Gemsol

Patient Information Leaflet

Gemsol, 40 mg/ml, concentrate for solution for infusion
Gemcitabinum
Please read the entire leaflet before using this medicine, as it contains important information for the patient.

• Keep this leaflet for future reference.
• If you have any questions, consult your doctor.
• If you experience any adverse reactions, including those not listed in this leaflet, inform your doctor. See section 4.

Table of contents:

1. What Gemsol is and what it is used for
2. Important information 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 destroy dividing cells, including cancer cells.
Gemsol may be used alone (monotherapy) or in combination with other anticancer drugs, depending on the type of cancer being treated.
Gemsol is used in the treatment of the following cancers:

• Non-small cell lung cancer (as monotherapy 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. Important information before using Gemsol

When not to use Gemsol

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

Warnings and precautions
Before the first infusion, a blood sample will be taken from the patient to check whether kidney and liver function are sufficient for administration of Gemsol. Before each infusion, a blood sample will be tested to ensure that blood cell counts are adequate for administering this medicine. Depending on the patient's general condition and if blood cell counts are too low, the doctor may adjust the dose or delay administration of the medicine. Blood samples will be periodically taken to monitor kidney and liver function.

Before using Gemsol, discuss with the doctor, nurse, or hospital pharmacist if:

• the patient has ever experienced severe skin rash or skin peeling, blistering, and/or oral mucosal ulceration after receiving gemcitabine;
• the patient currently has or has had in the past liver, heart, or blood vessel disease, lung or kidney problems, as administration of Gemsol may not be recommended;
• the patient has recently undergone or will soon receive radiotherapy, as administration of Gemsol may cause acute or delayed radiation reactions;
• the patient has recently been vaccinated (especially against yellow fever), as administration of Gemsol may lead to complications;
• the patient experiences difficulty breathing or feels very weak and appears very pale, as these may be symptoms of kidney failure or lung problems;
• the patient develops generalized swelling, shortness of breath, or increased body weight, as these may be signs of fluid leakage from small blood vessels into tissues.

Serious skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and acute generalized exanthematous pustulosis (AGEP), have been reported during treatment with gemcitabine. If the patient develops any of the symptoms related to these serious skin reactions described in section 4, contact the doctor immediately.
If during treatment with this medicine the patient experiences symptoms such as headache with disorientation, seizures, or vision disturbances, seek immediate medical advice, as these may indicate a very rare neurological adverse reaction known as reversible posterior encephalopathy syndrome (RPES).

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

Gemsol and other medicines
Inform the doctor or hospital pharmacist about all medicines the patient is currently taking or has recently taken, including vaccines and over-the-counter medicines, as well as any medicines the patient plans to take.

Pregnancy, breastfeeding, and effects on fertility
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult the doctor before using this medicine.

Pregnancy
If the patient is pregnant or planning a pregnancy, she should inform her doctor. Use of Gemsol should be avoided during pregnancy. The doctor will inform the patient about the risks associated with using Gemsol during pregnancy. Women of childbearing potential must use effective contraception during treatment with Gemsol and for 6 months after the last dose.

Breastfeeding
If the patient is breastfeeding, she should inform her doctor.
Breastfeeding must be discontinued during treatment with Gemsol.

Fertility
Men should be advised not to attempt conception during treatment with Gemsol and for 3 months after treatment ends. Therefore, effective contraception should be used during treatment with Gemsol and for 3 months after its completion. If the patient plans to have children during treatment or within 3 months after its end, he should consult the doctor or pharmacist. He may also seek advice regarding the possibility of sperm cryopreservation before starting treatment.

Driving and operating machinery
Gemsol may cause drowsiness, especially if alcohol is consumed. Do not drive or operate machinery until it is clear that Gemsol does not cause drowsiness.

3. How to use Gemsol

The usual dose of Gemsol is 1000 to 1250 mg per square meter of the patient's body surface area. The body surface area is calculated based on the patient's height and weight. Based on the body surface area, the doctor will determine the appropriate dose of the medicine. This dose may be adjusted or administration may be delayed depending on blood cell counts and the patient's general condition.

The frequency of Gemsol infusion depends on the type of tumor for which the medicine is being administered. Gemsol is always given diluted, as an intravenous infusion into one of the veins. The infusion lasts approximately 30 minutes.

If you have any further questions regarding the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
If any of the symptoms listed below occur, contact your doctor immediately:
bleeding from gums, nose or mouth, or other bleeding that does not stop; red or pink discoloration of urine, unexpected bruising (because the patient may have a reduced platelet count, which occurs very frequently);
fatigue, weakness, sudden shortness of breath or pale skin (because the patient may have reduced hemoglobin levels in the blood, which occurs very frequently);
mild to moderate skin rash (very frequently) / itching (frequently) or fever (very frequently) – allergic reactions;
fever of 38°C or higher, sweating or other signs of infection (because the patient may have reduced white blood cell count accompanied by fever – a condition known as neutropenic fever, which occurs frequently);
pain, redness, swelling or ulcers in the mouth (oral mucositis, which occurs frequently);
irregular heartbeat (cardiac arrhythmias, which occur rarely);
severe fatigue and weakness, petechiae or small skin hemorrhages (bruising), acute kidney failure (passing small amounts of urine or anuria) and signs of infection (hemolytic-uremic syndrome, which may be life-threatening and occurs uncommonly);
difficulty breathing (mild dyspnea occurs very frequently immediately after completion of Gemsol infusion and resolves quickly; however, severe lung disorders occur uncommonly or rarely);
severe chest pain (myocardial infarction, which occurs rarely);
severe hypersensitivity/allergic reaction with intense skin rash, including redness and itching of the skin, swelling of hands, feet, ankles, face, lips, mouth or throat (which may cause difficulty swallowing or breathing), wheezing, rapid heartbeat or feeling faint (anaphylactic reaction, which occurs very rarely);
generalized swelling, shortness of breath or weight gain, which may indicate leakage of fluid from small blood vessels into tissues (capillary leak syndrome, which occurs very rarely);
headache with visual disturbances, confusion, seizures (reversible posterior encephalopathy syndrome, which occurs very rarely);
severe rash with itching, blistering or peeling of the skin (Stevens-Johnson syndrome, toxic epidermal necrolysis – reactions which occur very rarely);
red, scaly, widespread rash with blisters under swollen skin (including in skin folds, trunk and upper limbs) and blisters accompanied by fever – acute generalized exanthematous pustulosis (AGEP – frequency unknown);
extreme fatigue and weakness, petechiae or minor bleeding under the skin (bruising), acute kidney failure (low urine output or no urine output) and signs of infection.
These may be symptoms indicating thrombotic microangiopathy (formation of blood clots in small blood vessels) and hemolytic-uremic syndrome, which may lead to death.

Other adverse reactions of Gemsol may include:
Very common adverse reactions (may affect more than 1 in 10 people)

• low white blood cell count
• vomiting
• nausea
• hair loss
• liver function abnormalities: detected in blood tests
• presence of blood in urine
• abnormal urine test result: proteinuria
• flu-like symptoms with fever
• swelling of ankles, fingers, feet, face

Common adverse reactions (may affect less than 1 in 10 people)

• loss of appetite (anorexia)
• headache
• difficulty sleeping
• drowsiness
• cough
• watery nasal discharge
• constipation
• diarrhea
• itching
• excessive sweating
• muscle pain
• back pain
• fever
• weakness
• chills
• increased liver function test results (increased bilirubin levels)
• infections

Uncommon adverse reactions (may affect less than 1 in 100 people)

• pulmonary cystic scarring (interstitial lung disease)
• wheezing (bronchospasm)
• lung fibrosis (abnormal chest X-ray findings)
• stroke
• heart failure
• kidney failure
• severe liver damage, including liver failure and death

Rare adverse reactions (may affect less than 1 in 1,000 people)

• low blood pressure
• skin peeling, ulceration or blistering
• skin exfoliation and massive blister formation
• reactions at the site of drug administration
• severe pneumonia causing respiratory failure (adult respiratory distress syndrome)
• skin rash resembling severe sunburn, which may occur in previously irradiated areas (radiation recall phenomenon)
• presence of fluid in the lungs
• pulmonary cystic fibrosis due to radiotherapy (radiation toxicity)
• gangrene of fingers or toes
• vasculitis
• increased liver function test results (increased GGT enzyme activity - gamma-glutamyltransferase)

Very rare adverse reactions (may affect less than 1 in 10,000 people):

• increased platelet count
• inflammation of the large intestine mucosa due to reduced blood supply (ischemic colitis)
• thrombotic microangiopathy: formation of blood clots in small blood vessels

Adverse reactions with unknown frequency (frequency cannot be estimated from available data):

• sepsis: a condition in which bacteria and their toxins circulate in the blood and begin to damage organs
• erythema nodosum: redness and swelling of the skin
• Blood tests show low hemoglobin levels (anemia), low white blood cell count and changes in platelet count

Any of the listed symptoms and/or conditions may occur. Any occurrence of the adverse reactions listed above must be reported to the doctor immediately. Consult a doctor if any disturbing symptoms appear.
Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor, pharmacist or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products: Al. Jerozolimskie 181C, 02-222 Warsaw
tel.: + 48 22 49 21 301, fax: + 48 22 49 21 309, website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
By reporting adverse reactions, additional information on the safety of the medicine can be collected.

5. How to store Gemsol

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and on the label after EXP. The expiry date refers to the last day of the stated month.
Hospital pharmacy should store Gemsol vials at a temperature of 2°C-8°C. Do not freeze.
If vials are stored at temperatures below 2°C, a precipitate may form in the solution.
If the solution appears discoloured or contains visible particles, it should be discarded.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack 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 gemcitabine 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).
Other ingredients: water for injections and diluted hydrochloric acid (for pH adjustment).

What Gemsol looks like and contents of the pack
Gemsol is a concentrate for solution for infusion.
The concentrate is a clear, colourless to pale yellow solution in vials made of colourless type I glass with a halobutyl rubber stopper coated with fluoropolymer, and an aluminium seal, placed in protective packaging (Onco-Safe or Sleeving) or without such packaging, in a cardboard box. The Onco-Safe and Sleeving packaging do not come into contact with the medicinal product and provide additional protection during transport, thereby enhancing safety for medical and pharmaceutical personnel.

Pack sizes:
200 mg vials: 1, 5 or 10 vials
1000 mg vials: 1 vial
2000 mg vials: 1 vial

Marketing Authorisation Holder and Manufacturer:
EBEWE Pharma Ges.m.b.H. Nfg. KG
Mondseestrasse 11
4866 Unterach
Austria

Manufacturer:
Fareva Unterach GmbH
Mondseestraße 11
4866 Unterach
Austria

For further information about this medicinal product and its names in other European Economic Area countries, please contact:
Sandoz Polska Sp. z o.o.
ul. Domaniewska 50 C
02-672 Warszawa
tel. 22 209 70 00

Ebewe logo
Information intended exclusively for healthcare professionals

Mixing Gemsol with other medicinal products is not recommended due to lack of compatibility data.
Parenteral medicinal products should be inspected visually for particulate matter and discoloration prior to administration, if the solution and container permit.

The required amount of solution should be transferred under aseptic conditions into an infusion bag or bottle. The solution must be diluted with 0.9% sodium chloride solution or 5% glucose solution.
Solutions should be thoroughly mixed by gently inverting the bottle or bag.

Handling of the medicinal product
During preparation and disposal of the infusion solution, standard safety procedures for cytotoxic drugs must be observed. The solution should be prepared in a laminar flow hood or in a safe cabinet for handling cytostatic agents. Protective clothing (protective gown, gloves, mask, and eye protection) should be worn as required.

The solution may cause severe irritation if it comes into contact with the eyes. In case of contamination, the eye should be immediately and thoroughly rinsed with water. If irritation persists, immediate consultation with an ophthalmologist is necessary. In case of skin contact, the affected area should be thoroughly rinsed with water.

Any unused remnants of the product, as well as materials used for preparation, dilution, and administration of the solution, must be disposed of in accordance with hospital regulations for cytotoxic drugs and local regulations for disposal of hazardous waste.

Shelf life
Unopened vial:
2 years

Stability after first opening of the container:
Chemical and physical stability of the product has been demonstrated for 28 days at temperatures from 2°C to 8°C and at room temperature (15°C – 25°C).
From a microbiological point of view, the product should be used immediately after reconstitution.
If not used immediately, the user is responsible for the storage duration and conditions prior to use. Generally, storage should not exceed 24 hours at 2°C to 8°C, unless the vial was opened under controlled and validated aseptic conditions.

Shelf life after dilution
Chemical and physical stability of the solution diluted with 5% glucose solution or 0.9% sodium chloride solution (1.0 mg/ml, 7.0 mg/ml and 25 mg/ml) has been demonstrated for 28 days at temperatures from 2°C to 8°C and at room temperature.
From a microbiological point of view, the product should be used immediately after dilution.
If not used immediately, the user is responsible for the storage duration and conditions prior to use. Generally, storage should not exceed 24 hours at 2°C to 8°C, unless dilution was performed under controlled and validated aseptic conditions.