PATIENT INFORMATION LEAFLET

Gemcitabina Hikma 200 mg concentrate for infusion solution

Gemcitabina Hikma 1000 mg concentrate for infusion solution

Gemcitabina Hikma 2000 mg concentrate for infusion solution

Read this leaflet carefully before you start using this medicine because it contains important information for you.

- Keep this leaflet, as you may need to read it again.

- If you have any questions, consult your doctor, pharmacist or nurse.

- If you experience any side effects, consult your doctor, pharmacist or nurse, even if they are not listed in this leaflet. See section 4.

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

2. What you need to know before using Gemcitabina Hikma

3. How to use Gemcitabina Hikma

4. Possible side effects

5. Storage of Gemcitabina Hikma

6. Contents of the pack and additional information

Gemcitabina belongs to a group of medicines called “cytotoxics”. These medicines destroy cells that are dividing, including cancerous cells.

Gemcitabina Hikma may be administered alone or in combination with other anticancer medicines (e.g. cisplatin, paclitaxel, carboplatin),depending on the type of cancer.

This medicine is used to treat the following types of cancer:

• non-small cell lung cancer (NSCLC), alone or in combination with cisplatin
• pancreatic cancer
• breast cancer, in combination with paclitaxel
• ovarian cancer, in combination with carboplatin
• bladder cancer, in combination with cisplatin.

No use Gemcitabina Hikma:

- If you are allergic to the active ingredient or to any of the other components of this medication (listed in section 6).

- If you are breastfeeding.

Warnings and precautions

Before the first infusion, blood samples will be taken to evaluate if your liver and kidney function is correct. Before each infusion, blood samples will be taken to evaluate if you have enough red blood cells to receive the gemcitabina treatment.

Your doctor may decide to change the dose or delay treatment depending on your general condition and if your blood cell counts are too low. Periodically, blood samples will be taken to evaluate the function of your kidneys and liver.

Consult your doctor, pharmacist, or nurse before starting to use gemcitabina.

If you have or have had previously liver disease, heart disease, vascular disease, or kidney problems, consult your doctor or hospital pharmacist, as it may be possible that you cannot receive gemcitabina.

If you have recently received or will receive radiation therapy, consult your doctor, as there may be an early or late radiation reaction with gemcitabina.

If you have recently been vaccinated, consult your doctor, as this could cause negative effects with gemcitabina.

If during treatment with this medication you experience symptoms such as headache with confusion, seizures, or changes in vision, call your doctor immediately. This can be a very rare adverse effect of the nervous system called reversible posterior encephalopathy syndrome.

If you experience difficulty breathing or feel very weak and very pale (it can be a sign of lung problems or kidney failure).

If you experience swelling, shortness of breath, weight gain, please inform your doctor, as it may be a sign that the fluids from your small blood vessels filter into the tissues.

If you have ever developed a severe skin rash or skin peeling, blisters, and/or mouth sores after using gemcitabina.

Severe skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and acute generalized pustular psoriasis (PEGA), have been reported in association with gemcitabina treatment. Seek medical attention immediately if you observe any of the symptoms related to these severe skin reactions described in section 4.

Children and adolescents

This medication is not recommended for use in children under 18 years due to the lack of safety and efficacy data in this population.

Other medications and Gemcitabina Hikma

Inform your doctor or pharmacist if you are using, have used recently, or may need to use another medication, including vaccines and over-the-counter medications.

Pregnancy, breastfeeding, and fertility

Pregnancy

If you are pregnant or think you may be pregnant or intend to become pregnant, consult your doctor or pharmacist before using this medication.

Gemcitabina should be avoided during pregnancy. Your doctor will discuss the potential risk of taking gemcitabina during pregnancy with you.

Breastfeeding

Inform your doctor if you are breastfeeding.

You must interrupt breastfeeding during gemcitabina treatment.

Fertility

Men are advised not to decide to have a child during treatment with gemcitabina or during the 6 months following treatment. If you wish to have a child during treatment or in the 6 months following treatment, consult your doctor or pharmacist. You may wish to request information on sperm conservation before starting your treatment.

Driving and operating machinery

This medication may cause drowsiness, especially if you have consumed alcohol. Avoid driving or operating machinery until you are sure that the gemcitabina treatment does not cause drowsiness.

This medication contains sodium:

Gemcitabina Hikma 200 mg contains a maximum of 4.9 mg of sodium (<1>“exempt from sodium”.

Gemcitabina Hikma 1000 mg contains a maximum of 24.2 mg (1.05 mmol) of sodium (main component of table salt/for cooking) in each vial. This is equivalent to 1.2% of the maximum daily sodium intake recommended for an adult.

Gemcitabina Hikma 2000 mg contains a maximum of 48.4 mg (2.10 mmol) of sodium (main component of table salt/for cooking) in each vial. This is equivalent to 2.4% of the maximum daily sodium intake recommended for an adult.

Your doctor will calculate the initial dose of gemcitabinaand it will depend on the type of cancer you have and your body surface area in square meters (m2).

Your height and weight will be measured to calculate your body surface area. Your doctor will use this body surface area to calculate the correct dose for you. The usual dose is between 1g/m2and 1.25g/m2.

This dose may be adjusted or treatment may be delayed depending on your overall health and blood cell counts.

The frequency at which you receive your gemcitabina infusion will depend on the type of cancer you are being treated for.

You will always receive gemcitabina through an infusion (a slow injection through a drip) into one of your veins. The infusion will last approximately 30 minutes.

Since gemcitabina will be administered under the supervision of your doctor, it is unlikely that you will receive an incorrect dose. However, if you have any other questions about the dose you received or the use of this medication, ask your doctor, nurse, or pharmacist.

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

Contact your doctor immediately if you notice any of the following:

• Bleeding gums, nose, or mouth, or any bleeding that does not stop, pink or red urine, unexpected bruises (since you may have fewer platelets than normal, which is very common).
• Extreme fatigue, feeling of fainting, easily getting winded, or if you are pale (since you may have lower than normal hemoglobin, which is very common).
• Mild to moderate skin rash (very common) / itching (common), or fever (very common); (allergic reactions).
• Temperature of 38°C or higher, sweating, or other signs of infection (since you may have fewer than normal white blood cells, accompanied by fever, also known as febrile neutropenia) (common).
• Pain, redness, swelling, or sores in the mouth (stomatitis) (common).
• Irregular heart rate (arrhythmia) (unknown frequency).

Extreme fatigue and weakness, purple spots or small areas of bleeding on the skin (petechiae), acute kidney injury (low urine output or absence of urine), and signs of infection. These may be signs of microangiopathic thrombosis (clots that form in small blood vessels) and hemolytic uremic syndrome, which can be fatal.

• Difficulty breathing (it is very common to have mild difficulty breathing immediately after gemcitabine infusion, which passes quickly, however, it is infrequently or rarely possible to have more serious lung problems).
• Severe chest pain (myocardial infarction) (rare).
• Severe hypersensitivity / allergic reaction with severe skin rash including itching and redness on the skin, swelling of hands, feet, ankles, face, lips, mouth, and throat (which can cause difficulty swallowing or breathing), wheezing, rapid heartbeat, and may feel like fainting (anaphylactic reaction) (very rare).
• Generalized swelling, difficulty breathing, or weight gain, as you may experience fluid extravasation from small blood vessels to tissues (capillary leak syndrome) (very rare).
• Headache with changes in vision, confusion, seizures, or attacks (posterior reversible encephalopathy syndrome) (very rare).
• Severe rash with itching, blisters, or skin peeling (Stevens-Johnson syndrome, toxic epidermal necrolysis) (very rare).
• Generalized red and scaly rash with inflamed skin lumps under the skin (including skin folds, trunk, and upper limbs) and blisters accompanied by fever (Generalized Acute Pustular Exanthem [PEGA]) (unknown frequency).

Other side effects of the medication may include:

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

• Low white blood cell count

• Difficulty breathing
• Vomiting
• Nausea
• Hair loss
• Liver problems: identified through abnormal blood test results
• Blood in the urine
• Abnormal urine test results: protein in the urine
• Pseudo-grip syndrome including fever
• Swelling of ankles, toes, feet, face (edema)

Common(may affect up to 1 in 10 people)

• Poor appetite (anorexia)
• Headache
• Insomnia
• Drowsiness
• Cough
• Runny or stuffy nose
• Constipation
• Diarrhea
• Itching
• Sweating
• Muscle pain
• Back pain
• Fever
• Weakness
• Chills
• Infections

Rare(may affect up to 1 in 100 people)

• Interstitial lung disease (hardening of the walls of the lung alveoli)
• Wheezing (spasm of the airways)
• Hardening of the walls of the lungs (abnormal chest X-ray/CT scan)
• Heart failure
• Kidney failure
• Severe liver damage, including liver failure
• Cerebral infarction (stroke)

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

• Low blood pressure
• Peeling of the skin, ulceration, or blister formation
• Severe skin peeling and blister formation on the skin.
• Reactions at the injection site
• Severe pulmonary inflammation that causes respiratory distress (adult respiratory distress syndrome).
• Severe skin rash similar to sunburn, which can occur on skin that has been previously exposed to radiation (late cutaneous toxicity)Liquid in the lungs
• Hardening of the walls of the lung alveoli associated with radiation (radiation-associated toxicity)
• Foot or hand gangrene
• Peripheral vasculitis (inflammation of blood vessels).

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

• Increased platelet count
• Inflammation of the large intestine membrane, caused by reduced blood supply (ischemic colitis).
• Low hemoglobin levels (anemia), low white blood cell count, and low platelet count will be detected through blood tests.
• Microangiopathic thrombosis: clots that form in small blood vessels.

Unknown frequency(cannot be estimated from available data)

• Sepsis: when a bacterium and its toxins circulate in your blood and start damaging your organs.
• Pseudocellulitis: skin redness with swelling.

You may experience any of these symptoms and/or disorders. Inform your doctor as soon as possible if you start experiencing any of these side effects.

If you are concerned about any of the side effects, consult your doctor.

Reporting side effects

If you experience side effects, consult your doctor, hospital pharmacist, or nurse, even if they do not appear in this leaflet. You can also report them directly through the Spanish System for the Vigilance of Medicinal Products for Human Use:www.notificaRAM.es. By reporting side effects, you can contribute to providing more information on the safety of this medication.

This medication will be stored and administered by healthcare personnel, who will follow the following instructions:

• Keep this medication out of the sight and reach of children.
• Do not use this medication after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.
• Store in refrigerator (between 2°C and 8°C).
• This medication is for single use; the disposal of unused medication and all materials that have been in contact with it will be carried out in accordance with local regulations.

Composition of Gemcitabina Hikma

• The active ingredient is gemcitabina (as hydrochloride). The concentrated solution has a dose of 38 mg/ml, which means that each milliliter of concentrate contains 38 mg/ml ofgemcitabina(as hydrochloride).

• The other components (excipients) are water for injectable preparations, hydrochloric acid (to adjust the pH) and sodium hydroxide (to adjust the pH).

Appearance of Gemcitabina Hikma and contents of the package

Clear, colorless or slightly yellowish solution.

It is presented in glass vials.

There are 3 sizes of packaging available, containing

200 mg gemcitabina (as hydrochloride) in 5.26 ml of solution

1000 mg gemcitabina (as hydrochloride) in 26.3 ml of solution

2000 mg gemcitabina (as hydrochloride) in 52.6 ml of solution

Each vial is individually packaged in a cardboard box.

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, Fervença

2705-906 Terrugem SNT

Portugal

Responsible manufacturer

Thymoorgan Pharmazie GmbH

Schiffgraben 23

38690 Goslar

Germany

Further information about this medicinal product can be obtained 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

Last review date of this leaflet:February 2024

The detailed and updated information about this medicinal product is available on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS) http://www.aemps.es/
The following information is intended only for healthcare professionals:

Instructions for use, handling and disposal

Shelf life after opening:

Chemical and physical stability has been demonstrated for 35 days at 20-25 °C exposed to light and for 35 days at 2-8 °C protected from light.

From a microbiological point of view, unless the opening method excludes the risk of microbial contamination, the product must be used immediately. If not used immediately, the storage times and conditions in use are the responsibility of the user.

Use

• Consult the Technical Data Sheet to calculate the dose and the number of vials needed.A diluent approved for the gemcitabina concentrate is sodium chloride 9 mg/ml (0.9%) injectable solution (without preservatives). Use aseptic techniques during any additional dilution of the gemcitabina concentrate, before administration.
• Before administration, the parenteral medications must be visually inspected to detect possible particles in suspension and color change. If particles are observed, do not administer.
• After dilution, chemical and physical stability in use has been demonstrated for:

From a microbiological point of view, the prepared solutions must be used immediately. If not used immediately, the storage times and conditions in use and before use are the responsibility of the user and are normally not more than 24 hours between 2 and 8°C, unless the dilution has taken place in controlled and validated aseptic conditions.

Handling

• Normal safety measures for cytostatic agents must be taken into account when preparing and disposing of the infusion solution. The handling of the solution must be performed in a safety cabinet and protective clothing and gloves must be used. If a safety cabinet is not available, the equipment must be supplemented with masks and eye protection.
• If the solution comes into contact with the eyes, it may cause severe irritation. The eyes must be thoroughly flushed with plenty of water immediately. If the irritation persists, a doctor should be consulted. If the solution spills on the skin, it must be thoroughly washed with plenty of water.

Disposal

The disposal of unused medicinal product and all materials that have come into contact with it will be carried out in accordance with local regulations.