Oxaliplatin kalceks

Package leaflet: Information for the user

Oxaliplatin Kalceks, 5 mg/mL, concentrate for solution for infusion
Oxaliplatinum
Please read all of this leaflet carefully before this medicine is administered, because it contains
important information for the patient.

• Keep this leaflet, so that you can read it again if necessary.
• If you have any questions, please consult your doctor or nurse.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of the leaflet

1. What Oxaliplatin Kalceks is and what it is used for
2. Important information before Oxaliplatin Kalceks is administered
3. How to use Oxaliplatin Kalceks
4. Possible side effects
5. How to store Oxaliplatin Kalceks
6. Contents of the pack and other information

1. What Oxaliplatin Kalceks is and what it is used for

The active substance in Oxaliplatin Kalceks is oxaliplatin.
Oxaliplatin is used in the treatment of advanced colorectal cancer (stage III after complete resection of the primary tumour, metastatic colon and rectal cancer). Oxaliplatin is used in combination with other anticancer medicines such as 5-fluorouracil (5-FU) and folinic acid (FA).
Oxaliplatin Kalceks is an anticancer medicinal product containing platinum.

2. Important information before using Oxaliplatin Kalceks

When not to use Oxaliplatin Kalceks:

• if the patient is allergic to oxaliplatin or any of the other ingredients of this medicine (listed in section 6).
• if the patient is breastfeeding.
• if the patient has a low blood cell count.
• if the patient experiences tingling and numbness in the fingers and (or) toes and has difficulty performing precise movements such as buttoning buttons.
• if the patient has severe kidney function impairment.

Warnings and precautions
Before starting treatment with Oxaliplatin Kalceks, discuss the following with the doctor or
nurse:

• if the patient has ever experienced an allergic reaction to platinum-containing medicines such as carboplatin or cisplatin. Allergic reactions may occur during any infusion of oxaliplatin.
• 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 abnormal heart electrical activity known as QT prolongation, irregular heartbeat, or a family history of heart disorders.
• if the patient has recently received or plans to receive any vaccinations. During treatment with oxaliplatin, "live" or "attenuated" vaccines such as the yellow fever vaccine should not be administered.

Children and adolescents
Oxaliplatin should not be used in children and adolescents under 18 years of age.
Oxaliplatin Kalceks and other medicines
Inform the doctor about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.
Pregnancy, breastfeeding and effects on 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 before using this medicine.

• It is not recommended for a patient to become pregnant during treatment with oxaliplatin; the patient must use an effective method of contraception. Female patients should use appropriate contraceptive methods during therapy and for 9 months after completion of treatment.
• If the patient is pregnant or planning a pregnancy, it is very important to discuss this with the doctor before starting treatment.
• If the patient becomes pregnant during treatment, she must immediately inform the doctor.

Breastfeeding
Breastfeeding is not allowed during treatment with oxaliplatin.
Fertility

• Oxaliplatin may cause infertility, which may be irreversible. Before starting treatment, men should seek advice regarding the possibility of sperm storage.
• Men are advised to avoid fathering a child and to use appropriate contraceptive methods during treatment and for 6 months after its completion.

Driving and operating machinery
Treatment with oxaliplatin may increase the risk of dizziness, nausea and vomiting, as well as 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, he or she should not drive, operate machinery, or perform hazardous activities.

3. How to use Oxaliplatin Kalceks

For intravenous infusion.
Oxaliplatin is intended for use in adults only.
The oxaliplatin concentrate for solution for infusion is administered by medical personnel and must be diluted and prepared as a solution prior to intravenous administration.

Dosage
The oxaliplatin dose is determined based on body surface area, calculated from the patient's height and body weight.
The usual dose in adult 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 has previously experienced oxaliplatin-related adverse reactions.

Method and route of administration

• Oxaliplatin is prescribed by an oncologist.
• The patient will be treated by medical staff who will prepare the required dose of oxaliplatin.
• Oxaliplatin is administered by slow injection into one of the patient's veins (intravenous infusion) lasting from 2 to 6 hours.
• Oxaliplatin is administered at the same time as folinic acid, and prior to the 5-fluorouracil infusion.

Frequency of administration
The patient usually receives the drug by intravenous infusion once every 2 weeks.

Duration of treatment
The duration of treatment will be determined by the physician.
Treatment lasts up to a maximum of 6 months when oxaliplatin is used following complete resection of the tumour.

Overdose of Oxaliplatin Kalceks
Since this medicine is administered by medical personnel, it is unlikely that the patient will receive too low or too high a dose.
In the event of overdose, adverse reactions may become more severe. The physician may initiate appropriate treatment for adverse reactions.
If there are any further doubts regarding the use of this medicine, consult the doctor or nurse.

4. Possible adverse reactions

Like any medicine, this medicine can cause adverse reactions, although they do not occur in everyone.
If any adverse reactions occur, it is important to inform your doctor before
the next treatment cycle.
The adverse reactions that may occur are described below.
You should contact your doctor immediately if any of the following occur:

• Symptoms 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 parts of the body, shortness of breath, wheezing or difficulty breathing, extreme fatigue (the patient may feel as if they are about to faint). In most cases, these symptoms occur during or immediately after infusion, but delayed allergic reactions have also been observed several hours or even days after infusion.
• Unusual bruising, bleeding or signs of infection such as sore throat and high fever (due to reduced platelet or white blood cell count).
• Persistent or severe diarrhoea or vomiting.
• Presence of blood or dark brown particles (like coffee grounds) in vomit.
• Pain in the lips or mouth ulcers.
• Unexplained respiratory symptoms such as dry cough, difficulty breathing.
• A group of symptoms such as headache, psychiatric disturbances, seizures and visual disturbances ranging from blurred vision to loss of vision (symptoms of reversible posterior leukoencephalopathy syndrome, a rare neurological disorder).
• Stroke symptoms (including sudden severe headache, disorientation, 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 difficulty speaking).
• Extreme fatigue with reduced red blood cell count and shortness of breath (haemolytic anaemia), occurring with or without reduced platelet count, and kidney disease in which the patient passes little or no urine (symptoms of haemolytic-uraemic syndrome), which may lead to death.

Other known adverse reactions of oxaliplatin include:
Very common (may affect more than 1 in 10 people)

• Oxaliplatin may affect the nerves (peripheral neuropathy). The patient may experience tingling and/or numbness in the fingers, hands and feet, around the mouth or throat, sometimes accompanied by muscle cramps. This adverse reaction is often triggered when the patient is exposed to cold, e.g. when opening a refrigerator or holding a cold drink. The patient may also experience difficulty performing precise tasks, such as buttoning buttons. Although in most cases these symptoms resolve completely, peripheral neuropathy symptoms may persist after treatment has ended. Some patients may experience a sensation of tingling resembling an electric current running down the arms or chest when bending the neck.
• Oxaliplatin may occasionally cause unpleasant sensations in the throat, especially when swallowing, and a feeling of breathlessness. If these sensations occur, they usually appear during or within a few hours after the infusion and may be triggered by exposure to cold temperatures. These sensations are unpleasant but short-lived and resolve without any treatment. As a result, the doctor may decide to modify the treatment.
• Oxaliplatin may cause diarrhoea, mild nausea and vomiting; however, the doctor will administer an antiemetic, usually given before treatment and which may also be taken after the treatment cycle.
• Oxaliplatin causes transient reduction in blood cell counts. A reduction in red blood cells may cause anaemia, a reduction in platelets may lead to unusual bleeding or bruising, and a reduction in white blood cells may increase susceptibility to infections. Before starting treatment and before each subsequent cycle, the doctor will order blood tests to check whether the patient has sufficient blood cell counts.
• Discomfort at or around the injection site during infusion.
• Fever, chills (shivering), mild to 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 of the tongue affecting speech, pain in the lips or mouth ulcers.
• Abdominal pain.
• Unusual 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)

• Infections due to reduced white blood cell count.
• Severe blood infection with reduced white blood cells (neutropenic sepsis), which may be fatal.
• Reduced white blood cell count accompanied by a temperature > 38.3°C or prolonged temperature > 38°C for more than one hour (febrile neutropenia).
• Presence of blood or dark brown particles (like coffee grounds) in vomit.
• Indigestion and heartburn, hiccups, hot flushes, dizziness.
• Excessive sweating and nail disorders, skin peeling.
• Chest pain.
• Lung disorders and catarrh.
• Joint and bone pain.
• Pain during urination and changes in kidney function, changes in frequency of urination, dehydration.
• Presence of blood in urine and stool, blood vessel swelling, blood clots in the lungs.
• High blood pressure.
• Depression and insomnia.
• Conjunctivitis, vision disturbances.
• Reduced calcium levels in the blood.
• Vertigo.

Uncommon (may affect up to 1 in 100 people)

• Severe blood infections (sepsis), which may lead to death.
• Low blood pH (metabolic acidosis).
• Hearing difficulties, dizziness, tinnitus (ringing in the ears).
• 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 loss of vision.
• Unexpected bleeding or bruising caused by widespread blood clots in small blood vessels of the body (disseminated intravascular coagulation), which may lead to death.

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

• Kidney disease in which the patient passes small amounts of urine or no urine at all (symptoms of acute kidney failure).
• Vascular liver disease.

Frequency not known (frequency cannot be determined from available data)

• Allergic vasculitis (inflammation of blood vessels).

• Autoimmune reaction causing reduction in all blood cells (autoimmune pancytopenia), pancytopenia.

• Severe blood infections and low blood pressure (septic shock), which may lead to death.

• Seizures (uncontrolled body shaking).

• Laryngospasm causing breathing difficulties.

• Pneumonia (serious lung infection), which may lead to death.

• Extreme fatigue with reduced red blood cell count and shortness of breath (haemolytic anaemia), occurring with or without reduced platelet count,
  and kidney disease in which the patient passes little or no urine (symptoms of haemolytic-uraemic syndrome), which may lead to death.

• Irregular heart rhythm (QT interval prolongation), detectable on electrocardiogram (ECG) – a condition that may lead to death.

• Myocardial infarction (heart attack), chest pain or discomfort (angina pectoris).

• Muscle pain and swelling associated with weakness, fever or red-brown urine (symptoms of muscle damage known as rhabdomyolysis), which may be fatal.

• Inflammatory condition of the mucous lining of the oesophagus – connecting the mouth to the stomach – resulting in pain and difficulty swallowing (oesophagitis).

• Abdominal pain, nausea, vomiting blood or vomiting material resembling "coffee grounds" or dark/tarry stools (symptoms of stomach and intestinal ulcers with potential bleeding or perforation), which may be fatal.

• Reduced blood flow to the intestine (intestinal ischaemia) – a condition that may lead to death.

• Risk of developing new tumours. Leukaemia, a type of blood cancer, has been reported in patients receiving oxaliplatin in combination with other medicines. The possibility of increased risk of such tumours when oxaliplatin is taken with certain other medicines should be discussed with the doctor.

• Non-tumorous abnormal nodules in the liver (focal nodular hyperplasia).

Reporting of adverse reactions
If any symptoms of adverse reactions occur, including any adverse reactions not listed
in this leaflet, inform your doctor or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products,
Al. Jerozolimskie 181C
PL-02-222 Warsaw
tel.: +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 authorisation holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Oxaliplatin Kalceks

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 carton after "EXP". The expiry date refers to the last day of the stated month.
EXP – expiry date.
Lot – batch number.
No special storage instructions apply for this medicine.

Storage period after dilution
It has been demonstrated that the diluted solution at concentrations from 0.2 mg/mL to 2 mg/mL in glucose solution at a concentration of 50 mg/mL (5%) maintains chemical and physical stability for 24 hours at 25°C and for 4 days at temperatures from 2°C to 8°C.
From a microbiological point of view, the diluted 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 temperatures from 2°C to 8°C, unless dilution was carried out under controlled and validated aseptic conditions.

Oxaliplatin must not come into contact with the eyes or skin. In such a case, a doctor or nurse must be informed immediately.
After completion of the infusion, any remaining medicine must be carefully removed by a doctor or nurse.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Oxaliplatin Kalceks contains

• The active substance is oxaliplatin. Each mL of concentrate for solution for infusion contains 5 mg of oxaliplatin. Each 10 mL vial contains 50 mg of oxaliplatin. Each 20 mL vial contains 100 mg of oxaliplatin. Each 40 mL vial contains 200 mg of oxaliplatin.
• The other component is water for injections.

What Oxaliplatin Kalceks looks like and contents of the pack
This medicinal product is available as a concentrate for solution for infusion (sterile concentrate). It is
a clear, colourless solution, practically free from visible particles.
10 mL, 20 mL or 40 mL of solution in a vial made of colourless glass type I, with a bromobutyl rubber stopper and an aluminium flip-off seal. The vials are placed in cardboard boxes.
Pack sizes: 1 vial of 10 mL, 20 mL or 40 mL
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Importer
AS KALCEKS
Krustpils iela 71E
LV-1057 Rīga
Latvia
Tel.: +371 67083320
E-mail: [email protected]

This medicinal product is authorised in the European Economic Area under the following names:
Latvia Oxaliplatin Kalceks 5 mg/ml koncentrāts infūziju šķīduma pagatavošanai
Czech Republic,
Norway,
Poland Oxaliplatin Kalceks
Belgium Oxaliplatin Kalceks 5 mg/ml concentraat voor oplossing voor infusie
Oxaliplatin Kalceks 5 mg/ml solution à diluer pour perfusion
Oxaliplatin Kalceks 5 mg/ml Konzentrat zur Herstellung einer Infusionslösung
Croatia Oksaliplatin Kalceks 5 mg/ml koncentrat za otopinu za infuziju
France OXALIPLATINE KALCEKS 5 mg/mL, solution à diluer pour perfusion
Germany Oxaliplatin Kalceks 5 mg/ml Konzentrat zur Herstellung einer Infusionslösung
Spain Oxaliplatino Kalceks 5 mg/ml concentrado para solución para perfusión EFG

Information intended exclusively for medical professionals:

SPECIAL PRECAUTIONS FOR DISPOSAL AND OTHER HANDLING
As with other potentially toxic substances, special care must be taken during the use and preparation of oxaliplatin solutions.

Instructions for preparation and administration of medicinal products
The preparation and administration of cytotoxic injectable solutions by medical personnel require special precautions to ensure safety for the person preparing the solution and for their surroundings.

Preparation of cytotoxic drug solutions must be performed by trained and specialized personnel with knowledge of the medicinal products used, under conditions ensuring the integrity of the medicinal product, environmental protection, and in particular, protection of personnel handling cytotoxic agents, in accordance with hospital policy. This requires designating areas exclusively for these activities. Smoking, drinking, and eating are prohibited in such areas.

Personnel preparing cytotoxic drugs must be equipped with appropriate personal protective equipment, in particular long-sleeved gowns, protective masks, protective head covers, safety goggles, sterile disposable gloves, protective coverings for the work area, containers, and waste bags.

Extreme caution must be exercised when handling secretions or vomit.

Pregnant women must be warned to avoid contact with cytotoxic drugs.

Any damaged packaging must be handled with the same caution 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 oxaliplatin concentrate or infusion solution with skin, the affected area must be immediately and thoroughly rinsed with water.

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

Special precautions for administration of the medicinal product

• DO NOT use injection equipment containing aluminium.
• DO NOT administer undiluted solutions.
• For dilution, use only glucose solution at a concentration of 50 mg/mL (5%) for infusion. DO NOT dilute the infusion solution with sodium chloride solution or chloride-containing solutions.
• 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, and 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 administered as an intravenous infusion in 250 mL to 500 mL of glucose solution at a concentration of 50 mg/mL (5%) may be given concurrently with a folinic acid infusion in glucose solution at a concentration of 50 mg/mL (5%), over 2 to 6 hours, using a Y-type connector placed immediately before the infusion site. The two medicinal products must not be mixed in the same infusion bag. Folinic acid must not contain trometamol as an excipient and must be diluted only with isotonic glucose solution at a concentration of 50 mg/mL (5%). 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, i.e., 5-fluorouracil.
After oxaliplatin infusion, the infusion set must 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.

Concentrate for solution for infusion
Before use, visually inspect the medicinal product. Only clear solutions without particulate matter should be used.
Any concentrate showing signs of precipitation must not be used and must be destroyed in accordance with legal requirements for disposal of hazardous waste (see section "Disposal of residues" below).
For single use only. Any unused portion of the solution must be discarded (see section "Disposal of residues" below).

Dilution of intravenous infusion solution
USE ONLY the recommended diluent (glucose solution for infusion at a concentration of 50 mg/mL (5%)).
Withdraw the required amount of concentrate from the vial(s), then dilute in 250 mL to 500 mL of glucose solution at a concentration of 50 mg/mL (5%), to achieve an oxaliplatin concentration between 0.2 mg/mL and 0.7 mg/mL. The concentration range for which physico-chemical stability of oxaliplatin has been demonstrated is from 0.2 mg/mL to 2.0 mg/mL.
Administer by intravenous infusion.

It has been demonstrated that the solution diluted in glucose solution at a concentration of 50 mg/mL (5%) remains chemically and physically stable for 24 hours at 25°C and for 4 days at 2°C to 8°C, within the concentration range of 0.2 mg/mL to 2.0 mg/mL.

From a microbiological standpoint, the diluted solution should be used immediately. If 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 was performed under controlled and validated aseptic conditions.

NEVER use sodium chloride solution or chloride-containing solutions for dilution.

Compatibility of oxaliplatin infusion solution has been tested using infusion sets made of PVC.

Before use, visually inspect the solution. Only clear solutions without particulate matter should be used. Unused solution must be discarded (see section "Disposal of residues" below).

Infusion
Administration of oxaliplatin does not require prior excessive hydration of the patient.
Oxaliplatin diluted in 250 mL to 500 mL of glucose solution at a concentration of 50 mg/mL (5%), to achieve a concentration of at least 0.2 mg/mL, must be administered intravenously over 2 to 6 hours, either 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
Any remaining medicinal product, as well as all materials used for dilution and administration, must be disposed of in accordance with standard hospital procedures for handling cytotoxic drugs, taking into account local regulations regarding disposal of hazardous waste.