbiological reasons, the infusion solution should be used immediately. If it is not used immediately, the storage times and conditions prior to use are the responsibility of the user and, under normal circumstances, the medicine should not be stored for more than 24 hours at 2–8 °C, unless the dilution was carried out under controlled and validated aseptic conditions.

Do not use this medicine if you notice that the solution is not clear or contains visible particles.
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 Oxaliplatino Fosun Pharma contains

The active substance is oxaliplatin. 1 mL of concentrate for infusion solution contains 5 mg of oxaliplatin. 10 mL of concentrate for infusion solution contains 50 mg of oxaliplatin. 20 mL of concentrate for infusion solution contains 100 mg of oxaliplatin.
The excipient is water for injections.

Description of the appearance of Oxaliplatino Fosun Pharma and contents of the pack
This medicinal product is a concentrate for infusion solution. It is a clear, colourless, particle-free concentrate for infusion solution.
Each vial contains 50 mg or 100 mg of oxaliplatin. The medicine is supplied in 10 mL and 20 mL clear glass type I vials with bromobutyl rubber stoppers and aluminium flip-off seals with yellow caps (vial 50 mg/10 mL) or dark blue caps (vial 100 mg/20 mL).
Pack contents:
50 mg/10 mL: 1 vial
100 mg/20 mL: 1 vial
The packs contain one vial.
Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
FOSUN PHARMA Sp. Z.o.o.,
Zajęcza n.15 Str, 00-351, Warsaw, Poland

This medicinal product is authorized in the Member States of the European Economic Area under the following names:
Austria: Oxaliplatin Fosun Pharma
Germany: Oxaliplatin Fosun Pharma 5 mg/ml Konzentrat zur Herstellung einer Infusionslösung
France: Oxaliplatine Fosun Pharma
Italy: Oxaliplatino Fosun Pharma
Poland: Oxaliplatin Fosun Pharma

This leaflet was last updated on

The following information is intended exclusively for healthcare professionals

RECOMMENDATIONS FOR SAFE HANDLING OF THE PRODUCT
As with other potentially toxic compounds, caution must be exercised when handling and preparing
oxaliplatin solutions.
Handling instructions
This cytotoxic agent must be used with great care by healthcare personnel to protect both the handler and the surrounding environment.
The preparation of injectable solutions of cytotoxic agents should be carried out by specially trained, experienced personnel who are familiar with the drugs used, under conditions ensuring the integrity of the medicinal product, protection of the environment, and in particular, protection of personnel handling the drugs, in accordance with hospital procedures. This requires a dedicated preparation area. Smoking, eating or drinking is strictly prohibited in this area.
Personnel must have access to appropriate handling materials, including long-sleeved gowns, protective masks, head covers, protective goggles, sterile disposable gloves, protective absorbent pads for the work surface, and containers and bags for waste collection.
Excreta and vomit must be handled with caution.
Pregnant women should be advised to avoid handling cytotoxic drugs.
All broken containers must be handled with the same precautions and considered as contaminated waste. Contaminated waste must be incinerated in rigid, designated containers.
See the section “Disposal” below.
In case of accidental skin contact with the concentrate for infusion solution, immediately and thoroughly rinse the skin with water.
In case of accidental contact with mucous membranes, immediately and abundantly rinse the mucous membranes with water.
Special administration precautions

NEVER use injection devices containing aluminum;
NEVER administer the product undiluted;
Use only 5% glucose solution (50 mg/mL) as diluent. DO NOT dilute the infusion with sodium chloride solutions or solutions containing chloride;
DO NOT mix with any other medicinal product in the same infusion bag and NEVER administer simultaneously with other drugs through the same infusion line;
DO NOT mix with alkaline medicinal products or solutions, particularly 5-fluorouracil, folinic acid preparations containing tromethamine as excipient, and tromethamine salts of other active substances. Alkaline solutions or medicinal products negatively affect the stability of oxaliplatin.

Instructions for use with folinic acid (as calcium folinate or sodium folinate)
Intravenous infusion of oxaliplatin 85 mg/m² in 250–500 mL of 5% glucose solution (50 mg/mL) is administered simultaneously with intravenous infusion of folinic acid in 5% glucose solution (50 mg/mL) 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 tromethamine as excipient and must be diluted using only isotonic 5% glucose solutions (50 mg/mL), never alkaline solutions or solutions containing sodium chloride or chlorides.
Instructions for use with 5-fluorouracil (5-FU)
Administration of oxaliplatin must always precede that of fluoropyrimidines – i.e., 5-fluorouracil (5-FU). 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).

Any concentrate showing signs of precipitation must not be used and must be destroyed in accordance with local requirements for disposal of hazardous waste (see below).

Concentrate for infusion solution
Visually inspect before use. Only clear, particle-free solutions should be used.
The medicinal product is for single use only. All unused infusion solutions must be discarded.
Dilution prior to intravenous infusion
Withdraw the required amount of concentrate from the vial(s) and dilute with 250–500 mL of 5% glucose solution to achieve an oxaliplatin concentration between 0.2 mg/mL and 2 mg/mL, which is the concentration range for which physicochemical stability of oxaliplatin has been demonstrated.
Administer by intravenous infusion.
After dilution with 5% glucose solution, chemical and physical stability has been demonstrated for 96 hours at 2–8°C and for 24 hours at 2–8°C, unless the dilution was performed under controlled and validated aseptic conditions.
For microbiological reasons, the infusion preparation should be used immediately. If not used immediately, the duration and conditions of storage prior to use are the responsibility of the user and normally should not exceed 24 hours at 25°C.
Visually inspect before use. Only clear, particle-free solutions should be used.
The medicinal product is for single use only. All unused infusion solutions must be discarded (see section “Disposal” below).
NEVER use sodium chloride solutions or solutions containing chloride for dilution.
Infusion
Pre-hydration is not required prior to oxaliplatin administration.
Oxaliplatin diluted in 250–500 mL of 5% glucose solution to achieve a concentration of not less than 0.2 mg/mL must be infused either via a peripheral vein or through a central venous line over a period of 2 to 6 hours. When oxaliplatin is administered with 5-fluorouracil, the oxaliplatin infusion must precede the administration of 5-fluorouracil.
Disposal
Any unused portion of the medicinal product and any materials used for dilution and administration must be destroyed in accordance with standard hospital procedures for disposal of cytotoxic waste, in compliance with local requirements for disposal of hazardous waste.
Administration
FOR USE IN ADULTS ONLY
The recommended dose of oxaliplatin for adjuvant therapy is 85 mg/m² of body surface area, administered as repeated intravenous infusions every 2 weeks for 12 cycles (6 months).
The recommended dose of oxaliplatin for the treatment of metastatic colorectal cancer is 85 mg/m² administered as repeated intravenous infusions every two weeks, until disease progression or unacceptable toxicity occurs.
The dose should be adjusted according to tolerability (see section 4.4 Special Warnings and Precautions for Use in the SmPC).
Administration of oxaliplatin must always precede that of fluoropyrimidines – i.e., 5-fluorouracil.
Oxaliplatin should be administered as an intravenous infusion lasting 2–6 hours in 250–500 mL of 5% glucose solution (50 mg/mL), to achieve a concentration between 0.2 mg/mL and 0.70 mg/mL; 0.70 mg/mL is the highest concentration used in clinical practice for an oxaliplatin dose of 85 mg/m².
Shelf life
2 years
Special precautions for storage
Store the vial in the original packaging to protect from light.
Store below 30°C.