Epirubicin Hikma

Patient Information Leaflet: Information for the User

Epirubicin Hikma 2 mg/ml Intravesical Solution / Injectable Solution

Epirubicin hydrochloride
Equivalent medicinal product
Please read all of 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 or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, inform your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

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

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

• Epirubicin Hikma is an injectable solution containing epirubicin hydrochloride. It belongs to a group of medicines called cytotoxic agents used in chemotherapy. Epirubicin Hikma causes cells that are actively growing, such as cancer cells, to slow down or stop their growth, increasing the likelihood that these cells will die. This medicine helps selectively kill cancerous tissue compared to normal healthy tissue.
• Epirubicin Hikma is used to treat a variety of tumours, either alone or in combination with other medicines. The route of administration depends on the type of cancer being treated.
• It has been found particularly useful in the treatment of breast, ovarian, stomach, intestinal, and lung cancer.
• Epirubicin Hikma may be introduced directly into the bladder through a catheter. This is sometimes used to treat abnormal cells or tumours of the bladder wall. It may be used after other treatments in an attempt to prevent the regrowth of cells.
• You must speak to a doctor if you do not feel better or if you feel worse.

2. What you should know before using Epirubicin Hikma

Do not use Epirubicin Hikma:

• if you are allergic to epirubicin or to any of the other ingredients of this medicine (listed in section 6), or to chemotherapeutic drugs similar to epirubicin (anthracyclines or anthracenediones)
• if you have infections affecting multiple organs
• if you have a urinary tract infection
• if you have inflammation of the bladder
• if you have invasive tumours invading the bladder
• if you have problems with catheterization (your doctor has difficulty inserting a catheter (tube) into your bladder)
• if there is blood in the urine
• if you have a reduced ability to produce blood cells, resulting in low blood cell counts, as this medicine may further reduce them
• if you have been previously treated with Epirubicin Hikma or similar chemotherapeutic drugs, since prior treatment with these medicines may increase the risk of side effects
• if you have recently suffered from myocardial infarction, reduced heart muscle function, severe irregular heartbeat, sudden chest pain, non-inflammatory heart muscle disease, or other serious heart problems in the past, or are currently receiving treatment for such conditions
• if you have severe liver problems
• if you are pregnant or breastfeeding

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before receiving
Epirubicin Hikma:

• if your liver or kidneys are not functioning properly
• if you have received or plan to receive a vaccination
• if you are currently experiencing episodes of acute toxicity such as: acute inflammation of the mouth, low white blood cell count, low platelet count, or general infections

This will help your doctor decide whether the medicine is suitable for you.
Other medicines and Epirubicin Hikma:
Inform your doctor or pharmacist if you are taking, have recently taken, or
might take any other medicines, including those obtained without a prescription,
especially the following:

• Cimetidine (a medicine usually used to treat stomach ulcers and heartburn). Cimetidine may increase the effects of Epirubicin Hikma.
• Calcium channel blockers (medicines for heart conditions)
• Quinine (an antimalarial medicine)
• Antibiotics such as sulfonamides or chloramphenicol
• Antiretrovirals (medicines used to treat HIV infection)
• Phenytoin (a medicine used to treat epilepsy)
• Analgesics such as aminopyrine derivatives
• Treatment with Trastuzumab for cancer. Your doctor must avoid using Epirubicin Hikma for up to 27 weeks after stopping trastuzumab, when possible. If Epirubicin Hikma is used before this time, careful monitoring of cardiac function is recommended.
• Live vaccines should be avoided in patients who have received epirubicin
• Paclitaxel or docetaxel (medicines used to treat cancer). When paclitaxel is administered before epirubicin, it may increase the concentration of epirubicin in the blood. However, when paclitaxel and docetaxel are administered together and after epirubicin, they do not affect epirubicin concentration.
• Dexverapamil (used to treat certain heart disorders)
• Dexrazoxane (used to prevent cumulative chronic cardiotoxicity caused by epirubicin)
• Interferon α2b (used to treat tumours)

Pregnancy, breastfeeding, and fertility
Pregnancy
If you are pregnant, suspect you may be pregnant, or are planning to have
a baby, consult your doctor for advice before taking this
medicine. Avoid becoming pregnant when you or your partner are being treated with
this medicine. If you are sexually active, you are advised to use an effective
contraceptive method to prevent pregnancy during treatment, whether you are
male or female. This medicine may cause birth defects; therefore, it is important
to inform your doctor if you think you may be pregnant.
Breastfeeding
You must stop breastfeeding before starting treatment with this
medicine, as part of the drug may pass into your milk and could potentially
harm your baby.
Fertility
Men: There is a risk of infertility due to epirubicin therapy, and male
patients should consider sperm preservation before starting treatment.
Women: Epirubicin may cause absence of menstrual cycles or premature menopause in
premenopausal women.
Driving and using machines
No special precautions are required, provided you feel fully recovered after
hospital treatment and have discussed this with your doctor.
Epirubicin Hikma contains sodium
Epirubicin Hikma 10 mg/5 ml
This medicine contains less than 1 mmol of sodium (23 mg) per vial, i.e.
essentially “sodium-free”.
Epirubicin Hikma 20 mg/10 ml
This medicine contains 34.48 mg of sodium (the main component of table salt) in each vial, equivalent to 1.72% of the maximum recommended daily dietary intake of sodium for an adult.
Epirubicin Hikma 50 mg/25 ml
This medicine contains 86.19 mg of sodium (the main component of table salt) in each vial, equivalent to 4.31% of the maximum recommended daily dietary intake of sodium for an adult.
Epirubicin Hikma 200 mg/100 ml
This medicine contains 344.73 mg of sodium (the main component of table salt) in each vial, equivalent to 17.24% of the maximum recommended daily dietary intake of sodium for an adult.

3. How to use Epirubicin Hikma

If you are prescribed Epirubicin Hikma, it will be administered only by doctors or
nurses experienced in chemotherapy administration.
This medicine is normally given to you by a doctor or nurse through an intravenous infusion (a drip) into a vein. Your doctor will decide the dose to administer and the number of treatment days based on your condition.
The dose is determined according to your condition, height, and weight. From your height and weight, your doctor will calculate your body surface area, which is used to determine your dose. Epirubicin Hikma may also be administered directly into the bladder to treat bladder cancer or to prevent its recurrence. The dose depends on the type of bladder cancer you have.
When this medicine is injected directly into the bladder, you will be asked not to drink liquids for 12 hours before treatment to avoid diluting the medicine with urine in the bladder.
Although sometimes one treatment cycle may be sufficient, your doctor will often recommend additional cycles after three or four weeks. Several cycles may be needed before your disease is under control and you start to feel better.

Regular check-ups with your doctor during treatment with Epirubicin Hikma
During treatment, your doctor will perform regular checks on your:

• Blood – to monitor for reduced blood cell counts, which may require treatment
• Heart function – heart damage may occur when high doses of Epirubicin Hikma are administered. This may not become apparent for several weeks, so regular tests may be required during this period
• Liver – using blood tests to ensure this medicine is not adversely affecting liver function
• Blood levels of uric acid – Epirubicin Hikma may increase blood uric acid levels, which could lead to gout. If uric acid levels are too high, another medicine may be administered.

If you receive high doses of Epirubicin Hikma
High doses may worsen side effects such as mouth sores or may reduce the number of white blood cells (which fight infections) and platelets (which help blood to clot). If this occurs, antibiotics or blood transfusions may be required. Mouth ulcers can be treated to make them less uncomfortable while they heal.
If you have any further questions about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

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

• Infections
• Ocular inflammation with red, watery eyes
• Reduced red blood cell count (anemia), which may make you feel tired and lethargic
• White blood cell count (which fight infections) may decrease, increasing the risk of infections and fever (leucopenia)
• Platelet count (blood platelets that help blood to clot) may decrease, which could cause bruising or bleeding more easily when injured
• Reduction in the number of certain types of white blood cells – granulocytes and neutrophils (granulocytopenia and neutropenia)
• Reduction in certain types of white blood cells accompanied by fever (febrile neutropenia)
• Inflammation of the transparent part of the eye called the cornea
• Hot flushes
• Inflammation of a vein
• Nausea
• Vomiting
• Inflammation of the mucous lining of the mouth
• Diarrhea
• Hair loss
• Skin damage
• Red-coloured urine for 1 to 2 days after administration of epirubicin
• Absence of menstruation
• Inflammation and painful ulceration of the mucous membranes lining the digestive tract
• General feeling of malaise
• Fever
• Changes in levels of certain liver enzymes
• After direct administration of epirubicin into the bladder, inflammation (cystitis) may occur.

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

• Decreased appetite / loss of appetite
• Loss of body water or fluids
• Severe heart rhythm disorder (ventricular arrhythmia)
• Disorders in the conduction of electrical impulses in the heart
• Some forms of heart rhythm disorders (AV block, bundle branch block)
• Slow heartbeat (bradycardia)
• Reduced pumping of blood by the heart, which may cause shortness of breath, fluid accumulation, and abnormal heart rhythm
• Bleeding
• Skin redness
• Pain behind the breastbone, indigestion, and difficulty swallowing due to inflammation of the esophagus
• Pain or burning in the gastrointestinal tract
• Inflammation of the mucous lining of the gastrointestinal tract
• Ulcers in the gastrointestinal tract
• Rash, itching
• Abnormal discolouration of the nails
• Skin changes
• Abnormal skin discolouration
• Frequent urination
• Redness at the infusion site
• Chills
• Local reactions such as burning sensation
• Reduced heart function

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

• High fever, chills, general malaise, possibly cold arms or legs due to blood poisoning (sepsis)
• Lung infection (pneumonia)
• Certain types of blood cancer (acute lymphocytic leukemia, acute myeloid leukemia)
• Blockage of a blood vessel
• Swelling and pain in the arms or legs due to inflammation of a blood vessel, which may include blood clotting
• Blood clots in the lungs causing chest pain and shortness of breath
• Gastrointestinal bleeding
• Hives
• Skin redness
• Feeling of weakness

Please contact your doctor or nurse immediately if you notice any of the following side effects. Although rare, these symptoms can be serious:
Rare: (may affect up to 1 in 1,000 people)

• Sudden, potentially life-threatening allergic reaction. Symptoms include sudden signs of allergy such as skin rash, itching or hives, swelling of the face, lips, tongue or other body parts, shortness of breath, wheezing or difficulty breathing
• Increased level of uric acid in the blood
• Heart damage (cardiotoxicity)
• Absence of sperm in semen
• Mild dizziness

Not known: (frequency cannot be determined from available data)

• Potentially life-threatening condition occurring when blood pressure is too low due to blood poisoning (septic shock)
• Potentially life-threatening condition in which blood pressure is too low
• Inadequate oxygen supply to tissues due to inhibition of blood cell production in the bone marrow
• Appearance of dark spots inside the mouth
• Abdominal discomfort
• Skin redness or other sunburn-like reactions if exposed to sunlight or ultraviolet rays
• Changes in the skin where you previously received radiation therapy

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system at:
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 Epirubicin Hikma

Store and transport in a refrigerator (between 2°C and 8°C).
Keep in the original packaging, protected from light.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton box after EXP. The expiry date refers to the last day of that month.
Chemical and physical stability has been demonstrated for 72 hours after dilution in 0.9% sodium chloride or 5% glucose solution, when stored refrigerated.
From a microbiological standpoint, the product should be used immediately. If not used immediately, the storage times and conditions prior to use are the responsibility of the user and should normally not exceed 24 hours at a temperature between 2 and 8°C, unless the dilution was carried out under controlled, validated aseptic conditions.
Do not dispose of medicines via wastewater. Ask your pharmacist how to dispose of medicines you no longer use. These measures will help protect the environment.

6. Package contents and other information

Medicinal product subject to medical prescription with restricted use, usable exclusively
in a hospital setting.
What Epirubicin Hikma contains

• The active substance is epirubicin hydrochloride.
• The other components are sodium lactate (50% solution), hydrochloric acid (1N), for pH adjustment; sodium chloride and water for injections.

Epirubicin Hikma is an intravesical solution/injectable solution.
Description of the appearance of Epirubicin Hikma and contents of the pack
Red-colored injection solution contained in a clear glass vial (Type I glass) with a chlorobutyl rubber stopper and an aluminum cap.
10 mg/5 ml: pack containing 1 vial with 5 ml of solution
20 mg/10 ml: pack containing 1 vial with 10 ml of solution
50 mg/25 ml: pack containing 1 vial with 25 ml of solution
200 mg/100 ml: pack containing 1 vial with 100 ml of solution.
It is possible that not all pack sizes are marketed.
Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
Hikma Farmacêutica (Portugal), S.A.
Estrada do Rio da Mó, 8, 8A and 8B
Fervença
2705-906 Terrugem SNT
Portugal
Tel.: +351 219608410
e-mail: [email protected]
Manufacturer
THYMOORGAN Pharmazie GmbH
Schiffgraben 23
D-38690 Goslar
Germany
This medicinal product is authorized in the EEA Member States under the following names:

The following information is intended exclusively for medical or healthcare personnel:
Epirubicin Hikma 2 mg/ml Intravesical Solution/Injectable Solution
Epirubicin hydrochloride
FOR INTRAVENOUS INJECTION OR INTRAVESICAL ADMINISTRATION
Incompatibilities
Prolonged contact with any alkaline pH solution must be avoided,
including solutions containing sodium bicarbonate, as this causes drug hydrolysis.
Only the solvents described in the section “Instructions for dilution” should be used.
Do not mix either the injectable solution or the diluted solution with other medicinal products.
Epirubicin must not be mixed with heparin due to physical incompatibility (precipitation).
Instructions for dilution
The injectable solution may be administered through a continuous intravenous infusion line of saline solution. If, however, the injectable solution is to be administered after dilution, the following instructions must be followed.
Epirubicin Hikma may be further diluted under aseptic conditions in 5% glucose or 0.9% sodium chloride and administered by intravenous infusion. The infusion solution must be prepared immediately before use.
The injectable solution contains no preservatives and any residue remaining in the vial must be discarded immediately.
Safety during handling
This medicinal product is cytotoxic; follow local guidelines for instructions on the safe handling/disposal of cytotoxic products.
Storage
Store and transport refrigerated (between 2°C and 8°C).
Keep in the original packaging, protected from light.
Chemical and physical stability has been demonstrated for up to 72 hours after dilution in 0.9% sodium chloride or 5% glucose solution when stored refrigerated.
From a microbiological standpoint, the product should be used immediately.
If not used immediately, the storage times and conditions prior to use are the responsibility of the user and normally should not exceed 24 hours at a temperature between 2 and 8°C, unless the dilution was carried out under controlled, validated aseptic conditions.
Marketing Authorization Holder
Hikma Farmacêutica (Portugal), S.A.
Estrada do Rio da Mó, 8, 8A and 8B
Fervença
2705-906 Terrugem SNT
Portugal
[email protected]