CISPLATIN HIKMA 1 mg/ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the Patient

Cisplatino Hikma 1 mg/ml Concentrate for Solution for Infusion EFG

Read all of this leaflet carefully before you start 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.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• 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 pack

1. What is Cisplatino Hikma and what is it used for
2. What you need to know before you use Cisplatino Hikma
3. How to use Cisplatino Hikma
4. Possible side effects
5. Storage of Cisplatino Hikma
6. Contents of the pack and other information

1. What is Cisplatino Hikma and what is it used for

Cisplatino belongs to a group of medicines called cytostatics, which are used in the treatment of cancer. Cisplatino can be used alone, but it is commonly used in combination with other cytostatics.

What it is used for

Cisplatino is able to destroy cells in your body that can cause certain types of cancer (testicular tumor, ovarian tumor, bladder tumor, epithelial head and neck tumor, lung cancer, and cervical cancer in combination with radiotherapy).

2. What you need to know before you use Cisplatino Hikma

Do not use Cisplatino Hikma

• if you are allergic to cisplatino or any of the other ingredients of this medicine (listed in section 6);
• if you are allergic (hypersensitive) to any other medicine that contains platinum components;
• if you have kidney problems (renal insufficiency);
• if you have dehydration;
• if you have severe suppression of bone marrow function, these are some of the symptoms: extreme fatigue, easy bleeding or bruising, appearance of infections;
• if you have hearing problems;
• if you have nervous disorders caused by cisplatino;
• if you are breastfeeding;
• in combination with live vaccines, including the yellow fever vaccine
• in combination with phenytoin for prophylactic use (see the section "Taking Cisplatino Hikma with other medicines").

Warnings and precautions

Your doctor should perform tests to determine the levels of calcium, sodium, potassium, and magnesium in the blood, as well as to check your blood count and liver and kidney function and neurological function.

• This medicine should only be administered under the strict supervision of a specialist doctor with experience in the administration of chemotherapy.
• You will have a hearing test before each treatment with this medicine.
• If you have a nervous disorder not induced by this medicine.
• If you have received radiotherapy in the head.
• If you have an infection, please consult your doctor.
• If you wish to have children (see the section "Pregnancy, breastfeeding, and fertility").

Consult your doctor if any of the above conditions apply to you before starting to use this medicine.

In case of cisplatino spill, the contaminated skin should be washed immediately with water and soap. If cisplatino is injected outside the blood vessels, administration should be stopped immediately. Cisplatino on the skin can cause tissue damage (cellulitis, fibrosis, and necrosis).

Inform your doctor, even if any of the above circumstances have occurred to you at any time.

T

Please note that these instructions may also apply to medicines that have been used before or may be used in the future. Inform your doctor or pharmacist if you are using, have recently used, or may need to use any other medicine.

• The simultaneous use of medicines that inhibit bone marrow function or radiation may increase the adverse effects of cisplatino on the bone marrow.
• The toxicity of this medicine may increase when administered simultaneously with other cytostatics (other cancer medicines), such as bleomycin and methotrexate.
• Medicines for the treatment of high blood pressure (antihypertensives with furosemide, hydralazine, diazoxide, or propranolol) may increase the toxic effect of cisplatino on the kidneys.
• The toxicity of cisplatino may severely affect the kidneys when administered with medicines that may cause adverse effects on the kidney, such as those used in the prevention/treatment of certain infections (antibiotics: cephalosporins, aminoglycosides, and/or antifungals: Amphotericin B) and contrast media.
• The toxicity of cisplatino may also affect hearing when administered with agents that have adverse reactions that affect hearing, such as aminoglycosides.
• If you take medicines to treat gout during your treatment with cisplatino, it may be necessary to adjust the dose of these medicines (e.g., allopurinol, colchicine, probenecid, and/or sulfinpyrazone).
• The administration of medicines to increase urine production (loop diuretics) in combination with cisplatino (when the dose of cisplatino is not higher than 60 mg/m2, and urine secretion is not lower than 1,000 ml per 24 hours) may produce toxic effects on the kidney and ear.
• The first signs of hearing problems (such as dizziness and tinnitus) may be masked if, during treatment with cisplatino, you are given medicines to treat hypersensitivity, feeling sick, or having mental problems (antihistamines such as buclizine, cyclizine, loxapine, meclozine, phenothiazines, thioxanthenes, and/or trimethobenzamides).
• Cisplatino in combination with ifosfamide may cause ear damage.
• The administration of pyridoxine and hexamethylmelamine may reduce the response to treatment with cisplatino.
• Cisplatino in combination with bleomycin and vinblastine may cause paleness or bluish discoloration of the fingers of the hands and/or feet (Raynaud's phenomenon).
• The administration of cisplatino for treatment with paclitaxel or in combination with docetaxel

may cause severe nerve damage.

• It is recommended to regularly check lithium levels, as a reduction in lithium levels in the blood has been observed after treatment with cisplatino combined with bleomycin and etoposide.
• Cisplatino reduces the effects of phenytoin in the treatment of epilepsy.
• Penicillamine and other chelating agents may decrease the efficacy of this medicine.
• Cisplatino may have a negative impact on the efficacy of medicines that prevent blood clotting (anticoagulants). Therefore, it is recommended to increase the frequency of coagulation checks during the combined use of these medicines.
• Cisplatino in combination with cyclosporin may cause suppression of the immune system with a risk of proliferation of white blood cells (lymphocytes).
• You should not receive live vaccines in the first three months after completing a treatment with cisplatino.
• You should not receive the yellow fever vaccine while undergoing this treatment (see the section "Do not use Cisplatino Hikma").

Pregnancy, breastfeeding, and fertility

Pregnancy

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor, pharmacist, or nurse for advice before using this medicine. Cisplatino should not be used during pregnancy unless your doctor considers it necessary. You should use effective contraception to avoid becoming pregnant while using Cisplatino Hikma and for at least 6 months after treatment.

Breastfeeding

This medicine should not be used by women who are breastfeeding.

Fertility

Men treated with cisplatino are advised not to father a child during and for up to 6 months after treatment. Additionally, men wishing to father children in the future should seek advice on the conservation of sperm before treatment.

Driving and using machines

Cisplatino may cause drowsiness and/or vomiting. If you experience any of these effects, you should not use machines that require special attention.

Cisplatino Hikma contains sodium

Cisplatino Hikma 50 mg/50 ml contains 177 mg of sodium (main component of cooking/table salt) in each 50 ml vial. This is equivalent to 8.9% of the maximum recommended daily intake of sodium for an adult.

Cisplatino Hikma 100 mg/100 ml contains 354 mg of sodium (main component of cooking/table salt) in each 100 ml vial. This is equivalent to 17.7% of the maximum recommended daily intake of sodium for an adult.

3. How to use Cisplatino Hikma

Dosage and administration

Cisplatino can only be administered by a specialist in cancer treatment. The concentrate is diluted with sodium chloride solution.

Cisplatino should be administered only by intravenous injection. There should be support equipment to control allergic reactions.

Cisplatino must not come into contact with materials that contain aluminum.

The recommended dose of cisplatino depends on your state of health, the expected effects of treatment, and whether cisplatino is used alone (monotherapy) or in combination with other medicines (combination chemotherapy).

Cisplatino Hikma (monotherapy):

The following doses are recommended:

• Single dose of 50 to 120 mg/m² of body surface area every 3-4 weeks.
• 15 to 20 mg/m² per day for 5 days, every 3-4 weeks.

This medicine in combination with other chemotherapeutic agents (combination chemotherapy):

• The recommended dose is 20 mg/m² or more, every 3-4 weeks.

For the treatment of cervical cancer, cisplatino is used in combination with radiotherapy. A usual dose is 40 mg/m² per week for 6 weeks.

In order to avoid or reduce kidney problems, it is recommended that you drink large amounts of water during a 24-hour period after treatment with cisplatino.

If you receive more Cisplatino Hikma than you should

Your doctor will make sure you are given the correct dose. In case of overdose, you may experience increased side effects. Your doctor may give you symptomatic treatment for these side effects. If you think you have received too much cisplatino, contact your doctor immediately.

If you have any further questions on the use of this medicine, ask your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

If you experience any side effect, it is important that you inform your doctor before the next treatment.

Tell your doctor immediately if you experience any of the following:

• persistent or severe diarrhea or vomiting
• stomatitis/mucositis (pain in the lips or ulcers in the mouth)
• swelling of the face, lips, mouth, or throat
• unexplained respiratory symptoms such as non-productive cough, difficulty breathing, or crackles
• difficulty swallowing
• numbness or tingling in the fingers of the hands or feet
• extreme fatigue
• unusual bruising or bleeding
• signs of infection, such as sore throat and high fever
• feeling unwell near or at the injection site during infusion.
• severe pain or swelling in any of the legs, chest pain, or difficulty breathing (which may indicate harmful blood clots in a vein) (common: may affect up to 1 in 10 people)

Other possible side effects may appear:

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

• decrease in white blood cells, making infections more likely (leucopenia)
• decrease in platelets, increasing the risk of bruising and bleeding (thrombocytopenia)
• decrease in the number of red blood cells, which can make the skin pale and cause weakness or shortness of breath (anemia)
• kidney dysfunction, such as lack of urine production (anuria)
• blood poisoning (uremia)
• reduced levels of electrolytes (sodium).
• Hyperuricemia (high levels of uric acid in the blood)

Common (may affect up to 1 in 10 people)

• Infection (sepsis).
• Damage to the nervous system (neurotoxicity).
• Arrhythmia, including decreased heart rate (bradycardia) and increased heart rate (tachycardia).
• Inflammation of a vein (phlebitis)
• Difficulty breathing (dyspnea), inflammation of the lungs (pneumonia), and respiratory failure.
• Redness and inflammation of the skin (erythema, skin ulceration) at the injection site, fluid retention (edema), and pain at the injection site.
• Dizziness

Uncommon (may affect up to 1 in 100 people)

• severe allergic reactions (anaphylactic) including skin rash, itching, and hives, redness and inflammation of the skin (erythema) or itching (pruritus), anaphylactoid reactions with symptoms such as swelling of the face and fever, low blood pressure (hypotension), rapid heartbeat (tachycardia), breathing difficulties (dyspnea), anxiety due to muscle spasms in the airways (bronchospasms)
• low magnesium levels in the blood.
• Hearing problems (ototoxicity).
• Abnormal sperm production (spermatogenesis dysfunction) and abnormal ovulation, painful abnormal development of the breasts in men (gynecomastia).

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

• A type of blood cancer (severe leukemia).
• Suppression of the immune system (immunosuppression).
• Increased levels of cholesterol in the blood (hypercholesterolemia).
• Peripheral neuropathy of the sensory nerves (bilateral sensory neuropathy), characterized by tingling, itching, or numbness without cause and, sometimes, characterized by loss of taste, touch, sight, as well as brain dysfunction (confusion, difficulty speaking, sometimes blindness, memory loss, and paralysis); sudden sharp pains from the neck through the back to the legs when bending forward, spinal disease, seizures, loss of certain types of brain function, including brain dysfunction characterized by spasms and reduced levels of consciousness (encephalopathy), as well as carotid artery occlusion.
• Inflammation of the optic nerve combined with pain and reduced nerve function (optic neuritis), dysfunction of eye movement.
• Disease of the heart arteries, myocardial infarction.
• Increased blood pressure (hypertension).
• Inflammation of the mucous membranes of the mouth (stomatitis).
• Reduced levels of albumin (protein) in the blood.

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

• Seizures (convulsions)
• Increased iron levels in the blood

Frequency not known (cannot be estimated from the available data)

• Increased levels of amylase in the blood (enzymes),
• reduced levels of electrolytes (magnesium, calcium, sodium, phosphate, potassium) in the blood with muscle cramps and/or changes in an electrocardiogram (ECG), dehydration, involuntary muscle contraction (tetany).
• Stroke (stroke)
• Loss of vision (blindness), difficulty perceiving colors, blurred vision, swelling (papilledema)
• Tinnitus, deafness.
• Heart disorder
• Disorders of blood flow, for example, in the brain, but also in the fingers of the hands and feet (Raynaud's syndrome).
• Pulmonary embolism (blockage of a pulmonary artery)
• Lack of appetite (anorexia), nausea, vomiting, diarrhea
• Hiccups
• Hair loss (alopecia), skin rash
• Fever, weakness (asthenia), general malaise
• Stroke (stroke).

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if it is possible that the side effects are not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Cisplatino Hikma

Keep this medicine out of sight and reach of children.

Expiry Date

Do not use this medicine after the expiry date stated on the vial and on the outer packaging after 'EXP'. The expiry date is the last day of the month stated.

Do not use this medicine if you notice visible signs of deterioration.

Storage

Do not store above 25°C. Do not refrigerate or freeze. Keep the vial in the outer packaging to protect it from light.

After dilution, the product must be used immediately, if not possible, it can be stored for up to 48 hours at room temperature (15 to 25 °C) under protection from light, provided that it has been prepared in a way that excludes microbial contamination. Prepared infusions should not be refrigerated.

6. Package Contents and Additional Information

Composition of Cisplatino Hikma

The active substance is cisplatin.

Each milliliter (ml) of concentrate for solution for infusion contains 1 milligram (mg) of cisplatin.

The other ingredients are sodium chloride, hydrochloric acid 37%, sodium hydroxide, and water for injectable preparations.

Appearance of Cisplatino Hikma and Package Contents

Cisplatino Hikma is a clear, colorless to pale yellow concentrate for solution for infusion in a 50 or 100 ml amber glass vial.

The vials are packaged in boxes of 1 vial.

Only certain pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder: Hikma Farmacêutica (Portugal), S.A.

Estrada do Rio da Mó 8,8A e 8B

2705-906 Terrugem SNT, Portugal

Manufacturer:

Thymoorgan Pharmazie GmbH

Schiffgraben 23

D-38690 Goslar

Germany

You can request more information about this medicine by contacting the local representative of the Marketing Authorization Holder:

Hikma España, S.L.U.

Calle Anabel Segura nº11, Edificio A, planta 1ª, oficina 2

28108 - Alcobendas, Madrid

Spain

This medicine is authorized in the Member States of the European Economic Area under the following names:

Date of last revision of this leaflet: October 2021

Detailed information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

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Cisplatino Hikma 1 mg/ml concentrate for solution for infusion EFG

This information is intended only for healthcare professionals:

In addition to the information included in section 3, practical information on the preparation/handling of the medicine is provided here.

Incompatibilities

It must not come into contact with aluminum. Cisplatin may react with aluminum, causing the formation of a black platinum precipitate. Contact with any intravenous administration utensils, needles, catheters, and syringes containing aluminum should be avoided. Cisplatin decomposes if dissolved in media with low chloride content; the chloride concentration should be at least equivalent to 0.45% sodium chloride.

In the absence of compatibility studies, this medicine must not be mixed with other medicines.

Antioxidants (such as sodium metabisulfite), bicarbonates (sodium bicarbonate), sulfates, fluorouracil, and paclitaxel may inactivate cisplatin in infusion systems.

Expiry Date after Opening:

Chemical and physical stability in use of the diluted solution has been demonstrated for 56 days at 20 - 25 °C, exposed or protected from light. From a microbiological point of view, the product must be used immediately, unless the opening method excludes the risk of microbial contamination. If not used immediately, the storage times and conditions after opening are the responsibility of the user.

Expiry Date after Dilution

The chemical and physical stability in use after dilution with infusion fluids described in section 6.6 of the SmPC indicates that after dilution with recommended intravenous fluids, cisplatino hikma remains stable for up to 48 hours at room temperature (15 to 25 °C) under protection from light.

The diluted solution must be protected from light.

Do not store the diluted solutions in the refrigerator or freezer.

From a microbiological point of view, the diluted solution must be used immediately. If not used immediately, the storage times and conditions before use are the responsibility of the user, and dilution must take place in controlled and validated aseptic conditions.

Preparation for Intravenous Administration

Take the required amount of solution from the vial and dilute it with at least 1 or 2 liters of the following solutions:

• sodium chloride 9 mg/ml (0.9%);
• mixture of 0.9% sodium chloride / 5% glucose (1:1), (resulting final concentrations: sodium chloride 0.45%, glucose 2.5%);
• sodium chloride 0.9% and mannitol 1.875%;
• sodium chloride 0.45%, glucose 2.5%, and mannitol 1.875%.

Compatibility has been demonstrated with the above solutions at concentrations of 0.1 and 0.22 mg/ml.

Do not bring it into contact with injection materials containing aluminum.

Do not administer undiluted.

Administration:

It should be administered only by or under the direct supervision of a qualified physician experienced in the use of cancer chemotherapeutic agents.

Product Preparation (Guide):

1. Chemotherapeutic agents should be prepared for administration only by professionals trained in the safe handling of the preparation.

2. Operations such as reconstitution, dilution, and transfer to syringes should only be performed in the designated area.

3. Personnel carrying out these procedures should be adequately protected with clothing, gloves, and eye protection.

Contamination:

(a) In case of contact with skin or eyes, the affected area should be washed with plenty of water or normal saline solution. A mild cream can be used to treat transient skin irritation. Medical advice should be sought if the eyes are affected.

(b) In case of spillage, operators should wear gloves and clean up the spilled material with a sponge kept in the area for this purpose. Rinse the area twice with water. Put all solutions and sponges in a plastic bag and seal it.

Disposal:

Syringes, containers, absorbent materials, solution, and any other contaminated material should be placed in a thick plastic bag or other impermeable container and incinerated.

Any unused medicine or waste material should be disposed of in accordance with local requirements.