Prospecto: information for the patient

Cisplatino Hikma 1 mg/ml concentrate for infusion solution EFG

Read this prospect carefully before starting to use this medicine, because it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor, pharmacist or nurse.
• This medicine has been prescribed to you alone, and you must not give it to other people, even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist or nurse, even if they are not listed in this prospect. See section 4.

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

What it is used for

Cisplatino is able to destroy the cells in your body that may cause certain types of cancer (testicular tumor, ovarian tumor, bladder tumor, epidermoid carcinoma of the head and neck, lung cancer and cervical cancer in combination with radiation therapy).

No use Cisplatino Hikma

• If you are allergic to cisplatin or any of the other components of this medication (listed in section 6);
• If you are allergic (hypersensitive) to any other medication that contains platinum components;
• If you have kidney problems (renal insufficiency);
• If you have dehydration;
• If you have severe suppression of bone marrow function, which can cause symptoms such as extreme fatigue, easy bleeding, or the appearance of petechiae, or the appearance of infections;
• If you have hearing problems;
• If you have nervous disorders caused by cisplatin;
• 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 medications").

Warnings and Precautions:

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

• This medication should only be administered under the strict supervision of a specialist doctor with experience in administering chemotherapy.
• You will undergo an audiometry test before each treatment with this medication.
• If you have a non-cisplatin-induced nervous disorder.
• If you have received radiation therapy to 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 you are subject to the above conditions before starting to use this medication.

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

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

Taking Cisplatino Hikma with other medications

Be aware that these instructions may also apply to medications that have been used before or may be used in the future. Inform your doctor or pharmacist if you are using, have used recently, or may have to use any other medication.

• The simultaneous use of medications that inhibit bone marrow function or radiation can increase the adverse effects of cisplatin on the bone marrow.
• The toxicity of this medication can increase when administered simultaneously with otherchemotherapeutic agents(other cancer medications), such as bleomycin and methotrexate.
• Medications for the treatment of high blood pressure (antihypertensiveswith furosemide, hydralazine, diazoxide, or propranolol) can increase the toxic effect of cisplatin on the kidneys.
• The toxicity of cisplatin can severely affect the kidneys when administered with medications that can cause adverse effects on the kidneys, such as those used to prevent or treat certain infections (antibiotics: cephalosporins, aminoglycosides, and/or antifungals: amphotericin B) andcontrast media.
• The toxicity of cisplatin can also affect hearing when administered with agents that have adverse reactions that affect auditory capabilities, such as aminoglycosides.
• If you take medications to treat gout during your treatment with cisplatin, you may need to adjust the dose of these medications (e.g., allopurinol, colchicine, probenecid, and/or sulfinpyrazone).
• The administration of medications to increase urine production (diuretics) in combination with cisplatin (when the cisplatin dose is not greater than 60 mg/m2, and urine production is not less than 1,000 ml per 24 hours) can produce toxic effects on the kidneys and ears.
• The first signs of hearing problems (such as dizziness and tinnitus) may be masked if, during treatment with cisplatin, you are administered medications to treat hypersensitivity, nausea, or mental problems (antihistaminessuch as buclizine, cyclizine, loxapine, meclozine, phenothiazines, thioxanthenes, and/or trimethobenzamides).
• Cisplatin in combination with ifosfamide can cause ear damage.
• The administration ofpyridoxineandhexamethylmelaminecan reduce the response to treatment with cisplatin.
• Cisplatin in combination withbleomycinandvinblastinecan cause paleness or blue discoloration of the fingers of the hands and/or feet (Raynaud's phenomenon).
• The administration of cisplatin for treatment withpaclitaxelor in combination withdocetaxel

can cause severe nerve damage.

• It is recommended to regularly control lithium levels since a reduction in lithium levels in the blood has been observed after treatment with cisplatin combined withbleomycinandetoposide.
• Cisplatin reduces the effects ofphenytoinin the treatment of epilepsy.
• Thepenicillamineand other chelating agentscan decrease the effectiveness of this medication.
• Cisplatin can have a negative impact on the effectiveness of medications that prevent coagulation (anticoagulants). Therefore, it is recommended to increase the frequency of coagulation control during combined use of these medications.
• Cisplatin in combination withciclosporincan produce immunosuppression with a risk of proliferation of white blood cells (lymphocytes).
• You should not receivelive vaccinesin the three months following completion of treatment with cisplatin.
• You should not receive theyellow fever vaccinewhile 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 intend to become pregnant, consult your doctor, pharmacist, or nurse before using this medication. Cisplatin should not be used duringpregnancyunless your doctor indicates otherwise. Measures should be taken to avoid conception if you are fertile during and, at least, 6 months after treatment with Cisplatino Hikma.

Breastfeeding

This medication should not be used by women during breastfeeding.

Fertility

It is recommended that men treated with cisplatin not have children during treatment and for at least 6 months after treatment. Additionally, it is recommended that men who wish to become fathers in the future seek advice regarding sperm cryopreservation before treatment.

Driving and operating machinery

Cisplatin can cause drowsiness and/or nausea. If you experience either of these effects, avoid operating machinery that requires special attention.

Cisplatino Hikma contains sodium

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

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

Dosage and Administration

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

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

Cisplatino should not come into contact with materials containing aluminum.

The recommended dose of cisplatino depends on your health status, the expected effects of treatment, and whether cisplatino is used alone (monotherapy) or in combination with other medications (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 medication in combination with other chemotherapeutic agents (combination chemotherapy):

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

For cervical cancer treatment, cisplatino is used in combination with radiation therapy. A typical dose is 40 mg/m² per week for 6 weeks.

To avoid or reduce kidney problems, it is recommended that you drink large amounts of water for 24 hours after cisplatino treatment.

If You Receive More Cisplatino Hikma Than You Should

Your doctor will ensure that you receive the correct dose. In case of overdose, you may experience increased adverse effects. Your doctor may provide symptomatic treatment for these adverse effects. If you believe you have received too much cisplatino, contact your doctor immediately.

If you have any other questions about the use of this medication, ask your doctor or nurse.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

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

Inform your doctor immediately if you experience any of the following side effects:

• Persistent or severe diarrhea or vomiting
• Stomatitis/mucositis (pain in the lips or ulcer 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 bleeding or bruising
• Signs of infection, such as sore throat and high fever
• Sensation of discomfort 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)

• Decreased white blood cells, making infections more likely (leucopenia)
• Decreased platelets, increasing the risk of bruising and bleeding (thrombocytopenia)
• Decreased red blood cells, which can cause pale skin and cause weakness or shortness of breath (anemia)
• Renal dysfunction, such as lack of urine production (anuria)
• Blood poisoning due to urine (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)
• Nervous system damage (neurotoxicity)
• Arrhythmia, including decreased heart rate (bradycardia) and increased heart rate (tachycardia)
• Phlebitis (inflammation of a vein)
• Difficulty breathing (dyspnea), 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

Rare (may affect up to 1 in 100 people)

• Severe allergic reactions (anaphylactic) including skin rash, severe itching eczema, and formation of blisters (urticaria), skin redness and inflammation (erythema), or itching (pruritus), anaphylactoid reactions with symptoms such as facial swelling and fever, low blood pressure (hypotension), rapid heart rate (tachycardia), difficulty breathing (dyspnea), angina due to muscle cramps in the respiratory tract (bronchospasm)
• Low magnesium levels in the blood
• Auditory problems (ototoxicity)
• Disfunctional spermatogenesis (alteration in sperm formation) and abnormal ovulation, painful breast development in men (gynecomastia)

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

• A type of blood cancer (severe leukemia)
• Decreased immune system (immunosuppression)
• Increased normal levels of cholesterol in the blood (hypercholesterolemia)
• Peripheral neuropathy of sensory nerves (sensory neuropathy), characterized by tingling, itching, or numbness without cause, and sometimes characterized by loss of taste, touch, vision, as well as brain dysfunction (confusion, difficulty speaking, sometimes blindness, memory loss, and paralysis); sudden stabbing pains from the neck through the back to the legs when bending forward, spinal disease, convulsions, loss of certain types of brain function, including brain dysfunction characterized by spasms and reduced levels of consciousness (encephalopathy), as well as carotid artery closure
• Inflammation of the optic nerve combined with pain and reduced nerve function (neuritis optica), eye movement dysfunction
• Alteration 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 in the blood

Frequency unknown (cannot be estimated from 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 contractions (tetany)
• Stroke (cerebrovascular accident)
• Loss of vision (blindness), difficulty perceiving colors, blurry vision, swelling (papilledema)
• Tinnitus, deafness
• Cardiac disorder
• Impaired 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)
• Loss of appetite (anorexia), nausea, vomiting, diarrhea
• Hypophagia
• Hair loss (alopecia), skin rash
• Fever, weakness (asthenia), general discomfort
• Stroke (cerebrovascular accident)

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Use: https://www.notificaram.es.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Expiration Date

Do not use this medication after the expiration date that appears on the vial and on the outer packaging after ‘CAD’. The expiration date is the last day of the month indicated. Do not use this medication if you notice visible signs of deterioration.

Storage

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

After dilution, the product must be used immediately. If this is not possible, it can be stored for up to 48 hours at an ambient temperature of 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.

Cisplatino Hikma Composition

The active ingredient is cisplatino.

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

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

Appearance of Cisplatino Hikma and packaging contents

Cisplatino Hikma is a transparent, colorless to pale yellow concentrate for solution for infusion in an amber glass vial of 50 or 100 mL.

The vials are packaged in boxes of 1 vial.

Only some sizes of packaging may be commercially available.

Marketing authorization holder and responsible manufacturer

Marketing authorization holder:Hikma Farmacêutica (Portugal), S.A.

Estrada do Rio da Mó 8,8A e 8B

2705-906 Terrugem SNT, Portugal

Responsible manufacturer:

Thymoorgan Pharmazie GmbH

Schiffgraben 23

D-38690 Goslar

Germany

For more information about this medicinal product, please contact 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 medicinal product is authorized in the member states of the European Economic Area with the following names:

Last review date of this leaflet: October 2021

More detailed information about this medicinal product is available on the website of the Spanish Agency for Medicines and Medical Devices (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 medical professionals or healthcare professionals:

In addition to the information included in section 3, the following practical information on the preparation/manipulation of the medicinal product is provided.

Incompatibilities

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

In the absence of compatibility studies, this medicinal product should not be mixed with other medicinal products.

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

Shelf life after opening:

Chemical and physical stability has been demonstrated in use for 56 days at 20-25 °C, exposed or protected from light. From a microbiological point of view, the product should 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.

Shelf life after dilution

Chemical and physical stability in use after dilution with infusion fluids described in section 6.6 of the SPC indicates that after dilution with recommended intravenous fluids, cisplatino Hikma remains stable for a period of up to 48 hours at ambient temperature of 15 to 25 °C under protection against light.

The diluted solution should be protected from light.

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

From a microbiological point of view, the diluted solution should be used immediately. If not used immediately, the storage times in use and the conditions prior to use are the responsibility of the user, and the dilution should 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%);
• 0.9% sodium chloride and 5% glucose (1:1) mixture (resulting 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 put it in contact with aluminum-containing injection materials.

Do not administer without diluting.

Administration:

It should only be administered under the direct supervision of a qualified medical doctor with experience in the use of anticancer chemotherapeutic agents.

Preparation of the product (guide):

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

2. Operations such as reconstitution, dilution, and transfer to syringes should only be performed in the designated area. 3. The personnel performing these procedures should be adequately protected with clothing, gloves, and eye protection.4. Pregnant personnel are advised not to handle chemotherapeutic agents.

Contamination:

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

(b) In the event of a spill, operators should put on gloves and clean the spilled material with a sponge kept for this purpose. Rinse the area twice with water. Place all solutions and sponges in a plastic bag and seal it.

Disposal:

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

Any unused medicinal product or waste should be disposed of in accordance with local requirements.