Package leaflet: Information for the user

Oxaliplatin Fosun Pharma, 5 mg/mL, concentrate for solution for infusion
Oxaliplatinum
Please read all of 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 further questions, ask your doctor, pharmacist, or nurse.
If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the leaflet

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

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

The active substance in Oxaliplatin Fosun Pharma, concentrate for solution for infusion, is
oxaliplatin.
Oxaliplatin Fosun Pharma is used in the treatment of colorectal cancer (treatment of stage III colon cancer after complete resection of the primary tumour, 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 anticancer agent and contains platinum.

2. Important information before using Oxaliplatin Fosun Pharma

When not to use Oxaliplatin Fosun Pharma

if the patient is allergic to oxaliplatin or any of the other ingredients of this medicine (listed in section 6);
during breastfeeding;
if the patient has reduced blood cell counts;
if the patient experiences tingling and numbness in fingers and (or) toes and problems with performing precise movements such as buttoning clothes;
if the patient has severe kidney function impairment.

Warnings and precautions
Before starting treatment with Oxaliplatin Fosun Pharma, discuss the following with your doctor,
pharmacist, or nurse:

if the patient has ever had an allergic reaction to platinum-containing medicines such as carboplatin or cisplatin. An allergic reaction may occur during oxaliplatin infusion;
if the patient has mild or moderate kidney function impairment;
if the patient has liver function disorders or abnormal liver function test results during treatment;
if the patient has or has had heart problems, such as electrical disturbances of the heart (so-called QT prolongation), irregular heartbeat, or family history of heart disorders.

If any of the following conditions apply to the patient at any time, inform the doctor immediately.
The doctor may decide to initiate appropriate treatment and/or reduce the dose of Oxaliplatin Fosun Pharma,
or delay or discontinue treatment.

If during treatment the patient experiences discomfort in the throat (especially when swallowing) and has difficulty breathing, inform the doctor.
If the patient has nerve disorders in the hands or feet, such as numbness or tingling, or reduced sensation in the hands or feet, inform the doctor.
If the patient has headaches, mental disturbances, seizures, or visual disturbances ranging from blurred vision to loss of vision, inform the doctor.
If the patient has nausea or vomiting, inform the doctor.
If the patient has severe diarrhea, inform the doctor.
If the patient has lip pain or mouth ulcers (mucositis and (or) stomatitis), inform the doctor.
If the patient has diarrhea or reduced white blood cell or platelet counts, inform the doctor. The doctor may reduce the dose of Oxaliplatin Fosun Pharma or delay administration.
If the patient has unexplained respiratory symptoms such as cough or any breathing difficulties, inform the doctor. The doctor may decide to discontinue treatment with Oxaliplatin Fosun Pharma.
If the patient experiences severe fatigue, shortness of breath, or has kidney disease and passes little or no urine (symptoms of acute kidney failure), inform the doctor.
If the patient has fever (38°C or higher) or chills, which may indicate infection, inform the doctor immediately due to the risk of developing sepsis.
If the patient has a fever > 38°C, inform the doctor. The doctor may check whether white blood cell count has also decreased.
If the patient experiences unexpected bleeding or develops bruises (disseminated intravascular coagulation), inform the doctor, as these may be signs of blood clots forming in small blood vessels.
If the patient faints (loses consciousness) or has an irregular heartbeat during treatment with Oxaliplatin Fosun Pharma, inform the doctor immediately, as these may be symptoms of severe heart problems.
If the patient experiences muscle pain, swelling, weakness, fever, or reddish-brown discoloration of urine, inform the doctor, as these may be symptoms of muscle damage (rhabdomyolysis), which may lead to kidney dysfunction or other complications.
If the patient experiences abdominal pain, nausea, vomiting blood or dark brown particles resembling coffee grounds, or has very dark (tarry) stools, which may indicate intestinal ulcer (gastric or intestinal ulcer with possible bleeding or perforation), inform the doctor.
If the patient experiences abdominal pain, bloody diarrhea, and nausea and (or) vomiting, which may be caused by reduced blood flow to the intestinal wall (intestinal ischemia), inform the doctor.

Oxaliplatin Fosun Pharma and other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking, has recently taken,
or plans to take.
Pregnancy, breastfeeding, and fertility
Pregnancy
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child,
she should consult her doctor or pharmacist before using this medicine.

Pregnancy is not recommended during oxaliplatin treatment. Effective contraception methods should be used. Women should use appropriate contraception during treatment and for 15 months after its completion.
If the patient is pregnant or planning pregnancy, it is very important to discuss this with the doctor before starting treatment.
If pregnancy occurs during treatment, inform the doctor immediately.

Breastfeeding

Breastfeeding must not be performed during oxaliplatin treatment.

Fertility

Oxaliplatin may have irreversible effects on fertility. Before starting treatment, men should seek advice regarding the possibility of sperm storage.
Men are advised to avoid fathering a child during treatment and for 12 months after its completion. During this time, appropriate contraception methods should be used.

Before taking any medicine, consult a doctor or pharmacist.
Driving and operating machinery
Treatment with oxaliplatin may increase the risk of dizziness, nausea, vomiting,
and other neurological symptoms that may affect gait and balance.
If these occur, the patient should not drive or operate machinery. If the patient experiences visual disturbances
during treatment with Oxaliplatin Fosun Pharma, he or she should not drive, operate machinery,
or perform hazardous activities.

3. How to use Oxaliplatin Fosun Pharma

Oxaliplatin Fosun Pharma is intended only for adults. For single use only.
Dosage
The dose of Oxaliplatin Fosun Pharma is determined based on body surface area. It is calculated according to the patient's height and body weight.
The usual dose in adults, including elderly patients, is 85 mg/m² of body surface area. The actual dose received by the patient may also depend on blood test results and whether the patient previously experienced adverse reactions related to the use of Oxaliplatin Fosun Pharma.
Method and route of administration

Oxaliplatin Fosun Pharma must be prescribed by a physician specialized in cancer treatment.
The patient will be treated by trained medical personnel who will prepare the required dose of oxaliplatin.
Oxaliplatin Fosun Pharma is administered as a slow intravenous infusion lasting from 2 to 6 hours.
Oxaliplatin Fosun Pharma is administered at the same time as folinic acid and prior to the 5-fluorouracil infusion.

Frequency of administration
The patient usually receives an intravenous infusion once every 2 weeks.
Duration of treatment
The physician will decide on the duration of treatment.
Treatment will last up to a maximum of 6 months when oxaliplatin is used following complete tumor resection.
Administration of a higher than recommended dose of Oxaliplatin Fosun Pharma
Since this medicine is administered by trained medical personnel, it is highly unlikely that the patient will receive too low or too high a dose.
In case of overdose, adverse reactions may become more severe. The physician may initiate appropriate treatment for adverse reactions.
If you have any further doubts regarding the use of this medicine, please consult your doctor, pharmacist, or nurse.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
If any adverse reactions occur, it is important to inform your doctor before the
next treatment cycle.
The adverse reactions listed below may occur.
Contact your doctor immediately if any of the following symptoms occur:

signs of allergy or anaphylactic reaction with sudden symptoms such as rash, itching or hives, difficulty swallowing, swelling of the face, lips, tongue or other parts of the body, shortness of breath, wheezing or difficulty breathing, extreme exhaustion (the patient may feel as if they are about to faint); in most cases, these symptoms occur during or immediately after infusion, although delayed allergic reactions have also been observed several hours or even days after infusion; very common (may affect more than 1 in 10 people);
unusual bruising, bleeding or signs of infection such as sore throat and high fever; very common (may affect more than 1 in 10 people);
persistent or severe diarrhea, or vomiting; very common (may affect more than 1 in 10 people);
presence of blood or dark brown particles (resembling coffee grounds) in vomit; very rare (may affect up to 1 in 10,000 people);
inflammation of the mouth and/or mucositis (pain in lips or mouth ulcers); very common (may affect more than 1 in 10 people);
respiratory symptoms such as dry or wet cough, difficulty breathing or crackling sounds, shortness of breath and wheezing, which may indicate a severe lung disease that can be fatal; very common (may affect more than 1 in 10 people);
a group of symptoms such as: headache, changes in mental state, seizures and vision disturbances from blurred vision to loss of vision (symptoms of reversible posterior leukoencephalopathy syndrome, a rare neurological disorder); rare (may affect up to 1 in 1,000 people);
stroke symptoms (including sudden severe headache, confusion, vision problems in one or both eyes, numbness or weakness of the face, arm or leg, usually on one side, facial drooping, difficulty walking, dizziness, loss of balance and speech problems); frequency unknown (frequency cannot be determined from available data);
extreme exhaustion with reduced red blood cell count and shortness of breath (hemolytic anemia) – rare (may affect up to 1 in 1,000 people), occurring with or without reduced platelet count, abnormal bruising (thrombocytopenia), and kidney disease with reduced or no urine output (symptoms of hemolytic-uremic syndrome) – frequency unknown (frequency cannot be determined from available data).

Other known adverse reactions of oxaliplatin include:

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

Oxaliplatin Fosun Pharma affects the nerves (peripheral neuropathy). The patient may experience tingling and/or numbness in the fingers and toes, around the mouth or in the throat, sometimes accompanied by muscle cramps. This adverse reaction is often triggered when the patient is exposed to cold, for example when opening a refrigerator or holding a cold drink. The patient may also have difficulty performing precise movements, such as buttoning buttons. Although in most cases these symptoms resolve completely, there is a possibility of persistent sensory peripheral neuropathy symptoms after completion of treatment. Some patients may experience a sensation of electric-like tingling running along the arms or torso when bending the neck;
Oxaliplatin Fosun Pharma may occasionally cause unpleasant sensations in the throat, especially when swallowing, and a feeling of breathlessness. These sensations, if they occur, usually appear during or within a few hours after the infusion and may be triggered by exposure to low temperatures. They are unpleasant but short-lived and resolve without any treatment. Your doctor may decide to adjust the treatment if necessary;
Oxaliplatin Fosun Pharma may cause diarrhea, mild nausea and vomiting. Your doctor will prescribe an antiemetic medicine, which is usually given before treatment and may be continued after the treatment cycle;
Oxaliplatin Fosun Pharma causes transient reduction in blood cell counts: reduced red blood cells may lead to anemia, reduced platelets may cause unusual bleeding or bruising, and reduced white blood cells may increase susceptibility to infections. Before starting treatment and before each subsequent cycle, your doctor will order blood tests to check whether you have sufficient blood cell counts;
discomfort at or near the infusion site during infusion;
fever, chills, mild or moderate fatigue, body aches;
changes in body weight, decreased or loss of appetite, taste disturbances, constipation;
headache, back pain;
swelling of nerves leading to muscles, neck stiffness, unusual sensation in the tongue which may affect speech, inflammation of the mouth and/or mucositis (pain in lips or mouth ulcers);
abdominal pain;
abnormal bleeding, including nosebleeds;
cough, difficulty breathing;
allergic reactions, skin rash which may be red and itchy, mild hair loss (alopecia);
changes in blood test results, including those indicating abnormal liver function.

Common (may affect up to 1 in 10 people):

infection due to reduced white blood cell count;
severe blood infection together with reduced white blood cell count (neutropenic sepsis), which may be fatal;
reduced white blood cells with fever > 38.3°C or prolonged fever > 38°C lasting more than one hour (febrile neutropenia);
indigestion and heartburn, hiccups, sudden flushing of the face, dizziness;
excessive sweating and nail disorders, skin peeling;
chest pain;
lung diseases and cold;
bone and joint pain;
pain during urination and kidney changes, changes in frequency of urination, dehydration;
presence of blood in urine and/or stool, blood vessel swelling, blood clots in the lungs;
high blood pressure;
depression, insomnia;
conjunctivitis, vision disturbances;
decreased blood calcium levels;
falls.

Uncommon (may affect up to 1 in 100 people):

severe blood infection (sepsis), which may be fatal;
intestinal obstruction or swelling;
nervousness.

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

hearing loss;
lung scarring and thickening, with breathing difficulties, sometimes leading to death (interstitial lung disease);
transient, short-term vision loss;
unexpected bleeding or bruising due to blood clots forming in small blood vessels (disseminated intravascular coagulation) – a condition that may be fatal.

Very rare (affects fewer than 1 in 10,000 people):

presence of blood or dark brown particles (resembling coffee grounds) in vomit;
kidney disease with low urine output or no urine output (symptoms of acute kidney failure);
vascular liver disease.

Frequency unknown (frequency cannot be determined from available data):

allergic vasculitis (inflammation of blood vessels);
autoimmune reaction causing reduced counts of all blood cells (autoimmune pancytopenia), pancytopenia;
severe blood infection with low blood pressure (septic shock), which may be fatal;
seizures (uncontrolled body shaking);
throat spasm causing breathing difficulties;
extreme exhaustion with reduced red blood cell count and shortness of breath (hemolytic anemia), with or without reduced platelet count, and kidney disease with low or no urine output (symptoms of hemolytic-uremic syndrome), which may be fatal;
irregular heart rhythm (QT interval prolongation), detectable on electrocardiogram (ECG) – a condition that may be fatal;
muscle pain and swelling with weakness, fever or red-brown discoloration of urine (symptoms of muscle damage called rhabdomyolysis) – a condition that may be fatal;
abdominal pain, nausea, vomiting blood or presence of dark brown particles resembling coffee grounds in vomit, or very dark (tarry) stools (symptoms of stomach or intestinal ulceration, possibly with bleeding or perforation) – a condition that may be fatal;
reduced blood flow to the intestine (intestinal ischemia) – a condition that may be fatal;
risk of developing new tumors. Cases of leukemia – a type of blood cancer – have been reported in patients treated with Oxaliplatin Fosun Pharma in combination with certain other medicines. You should consult your doctor about the possibility of developing this type of tumor during treatment with Oxaliplatin Fosun Pharma and certain other medicines;
myocardial infarction (heart attack), angina (pain or discomfort in the chest);
esophagitis (inflammatory condition of the esophageal mucosa, i.e. the passage connecting the mouth to the stomach – resulting in pain and difficulty swallowing).

Reporting of adverse reactions
If any adverse symptoms occur, including any adverse symptoms not listed in this leaflet, inform your doctor, pharmacist or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Oxaliplatin Fosun Pharma

The medicine should be stored out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label and the outer carton following: Expiry date (EXP). The expiry date refers to the last day of the stated month.
Store the vial in its outer packaging to protect it from light.
Store below 30°C.

Stability after dilution:
It has been demonstrated that the diluted solution in 5% glucose maintains chemical and physical stability for 96 hours at a temperature of 2°C to 8°C and for 24 hours at 25°C.
From a microbiological standpoint, the infusion solution should be used immediately.
If the solution is not used immediately, the user is responsible for the storage conditions and duration prior to use. The storage period should not exceed 24 hours at 2°C to 8°C, unless dilution has been carried out under controlled and validated aseptic conditions.

Do not use Oxaliplatin Fosun Pharma if the solution is not clear or if particulate matter is visible.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures will help protect the environment.

6. Contents of the package and other information

What Oxaliplatin Fosun Pharma contains

The active substance is oxaliplatin. 1 mL of concentrate for solution for infusion contains 5 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.
The other component is: water for injections.

What Oxaliplatin Fosun Pharma looks like and contents of the pack
This medicine is a concentrate for solution for infusion. It is a clear, colourless solution,
without visible solid particles.
Each vial contains 50 mg or 100 mg of oxaliplatin. The concentrate is supplied in vials
with a capacity of 10 mL or 20 mL made of colourless type I glass, with bromobutyl-fluoropolymer rubber stoppers and aluminium flip-off seals with yellow caps (vial 50 mg/10 mL) or royal blue caps (vial 100 mg/20 mL).
Pack sizes:
50 mg/10 mL: 1 vial
100 mg/20 mL: 1 vial
Vials are supplied in cardboard boxes containing one vial.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Fosun Pharma Sp. z o.o.
ul. Zajęcza 15
00-351 Warsaw
Tel.: + 48 22 244 11 05
This medicine is authorised in the European Economic Area countries under the following names:
Austria: Oxaliplatin Fosun Pharma
France: Oxaliplatine Fosun Pharma
Germany: Oxaliplatin Fosun Pharma 5 mg/ml Konzentrat zur Herstellung einer Infusionslösung
Poland: Oxaliplatin Fosun Pharma
Italy: Oxaliplatina Fosun Pharma

Information intended exclusively for healthcare professionals:

SPECIAL PRECAUTIONS FOR HANDLING
AND PREPARATION OF THE MEDICINAL PRODUCT FOR ADMINISTRATION
As with other potentially toxic substances, special precautions should be taken during handling and preparation of oxaliplatin solutions.

Preparation instructions
Preparation of cytotoxic drug solutions by healthcare personnel requires special precautions to ensure safety for the person preparing the solution and their environment.
Solutions for cytotoxic injections must be prepared by appropriately trained personnel who have knowledge of the drugs used, under conditions ensuring product integrity, environmental protection, and particularly the safety of personnel handling cytotoxic drugs, in accordance with hospital regulations. This requires preparation of a dedicated area for this purpose. Smoking, eating, or drinking is prohibited in the designated area.

Personnel preparing cytotoxic drugs must be equipped with appropriate personal protective equipment, particularly long-sleeved gowns, protective masks, protective head covers, protective goggles, sterile disposable gloves, appropriate protective barriers at workstations, and containers and bags for waste disposal.

Extreme caution should be exercised when handling excreta and vomit.
Pregnant women should be warned to avoid contact with cytotoxic drugs.
Damaged packaging should be handled with the same precautions as contaminated waste.
Contaminated waste must be incinerated after being placed in appropriately labeled, rigid containers. See section "Disposal of residues" below.

In case of contact of the concentrate for infusion solution or the infusion solution of oxaliplatin with the skin, the affected area should be immediately and thoroughly rinsed with water.
In case of contact of the concentrate for infusion solution or the infusion solution of oxaliplatin with mucous membranes, the affected area should be immediately and thoroughly rinsed with water.

Special precautions for administration

DO NOT use injection equipment containing aluminium.
DO NOT administer undiluted solutions.
Dilute only with 5% glucose infusion solution. DO NOT dilute the infusion solution with sodium chloride solution or solutions containing chlorides.
DO NOT mix with other medicinal products in the same infusion bag and DO NOT administer simultaneously through the same infusion set.
DO NOT mix with medicinal products or solutions of alkaline pH, particularly 5-fluorouracil, folinic acid products containing trometamol as an excipient, or trometamol salts of other active substances. Medicinal products or solutions of alkaline pH negatively affect the stability of oxaliplatin.

Instructions for use with folinic acid (FA) (as calcium folinate or disodium folinate)
Oxaliplatin at a dose of 85 mg/m² BSA administered as an intravenous infusion in 250 mL to 500 mL of 5% glucose solution should be given concurrently with a folinic acid (FA) infusion in 5% glucose solution over 2 to 6 hours, using a Y-connector placed immediately before the infusion site. The two drugs should not be mixed in the same infusion bag. Folinic acid must not contain trometamol as an excipient and must be diluted only with isotonic 5% glucose solution; alkaline solutions, sodium chloride solution, or chloride-containing solutions must never be used for dilution.

Instructions for use with 5-fluorouracil (5-FU)
Oxaliplatin must always be administered before fluoropyrimidines, e.g., 5-fluorouracil. After oxaliplatin infusion, the infusion set should be flushed before administering 5-fluorouracil.
For additional information on medicinal products used concomitantly with oxaliplatin, refer to the relevant sections of the Summary of Product Characteristics.

USE ONLY the recommended solvents (see below).
Any concentrate showing signs of precipitation must not be used and should be disposed of in accordance with legal requirements for disposal of hazardous waste (see below).

Concentrate for solution for infusion
The solution should be visually inspected before use. Only clear solutions, free from any particulate matter, should be used. The medicinal product is intended for single use only. Any unused solution residues must be discarded.

Dilution of intravenous infusion solution
Withdraw the required amount of concentrate from the vial(s) and dilute with 250 mL to 500 mL of 5% glucose solution to obtain an oxaliplatin concentration between 0.2 mg/mL and 2 mg/mL. This concentration range has been shown to maintain the physical and chemical stability of oxaliplatin.
Administer by intravenous infusion.

It has been demonstrated that the solution diluted with 5% glucose solution maintains chemical and physical stability for 96 hours at temperatures from 2°C to 8°C and for 24 hours at 25°C.
From a microbiological standpoint, the infusion solution should be used immediately.
If the solution is not used immediately, the responsibility for storage conditions and duration prior to use lies with the user. The storage period should not exceed 24 hours at temperatures from 2°C to 8°C, unless dilution was performed under controlled and validated aseptic conditions.

The solution, both before and after dilution, should be practically free from visible particulate matter. The solution should be visually inspected before use. Only clear solutions, free from any particulate matter, should be used.
The medicinal product is intended for single use only. Any unused solution residues must be discarded (see section "Disposal of residues" below).
DO NOT use sodium chloride solutions or chloride-containing solutions for dilution.

Infusion
Prior hydration of the patient is not required for oxaliplatin administration.
Oxaliplatin diluted in 250 mL to 500 mL of 5% glucose solution to achieve a concentration of at least 0.2 mg/mL must be administered intravenously over 2 to 6 hours via a peripheral or central vein.
When oxaliplatin is administered together with 5-fluorouracil, the oxaliplatin infusion must precede the administration of 5-fluorouracil.

Disposal of residues
Residues of the medicinal product and all materials used for dilution and administration must be destroyed in accordance with standard hospital procedures for handling cytotoxic agents and in compliance with local requirements for disposal of hazardous waste.

Route of administration
FOR USE IN ADULTS ONLY

The recommended dose of oxaliplatin in adjuvant treatment is 85 mg/m² BSA, administered intravenously every two weeks for 12 cycles (6 months).
The recommended dose of oxaliplatin in the treatment of metastatic colorectal cancer is 85 mg/m² BSA, administered intravenously every two weeks until disease progression or until an unacceptable level of toxicity occurs.
The administered dose should be adjusted according to tolerance (see section 4.4 "Special warnings and precautions for use" in SmPC).

Oxaliplatin must always be administered before fluoropyrimidines, e.g., 5-fluorouracil (5-FU).
Oxaliplatin is administered as an intravenous infusion lasting from 2 to 6 hours, diluted in 250 mL to 500 mL of 5% glucose solution (50 mg/mL), to achieve a concentration between 0.2 mg/mL and 0.7 mg/mL.
The concentration of 0.7 mg/mL is the highest concentration used in clinical practice for an oxaliplatin dose of 85 mg/m² BSA.

Shelf life
2 years

Special precautions during storage
Store the vial in its outer packaging to protect from light.
Store below 30°C.

Oxaliplatin fosun pharma