Oxaliplatin Kalceks

Package Leaflet: Information for the User

Oxaliplatin Kalceks, 5 mg/mL, Concentrate for Solution for Infusion

Oxaliplatinum

Read All of This Leaflet Carefully Before You Start Using This Medicine Because It Contains Important Information for You.

• You should keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the Pack and Other Information

• 1. What Oxaliplatin Kalceks is and What It is Used For
• 2. Before You Use Oxaliplatin Kalceks
• 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 of Oxaliplatin Kalceks is oxaliplatin.
Oxaliplatin is used to treat advanced colorectal cancer (stage III after complete removal of the primary tumor, colon and rectal cancer with metastases). Oxaliplatin is used in combination with other anticancer medicines such as 5-fluorouracil (5-FU) and folinic acid (FA).
Oxaliplatin Kalceks is an anticancer medicine and contains platinum.

2. Before You Use Oxaliplatin Kalceks

When Not to Use Oxaliplatin Kalceks:

• If you are allergic to oxaliplatin or any of the other ingredients of this medicine (listed in section 6).
• If you are breastfeeding.
• If you have a reduced number of blood cells.
• If you have tingling and numbness of the fingers of the hands and (or) feet and problems with performing precise tasks such as buttoning.
• If you have severe kidney problems.

Warnings and Precautions

Before starting treatment with Oxaliplatin Kalceks, you should discuss this with your doctor or nurse:

• If you have ever had an allergic reaction to platinum-containing medicines such as carboplatin, cisplatin. Allergic reactions can occur during any infusion of oxaliplatin.
• If you have mild or moderate kidney problems.
• If you have liver problems or abnormal liver function tests during treatment.
• If you have or have had heart problems, such as abnormal heart rhythm, irregular heartbeat, or a family history of heart problems.
• If you have recently received or plan to receive any vaccines. You should not be vaccinated with "live" or "attenuated" vaccines, such as the yellow fever vaccine, during treatment with oxaliplatin.

Children and Adolescents

Oxaliplatin should not be used in children and adolescents under 18 years of age.

Oxaliplatin Kalceks and Other Medicines

Tell your doctor about all the medicines you are taking now or have taken recently, and about any medicines you plan to take.

Pregnancy, Breastfeeding, and Fertility

Pregnancy
If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a baby, ask your doctor for advice before using this medicine.

• It is not recommended to become pregnant during treatment with oxaliplatin; you must use effective contraception. Women should use appropriate contraceptive measures during treatment and for 9 months after the end of treatment.
• If you are pregnant or plan to become pregnant, it is very important to discuss this with your doctor beforestarting treatment.
• If you become pregnant during treatment, you must immediatelyinform your doctor.

Breastfeeding
Do not breastfeedduring treatment with oxaliplatin.
Fertility

• Oxaliplatin may cause infertility, which may be irreversible. Men should seek advice on the possibility of storing sperm before starting treatment.
• Men are advised to avoid fathering a child and to use appropriate contraceptive measures during treatment and for 6 months after the end of treatment.

Driving and Using Machines

Treatment with oxaliplatin may increase the risk of dizziness, nausea, and vomiting, as well as other neurological symptoms that may affect gait and balance.
In case of their occurrence, do not drive vehicles or operate machinery. If you experience vision disturbances during treatment with oxaliplatin, you should not drive vehicles, operate machinery, or perform hazardous activities.

3. How to Use Oxaliplatin Kalceks

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

Dosage

The dose of oxaliplatin is determined based on body surface area. It is calculated based on the patient's height and weight.
The usual dose in adult patients is 85 mg/m² of body surface area. The dose that the patient receives also depends on the results of blood tests and whether the patient has previously experienced side effects related to oxaliplatin.

Method and Route of Administration

• Oxaliplatin is prescribed by a doctor specializing in cancer treatment.
• The patient will be treated by medical personnel who will prepare the required dose of oxaliplatin.
• Oxaliplatin is administered in a slow intravenous infusion 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 before the infusion of 5-fluorouracil.

Frequency of Administration

The patient usually receives the medicine in an intravenous infusion once every 2 weeks.

Duration of Treatment

The doctor will decide on the duration of treatment.
Treatment lasts for a maximum of 6 months in the case of using oxaliplatin after complete removal of the tumor.

Use of a Higher Than Recommended Dose of Oxaliplatin Kalceks

This medicine is administered by medical personnel, so it is unlikely that the patient will receive too little or too much of the medicine.
In case of overdose, side effects may worsen. The doctor may use appropriate treatment for side effects.
If you have any further questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible Side Effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
If side effects occur, it is important to inform your doctor beforethe next treatment cycle.
The following side effects may occur.

You Should Immediately Contact Your Doctor If You Experience Any of the Following:

• Symptoms of an allergic reaction or anaphylaxis 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 fatigue (the patient may feel like they are going to faint). In most cases, these symptoms occur during or immediately after infusion, but delayed allergic reactions have also been observed many hours or even days after infusion.
• Unusual bruising, bleeding, or signs of infection, such as sore throat and high fever (resulting from a reduced number of platelets or white blood cells).
• Persistent or severe diarrhea or vomiting.
• Blood in vomit or black or tarry stools.
• Pain in the lips or mouth sores.
• Unexplained respiratory symptoms, such as dry cough, difficulty breathing.
• A group of symptoms such as headache, mental disorders, seizures, and vision disturbances 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, 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 a reduced number of red blood cells and shortness of breath (hemolytic anemia) occurring with a reduced number of platelets or without, and kidney disease in which the patient urinates little or no urine (symptoms of hemolytic-uremic syndrome), which can lead to death.

Other Known Side Effects of Oxaliplatin are:

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 of the fingers of the hands and feet, in the mouth or throat, sometimes occurring with spasms. This side effect is often triggered when the patient is exposed to cold, e.g., when opening the refrigerator or holding a cold drink. The patient may also experience difficulty performing precise tasks such as buttoning. Although in most cases, these symptoms disappear completely, there is a possibility of persistent peripheral neuropathy symptoms after the end of treatment. In some patients, a tingling sensation similar to an electric current passing through the arms or chest may occur after bending the neck.
• Oxaliplatin may sometimes cause unpleasant sensations in the throat, especially when swallowing, as well as a feeling of shortness of breath. Such sensations, if they occur, usually appear during infusion or within a few hours after its completion and may be triggered by exposure to low temperatures. They are unpleasant but do not last long and disappear without the need for any treatment. As a result, the doctor may decide to change the treatment.
• Oxaliplatin may cause diarrhea, mild nausea (nausea), and vomiting, but the doctor will use an anti-emetic medicine that is usually given before treatment and can be taken after the end of the treatment cycle.
• Oxaliplatin causes a temporary decrease in the number of blood cells. A decrease in the number of red blood cells may cause anemia, a decrease in the number of platelets may cause unusual bleeding or bruising, and a decrease in the number of white blood cells may increase the susceptibility to infections. Before starting treatment and before each subsequent cycle, the doctor will order a blood test to check if the patient has a sufficient number of blood cells.
• Feeling of discomfort at the injection site or in its vicinity during infusion.
• Fever, chills (shivering), mild or moderate fatigue, body aches.
• Weight changes, decreased or lost appetite, taste disturbances, constipation.
• Headache, back pain.
• Numbness of the nerves going to the muscles, stiffness of the neck, unusual sensation of the tongue that can disrupt speech, pain in the lips or mouth sores.
• Abdominal pain.
• Unusual bleeding, including nosebleeds.
• Cough, difficulty breathing.
• Allergic reactions, skin rash, which can 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 caused by a reduced number of white blood cells.
• Severe blood infection with a reduced number of white blood cells (neutropenic sepsis), which can be fatal.
• A reduced number of white blood cells, accompanied by a temperature > 38.3°C or prolonged temperature > 38°C for more than an hour (febrile neutropenia).
• Blood in vomit or black or tarry stools.
• Indigestion and heartburn, hiccups, hot flashes, dizziness.
• Excessive sweating and nail disorders, skin peeling.
• Chest pain.
• Lung disorders and colds.
• Joint and bone pain.
• Pain when urinating and changes in kidney function, changes in the frequency of urination, dehydration.
• Blood in urine and stool, swelling of blood vessels, blood clots in the lungs.
• High blood pressure.
• Depression and insomnia.
• Conjunctivitis, vision disturbances.
• Decreased calcium levels in the blood.
• Fainting.

Uncommon(may affect up to 1 in 100 people)

• Severe blood infections (sepsis), which can lead to death.
• Low blood pH (metabolic acidosis).
• Hearing difficulties, dizziness, ringing in the ears.
• Intestinal obstruction or swelling.
• Nervousness.

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

• Hearing loss.
• Scarring and thickening of the lungs, with difficulty breathing, sometimes leading to death (interstitial lung disease).
• Temporary, 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 can lead to death.

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

• Kidney disease in which the patient urinates little or no urine (symptoms of acute renal failure).
• Vascular liver disease.

Frequency Not Known(frequency cannot be estimated from the available data)

• Allergic vasculitis (vasculitis).
• An autoimmune reaction causing a decrease in the number of all blood cells (autoimmune pancytopenia), pancytopenia.
• Severe blood infections and low blood pressure (septic shock), which can lead to death.
• Seizures (uncontrolled body shaking).
• Laryngospasm causing difficulty breathing.
• Pneumonia (severe lung infection), which can lead to death.
• Reports of extreme fatigue with a reduced number of red blood cells and shortness of breath (hemolytic anemia) occurring with a reduced number of platelets or without.

and kidney disease in which the patient urinates little or no urine (symptoms of hemolytic-uremic syndrome), which can lead to death.

• Abnormal heart rhythm (prolonged QT interval), which can be detected in an electrocardiogram (ECG) - a condition that can lead to death.
• Heart attack (myocardial infarction), pain or discomfort in the chest (angina pectoris).
• Pain and swelling of the muscles in combination with weakness, fever, or brown urine (symptoms of muscle damage called rhabdomyolysis), which can be fatal.
• Inflammation of the mucous membrane of the esophagus - the connection between the mouth and the stomach - resulting in pain and difficulty swallowing (esophagitis).
• Abdominal pain, nausea, vomiting blood or vomit resembling "coffee grounds" or dark/tarry stools (symptoms of stomach and intestinal ulcers with potential bleeding or perforation), which can be fatal.
• Reduced blood flow to the intestine (intestinal ischemia) - a condition that can lead to death.
• Risk of developing new tumors. In patients taking oxaliplatin in combination with other medicines, leukemia, a type of blood cancer, has been reported. You should discuss with your doctor the possibility of an increased risk of this type of cancer during concomitant administration of oxaliplatin and certain other medicines.
• Non-cancerous abnormal growths in the liver (focal nodular hyperplasia).

Reporting of Side Effects

If you experience any side effects, including any not listed in this leaflet, you should inform your doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring 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
Side effects can also be reported to the marketing authorization holder.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to Store Oxaliplatin Kalceks

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the label and carton after "EXP". The expiry date refers to the last day of that month.
EXP - expiry date.
Lot - batch number.
There are no special storage instructions for this medicine.
Shelf life after dilution

It has been demonstrated that the solution in concentrations from 0.2 mg/mL to 2 mg/mL after dilution in glucose solution at a concentration of 50 mg/mL (5%) remains chemically and physically stable for 24 hours at 25°C and 4 days at a temperature of 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 responsibility for the storage time and conditions before use lies with the user. The storage time should not exceed 24 hours at a temperature of 2°C to 8°C, unless dilution is performed under controlled and validated aseptic conditions.
Oxaliplatin should not come into contact with the eyes or skin. In such a situation, you should immediatelyinform your doctor or nurse.
After the end of the infusion, the remaining medicine must be carefully disposed of by your doctor or nurse.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the Pack and Other Information

What Oxaliplatin Kalceks Contains

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

What Oxaliplatin Kalceks Looks Like and Contents of the Pack

This medicine is a concentrate for solution for infusion (sterile concentrate). It is a clear, colorless solution, practically free from visible particles.
10 mL, 20 mL, or 40 mL solution in a vial made of colorless glass type I, with a stopper made of bromobutyl rubber and an aluminum 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 Authorization Holder and Manufacturer

AS KALCEKS
Krustpils iela 71E
LV-1057 Rīga
Latvia
Tel.: +371 67083320
Email: kalceks@kalceks.lv

This Medicine is Authorized in the Member States of 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

Date of Last Revision of the Leaflet: -------------------------------------------------------------------------------------------------------------------------

Information intended for healthcare professionals only:
SPECIAL PRECAUTIONS FOR DISPOSAL AND OTHER HANDLING
Similarly to other potentially toxic substances, special precautions should be taken when handling and preparing oxaliplatin solutions.
Instructions for Preparation and Administration of the Medicinal Product

• DO NOT use injection equipment containing aluminum.
• 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 solutions containing chlorides.
• DO NOT mix with other medicinal products in the same infusion bag and DO NOT administer simultaneously in the same infusion set.
• DO NOT mix with medicinal products or solutions with an alkaline pH, in particular with 5-fluorouracil, folinic acid products containing trometamol as an excipient, and trometamol salts of other active substances. Medicinal products or solutions with an alkaline pH have a negative effect on the stability of oxaliplatin.

Instructions for Use with Folinic Acid (FA) (as Folinic Acid Calcium or Folinic Acid Disodium)
Oxaliplatin at a dose of 85 mg/m², administered in an intravenous infusion in 250 mL to 500 mL glucose solution at a concentration of 50 mg/mL (5%), is administered at the same time as the folinic acid infusion in glucose solution at a concentration of 50 mg/mL (5%), over 2 to 6 hours, using a Y-connector placed directly before the infusion site. The two medicinal products should not be mixed in the same infusion bag. Folinic acid should not contain trometamol as an excipient and should be diluted only with isotonic glucose solution at a concentration of 50 mg/mL (5%), never with alkaline solutions, sodium chloride solution, or solutions containing chlorides.
Instructions for Use with 5-Fluorouracil (5-FU)

Oxaliplatin Should Always be Administered Before Fluoropyrimidines, i.e., 5-Fluorouracil.

After administration of oxaliplatin, the infusion set should be flushed, and then 5-fluorouracil should be administered.
For further information on medicinal products used in combination with oxaliplatin, see the relevant Summary of Product Characteristics.
Concentrate for Solution for Infusion

Before use, the product should be inspected. Only clear solutions without particles should be used.
Any concentrate showing signs of precipitation should not be used and should be disposed of in accordance with legal requirements for the disposal of hazardous waste (see below "Disposal of Unused Material").
For single use only. Any unused solution should be disposed of (see below "Disposal of Unused Material").
Dilution of the Infusion Solution

USE ONLY the recommended diluent (glucose solution for infusion at a concentration of 50 mg/mL (5%)).
Take the required amount of concentrate from the vial (vials), and then dilute in 250 mL to 500 mL glucose solution at a concentration of 50 mg/mL (5%), to achieve a concentration of oxaliplatin solution between 0.2 mg/mL and 0.7 mg/mL; the range of concentrations for which the 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 in concentrations from 0.2 mg/mL to 2 mg/mL after dilution in glucose solution at a concentration of 50 mg/mL (5%) remains chemically and physically stable for 24 hours at 25°C and 4 days at a temperature of 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 responsibility for the storage time and conditions before use lies with the user. The storage time should not exceed 24 hours at a temperature of 2°C to 8°C, unless dilution is performed under controlled and validated aseptic conditions.
NEVER use sodium chloride solution or solutions containing chlorides for dilution.
The compatibility of the oxaliplatin infusion solution has been tested using infusion sets made of PVC.
Before use, the solution should be inspected. Only clear solutions without particles should be used. Unused solution should be disposed of (see below "Disposal of Unused Material").
Infusion

Administration of oxaliplatin does not require prior excessive hydration of the patient.
Oxaliplatin diluted in 250 mL to 500 mL glucose solution at a concentration of 50 mg/mL (5%) to achieve a concentration of not less than 0.2 mg/mL should be administered into a peripheral or central vein over 2 to 6 hours.
When oxaliplatin is administered with 5-fluorouracil, the oxaliplatin infusion should precede the administration of 5-fluorouracil.
Disposal of Unused Material

Unused medicinal products, as well as all materials used for dilution and administration of the medicinal product, should be disposed of in accordance with standard hospital procedures for the disposal of cytotoxic medicines, taking into account local regulations regarding the disposal of hazardous waste.