Gemsol

Patient Information Leaflet

Gemsol 40 mg/ml concentrate for solution for infusion

Gemcitabine
Please read this leaflet carefully before using this medicine because it contains important information for you

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor. See section 4.

Contents of this leaflet:

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

1. What Gemsol is and what it is used for

Gemsol belongs to a group of medicines called "cytotoxic agents". These medicines kill dividing cells, including tumour cells.
Gemsol may be given alone or in combination with other anticancer medicines, depending on the type of tumour.
Gemsol 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.

2. What you should know before using Gemsol

Do not use Gemsol:

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

Warnings and precautions
Before the first infusion, blood tests will be performed to check whether your liver and kidneys are functioning well enough for you to receive this medicine. Before each infusion, blood tests will be carried out to ensure that you have sufficient blood cells to receive Gemsol. Your doctor may decide to adjust the dose or delay treatment depending on your general condition and if blood counts (white blood cells and platelets) are too low. Periodically, blood tests will be performed to assess how well your kidneys and liver are functioning.

Talk to your doctor, pharmacist, or nurse before using Gemsol if:

• you have or have had liver, heart, or vascular diseases
• you have lung or kidney problems, as treatment with Gemsol may not be suitable
• you have recently undergone or are scheduled to undergo radiotherapy, as early or late radiation reactions may occur when using Gemsol
• you have recently been vaccinated (especially against yellow fever), as this may cause harmful effects when using Gemsol
• you develop breathing difficulties or feel very weak and look very pale, as this may be a sign of kidney failure or lung problems
• you experience generalized swelling, shortness of breath, or weight gain, as these may be signs of fluid leaking from blood vessels into tissues
• you develop symptoms such as headache with confusion, seizures (fits), or changes in vision. This could be a very rare side effect affecting the nervous system called reversible posterior encephalopathy syndrome
• you are pregnant or planning a pregnancy
• you experience pain at the infusion site or any other symptoms related to extravasation (injection site reactions such as swelling, redness, or localized warmth). If during treatment with this medicine you develop symptoms such as headache with confusion, seizures (fits), or changes in vision, contact your doctor immediately. This could be a very rare side effect of the nervous system called reversible posterior encephalopathy syndrome.

Children and adolescents
This medicine is not recommended for use in children under 18 years of age due to insufficient data on efficacy and safety.

Other medicines and Gemsol
Inform your hospital doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those obtained without a prescription, and about any vaccinations.

Pregnancy, breastfeeding, and fertility

Pregnancy
If you are pregnant, suspect you may be pregnant, or are planning a pregnancy, consult your doctor before taking this medicine.
If you are pregnant or planning a pregnancy, inform your doctor. Use of Gemsol should be avoided during pregnancy. Your doctor will discuss with you the potential risks associated with using Gemsol during pregnancy.

Breastfeeding
Inform your doctor if you are breastfeeding.
You must stop breastfeeding during treatment with Gemsol.

Fertility
Men are advised not to father a child during treatment with Gemsol and for 6 months after treatment ends. If you wish to father a child during treatment or within 6 months after, consult your doctor or pharmacist. You may wish to discuss sperm preservation options before starting therapy.

Driving and using machines
Gemsol may cause drowsiness, particularly if alcohol is consumed. Do not drive or operate machinery until you are certain that treatment with Gemsol does not make you drowsy.

3. How to use Gemsol

The normal dose of Gemsol ranges from 1000 to 1250 mg per square metre of your body surface area.
To calculate your body surface area, your weight and height will be measured. Your doctor will use
these measurements to determine the most appropriate dose. This dose may be adjusted or the
treatment delayed, depending on your blood counts and your general condition.
The frequency with which you will receive Gemsol infusions depends on the type of tumour being treated.
Gemsol will always be given to you as an intravenous infusion after dilution. The infusion will last approximately 30 minutes.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, Gemsol can cause side effects, although not everybody experiences them.
If you notice any of the following symptoms, contact your doctor immediately:

• bleeding from gums, nose or mouth, or any bleeding that does not stop; red or pink-colored urine; unusual bruising (you may have fewer platelets than normal – a very common condition)

• tiredness, feeling faint, shortness of breath or paleness (you may have lower than normal haemoglobin levels – a very common condition)

• mild to moderate skin rash (very common), itching (common), or fever (very common) (allergic reactions)

• body temperature of 38°C or higher, sweating, or other signs of infection (you may have fewer white blood cells than normal, accompanied by fever – a common condition known as neutropenic fever) (common)

• pain, redness, swelling or ulcers in the mouth (stomatitis) (common)

• irregular heartbeat (arrhythmia) (uncommon)

• extreme tiredness and weakness, purpura or small areas of bleeding under the skin (bruising), acute kidney failure (low urine output or no urine), and signs of infection. This may be fatal (uncommon)

• difficulty breathing (it is very common to experience mild breathing difficulty shortly after Gemsol infusion, which usually resolves quickly; however, more serious lung problems may uncommonly or rarely occur)

• severe chest pain (myocardial infarction) (rare)

• severe hypersensitivity/allergic reactions associated with development of severe skin rashes including itchy red skin, swelling of hands, feet, ankles, face,
  lips, mouth or throat (which may cause difficulty swallowing or breathing), wheezing, rapid heartbeat, and feeling faint (anaphylactic reaction) (very rare)

• generalized swelling, shortness of breath, or weight gain – this may be a sign of fluid leakage from small blood vessels into tissues (capillary leak syndrome) (very rare)

• headache with changes in vision, confusion, seizures (reversible posterior encephalopathy syndrome) (very rare)

• severe skin rash with itching, blistering and peeling of the skin (Stevens-Johnson syndrome, toxic epidermal necrolysis) (very rare)

• extreme tiredness and weakness, purpura or small areas of bleeding under the skin (bruising), acute kidney failure (low urine output or no urine), and signs of infection. These may be features of thrombotic microangiopathy (blood clots forming in small blood vessels) and haemolytic uraemic syndrome, which may be fatal.

Other side effects with Gemsol may include the following
Very common side effects (may affect more than 1 in 10 people)

• Low white blood cell count
• Vomiting
• Nausea
• Hair loss
• Liver problems, detected by abnormal blood test results
• Blood in urine
• Abnormal urine test results: presence of protein in urine
• Flu-like symptoms, including fever
• Swelling of ankles, fingers, feet and face (oedema)

Common side effects (may affect up to 1 in 10 people)

• Loss of appetite (anorexia)
• Headache
• Trouble sleeping
• Drowsiness
• Cough
• Runny nose
• Constipation
• Diarrhoea
• Itching
• Sweating
• Muscle pain
• Back pain
• Fever
• Weakness
• Chills
• Increased liver values (bilirubin)
• Infections

Uncommon side effects (may affect up to 1 in 100 people)

• Scarring of the air sacs in the lungs (interstitial pneumonia)
• Dyspnoea (airway spasm)
• Scarring of the lungs (abnormal chest X-rays/scans)
• Stroke
• Heart failure
• Kidney failure
• Severe liver damage, including liver failure and death

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

• Low blood pressure
• Peeling, ulceration or blistering of the skin
• Skin detachment and severe subcutaneous blistering
• Reactions at the injection site
• Severe lung inflammation that may lead to respiratory failure (adult respiratory distress syndrome)
• Skin rash resembling a severe sunburn, which may occur on skin previously exposed to radiotherapy (radiation recall phenomenon)
• Fluid in the lungs
• Scarring of the air sacs in the lungs associated with radiation therapy (radiation toxicity)
• Gangrene of fingers or toes
• Inflammation of blood vessels
• Increased liver values (GGT)

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

• Increased platelet count
• Inflammation of the lining of the large intestine due to reduced blood supply (ischaemic colitis)
• Thrombotic microangiopathy: blood clots forming in small blood vessels

Not known (frequency cannot be estimated from available data)

• sepsis: when bacteria and their toxins circulate in the blood and begin to damage organs
• Pseudocellulitis: skin redness with swelling

Low haemoglobin levels (anaemia), low lymphocyte count, and changes in platelet count in blood tests.
Any one or more of these symptoms and/or conditions may occur. If you experience any of these side effects, inform your doctor as soon as possible.
If you are concerned about any side effect, consult your doctor.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Gemsol

Keep this medicine out of the sight and reach of children.
FI GEMSOL
Do not use Gemsol after the expiry date stated on the container and label, following the term EXP. The expiry date refers to the last day of the month.
Hospital pharmacy must store Gemsol vials at 2-8°C. Do not freeze.
If stored below 2°C, the solution may form precipitates.
If the solution appears discoloured or contains visible particles, it must be discarded.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package Contents and Other Information

What Gemsol contains
The active substance is gemcitabine (as hydrochloride).
Each ml of concentrate for solution for infusion contains 40 mg of gemcitabine (as hydrochloride).
Each 5 ml vial contains 200 mg of gemcitabine (as hydrochloride).
Each 25 ml vial contains 1000 mg of gemcitabine (as hydrochloride).
Each 50 ml vial contains 2000 mg of gemcitabine (as hydrochloride).
The other components are: water for injections and diluted hydrochloric acid (for pH adjustment).

Description of the appearance of Gemsol and contents of the package
This medicinal product is a concentrate for solution for infusion.
The concentrate is a clear, colourless to pale yellow solution, supplied in colourless glass vials (Type I) closed with grey rubber stoppers compliant with Ph.Eur (Type I). The vials are sealed, with or without a protective plastic overwrap (Onco-Safe). “Onco-Safe” does not come into contact with the medicinal product and provides additional protection during transport, enhancing safety for medical and pharmaceutical personnel.

Pack sizes:
200 mg/5 ml: 1 vial, 5 vials, 10 vials
1000 mg/25 ml: 1 vial
2000 mg/50 ml: 1 vial
Not all pack sizes may be marketed.

Marketing Authorization Holder
Sandoz Spa
Largo U. Boccioni 1
21040 Origgio (VA)
Italy

Manufacturer
EBEWE Pharma Ges.m.b.H. Nfg. KG
4866 Unterach
Austria

FI GEMSOL

This medicinal product has been authorized in the EEA Member States under the following names:
Austria    Gemsol 40 mg/ml Concentrate for the preparation of an infusion solution
Belgium    Gemcitabin Sandoz 40 mg/ml concentrate for solution for infusion
Bulgaria    ГЕМСОЛ 40 MG/ML КОНЦЕНТРАТ ЗА ИНФУЗИОНЕН РАЗТВОР
Cyprus     Gemsol 40 mg/ml Πυκνό διάλυμα για παρασκευή διαλύματος προς έγχυση
Czech Republic Gemcitabin Ebewe 40 mg/ml
Denmark    Gemcitabin “Sandoz”
Estonia     Gemsol 40 mg/ml
Finland     Gemcitabin Sandoz 40 mg/ml infuusiokonsentraatti, liuosta varten
France     GEMCITABINE SANDOZ 40 mg/ml solution to be diluted for perfusion
Greece     GEMLIQUID 40 mg/ml πυκνό διάλυμα για παρασκευή διαλύματος προς έγχυση
Italy       GEMSOL
Lithuania   Gemsol 40 mg/ml koncentratas infuziniam tirpalui
Luxembourg Gemcitabin Sandoz 40 mg/ml solution to be diluted for perfusion
Latvia     Gemsol 40 mg/ml koncentrāts infūziju šķīduma pagatavošanai
Netherlands Gemcitabine Sandoz 40 mg/ml, concentrate for solution for infusion
Norway    Gemcitabin Sandoz 40 mg/ml konsentrat til infusjonsvæske, oppløsning
Poland     GEMSOL 40 MG/ML, KONCENTRAT DO SPORZĄDZANIA ROZTWORU DO INFUZJI
Romania    Gemsol 40 mg/ml concentrat pentru soluţie perfuzabilă
Sweden    Gemcitabin Sandoz 40 mg/ml koncentrat till infusionsvätska, lösning
Slovenia    Gemcitabin Ebewe 40 mg/ml koncentrat za raztopino za infundiranje
Slovakia    Gemliquid 40 mg/ml

The following information is intended exclusively for healthcare professionals:

Compatibility with other medicinal products has not been studied; therefore, it is recommended not to mix Gemsol with other medicinal products.

FI GEMSOL

Parenteral medicinal products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Transfer the required amount of solution aseptically into a suitable infusion bag or bottle. The solution must be further diluted with 0.9% sodium chloride solution or 5% glucose solution, as appropriate. Mix the liquids thoroughly by gentle manual rotation.

Handling
Standard safety precautions for cytotoxic agents must be observed during preparation and disposal of the infusion solution. The handling of the infusion solution must be carried out in a safety isolator or in a cytotoxic safety cabinet. Protective clothing should be used as needed (protective gown, gloves, face mask, protective eyewear).

If the preparation comes into contact with the eyes, it may cause severe irritation. Eyes should be rinsed immediately and thoroughly with water. If irritation persists, a physician should be consulted. If the solution is spilled onto the skin, wash thoroughly with water.

Any unused medicinal product and all materials used for reconstitution, dilution, and administration must be disposed of according to standard hospital procedures applicable to cytotoxic drugs and in compliance with local regulations for the disposal of hazardous waste.

Shelf life
Unopened vials: 2 years

Stability after first opening
Chemical and physical stability has been demonstrated for 28 days at 2–8°C and at room temperature (15–25°C).
From a microbiological standpoint, this product should be used immediately. Otherwise, storage time and conditions prior to use are the responsibility of the user and in general should not exceed 24 hours at 2–8°C, unless opening occurred under controlled and validated aseptic conditions.

Stability after dilution
Chemical and physical stability in use has been demonstrated for 28 days at 2–8°C and at room temperature in 5% glucose solution or 0.9% sodium chloride solution (1.0 mg/ml, 7.0 mg/ml and 25 mg/ml).
From a microbiological standpoint, this product should be used immediately. Otherwise, storage time and conditions during use are the responsibility of the user and in general should not exceed 24 hours at 2–8°C, unless dilution occurred under controlled and validated aseptic conditions.

FI GEMSOL