EPIRUBICIN HYDROCHLORIDE 10 MG POWDER FOR SOLUTION FOR INJECTION - patient leaflet, side effects, dosage

Read all of the this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

The name of your medicine is Epirubicin Hydrochloride 10 mg or 50 mg powder for solution for injection, which will be referred as Epirubicin Hydrochloride throughout the leaflet.

What is in this leaflet

• 1. What Epirubicin Hydrochloride is and what it is used for

• 2. What you need to know before you use Epirubicin Hydrochloride

• 3. How to use Epirubicin Hydrochloride

• 4. Possible side effects

• 5. How to store Epirubicin Hydrochloride

• 6. Contents of the pack and other information

1.

This medicine contains the active substance epirubicin hydrochloride and belongs to a group of medicines called anthracyclines used to treat cancer. Epirubicin Hydrochloride is a medicine that acts upon cells that are actively growing, such as cancer cells in such a way as to slow or stop their growth, and increases the likelihood that the cells die. This medicine helps to selectively kill the cancer tissue rather than normal, healthy tissue.

Epirubicin Hydrochloride is used to treat a variety of cancers, either alone or in combination with other medicinal products.

The way in which it is used depends upon the type of cancer that is being treated.

When injected into the bloodstream, Epirubicin Hydrochloride has been found to be useful in the treatment of cancers of the breast, ovaries, stomach, bowel and lung. In addition, Epirubicin hydrochloride can be given the same way to treat cancers of the blood forming tissues such as malignant lymphomas, leukaemias and multiple myeloma.

In addition, Epirubicin Hydrochloride can be injected into the bladder through a tube. This is sometimes used to treat abnormal cells or cancers of the bladder wall. It can also be used after other treatments to try and prevent such cells from growing again.

2. what you need to know before you use epirubicin hydrochloride if you are allergic to epirubicin, similar medicines (called anthracyclines or anthracenediones, see below) or any of the other ingredients of this medicine (listed in section 6)

• 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 drugs as epirubicin (called anthracyclines). They have similar side effects (including those effects on the heart)
• if you have suffered or currently have problem with your heart
• if you have a severe infection
• if you have severe liver problem
• if you are breast-feeding

Epirubicin Hydrochloride should not be injected into the bladder if:

• you suffer from urinary tract infection
• the tumour has penetrated the bladder wall
• there are problems inserting the catheter into the bladder
• you have an inflammation of the bladder
• you have a large volume of urine left in your bladder after you attempt to empty
• your bladder is contracted
• your urine contains blood

Warnings and precautions

if you are elderly or a child, because of the higher risk of severe cardiac side effects. Your cardiac function will be checked before and after the treatment with epirubicin.

• if you have had problems with your heart in the past or if you are currently experiencing such problems. You should inform your doctor. The dose of epirubicin will have to be adjusted. Your doctor will regularly check if your heart is working properly.
• if you have previously been treated with products to fight cancer (such as with doxorubicin or daunorubicin, anthracenedion derivatives or trastuzumab) or if you have had radiation, because the risk of severe cardiac side effects is greater. Inform your doctor because this is included in determining the total dose of epirubicin you will be administered.
• if you desire to have children. Both men and women should use effective contraceptive measures both during and for 6 months after the treatment. Men are advised to request information about the possibility of storing sperm by means of freezing before the treatment.
• if you suffer from infections or bleedings. Epirubicin may affect the bone marrow. The number of white blood cells in your blood will be reduced, which makes you more susceptible to infections (leucopenia). Bleedings can occur more easily (thrombocytopenia). These side effects are temporary in nature. The reduction of the number of white blood cells is greatest 10–14 days after the administration and usually returns to normal 21 days after the administration.
• if you have recently received or want to receive any vaccination.
• to check the level of uric acid in your blood. Your doctor will check this.
• if you notice a sensation of discomfort close to or at the injection site during the infusion (possible leakage into the surrounding tissue)
• if the numbers of white and red blood cells and platelets are reduced
• if you suffer from stomatitis or mucositis (sore lips or mouth ulcers)
• if you have received or are receiving radiotherapy to the chest area.
• if you have liver disease
• if you have kidney disease

Other medicines and Epirubicin Hydrochloride

Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines.

• paclitaxel and docetaxel (products that are used for some cancers); when paclitaxel is administered before epirubicin or docetaxel is administered immediately after epirubicin, the amount of epirubicin in the blood is increased, which could lead to an increase of the side effects.
• dexverapamil (a product that is used to treat some cardiac disorders); when used together with epirubicin it may have a negative effect on bone marrow.
• interferon a2b (a product used in some cancers and lymphomas and some forms of hepatitis).
• quinine (a product used for treatment of malaria and for leg cramps); quinine may speed up the distribution of epirubicin into the body, which may have a negative effect on the red blood cells.
• dexrazoxane (a product sometimes used with doxorubicin to reduce the risk of heart problems); the time that epirubicin is present in the body may be decreased, which could lead to decreased effect of epirubicin.
• cimetidine (a product to reduce the acid in your stomach); the amount of epirubicin in the blood is increased, which could lead to an increase of the side effects.
• live vaccines; there is risk of fatal disease therefore this combination is not recommended.
• other medicines that may affect your heart for example; calcium channel blockers (e.g. verapamil, nifedipine and diltiazem), other cancer treatments such as doxorubicin and possibly cyclophosphamide and radiotherapy
• trastuzumab; epirubicin should not be taken within 27 weeks of taking trastuzumab
• previous or concomitant treatment with other products which influence the bone marrow (for instance other producs to treat cancer, sulfonamide, chloramphenicol, diphenylhydantoin, amidopyrine-derivate, products against certain virus); the formation of blood cells can be disturbed.

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy

Avoid becoming pregnant while you or your partner is being treated with this medicine.

Breast-feeding

You should stop breast feeding before starting treatment with this medicine as some of the drug may get into your milk and possibly harm your child.

Fertility

Men: There is a risk of sterility due to therapy with epirubicin and male patients should consider storage of sperm before treatment.

Women: Epirubicin may cause lack of menstrual cycles or premature menopause in premenopausal wo­men.

Driving and using machines

Epirubicin Hydrochloride may cause episodes of nausea and vomiting, which can temporarily lead to an impairment of the ability to drive or use machines.

Epirubicin Hydrochloride contains methylhydroxybenzoate

This medicine contains methylhydroxy­benzoate, which may cause allergic reactions (which may occur after treatment), and in rare cases, respiratory difficulties.

3. how to use epirubicin hydrochloride

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

If you are prescribed Epirubicin Hydrochloride, it will be given to you by doctors or nurses experienced in giving chemotherapy.

Epirubicin Hydrochloride will normally be given to you by a doctor or a nurse through a drip (infusion) into a vein.

Your doctor will decide what dose to give and the number of days of treatment you will receive depending upon your condition.

The dose is decided by taking into account the condition you have, your height and weight. From your height and weight the doctor will work out your body surface area; and it is this that your dose is calculated from.

Epirubicin Hydrochloride made into a solution can also be put directly into the bladder to treat bladder cancer, or to help prevent it returning. The dose depends on the type of bladder cancer you have.

When this medicine is injected directly into the bladder, you will be instructed not to drink any fluid for 12 hours before treatment to avoid dilution of the medicine with urine in your bladder.

While one course of treatment may sometimes be enough, more often your doctor will advise further courses in three or four weeks time. It may take several courses before your illness is under control and you feel better.

Regular checks by your doctor during Epirubicin Hydrochloride treatment

Before and during treatment your doctor will be making regular checks of your blood cell counts, blood uric acid levels, liver function and carefully monitoring your heart function. Monitoring of the heart function will be continued for several weeks following the end of treatment.

Use in children

Epirubicin Hydrochloride is not recommended for use in children.

If you receive more Epirubicin Hydrochloride than you should

As this medicine will be given to you by a doctor or nurse it is unlikely that you will be given too little or too much. However, tell your doctor if you have any concerns.

In case you are given a higher dose than required your heart function and blood cells will be closely monitored.

High doses can worsen side effects.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

4. possible side effects

Like all medicines, Epirubicin Hydrochloride can cause side effects, although not everybody gets them.

Please contact your doctor or nurse immediately if you notice any of the following side effects:

• Sudden life-threatening allergic reaction. Symptoms include sudden signs of allergy such as rash, itching or hives on the skin, swelling of the face, lips, tongue or other parts of the body, shortness of breath, wheezing or trouble breathing.
• Whole-body inflammation caused by severe infection through blood (sepsis)
• Severe infection leading to dangerously low blood pressure (septic shock)
• heart problems (congestive heart disease)

Other side effects that may occur:

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

• Hair loss (normally reversible), reduced growth of beard (in males).
• Red coloration of urine for 1 to 2 days after administration.
• decreased number of white blood cells (leucopenia)
• decreased number of specific form of white blood cells (granulocytopenia)
• neutropenia accompanied by fever (febrile neutropenia)
• decrease in red blood cells (anaemia)
• feeling and being sick (nausea and vomiting)
• diarrhoea (which can result in dehydration)
• loss of appetite
• abdominal pain
• inflammation of membranes in the digestive tract (mucositis) including inflammation of the linings of the mouth (stomatitis)
• infections
• Reduction in blood platelets, which increases risk of bleeding or bruising

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

• dehydration
• inflammation of the gullet (oesophagitis)
• hot flushes
• bladder inflammation (chemical cystitis) sometimes with blood following administration into the bladder
• redness along the infusion vein
• difficulty in breathing (dyspnoea)
• accumulation of fluid (oedema and pulmonary oedema)
• enlargement of the liver
• accumulation of fluid in the abdominal cavity (ascites)
• accumulation of fluid between the chest wall and lungs (pleural effusion)
• third heart sound (extrasystoles)
• fever
• feeling of discomfort or uneasiness (malaise)
• weakness
• absence of menstrual periods (amenorrhoea)
• Local reactions, rash, itch
• oral pain, burning sensation of the mucous membrane
• increased transaminase levels (increased levels of some liver enzymes)

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

• inflammation and a blood clot in a vein (thrombophlebitis)
• irritation or inflammation of the vein
• when given in combination with other anti-cancer medicinal products, some patients have developed a rare leukaemia (cancer of white blood cells) after completing treatment.
• inflammation to the eye (conjunctivitis and keratitis)
• skin changes, redness, flushes, changes in skin and nail (hyperpigmenta­tion), sensitivity to light (photosensitivity) or allergic reaction in the case of radiation (radiation-recall reaction)
• inflammation of the mucous membrane lining the stomach (gastric erosion)
• bleeding in the stomach or intestines (gastrointestinal haemorrhage)
• ulceration of the mouth
• coloration of the mouth cavity (hyperpigmentation of oral mucous membranes)

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

• ECG (electrocardiogram) changes
• rapid heart rate (tachycardia and ventricular tachycardia)
• slow heart rate (bradycardia)
• abnormal heart beats (arrhythmias)
• specific forms of arrhythmias (AV block and bundle-branch block)
• heart muscle disease (cardiomyopathy)
• hives (urticaria)
• fever
• chills
• dizziness
• increased levels of uric acid in the blood (hyperuricaemia)
• lack of levels of male sperm (azoospermia)

Not known (frequency cannot be estimated from the available data)

• Oral mucous membrane erosion, bleeding in the mouth (mouth haemorrhage)
• bleeding (haemorrhage)
• inadequate oxygen supply (tissue hypoxia)
• Infection of the lung (pneumonia)
• blockage of blood vessels by dislodged blood clot (thromboembolic events)

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.

5. how to store epirubicin hydrochloride

Keep this medicine out of the sight and reach of children.

Do not use Epirubicin Hydrochloride after the expiry date which is stated on the vial label & carton after “EXP”. The expiry date refers to the last day of that month.

If the solution is cloudy after preparation, the doctor or nurse who is preparing the medicine for you will dispose off it safely.

The unopened vials should be stored below 30°C in the original container until ready for use.

Reconstituted solution should be used immediately.

Do not throw away any medicines via wastewater or household water. Ask your pharmacist how to throw away medicines you no longer use. These measures will help to protect the environment.

6. contents of the pack and other information the active substance is epirubicin hydrochloride. each vial contains 10 mg and 50 mg of epirubicin hydrochloride. after reconstitution, each vial contains 2 mg/ml epirubicin hydrochloride.

• The other ingredients are lactose monohydrate, methylhydroxy­benzoate, hydrochloric acid (for pH adjustment) and water for injections.

What Epirubicin Hydrochloride looks like and contents of the pack

Epirubicin Hydrochloride is a sterile freeze dried orange red coloured lyophilized cake.

Epirubicin Hydrochloride 10 mg is produced in10 ml Type I moulded flint glass vial with 20 mm rubber stoppers and 20 mm aluminium flip-off tear-off seal.

Epirubicin Hydrochloride 50 mg is produced in 50 ml Type I moulded flint glass vial with 20 mm rubber stoppers and 20 mm aluminium flip-off tear-off seal.

Each pack contains a single vial.

Marketing Authorisation Holder

Dawa Ltd, 5 Sandridge Close, Harrow, Middlesex, HA1 1XD, United Kingdom.

Manufacturer:

APC Pharmaceuticals & Chemicals (Europe) Limited,

9th floor, C.P. House, 97 – 107 Uxbridge Road, Ealing, London, W5 5TL.

Distributed By:

APC Pharmaceuticals & Chemicals (Europe) Limited,

9th floor, C.P. House,

97 – 107 Uxbridge Road,

Ealing, London W5 5TL

This leaflet was last revised in - 06/2020

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

APC Pharmaceuticals & Chemicals (Europe) Ltd.,

9th floor, C.P. House,

97 – 107 Uxbridge Road,

Ealing, London W5 5TL

Telephone number: 0208 326 3220

The following information is intended only for doctors or healthcare professionals:

Prolonged contact of the medicinal product with any solution of an alkaline pH (including sodium bicarbonate solutions) should be avoided; this will result in hydrolysis (degradation) of the active substance.

A physical incompatibility of the medicinal product with heparin has been reported.

Epirubicin Hydrochloride can be used in combination with other antitumour agents, but it is not recommended that it be mixed with other medicinal products.

Interaction with other medicinal products and other forms of interaction

It is not recommended that Epirubicin Hydrochloride be mixed with other medicinal products. But Epirubicin Hydrochloride can be used in combination with other anticancer medicinal products.

Cimetidine increases the formation of the active metabolite of epirubicin and the exposure of the unchanged epirubicin by pharmacokinetic interaction.

Instructions for use, handling and disposal

Preparation of the freeze-dried powder for intravenous use.

The product should be dissolved in 5 ml or 25 ml 0.9% sodium chloride or water for injections to get the final concentration of 2 mg/ml. The vial contents will be under a negative pressure. To minimize aerosol formation during reconstitution, particular care should be taken when the needle is inserted. Inhalation of any aerosol produced during reconstitution must be avoided. After gentle agitation the reconstituted solution will be transparent and red in appearance.

Intravenous use

Epirubicin Hydrochloride should be administered into the tubing of a freely flowing infusion (0.9% sodium chloride). To minimize the risk of thrombosis or perivenous extravasation, the usual infusion times range between 3 and 20 minutes depending upon dosage and volume of the infusion solution. A direct push injection is not recommended due to the risk of extravasation, which may occur even in the presence of adequate blood return upon needle aspiration.

Discard any unused solution.

Intravesical use

The product should be dissolved in 5 ml or 25 ml 0.9% sodium chloride injection or water for injections to get the final concentration of 2 mg/ ml. Epirubicin Hydrochloride should be instilled using a catheter and retained intravesically for 1 hour. During instillation, the patient should be rotated to ensure that the vesical mucosa of the pelvis receives the most extensive contact with the solution. To avoid undue dilution with urine, the patient should be instructed not to drink any fluid in the 12 hours prior to instillation. The patient should be instructed to void at the end of the instillation.

The following protective recommendations are given due to the toxic nature of this substance:

Personnel should be trained in good technique for reconstitution and handling.

• Pregnant staff should be excluded from working with this drug.
• Personnel handling Epirubicin Hydrochloride Powder for Solution for Injection should wear protective clothing: goggles, gowns and disposable gloves and masks.
• A designated area should be defined for reconstitution (preferably under laminar flow system). The work surface should be protected by disposable, plastic-backed, absorbent paper.
• All items used for reconstitution, administration or cleaning including gloves, should be placed in high-risk, waste disposal bags for high temperature incineration.
• 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 indicated previously.
• 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. In case of contact with the eye(s), hold back the eyelid of the affected eye(s), and flush with copious amounts of water for at least 15 minutes. Then seek medical evaluation by a physician.
• Always wash hands after removing gloves.

Storage

Store unopened vials below 30°C in the original container until ready for use. Keep the vial in the outer carton.

In use:

In-use stability has been demonstrated for 24 hours at 15°C – 25°C and for 48 hours at 2 – 8°C in water for injections and 0.9% w/v sodium chloride solution.

From a microbiological point of view 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 – 8 °C, unless reconstitution has taken place in controlled and validated conditions.