Document: document 0 change

• document 0
• document 1

---

PATIENT INFORMATION LEAFLET

Epirubicin Hydrochloride 2 mg/ml Injection

In this leaflet:

1.    What Epirubicin Hydrochloride 2 mg/ml Injection is and what it is used for

2.    Before you use Epirubicin Hydrochloride

3.    How this medicine is used

4.    Possible side effects

5.    Howto store this medicine

6.    Contents of the pack and other information

1. What Epirubicin Hydrochloride 2 mg/ml Injection is and what it is used for

Epirubicin Hydrochloride Injection is an anti-cancer medicine in the form of a solution for injection. Treatment with an anti-cancer medicine is sometimes called cancer chemotherapy.

Epirubicin hydrochloride is used to treat a variety of cancers, either alone or in combination with other medicines. The way in which it is used depends upon the type of cancer that is being treated. It is useful in treating the following conditions:

•    Cancer of the breast, ovary, stomach, lung, bowel or rectum

•    Malignant lymphoma e.g. Hodgkin’s disease and non-Hodgkin’s lymphoma

•    Leukaemia - cancer of the blood

•    Multiple myeloma

•    Non-invasive bladder cancer

Epirubicin is also used to help prevent recurrence of bladder cancer after surgery.

Taking/using other medicines:

Special care is needed if you are taking/using other medicines as some could interact with epirubicin. These medicines include:

•    other medicines that may affect your heart for example; calcium channel blockers (e.g. verapamil, nifedipine and diltiazem), other cancer treatments such as doxorubicin, mitomycin-C, dacarbazine, dactinomycin and possibly cyclophosphamide and radiotherapy

•    other medicines that may affect your liver e.g. barbiturates (medicines used in epilepsy or sleep disorders) and rifampicin (a medicine used to treat TB)

•    trastuzumab; epirubicin should not be taken within 24 weeks of taking trastuzumab

•    cimetidine (a medicine used to reduce the acid in your stomach)

•    paclitaxel and docetaxel (medicines used in some cancers)

•    interferon alfa-2b (a medicine used in some cancers and lymphomas and for some forms of hepatitis)

•    quinine (medicine used for treatment of malaria and for leg cramps)

•    dexrazoxane (a medicine sometimes used with doxorubicin to reduce the risk of heart problems)

•    dexverapamil (a medicine used to treat some heart conditions).

Please tell your doctor if you are taking, or have recently taken, any other medicines, including those you have bought.

If you need to have any vaccinations, you must inform your doctor that you are being treated with epirubicin before receiving the vaccination as certain types of vaccines (live and live-attenuated) may have serious side effects.

Pregnancy and breast-feeding:

Tell your doctor if you are pregnant, trying to become pregnant or breast-feeding. Your doctor will decide if you should receive this medicine.

Due to the risk of birth defects, women of childbearing potential should use appropriate contraception methods during treatment with epirubicin.

You must not breast feed if you are taking epirubicin.

Male patients may wish to seek advice on sperm preservation before treatment starts and should use effective contraceptive methods during treatment.

Male patients are advised not to father a child during and for 6 months after stopping epirubicin treatment.

Ask your doctor or pharmacist for advice before taking any medicine.

2. Before you use Epirubicin Hydrochloride

You should not use this medicine:

•    if you have had an allergic reaction to it or similar medicines in the past

•    if you have fewer blood cells than normal. Your doctor will check this

•    if you have been treated with high doses of some other anti-cancer medicines including doxorubicin and daunorubicin which belong to the same group of medicines as epirubicin (called anthracyclines). They have similar side effects (including those effects on the heart).

•    if you have suffered or currently have problems with your heart

•    if you have severe liver problems

•    if you have a severe infection

•    if you are pregnant or breast-feeding

For instillation into the bladder, Epirubicin Hydrochloride Injection should not be used:

•    if you have a urine infection

•    if you have inflammation of your bladder

•    if your tumour penetrates the bladder wall

•    if your doctor has problems inserting a catheter (tube) into your bladder

•    if there is a large volume of urine left in your bladder after you attempt to empty it

Special care will be taken:

•    to make sure the number of cells in your blood does not drop too low. Your doctor will check this regularly

•    to check the level of uric acid in your blood. Your doctor will check this.

•    if you have liver disease

•    if you have kidney disease

•    to make sure your heart is working properly. Your doctor will check this regularly

•    if you have received or are receiving radiotherapy to the chest area

The dose of medicine given to you will depend on the type of cancer you have, your health, how well your liver and kidneys are working and any other medicines you may be taking.

By injection or infusion into a vein

The medicine will be given to you as an injection into a vein over 3-5 minutes. Or it may be diluted with glucose (sugar solution) or sodium chloride (salt water) before it is given slowly, usually via a drip into a vein over 30 minutes. You may be given another dose of this medicine in 3 weeks.

By being put into the bladder (intravesical administration)

The medicine may be given directly into the bladder using a catheter. If this method is used, you should not drink any fluids for 12 hours before treatment so that your urine will not dilute the medicine too much. The medicine should be kept in your bladder for 1 hour after being given. You will need to alter your position occasionally to ensure that the medicine reaches all parts of your bladder.

When emptying your bladder after the medicine has been given, take care that your urine does not come into contact with your skin. In case contact does happen, thoroughly wash the affected area with soap and water but do not scrub.

While you are receiving epirubicin your doctor will take regular blood tests. This is to measure the effect the medicine is having. Your doctor will also do regular tests on how your heart is working.

If the medicine has been added to a bag of fluid for injection, or to be given into the bladder, it should be labelled with the strength of the medicine, volume and the time after which it should not be used.

As this medicine will be given to you whilst you are in hospital, it is unlikely that you will be given too little or too much. However, tell your doctor or pharmacist if you have any concerns.

Epirubicin Hydrochloride 2 mg/ml Injection

This is an extract from the Summary of Product Characteristics to assist in the administration of Epirubicin Hydrochloride 2 mg/ml Injection. You should be experienced in the handling and use of cytotoxic agents and be familiar with the SmPC. Reference should also be made to the local policy guidelines on the safe handling of cytotoxic agents.

For Intravenous Injection and Intravesical Administration Incompatibilities

Prolonged contact with any solution of an alkaline pH should be avoided as it will result in hydrolysis of the drug, which includes sodium bicarbonate containing solutions. Only the diluents detailed in the ‘Dilution Instructions’ should be used.

Neither the injection nor any diluted solution should be mixed with any other drugs. (A physical incompatibility with heparin has been reported).

Dilution Instructions

The injection may be given via the tubing of a free-running intravenous saline infusion (see below). Where the injection is to be administered after dilution, the following instructions should be followed.

Epirubicin Hydrochloride solution for injection may be diluted under aseptic conditions in glucose 5% or sodium chloride 0.9% and administered as an intravenous infusion. The infusion solution should be prepared immediately before use.

The injection solution contains no preservative and any unused portion of the vial should be discarded immediately.

Safe Handling

This is a cytotoxic product, please follow your local policy guidelines for instructions on the safe handling/destruction of cytotoxics.

The following general advice appears in section 6.6 of the SPC.

Guidelines for the safe handling and disposal of antineoplastic agents:

1.    If an infusion solution is to be prepared, this should be performed by trained personnel under aseptic conditions

2.    Preparation of an infusion solution should be performed in a designated aseptic area

3.    Adequate protective disposable gloves, goggles, gown and mask should be worn

4.    Precautions should be taken to avoid the medicinal product accidentally coming into contact with the eyes. In the event of contact with the eyes, irrigate with large amounts of water and/or 0.9% sodium chloride solution. Then seek medical evaluation by a physician.

5.    In case of skin contact, thoroughly wash the affected area with soap and water or sodium bicarbonate solution. However, do not abrade the skin by using a scrub brush. Always wash hands after removing gloves.

6.    Spillage or leakage should be treated with dilute sodium hypochlorite (1% available chlorine) solution, preferably by soaking, and then water. All cleaning materials should be disposed of as detailed below.

7.    Pregnant staff should not handle the cytotoxic preparation.

8.    Adequate care and precautions should be taken in the disposal of items (syringes, needles etc) used to reconstitute and/or dilute cytotoxic medicinal products. Any unused product or waste material should be disposed of in accordance with local requirements.

Dosage and Administration Intravenous administration

It is advisable to administer epirubicin via the tubing of a free-running intravenous saline infusion. Care should be taken to avoid extravasation.

Conventional dose

When epirubicin is used as a single agent, the recommended dose in adults is 60-90 mg/m² body area. Epirubicin should be injected intravenously over 3-5 minutes. The dose should be repeated at 21-day intervals, depending upon the patient’s haematomedullary status.

If signs of toxicity, including severe neutropenia/neutropenic fever and thrombocytopenia occur, dose modification or postponement of the subsequent dose may be required.

Epirubicin as a single agent for high dose treatment of lung cancer should be administered according to the following regimens:

•    Small cell lung cancer (previously untreated): 120 mg/m² on day 1, every 3 weeks

•    Non-small cell lung cancer (squamous, large cell, and adenocarcinoma previously untreated): 135 mg/m² on day 1 or 45 mg/m² on days 1, 2 and 3 every 3 weeks.

For high dose treatment, epirubicin may be given as an intravenous bolus over 3-5 minutes or as an infusion of up to 30 minutes duration.

Breast cancer

In the adjuvant treatment of early breast cancer patients with positive lymph nodes, intravenous doses of epirubicin ranging from 100 mg/m² (as a single dose on day 1) to 120 mg/m² (in two divided doses on days 1 and 8) every 3-4 weeks, in combination with intravenous cyclophosphamide and 5-fluorouracil and oral tamoxifen, are recommended.

Lower doses (60-75 mg/m² for high dose treatment) are recommended for patients whose bone marrow function has been impaired by previous chemotherapy or radiotherapy, by age, or neoplastic bone marrow infiltration. The total dose per cycle may be divided over 2-3 successive days.

The following doses of epirubicin are commonly used in monotherapy and combination chemotherapy for various tumours, as shown:

^b Recommended doses as presented in Section 4.2 ‘Posology and method of administration’ of Hospira proposed SPC

Combination therapy

If epirubicin is used in combination with other cytotoxic products, the dose should be reduced accordingly. Commonly used doses are shown in the table above.

Impaired liver function

The major route of elimination of epirubicin is the hepatobiliary system. In patients with impaired liver function the dose should be reduced based on serum bilirubin levels as follows:

Serum Bilirubin    Dose Reduction

24-51 pmol/l    50%

51 pmol/l    75%

Impaired renal function

Moderate renal impairment does not appear to require dose reduction in view of the limited amount of epirubicin excreted by this route.

Intravesical administration

Epirubicin may be given by intravesical administration for the treatment of superficial bladder cancer and carcinoma-in-situ. It should not be given intravesically for the treatment of invasive tumours that have penetrated the bladder wall, systemic therapy or surgery is more appropriate in these situations. Epirubicin has also been successfully used intravesically as a prophylactic agent after transurethral resection of superficial tumours to prevent recurrence.

For the treatment of superficial bladder cancer the following regimen is recommended, using the dilution table below:

8 weekly instillations of 50 mg/50 ml (diluted with saline or distilled sterile water).

If local toxicity is observed: A dose reduction to 30 mg/50 ml is advised.

Carcinoma-in-situ: Up to 80 mg/50 ml (depending on individual tolerability of the patient).

For prophylaxis: 4 weekly administrations of 50 mg/50 ml followed by 11 monthly instillations at the same dose.

Dilution table for bladder installation solutions

Dose epirubicin required	Volume of 2 mg/ml epirubicin injection	Volume of diluent sterile water for injection or 0.9% sterile saline	Total volume for bladder instillation
30 mg	15 ml	35 ml	50 ml
50 mg	25 ml	25 ml	50 ml
80 mg	40 ml	10 ml	50 ml

The solution should be retained intravesically for 1 hour. To avoid undue dilution with urine, the patient should be instructed not to drink any fluid in the 12 hours prior to instillation.

During the instillation, the patient should be rotated occasionally and should be instructed to void urine at the end of the instillation time.

Storage

Store at 2-8°C.

Keep container in the outer carton in order to protect from light.

In use: Epirubicin Hydrochloride 2 mg/ml Injection may be further diluted in Glucose 5% or Sodium Chloride 0.9% and administered as an intravenous infusion. After dilution, physical and chemical in-use stability has been demonstrated for:

Diluent	Target Concentration	Storage Conditions	Time period
0.9% sodium chloride solution for infusion	0.2 mg/ml and 1.0 mg/ml	2-8°C in the absence of light in PVC infusion bags	84 days
5% glucose solution for infusion	0.2 mg/ml and 1.0 mg/ml	2-8°C in the absence of light in PVC infusion bags	84 days
0.9% sodium chloride solution for infusion	0.2 mg/ml and 1.0 mg/ml	25°C under normal lighting conditions in PVC infusion bags	14 days
5% glucose solution for infusion	0.2 mg/ml and 1.0 mg/ml	25°C under normal lighting conditions in PVC infusion bags	14 days

From a microbiological point of view however, 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 would normally not be longer than 24 hours at 2 to 8°C.

Marketing Authorisation Holder

Hospira UK Limited Warwickshire, CV31 3RW United Kingdom

Date of Revision

February 2014