GEMCITABINE KOANAA 1.000 mg CONCENTRATE FOR INFUSION SOLUTION

2. What you need to know before taking Gemcitabine Koanaa

Do not use Gemcitabine Koanaa:

• if you are allergic to gemcitabine or any of the other components of this medicine (listed in section 6).
• if you are breastfeeding.

Warnings and precautions

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

Before the first infusion, you will have blood samples taken to check if your liver and kidneys are working properly. Before each infusion, you will also have blood samples taken to check if you have enough blood cells to receive treatment with this medicine.

Depending on your general state of health and the results of the blood tests, your doctor may decide to change the dose or postpone treatment with gemcitabine if your blood cell count is too low.

Periodically, you will have blood samples taken to evaluate the functioning of your liver and kidneys.

Consult your doctor or nurse before receiving gemcitabine if:

• you have or have had liver, heart, or vascular diseases in the past
• you have received radiotherapy in the last few days or are going to receive it
• you have been vaccinated recently
• you have difficulty breathing or feel very weak and pale (may be a symptom of kidney failure).

Children and adolescents

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

Other medicines and Gemcitabine Koanaa

Tell your doctor or pharmacist if you are taking, have recently taken, or may take any other medicines.

Pregnancy, breastfeeding, and fertility

Pregnancy

If you are pregnant or plan to become pregnant, consult your doctor. The use of gemcitabine should be avoided during pregnancy. Your doctor will inform you about the possible risks of using gemcitabine during pregnancy.

Breastfeeding

Tell your doctor if you are breastfeeding.

You should stop breastfeeding during treatment with gemcitabine.

Fertility

If you are a man, you should avoid having children during treatment with gemcitabine and for 6 months after the end of treatment. If you want to be a father during treatment or in the 6 months following treatment, you should consult your doctor or pharmacist. You may want to learn about sperm preservation before starting treatment.

Driving and using machines

Treatment with this medicine may cause drowsiness, especially if you have consumed alcohol. You should not drive or use machines until you are sure that treatment with gemcitabine has not caused drowsiness or dizziness.

Gemcitabine Koanaa contains sodium

This medicine contains up to 2.4 mg of sodium (<1 mmol) in each 200 mg vial, up to 12.1 of sodium (<1 1,000 and 24.2 2,000 vial. this should be taken into account patients with a controlled diet.< p>

3. How to use Gemcitabine Koanaa

Follow the instructions for administration of this medicine exactly as indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

Your doctor will calculate the initial dose of gemcitabine and 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 information to calculate the correct dose. The usual dose is between 1 g/m2 and 1.25 g/m2.

This dose may be adjusted or treatment delayed depending on the results of the blood tests, your general state of health, and any adverse reactions you may have.

The frequency at which you will receive a dose of gemcitabine by infusion will depend on the type of cancer being treated.

Gemcitabine will always be administered as an infusion (a slow injection via a drip) into one of your veins. The infusion will last approximately 30 minutes.

Since you will receive Gemcitabine under the supervision of a doctor, it is unlikely that you will receive an incorrect dose. However, if you have any doubts about the dose you receive or if you have any other questions about the use of this medicine, talk to your doctor, pharmacist, or nurse.

4. Possible side effects

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

You should contact your doctor immediately if you notice any of the following effects:

• Bleeding from the gums, nose, or mouth, or any bleeding that does not stop, reddish or pinkish urine, unexpected bruising (as you may have fewer platelets than normal, which is very common).
• Fatigue, feeling of fainting, getting short of breath easily, or if you are pale (as you may have lower than normal hemoglobin, which is very common).
• Mild or moderate skin rash / itching (very common) / fever (very common); (allergic reactions).
• Temperature of 38°C or higher, sweating, or other signs of infection (as you may have fewer white blood cells than normal, accompanied by fever, also known as febrile neutropenia) (common).
• Pain, redness, swelling, or sores in the mouth (stomatitis) (common).
• Irregular heartbeat (arrhythmia) (uncommon).
• Extreme fatigue and weakness, purple spots or small areas of bleeding on the skin (hematomas), acute kidney failure (low or no urine production), and signs of infection. These may be signs of thrombotic microangiopathy (clots forming in small blood vessels) (very rare) and hemolytic uremic syndrome (uncommon), which can be fatal.
• Difficulty breathing (it is very common to have mild difficulty breathing immediately after gemcitabine infusion, which passes soon, however, uncommonly or rarely, there may be more serious lung problems).
• Severe chest pain (myocardial infarction (rare).
• Severe hypersensitivity / allergic reaction with severe skin rash including itching and redness of the skin, swelling of hands, feet, ankles, face, lips, mouth, and throat (which can cause difficulty swallowing or breathing), wheezing, rapid heartbeat, and you may feel like you are going to faint (anaphylactic reaction) (very rare).
• Generalized swelling, difficulty breathing, or weight gain, as you may suffer from 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 peeling of the skin (Stevens-Johnson syndrome, toxic epidermal necrolysis) (very rare).

Other side effects with gemcitabine 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: detected by abnormal blood test results
• Blood in the urine
• Abnormal urine test results: protein in the urine
• Pseudogrippal syndrome, including fever
• Swelling of ankles, fingers, feet, face (edema)

Common: (may affect up to 1 in 10 people)

• Lack of appetite (anorexia)
• Headache
• Insomnia
• Drowsiness
• Cough
• Stuffy nose
• Constipation
• Diarrhea
• Itching
• Sweating
• Muscle pain
• Back pain
• Fever
• Weakness
• Chills
• Infections

Uncommon: (may affect up to 1 in 100 people)

• Hardening of the walls of the lung alveoli (interstitial pneumonitis)
• Wheezing (bronchospasm)
• Scarring of the lungs (abnormal chest X-ray / scan)
• Heart failure
• Kidney failure
• Severe liver damage, including liver failure
• Stroke (cerebral infarction)

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

• Low blood pressure.
• Peeling of the skin, ulcers, or blisters.
• Severe peeling of the skin and blisters.
• Reactions at the injection site.
• Severe lung inflammation that causes respiratory failure (adult respiratory distress syndrome).
• Severe sunburn-like rash that can occur in skin that has been previously exposed to radiotherapy (radiation-induced late skin toxicity).
• Fluid in the lungs.
• Hardening of the walls of the lung alveoli associated with radiotherapy (radiation-induced toxicity).
• Gangrene of the toes or fingers.
• Inflammation of the blood vessels (peripheral vasculitis).

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

• Increased platelet count
• Inflammation of the membrane of the large intestine, caused by reduced blood supply (ischemic colitis)
• Low hemoglobin levels (anemia), low white blood cell count, and low platelet count can be detected by blood tests.
• Clots forming in small blood vessels (thrombotic microangiopathy)

Unknown: (cannot be estimated from the available data).

• Redness of the skin with swelling (pseudocellulitis)
• When bacteria and their toxins circulate in your blood and start damaging your organs (sepsis)

You may experience any of these symptoms and/or conditions. You should inform your doctor as soon as possible if you start to experience any of these side effects.

Talk to your doctor if you are concerned about any of the side effects.

Reporting of side effects

If you experience any side effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Conservation of Gemcitabine Koanaa

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

Store in the refrigerator (between 2°C and 8°C).

Do not use this medicine after the expiration date stated on the label and carton after expiration (CAD). The expiration date is the last day of the month indicated.

This medicine is for single use only; unused medicine will be disposed of in accordance with local regulations.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any unused medicine. This will help protect the environment.

6. Container Content and Additional Information

Composition of Gemcitabina Koanaa

• The active ingredient is gemcitabine. One ml of concentrate for solution for infusion contains gemcitabine (as hydrochloride), equivalent to 38 mg of gemcitabine.

Each 5.26 ml vial contains 200 mg of gemcitabine (as hydrochloride).

Each 26.3 ml vial contains 1000 mg of gemcitabine (as hydrochloride).

Each 52.6 ml vial contains 2000 mg of gemcitabine (as hydrochloride).

• The other components are water for injectable preparations, hydrochloric acid (for pH adjustment), and sodium hydroxide (for pH adjustment).

Appearance of the Product and Container Content

Gemcitabina Koanaa concentrate for solution for infusion is a clear, transparent or slightly yellowish solution.

Gemcitabine 200 mg concentrate for solution for infusion (200 mg/5.26 ml)

A 10 ml/20 mm Type 1 tubular glass vial with a 20 mm gray bromobutyl omniflex plus coated stopper (ready for sterilization) and sealed with a 20 mm red aluminum cap with a tab. Each vial of the 200 mg presentation contains 5.3 ml of the concentrate. Each package contains 1 vial.

Gemcitabine 1,000 mg concentrate for solution for infusion (1,000 mg/26.3 ml)

A 30 ml/20 mm Type 1 tubular glass vial with a 20 mm gray bromobutyl omniflex plus coated stopper (ready for sterilization) and sealed with a 20 mm red aluminum cap with a tab. Each vial of the 1 g presentation contains 26.3 ml of the concentrate. Each package contains 1 vial.

Gemcitabine 2,000 mg concentrate for solution for infusion (2,000 mg/52.6 ml)

A 100 ml/20 mm Type 1 tubular glass vial with a 20 mm gray bromobutyl omniflex plus coated stopper (ready for sterilization) and sealed with a 20 mm red aluminum cap with a tab. Each vial of the 2 g presentation contains 52.6 ml of the concentrate. Each package contains 1 vial.

Only some package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Koanaa Healthcare GmbH

Fehrgasse 7

A-2401 Fischamend

Austria

Manufacturer

Drehm Pharma GmbH

Hietzinger Hauptstraße 37/2

1130 Austria

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

Austria Gemcitabin Koanaa 38 mg/ml Konzentrat zur Herstellung einer Infusionslösung

France Gemcitabine Koanaa 38 mg/ml, solution à diluer pour perfusion

Germany Gemcitabin Koanaa 38 mg/ml Konzentrat zur Herstellung einer Infusionslösung

Spain Gemcitabina Koanaa 200 mg concentrate for solution for infusion

Gemcitabina Koanaa 1,000 mg concentrate for solution for infusion

Gemcitabina Koanaa 2,000 mg concentrate for solution for infusion

Date of the last revision of thisleaflet:September 2019.

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

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This information is intended only for healthcare professionals:

Instructions for Use, Handling, and Disposal

Use

• Consult the Summary of Product Characteristics to calculate the dose and the number of vials needed.
• The solution must be diluted: An authorized diluent for the solution of this medicinal product is sodium chloride 9 mg/ml (0.9%) solution for injectables (without preservative). Follow aseptic technique during the dilution of Gemcitabine concentrate, before administration.
• Before administration, parenteral medicinal products must be inspected visually for particles or discoloration. If particles are observed, do not administer.
• After dilution, chemical and physical stability has been demonstrated during use for:

From a microbiological point of view, the product should be used immediately. If not, the storage times during use and the conditions before use are the responsibility of the user and should not exceed 24 hours at 2 to 8°C, unless the dilution has taken place in controlled and validated aseptic conditions.

Handling

• Usual safety precautions for cytostatics should be taken into account when preparing and disposing of the infusion solution. Handling of the infusion solution should be carried out in a safety cabinet and with protective gloves and gowns worn. If a safety cabinet is not available, a mask and protective glasses should be added to the equipment.

• If the preparation comes into contact with the eyes, it could cause severe irritation. The eyes should be rinsed thoroughly and immediately with water. If irritation persists, a doctor should be consulted. If the skin is splashed with the solution, it should be rinsed thoroughly with water.

Disposal

Gemcitabina Koanaa is for single use only. Disposal of unused medicinal product and all materials that have come into contact with it should be carried out in accordance with local regulations for cytotoxic agents.