Cisplatin - Ebeve

Package Leaflet: Information for the Patient

Cisplatin-Ebewe

1 mg/ml, concentrate for solution for infusion

Cisplatinum

Read the package leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this package leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including those not listed in this package leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Package Leaflet Contents:

• 1. What is Cisplatin-Ebewe and what is it used for
• 2. Important information before using Cisplatin-Ebewe
• 3. How to use Cisplatin-Ebewe
• 4. Possible side effects
• 5. How to store Cisplatin-Ebewe
• 6. Package contents and other information

1. What is Cisplatin-Ebewe and what is it used for

Cisplatin-Ebewe is used to treat cancer. It can be given alone (monotherapy) or in combination with other medicines as part of chemotherapy.

Cisplatin-Ebewe is used to treat:

• malignant testicular and ovarian tumors,
• malignant tumors of the cervix, bladder, squamous cell carcinoma of the head and neck, and lung cancer.

2. Important information before using Cisplatin-Ebewe

When not to use Cisplatin-Ebewe

if you have had an allergic reaction (hypersensitivity) to cisplatin, other platinum-containing medicines, or any of the other ingredients of this medicine (listed in section 6),

if you have kidney problems,

if you are dehydrated (have lost a lot of fluid, e.g., due to diarrhea, vomiting),

if your bone marrow does not produce blood cells,

if you have hearing problems,

if you have nerve damage caused by cisplatin (called neuropathy),

in breastfeeding women,

if you are scheduled to receive a yellow fever vaccine.

• if you are taking phenytoin (used to treat epilepsy).

Warnings and precautions

Before starting treatment with Cisplatin-Ebewe, discuss it with your doctor, pharmacist, or nurse.

• Cisplatin-Ebewe can harm your nervous system (cause neuropathy), which can cause symptoms such as tingling, weakness, decreased deep sensation, and tremors.

Movement disorders can also occur. You will be regularly examined by a neurologist.

• Cisplatin-Ebewe can cause hearing loss. Symptoms can include ringing in the ears and/or hearing loss. Rarely, it can cause impaired speech recognition. Hearing loss can be one-sided or two-sided; it occurs more frequently and with greater severity after multiple administrations of the medicine. Before starting treatment and before each subsequent treatment cycle, your doctor will order a hearing test (so-called audiometric examination).
• Cisplatin-Ebewe can cause kidney damage. To prevent this, you will receive plenty of fluids through an infusion before and after administration of the medicine.
• Before starting treatment with cisplatin, during, and after treatment, your doctor will order blood tests and kidney and liver function tests. These tests should be repeated every week during the entire treatment period.
• During treatment with Cisplatin-Ebewe, an allergic reaction may occur, which can be life-threatening.
• If you plan to have children, you should have genetic counseling after treatment (cisplatin can cause genetic changes).
• Cisplatin-Ebewe can cause irreversible infertility in men, so men who plan to father children should seek advice on the possibility of freezing sperm before starting treatment.
• Patients must use effective contraception to prevent pregnancy during treatment with cisplatin and for some time after treatment (see section "Pregnancy, breastfeeding, and fertility").
• Certain medicines taken with cisplatin can increase the risk of harm to the ears, kidneys, and nervous system (see section "Cisplatin-Ebewe and other medicines").
• After administration of Cisplatin-Ebewe, nausea, vomiting, and diarrhea may occur. In most patients, these symptoms disappear within 24 hours, and mild nausea and loss of appetite may persist for up to a week after administration.
• If you experience nausea and vomiting after administration of Cisplatin-Ebewe, your doctor will use anti-emetic medicines. These medicines can also be taken preventively. It is essential to replenish lost fluids during vomiting and diarrhea.

Before using Cisplatin-Ebewe, tell your doctor if you:

• have peripheral nerve damage (called peripheral neuropathy) that was not caused by cisplatin,
• have a severe infection caused by bacteria or viruses.

Re-administration of Cisplatin-Ebewe is possible only after normal blood test results, kidney and liver function tests, and hearing tests have been obtained.

Cisplatin-Ebewe and other medicines

Tell your doctor, pharmacist, or nurse about all medicines you are taking or have recently taken, including those obtained without a prescription.

Do not take the following medicines with Cisplatin-Ebewe:

• medicines that suppress bone marrow function,
• radiation therapy (so-called radiotherapy),
• medicines that lower blood pressure (such as furosemide, hydralazine, diazoxide, and propranolol),
• medicines used to treat gout (such as allopurinol, probenecid, sulfinpyrazone, and colchicine),
• medicines that increase urine production (so-called loop diuretics, such as furosemide, torasemide, and ethacrynic acid),
• antihistamines (such as buclizine, cyclizine, loxapine, meclizine, phenothiazines, thioxanthenes, or trimethobenzamides), as they may mask symptoms of hearing loss (dizziness and ringing in the ears),
• medicines used to treat certain cancers (so-called cytostatics, such as methotrexate,

hexamethylmelamine, paclitaxel, docetaxel, etoposide),

• vitamin B6,
• antiepileptic medicines (such as phenytoin),
• penicillamine (a medicine used to treat lead or copper poisoning), as it may reduce the effect of Cisplatin-Ebewe,
• cyclosporine (an immunosuppressive medicine used in organ transplantation or atopic dermatitis),
• oral anticoagulants (medicines that prevent blood clotting),
• vaccines containing live viruses (should not be administered during treatment or within 3 months after treatment with Cisplatin-Ebewe),
• yellow fever vaccine. Medicines that can cause kidney damage:
• certain antibiotics, such as cephalosporins, aminoglycoside antibiotics, and amphotericin B,
• contrast agents used in diagnostic tests. Medicines that can cause hearing loss:
• aminoglycoside antibiotics (such as streptomycin, neomycin, and gentamicin),
• ifosfamide (a cytostatic medicine).

Medicines that can cause nerve damage:

• certain cytostatic medicines (such as paclitaxel, docetaxel, bleomycin, and vinblastine).

Pregnancy, breastfeeding, and fertility

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

Pregnancy

Cisplatin used in pregnant women can be toxic to the fetus and may cause severe birth defects. Cisplatin-Ebewe should not be used during pregnancy unless your doctor considers it absolutely necessary. Tell your doctor immediately if you are pregnant or think you may be pregnant.

Women of childbearing age should use effective contraception during treatment and for at least 7 months after treatment.

Men treated with cisplatin should use effective contraception and not father children during treatment and for at least 4 months after treatment.

If you plan to have children, you should have genetic counseling after treatment.

Fertility

Cisplatin can cause infertility, so men who plan to father children should seek advice on the possibility of freezing sperm before starting treatment.

Breastfeeding

Cisplatin passes into breast milk. Cisplatin-Ebewe should not be used during breastfeeding. Breastfeeding mothers should stop breastfeeding during treatment with cisplatin.

Driving and using machines

Cisplatin-Ebewe can affect your ability to drive and use machines, so be careful when performing these activities.

Patients who experience side effects such as drowsiness, vomiting, or nausea should not drive or operate machines.

Cisplatin-Ebewe contains sodium

The medicine contains 3.54 mg of sodium (the main component of common salt) per 1 ml of concentrate.

The medicine contains 35.4 mg of sodium per 10 ml vial. This corresponds to 1.77% of the maximum recommended daily intake of sodium in the diet for adults.

The medicine contains 71 mg of sodium per 20 ml vial. This corresponds to 3.55% of the maximum recommended daily intake of sodium in the diet for adults.

The medicine contains 177 mg of sodium per 50 ml vial. This corresponds to 8.85% of the maximum recommended daily intake of sodium in the diet for adults.

The medicine contains 354 mg of sodium per 100 ml vial. This corresponds to 17.7% of the maximum recommended daily intake of sodium in the diet for adults.

The medicine can be diluted in a 0.9% sodium chloride solution. The sodium content from the diluent should be taken into account when calculating the total sodium content in the prepared dilution.

3. How to use Cisplatin-Ebewe

Cisplatin-Ebewe is given under the supervision of an oncologist experienced in the use of chemotherapy. The medicine should not be taken by yourself.

The dose and duration of treatment are determined by your doctor.

Overdose of Cisplatin-Ebewe

Receiving too much Cisplatin-Ebewe is unlikely, but if you think you have been given too much medicine, tell your doctor or nurse immediately.

Acute overdose of cisplatin can cause kidney failure, liver failure, deafness, toxic effects on the eyes (including retinal detachment), severe bone marrow suppression, nausea, vomiting, and/or inflammation of the nerves. Overdose can be fatal.

Overdose (>200 mg/m2) can have a direct effect on the respiratory center due to cisplatin crossing the blood-brain barrier, which can cause respiratory disturbances leading to death and acid-base disturbances.

In case of overdose, your doctor will order the administration of plenty of fluids through an infusion and the use of diuretics.

Missed dose of Cisplatin-Ebewe

Do not take a double dose to make up for a missed dose.

If you have any further questions about using this medicine, ask your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, Cisplatin-Ebewe can cause side effects, although not everybody gets them.

Side effects that occur after administration of cisplatin depend on the dose used and can worsen with subsequent doses. In most patients, severe nausea and vomiting occur during treatment with cisplatin. Nausea can persist for up to 7 days after administration.

Severe side effects

Tell your doctor immediately if:

• you experience severe pain or swelling in your legs, chest pain, or difficulty breathing (which may indicate dangerous blood clots in a vein) (common: may occur in up to 1 in 10 patients). Very common side effects(may occur in more than 1 in 10 people):
• bone marrow suppression and decreased white blood cell count (increased risk of infection), decreased platelet count (increased risk of bruising), and decreased red blood cell count (may cause anemia);
• decreased sodium levels in the blood;
• fever. Common side effects(may occur in up to 1 in 10 people):
• infections, including sepsis (characterized by rapidly rising fever, chills, rapid breathing, and rapid heartbeat);
• heart rhythm disorders, including very slow heartbeat (bradycardia), very fast heartbeat (tachycardia), and other changes in the electrocardiogram (ECG). Uncommon side effects(may occur in up to 1 in 100 people): allergic reactions, including severe ones (facial swelling, wheezing, bronchospasm, rapid heartbeat, low blood pressure, and also rash, hives, redness, and itching of the skin); decreased magnesium levels in the blood; hearing loss; metallic deposits on the gums; disorders of sperm production and maturation; ovulation disorders; breast enlargement in men (gynecomastia). Rare side effects(may occur in up to 1 in 1,000 people):
• risk of developing secondary acute leukemia;
• weakened immune system (suppressed immune function);
• increased cholesterol levels in the blood (hypercholesterolemia);
• nervous system disorders (seizures, peripheral neuropathy, leukoencephalopathy, reversible posterior leukoencephalopathy syndrome, loss of brain function, including severe cerebrovascular complications, cerebral vasculitis, carotid artery occlusion, and encephalopathy);
• heart attack, high blood pressure (may occur even years after chemotherapy);
• inflammation of the mucous membranes of the mouth. Very rare side effects(may occur in up to 1 in 10,000 people):
• increased iron levels in the blood;
• cardiac arrest (especially after treatment in combination with other cytotoxic medicines).

Side effects with unknown frequency(frequency cannot be estimated from available data):

• infection (can be life-threatening);
• anemia due to red blood cell destruction (hemolytic anemia);
• positive Coombs test;
• increased amylase levels in the blood;
• inappropriate antidiuretic hormone secretion;
• dehydration;
• decreased calcium levels in the blood (hypocalcemia), tetany;
• decreased phosphate levels in the blood (hypophosphatemia);
• decreased potassium levels in the blood (hypokalemia);
• increased uric acid levels in the blood (hyperuricemia);
• cerebrovascular incident, hemorrhagic stroke, ischemic stroke, cerebral vasculitis;
• Lhermitte's sign (a sensation of an electric shock running down the spine when the head is bent forward);
• loss of taste;
• myelopathy;
• autonomic neuropathy (nerve damage);
• blurred vision, color vision disturbances, eye movement disorders, cortical blindness, optic neuritis, optic disc swelling;
• ringing in the ears, deafness, balance disorders with dizziness;
• microangiopathic hemolytic anemia (changes, e.g., thrombotic, in small blood vessels of various organs with hemolytic-uremic syndrome), Raynaud's disease;
• vomiting, nausea, loss of appetite, hiccups, diarrhea, stomach pain;
• increased liver enzyme activity, increased bilirubin levels in the blood, decreased albumin levels, increased urea, creatinine, uric acid, and/or decreased creatinine clearance;
• pulmonary embolism;
• rash, hair loss;
• muscle spasms;
• kidney failure (including acute), tubular disorders;
• weakness, general feeling of being unwell;
• heart problems;
• extravasation at the injection site (with local soft tissue damage, including inflammation of the connective tissue, fibrosis, and necrosis, pain, swelling, and redness).

Hearing loss is characterized by ringing in the ears and/or hearing loss of high-frequency sounds (4000-8000 Hz), which depends on the total dose used and can be irreversible and sometimes limited to one ear.

Hearing loss caused by cisplatin can be severe in children.

Previous or concurrent radiation therapy to the head increases the risk of hearing loss.

Loss of appetite, nausea, vomiting, stomach pain, and diarrhea occur frequently between 1 and 4 hours after administration of cisplatin and usually disappear within 24 hours in most patients. Mild nausea and loss of appetite may persist for up to 7 days after treatment.

After intravenous administration, local swelling and pain, redness, skin ulceration, and vein inflammation may occur at the injection site.

Approximately 14 days after administration of cisplatin, a significant decrease in white blood cell count (<1.5 x 10^9/l in 5% of patients) is observed. A decrease in platelet count is noticeable after about 3 weeks (<50 x 10^9 l in <10% of patients). the recovery period to normal values is about 39 days. anemia occurs with a similar frequency but usually starts later than leukopenia and thrombocytopenia.< p>

If neurological symptoms occur, treatment with cisplatin should be stopped immediately. Neurotoxicity caused by cisplatin can be reversible, but in 30-50% of patients, the changes are irreversible even after treatment is stopped. Neurotoxicity can occur after the first dose of cisplatin or after a long period of treatment. Severe neurotoxicity can occur in patients who have received cisplatin in high doses or for a long time.

Reporting side effects

If you experience any side effects, including those not listed in this package leaflet, tell your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Drug Safety, Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products: Al. Jerozolimskie 181 C, 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.

Reporting side effects will help to gather more information on the safety of this medicine.

5. How to store Cisplatin-Ebewe

Keep the medicine out of the sight and reach of children.

Store in a temperature below 25°C. Store in the original package to protect from light. Do not store in the refrigerator or freeze.

Do not use this medicine after the expiration date stated on the carton after EXP. The expiration date refers to the last day of the month.

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

6. Package contents and other information

What Cisplatin-Ebewe contains

The active substance is cisplatin. 1 ml of concentrate contains 1 mg of cisplatin.

The other ingredients are sodium chloride, hydrochloric acid, and water for injections.

What Cisplatin-Ebewe looks like and contents of the package

The concentrate is a clear, colorless solution.

Cisplatin-Ebewe is available in vials containing 10 mg/10 ml, 20 mg/20 ml, 50 mg/50 ml, or 100 mg/100 ml.

The vials may be placed in transparent plastic containers (e.g., ONKO-Safe or Sleeving).

Marketing authorization holder and manufacturer

EBEWE Pharma Ges.m.b.H. Nfg. KG, Mondseestrasse 11, 4866 Unterach, Austria

Manufacturer

Fareva Unterach GmbH, Mondseestraße 11, 4866 Unterach, Austria

For more information, contact:

Sandoz Polska Sp. z o.o., ul. Domaniewska 50 C, 02-672 Warszawa, tel. 22 209 70 00

Date of last revision of the package leaflet:09/2024

Information intended for healthcare professionals only

Dosage

The dose of cisplatin depends on the underlying disease, expected response, and whether cisplatin is used as monotherapy or as part of combination chemotherapy.

In monotherapy, the following two dosage regimens are recommended:

a single dose of 80-100 mg/m^2, given every 3 to 4 weeks,

20 mg/m^2/day for 5 consecutive days, every 3 to 4 weeks.

If cisplatin is used in combination chemotherapy, the dose of cisplatin should be reduced.

The dose is usually at least 20 mg/m^2, given every 3-4 weeks.

In patients with kidney problems or bone marrow suppression, the dose should be reduced accordingly.

The solution of cisplatin, prepared according to the instructions, should be administered as an intravenous infusion over 6 to 8 hours.

Adequate hydration of the patient is essential during the 2 to 12 hours before administration of the medicine and for at least 6 hours after administration of cisplatin. Hydration is necessary to induce sufficient urine production (diuresis) during and after treatment with cisplatin. This can be achieved by administering one of the following solutions intravenously:

• 0.9% sodium chloride solution,
• 0.9% sodium chloride solution with 5% glucose solution (1:1).

Hydration before administration of cisplatin:

intravenous infusion of 100 to 200 ml/hour for 6 to 12 hours.

Hydration after administration of cisplatin:

intravenous infusion of the next 2 liters at a rate of 100 to 200 ml/hour for 6 to 12 hours.

If urine production after hydration is less than 100 to 200 ml/hour, forced diuresis may be necessary. Forced diuresis can be induced by intravenous administration of 37.5 g of mannitol (375 ml of 10% mannitol solution) or by administration of a diuretic if kidney function is normal. Administration of mannitol or a diuretic is also necessary if the dose of cisplatin is greater than 60 mg/m^2. To ensure adequate urine production, the patient should drink plenty of fluids during the 24 hours after the infusion of cisplatin.

Extravasation

In case of extravasation, the infusion of cisplatin should be stopped immediately. The needle should not be removed.

The extravasated solution of cisplatin should be aspirated and the area should be flushed with 0.9% sodium chloride solution (if a solution of cisplatin with a concentration higher than recommended was used).

Storage of the medicine

Vials after opening, before dilution

The concentrate should be withdrawn from the vial immediately before use.

From a microbiological point of view, the product should be used immediately. If not used immediately, the responsibility for the conditions and duration of storage of the remaining product lies with the user. The physical and chemical stability of the product has been demonstrated for 28 days at a temperature below 25°C, regardless of light exposure, if the withdrawal was performed under controlled, validated aseptic conditions.

After dilution

From a microbiological point of view, the product should be used immediately. If not used immediately, the responsibility for the conditions and duration of storage of the prepared solution lies with the user.

The solution can be stored for no longer than 24 hours at a temperature of 2°C-8°C, protected from light, unless the dilution was performed under controlled, validated aseptic conditions.

The physical and chemical stability of the 0.10 mg/ml solution (diluted with 0.9% sodium chloride solution or 0.9% sodium chloride solution with 5% glucose solution) has been demonstrated for 28 days at a temperature below 25°C, protected from light. The stability of the cisplatin solution is affected by chloride ions, so the concentration of sodium chloride used for dilution must not be less than 0.45%.

Preparation of the medicine for administration

The Cisplatin-Ebewe concentrate should be diluted before use.

When preparing the solution for infusion, avoid contact between cisplatin and any aluminum-containing equipment (infusion sets, needles, catheters, syringes).

Preparation of the infusion solution should be performed under aseptic conditions.

Reconstitution of the concentrate and further dilution of the solution, as well as subsequent handling, should be performed under controlled, validated aseptic conditions.

For dilution of the concentrate, use one of the following solutions:

• 0.9% sodium chloride solution,
• 0.9% sodium chloride solution with 5% glucose solution (1:1) (the resulting solution contains 0.45% sodium chloride and 2.5% glucose).

If it is not possible to hydrate the patient before administration of cisplatin, the concentrate can be diluted with a mixture of 0.9% sodium chloride solution and 5% mannitol solution (1:1) (the resulting solution contains 0.45% sodium chloride and 2.5% mannitol).

Preparing the cisplatin solution for infusion

The required amount (dose) of cisplatin concentrate at a concentration of 1 mg/ml should be diluted with 1-2 liters of one of the above-mentioned solutions. The diluted solution should be administered only as an intravenous infusion. Only a clear, colorless solution that does not contain any visible particles should be administered.

Cytotoxic medicines can only be prepared by personnel who have been adequately trained and have knowledge of the products used, and under conditions that ensure their proper preparation and administration.

Similarly, as with other cytotoxic agents, handling cisplatin requires extreme caution: gloves, face mask, and protective clothing should be worn. If possible, all procedures with cisplatin should be performed under a fume cupboard. Contact with the skin and/or mucous membranes should be avoided. Pregnant women should not work with cisplatin.

Contact of the medicine with the skin: wash the skin with plenty of water. If a burning sensation occurs, apply a cream (note: in some individuals sensitive to platinum, skin reactions may occur).

Spilled solution should be wiped up (after wearing gloves) with a sponge intended for this purpose. The surface should be rinsed twice with water. The solution and sponges should be placed in a plastic bag and sealed. In case of spillage, all materials that have come into contact with cisplatin should be stored and disposed of according to local procedures for the disposal of cytotoxic preparations.

Disposal of leftover medicine

Any unused product or waste material should be disposed of in accordance with local regulations.

Incompatibilities

Cisplatin reacts with aluminum, resulting in the formation of a black platinum precipitate. Therefore, it is essential to avoid equipment containing aluminum parts (intravenous infusion sets, needles, catheters, syringes) that may come into contact with cisplatin.

The cisplatin concentrate at a concentration of 1 mg/ml should not be diluted with 5% glucose solution or 5% mannitol solution alone, but only with a mixture containing additional sodium chloride.

Antidotes (e.g., sodium thiosulfate), bicarbonates (sodium bicarbonate), sulfates, fluorouracil, and paclitaxel can inactivate cisplatin in infusion sets.