Gemcitabine Hikma

Package leaflet: Information for the user

Gemcitabina Hikma 200 mg powder for solution for infusion, 1 g powder 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, pharmacist or nurse.
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any side effects not listed in this leaflet. See section 4.

Contents of this leaflet:

1. What Gemcitabina Hikma is 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. How to store Gemcitabina Hikma
6. Contents of the pack and other information

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

Gemcitabine Hikma belongs to a group of medicines called "cytotoxic agents". These medicines
kill cells during cell division, including tumour cells.
Gemcitabine Hikma may be given alone or in combination with other anti-cancer
medicines, depending on the type of cancer.
Gemcitabine Hikma is used to treat the following types of cancer:

• Non-small cell lung cancer (NSCLC), either 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 need to know before using Gemcitabine Hikma

Do not use Gemcitabine Hikma

• If you are allergic to gemcitabine or to any of the excipients of this medicine (listed in section 6)
• If you are breastfeeding

Warnings and precautions
Before the first infusion, blood samples will need to be taken to check whether your liver and kidneys are functioning adequately enough for you to receive this medicine. Before each infusion, blood samples will need to be taken to check whether you have sufficient blood cells to receive Gemcitabine Hikma. Your doctor may decide to adjust the dose or delay treatment depending on your general health condition and if your blood cell count is too low.
Periodically, blood samples should be taken to monitor how well your kidneys and liver are working. Inform your doctor, nurse, or hospital pharmacist before using Gemcitabine Hikma.
If you have or have previously had liver disease, heart disease, vascular disorders, or kidney problems, discuss this with your doctor or hospital pharmacist, as you may not be able to receive Gemcitabine Hikma.
If you have recently received or are about to receive radiotherapy, please inform your doctor, as there may be an early or delayed radiation reaction with Gemcitabine Hikma.
If you have recently been vaccinated, inform your doctor, as this may potentially cause adverse effects with Gemcitabine Hikma.
If during treatment with this medicine you experience symptoms such as headache with confusion, seizures (fits), or changes in vision, contact your doctor immediately. These could be very rare nervous system side effects known as reversible posterior encephalopathy syndrome.
If you develop difficulty breathing or feel very weak and look very pale, inform your doctor, as this could be a sign of kidney failure or problems with your lungs.
If you develop widespread swelling, shortness of breath, or weight gain, inform your doctor, as this could be a sign of fluid leaking from your small blood vessels into the tissues.

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

Other medicines and Gemcitabine Hikma
Inform your doctor or hospital pharmacist if you are taking, or have recently taken, any other medicines, including vaccines and over-the-counter medicines.

Pregnancy, breastfeeding, and fertility

Pregnancy
If you are pregnant or planning to become pregnant, inform your doctor. The use of Gemcitabine Hikma should be avoided during pregnancy. Your doctor will inform you about the potential risks associated with taking Gemcitabine Hikma during pregnancy.

Breastfeeding
If you are breastfeeding, inform your doctor.
Breastfeeding must be discontinued during treatment with Gemcitabine Hikma.

Fertility
Men are advised not to father a child during treatment and for 6 months after treatment with Gemcitabine Hikma. If you wish to father a child during treatment or within 6 months afterwards, consult your doctor or pharmacist. It is recommended to seek information about sperm preservation methods before starting therapy.

Driving and use of machines
Gemcitabine Hikma may cause drowsiness, especially if you have consumed alcohol. Do not drive or operate machinery if you are not sure that treatment with Gemcitabine Hikma will not make you drowsy.

Gemcitabine Hikma contains sodium
Gemcitabine Hikma contains 3.5 mg (< 1 mmol) of sodium in each 200 mg vial and 17.53 mg (< 1 mmol) of sodium in each 1000 mg vial, meaning it is essentially sodium-free.

3. How to use Gemcitabina Hikma

The usual dose of Gemcitabina Hikma is 1000–1250 mg per square metre of body surface area.
Your height and weight will be measured to determine your body surface area. Your doctor will use
this body surface value to calculate the optimal dose for you. This dose may be adjusted, or treatment
may be delayed, depending on your blood counts and your general health condition.
The frequency of administration of Gemcitabina Hikma depends on the type of tumour for which
you are being treated.
A hospital pharmacist or doctor must dissolve the Gemcitabina Hikma powder before administration.
Administration of Gemcitabina Hikma must always be given by intravenous infusion into a vein.
The infusion will last approximately 30 minutes.
If you have any doubts about the use of this product, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, Gemcitabine Hikma can cause side effects, although not everyone experiences them.
You must contact your doctor immediately if you notice any of the following symptoms:

• Bleeding from gums, nose, or mouth, or any other bleeding that does not stop, redness or reddish urine, unexpected bruising (as you may have fewer platelets than normal, which is very common).
• Tiredness, feeling faint, becoming breathless easily, or looking pale (as you may have less haemoglobin than normal, 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 (as you may have fewer white blood cells than normal, accompanied by fever, also known as febrile neutropenia) (common).
• Pain, redness, swelling, or ulcers in your 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. These may be features of thrombotic microangiopathy (blood clots forming in small blood vessels) and haemolytic uraemic syndrome, which can be fatal. Difficulty breathing (it is common to experience mild to moderate breathing difficulty shortly after Gemcitabine Hikma infusion, which quickly resolves; however, more serious lung problems may rarely occur).
• Severe chest pain (myocardial infarction) (rare).
• Severe hypersensitivity/allergic reaction with severe skin rash including red, itchy skin, swelling of the hands, feet, ankles, face, lips, mouth, or throat (which may cause difficulty swallowing or breathing), shortness of breath, rapid heartbeat, and feeling faint (anaphylactic reaction) (very rare).
• Generalised swelling, shortness of breath, or weight gain; you may have fluid leaking from small blood vessels into tissues (capillary leak syndrome) (very rare).
• Headache with changes in vision, confusion, seizures, or fits (reversible posterior encephalopathy syndrome) (very rare).
• Severe rash with itching, blistering, or peeling of the skin (Stevens-Johnson syndrome, toxic epidermal necrolysis) (very rare).

Other side effects with Gemcitabine Hikma may include:
Very common side effects (may affect more than 1 in 10 people)

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

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

• Anorexia (loss of appetite)
• Headache
• Insomnia
• Drowsiness
• Cough
• Runny nose
• Constipation
• Diarrhoea
• Itching
• Sweating
• Muscle pain
• Back pain
• Fever
• Weakness
• Chills
• Infections

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

• Scarring in lung alveoli (interstitial pneumonitis)
• Hiccups (spasm of airways)
• Scarring in the lung (abnormal chest X-ray findings)
• Heart failure
• Kidney failure
• Severe liver damage, including liver failure
• Stroke

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

• Low blood pressure
• Skin peeling, ulceration, or blistering
• Skin peeling and formation of severe blisters
• Reactions at the injection site
• Severe lung inflammation causing respiratory failure (adult respiratory distress syndrome)
• A skin rash resembling a severe sunburn, which may occur on skin previously exposed to radiotherapy (radiation recall)
• Fluid in the lungs
• Scarring of lung alveoli associated with radiotherapy (radiation toxicity)
• Gangrene in fingers and toes
• Inflammation of blood vessels (peripheral vasculitis)

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

• Increased platelet count
• Inflammation of the lining of the large intestine caused by reduced blood supply (ischaemic colitis)
• Low haemoglobin levels (anaemia), low white blood cell count, and low platelet count, which will be detected by blood tests
• 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

You may experience any of these side effects and/or conditions. You must inform your doctor as soon as you notice any of these side effects.
If you are concerned about any of these side effects, talk to your doctor.
Reporting of adverse reactions
If you experience any side effect, including those not listed in this leaflet, consult your doctor or pharmacist. You can also report side effects directly via the national reporting system at http://www.aifa.gov.it/content/come-segnalare-una-sospetta-reazione-avversa. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Gemcitabina Hikma

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date (EXP) stated on the pack. The expiry date refers to the last day of that month.
Intact vial: do not store above 25°C.
Reconstituted solution:
The product should be used immediately. When prepared as described, gemcitabine reconstituted solutions have been shown to be chemically and physically stable for 24 hours at 20–25°C. Further dilutions may be carried out by medical personnel. Reconstituted gemcitabine solutions must not be frozen, as crystallization may occur.
This medicinal product is for single use only; any unused solution should be disposed of according to local applicable regulations.

6. Package contents and other information

What Gemcitabina Hikma contains
The active substance is Gemcitabine hydrochloride. Each vial contains 200 or 1000 mg of
gemcitabine (as gemcitabine hydrochloride).
The excipients are mannitol, sodium acetate, hydrochloric acid and sodium hydroxide used for
adjusting the pH, and nitrogen as inert gas.

Description of the appearance of Gemcitabina Hikma and contents of the package
White to almost white powder. After reconstitution with sterile sodium chloride, the solution is
clear, colourless or slightly yellowish.
Each package of Gemcitabina Hikma contains:
1 vial
5 vials

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Hikma Farmacêutica (Portugal), S.A.
Estrada do Rio da Mó n° 8, 8A and 8B
Fervença
2705-906 Terrugem SNT
Portugal

Selling Agent for Italy:
Hikma Italia SpA
Viale Certosa 10
27100 Pavia

Responsible manufacturer for batch release:
Thymoorgan Pharmazie GmbH
Schiffgraben 23, D-38690 Goslar
Germany

This medicinal product is authorised in the EEA Member States under the following
names:
Austria: Gemcitabin Hikma 200 mg (1g) Pulver zur Herstellung einer Infusionslösung
Germany: Ribozar, 200 mg (1g) Pulver zur Herstellung einer Infusionslösung
Italy: Gemcitabina Hikma 200 mg (1g), powder for solution for infusion
Netherlands: Gemcitabine Hikma 200 mg (1g) Poeder voor oplossing voor infusie
Portugal: Gemcitabina Hikma 200 mg (1g) Pó para solução para perfusão

This Patient Information Leaflet was last approved in 12/2018

The following information is intended exclusively for physicians or healthcare professionals:

Instructions for use, handling, and disposal.

1. Use aseptic techniques during reconstitution and any subsequent dilution of gemcitabine for intravenous infusion administration.
2. Calculate the required dosage and number of Gemcitabine vials needed.
3. To reconstitute the solution, add 5 mL of 0.9% Sodium Chloride Injection solution to the 200 mg vial or 25 mL of 0.9% Sodium Chloride Injection solution to the 1 g vial. Shake to dissolve the powder. The resulting solution contains 38 mg/mL of active substance. Complete administration of the vial contents provides 200 mg or 1 g of gemcitabine, respectively. The correct dose may be administered as prepared above or further diluted with 0.9% Sodium Chloride Injection solution to a concentration as low as 0.1 mg/mL.

The reconstituted Gemcitabine solution is clear, colorless or slightly yellow. After reconstitution with 0.9% Sodium Chloride Injection solution, the pH of the resulting solution ranges between 2.7 and 3.3. The solution should be inspected visually for the presence of particles or discoloration prior to administration, whenever solution and container permit such inspection. If particles or discoloration are observed, do not administer.

4. Parenteral medicinal products should be inspected visually for particulate matter and discoloration prior to administration. If particles are present, do not administer.
5. Reconstituted Gemcitabine solutions must not be frozen, as crystallization may occur. Chemical and physical stability has been demonstrated for 24 hours at 20–25 °C. From a microbiological standpoint, the product should be used immediately. If not used immediately, the duration and conditions of storage prior to use are the responsibility of the user and should not normally exceed 24 hours at 20–25 °C, unless reconstitution occurred under controlled and validated aseptic conditions.
6. Gemcitabine solutions are for single use only. Unused product or waste material must be disposed of in accordance with local regulations.

Precautions for preparation and administration
Standard safety precautions for cytotoxic agents should be observed during the preparation and handling of the infusion solution.
Preparation and handling of the infusion solution must be performed in a laminar flow hood, and protective clothing and gloves must be worn. If a laminar flow hood is not available, a mask and protective eyewear must also be used.
If the solution comes into contact with the eyes, it may cause severe irritation. Immediately and thoroughly rinse the eyes with water. If irritation persists, seek medical advice. If the solution contacts the skin, rinse thoroughly with water.

Disposal
Unused product must be disposed of in accordance with local regulations.

Package leaflet: information for the user

Gemcitabine Hikma 2 g powder 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, pharmacist or nurse.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.
  Contents of this leaflet:

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

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

Gemcitabine Hikma belongs to a group of medicines called "cytotoxic agents". These medicines destroy cells during cell division, including tumour cells.
Gemcitabine Hikma may be given alone or in combination with other anti-cancer medicines, depending on the type of cancer.
Gemcitabine Hikma is used in the treatment of the following types of cancer:

• Non-small cell lung cancer (NSCLC), either 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 need to know before using Gemcitabina Hikma

Do not use Gemcitabina Hikma

• 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 samples will need to be taken to check whether your
liver or kidneys are functioning well enough for you to receive this medicine.
Before each infusion, blood samples will be taken to check whether you have sufficient
blood cells to receive Gemcitabina Hikma. Your doctor may decide to adjust the dose or
delay treatment depending on your general health condition and if your blood cell count is too low.
Periodically, blood samples should be taken to monitor how well your kidneys and liver are functioning.
Talk to your doctor, nurse, or hospital pharmacist before using Gemcitabina Hikma.
If you have or have previously had liver disease, heart disease, vascular disorders,
or kidney problems, discuss this with your doctor or hospital pharmacist, as you may not be able to receive Gemcitabina Hikma.
If you have recently received or are about to receive radiotherapy, please inform your doctor, as there may be an early or delayed radiation reaction with Gemcitabina Hikma.
If you have recently been vaccinated, inform your doctor, as this may potentially cause adverse effects with Gemcitabina Hikma.
If during treatment with this medicine you experience symptoms such as headache with confusion, seizures (fits), or changes in vision, contact your doctor immediately.
This could be a very rare nervous system side effect known as reversible posterior encephalopathy syndrome.
If you develop difficulty breathing or feel very weak and look very pale, please inform your doctor, as this may be a sign of kidney failure or lung problems.
If you develop widespread swelling, shortness of breath, or weight gain, inform your doctor, as this may be a sign of fluid leaking from your small blood vessels into the tissues.

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

Other medicines and Gemcitabina Hikma
Inform your doctor or hospital pharmacist if you are taking, or have recently taken, any other medicines, including vaccines and over-the-counter medicines.

Pregnancy, breastfeeding and fertility

Pregnancy
If you are pregnant or planning a pregnancy, consult your doctor.
The use of Gemcitabina Hikma should be avoided during pregnancy. Your doctor will inform you about the potential risks associated with taking Gemcitabina Hikma during pregnancy.

Breastfeeding
If you are breastfeeding, inform your doctor.
Breastfeeding must be discontinued during treatment with Gemcitabina Hikma.

Fertility
Men are advised not to father a child during and for 6 months after treatment with Gemcitabina Hikma. If you wish to father a child during treatment or within 6 months afterwards, consult your doctor or pharmacist. You are advised to seek information about sperm preservation before starting therapy.

Driving and using machines
Gemcitabina Hikma may cause drowsiness, especially if you have consumed alcohol. Do not drive or operate machinery if you are not sure that treatment with Gemcitabina Hikma will not make you drowsy.

Gemcitabina Hikma contains sodium
This medicine contains 35 mg of sodium (a key component of table salt) per 2000 mg vial. This is equivalent to 1.75% of the maximum recommended daily dietary intake of sodium for an adult.

3. How to use Gemcitabina Hikma

The usual dose of Gemcitabina Hikma is 1000–1250 mg per square metre of body surface area.
Your height and weight will be measured to calculate your body surface area. Your doctor will use
this body surface value to determine the optimal dose for you. This dose may be adjusted, or the
treatment may be delayed, depending on your blood counts and your general health condition.
The frequency of administration of Gemcitabina Hikma depends on the type of cancer for which
you are being treated.
A hospital pharmacist or doctor must dissolve the Gemcitabina Hikma powder before administration.
Administration of Gemcitabina Hikma must always be given by intravenous infusion.
The infusion will last approximately 30 minutes.
If you have any doubts about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, Gemcitabine Hikma can cause side effects, although not everyone experiences them.
You must contact your doctor immediately if you notice any of the following symptoms:

• Bleeding from gums, nose, or mouth, or any other bleeding that does not stop, redness, or reddish urine, unexpected bruising (as you may have fewer platelets than normal, which is very common).
• Tiredness, feeling faint, becoming easily breathless, or appearing pale (as you may have less haemoglobin than normal, which is very common).
• Moderate to mild skin rash (very common) / itching (common), or 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 ulcers in your mouth (stomatitis) (common).
• Irregular heartbeat (arrhythmia) (uncommon).
• Extreme fatigue and weakness, purpura or small areas of bleeding under the skin (bruising), acute kidney failure (low urine output or absence of urine), and signs of infection. These may be features of thrombotic microangiopathy (clots forming in small blood vessels) and haemolytic uraemic syndrome, which can be fatal.
• Difficulty breathing (it is common to experience mild to moderate breathing difficulty shortly after Gemcitabine Hikma infusion, which quickly resolves; however, more serious lung problems may rarely occur).
• Severe chest pain (myocardial infarction) (rare).
• Severe hypersensitivity/allergic reaction with severe skin rash including red, itchy skin, swelling of hands, feet, ankles, face, lips, mouth, or throat (which may cause difficulty swallowing or breathing), shortness of breath, rapid heartbeat, and feeling faint (anaphylactic reaction) (very rare).
• Generalised swelling, shortness of breath, or weight gain; you may have fluid leaking from small blood vessels into tissues (capillary leak syndrome) (very rare).
• Headache with changes in vision, confusion, seizures, or fits (reversible posterior encephalopathy syndrome) (very rare).
• Severe rash with itching, blistering, or peeling of the skin (Stevens-Johnson syndrome, toxic epidermal necrolysis) (very rare).

Other side effects with Gemcitabine Hikma may include:
Very common side effects (may affect more than 1 in 10 people)

• Low levels of white blood cells in the blood
• Difficulty breathing
• Vomiting
• Nausea
• Hair loss
• Liver problems: abnormal blood test results
• Blood in the urine
• Abnormal urine test results: protein in the urine
• Flu-like symptoms, including fever
• Swelling of ankles, fingers, feet, face (oedema)

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

• Loss of appetite
• Anorexia
• Headache
• Insomnia
• Drowsiness
• Cough
• Runny nose
• Constipation
• Diarrhoea
• Itching
• Sweating
• Muscle pain
• Back pain
• Fever
• Weakness
• Chills
• Infections

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

• Scarring in lung alveoli (interstitial pneumonitis)
• Hiccups (airway spasm)
• Scarring in the lung (abnormal chest X-rays)
• Heart failure
• Kidney failure
• Severe liver damage, including liver failure
• Stroke

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

• Low blood pressure
• Skin peeling, ulceration, or blistering
• Skin peeling and formation of severe blisters
• Reactions at the injection site
• Severe lung inflammation causing respiratory failure (adult respiratory distress syndrome)
• A skin rash resembling a severe sunburn, which may occur on skin previously exposed to radiotherapy (radiation recall)
• Fluid in the lungs
• Scarring of lung alveoli associated with radiotherapy (radiation toxicity)
• Gangrene of fingers and toes
• Inflammation of blood vessels (peripheral vasculitis)

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

• Increased platelet count
• Inflammation of the lining of the large intestine caused by reduced blood supply (ischaemic colitis)
• Low haemoglobin levels (anaemia), low white blood cell count, and low platelet count will be detected by blood tests
• Thrombotic microangiopathy: 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

You may experience any of these side effects and/or conditions. You must inform your doctor as soon as you start experiencing any of these side effects.
If any of the side effects concern you, talk to your doctor.
Reporting of adverse reactions
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 the following website:
http://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 Gemcitabine Hikma

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date (EXP) stated on the carton. The expiry date refers to the last day of that month.
Intact vial: this medicine does not require any special storage conditions.
Reconstituted solution:
The product should be used immediately. When prepared as described, reconstituted gemcitabine solutions have been shown to be chemically and physically stable for 24 hours at 20–25°C. Further dilutions may be performed by medical personnel. Reconstituted gemcitabine solutions must not be refrigerated, as crystallization may occur.
This medicinal product is for single use; any unused solution should be disposed of according to local regulations.

6. Package contents and other information

What Gemcitabina Hikma contains
The active substance is gemcitabine hydrochloride. Each vial contains 2 g of gemcitabine (as
gemcitabine hydrochloride).
The excipients are mannitol, sodium acetate trihydrate, hydrochloric acid and sodium hydroxide used
to adjust pH, and nitrogen as inert gas.

Description of the appearance of Gemcitabina Hikma and contents of the pack
White to almost white powder. After reconstitution with sterile sodium chloride, the solution is
clear, colourless or slightly yellowish.
Each pack of Gemcitabina Hikma contains:
1 vial

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Hikma Farmacêutica (Portugal), S.A.
Estrada do Rio da Mó n° 8, 8A and 8B
Fervença
2705-906 Terrugem SNT
Portugal

Manufacturer:
Thymoorgan Pharmazie GmbH
Schiffgraben 23
38690 Vienenburg
Germany

This medicinal product is authorised in EEA Member States under the following
names:
Germany: Ribozar 2g Pulver zur Herstellung einer Infusionslösung
Italy: Gemcitabina Hikma 2 g powder for solution for infusion

This leaflet was last approved on

The following information is intended exclusively for physicians or healthcare professionals:

Instructions for use, handling, and disposal.

1. Use aseptic techniques during reconstitution and any subsequent dilution of gemcitabine for intravenous infusion administration.
2. Calculate the required dosage and the number of Gemcitabine vials needed.
3. To reconstitute the solution, add 50 mL of 0.9% Sodium Chloride Injection solution to the 2 g vial. Gently shake to dissolve the powder. The resulting solution contains 38 mg/mL of active substance. Complete administration of the vial contents delivers 2 g of gemcitabine. The correct dose may be administered as prepared above or further diluted with 0.9% Sodium Chloride Injection solution to a concentration as low as 0.1 mg/mL.

The reconstituted Gemcitabine solution is clear, colorless, or slightly yellow. After reconstitution with 0.9% Sodium Chloride Injection solution, the pH of the resulting solution ranges between 2.7 and 3.3. The solution should be visually inspected for the presence of particles or discoloration prior to administration, whenever the solution and container permit such inspection. If particles or discoloration are observed, do not administer.

4. Parenteral medicinal products should be inspected visually for particulate matter and discoloration prior to administration. If particles are present, do not administer.
5. Reconstituted Gemcitabine solutions must not be refrigerated, as crystallization may occur. Chemical and physical in-use stability has been demonstrated for 24 hours at 20–25°C. From a microbiological standpoint, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and should normally not exceed 24 hours at 20–25°C, unless reconstitution has taken place under controlled and validated aseptic conditions.
6. Gemcitabine solutions are for single use only. Unused product or waste material must be disposed of in accordance with local regulations.

Precautions for preparation and administration
Standard safety precautions for cytotoxic agents should be observed during the preparation and handling of the infusion solution.
The handling of the infusion solution should be performed in a laminar flow hood, and protective clothing and gloves must be worn. If a laminar flow hood is not available, a mask and protective eyewear must also be used.
If the solution comes into contact with the eyes, it may cause severe irritation. The eyes should be immediately and thoroughly rinsed with water. If irritation persists, medical advice must be sought. If the solution contacts the skin, wash thoroughly with water.

Disposal
Unused product must be disposed of in accordance with local regulations.