Epirubicin is a classic chemotherapy drug that is given as a treatment for many different cancers. This information describes epirubicin, how it is given and some of its possible side effects.

What epirubicin looks like

Epirubicin is a red fluid.

How it is given

Epirubicin may be given:

• By injection into a vein (intravenously) through a fine tube (cannula) placed into the vein, usually in your arm.
• Through a central line (Hickman / Portacath), inserted under the skin into a vein near the collarbone, or into a PICC line which is inserted into a vein in the crook of your arm.
• Chemotherapy is usually given as a course of several sessions (or cycles) of treatment over a few months. The length of your treatment and the number of cycles you have will depend on the type of cancer for which you are being treated.

Possible side effects

Each person’s reaction to chemotherapy is different. Some people have very few side effects, while others may experience more. The side effects described in this information will not affect everyone who is given epirubicin, and may be different if you are having more than one chemotherapy drug.

We have outlined the most common side effects and some of the less common ones, so that you can be aware of them if they occur. However, we have not included those that are very rare and therefore extremely unlikely to affect you. If you notice any effects which you think may be due to the drug, but which are not listed in this information, please discuss them with your doctor or chemotherapy nurse.

Hair loss

This usually starts 3–4 weeks after the first dose of epirubicin, although it may happen earlier. Your hair may fall out completely or it may just thin. You may also have thinning and loss of eyelashes, eyebrows and other body hair. Hair loss is temporary and all your hair will regrow once the treatment ends. To help reduce hair loss, scalp cooling may be suitable for some people.

Feeling sick (nausea) and being sick (vomiting)

If you do feel sick this may begin a few hours after the treatment is given and last for up to a day. Your doctor can prescribe very effective anti-sickness (anti-emetic) drugs to prevent, or greatly reduce, nausea. If the sickness is not controlled, or continues, tell your doctor; they can prescribe other anti-sickness drugs which may be more effective. Some anti-sickness drugs can cause constipation. Let your doctor or nurse know if this is a problem.

Lowered resistance to infection

Epirubicin can reduce the production of white blood cells by the bone marrow, making you more prone to infection. This effect can begin seven days after treatment has been given, and your resistance to infection usually reaches its lowest point 10–14 days after chemotherapy. Your blood cells will then increase steadily, and will usually have returned to normal levels before your next course of chemotherapy is due.

Contact your doctor or the hospital straightaway if:

• your temperature goes above 38ºC (100.5ºF)
• you suddenly feel unwell (even with a normal temperature).

You will have a blood test before having more chemotherapy, to make sure that your cells have recovered. Occasionally it may be necessary to delay your treatment if the number of blood cells (the blood count) is still low.

Bruising or bleeding

Epirubicin can reduce the production of platelets (which help the blood to clot). Let your doctor know if you have any unexplained bruising or bleeding, such as nosebleeds, blood spots or rashes on the skin, or bleeding gums.

Anaemia (low number of red blood cells)

While having treatment with epirubicin you may become anaemic. This may make you feel pale, tired and short of breath on exertion. Let your doctor or nurse know if these effects are a problem.

Sore mouth and ulcers

Your mouth may become sore, or you may notice small ulcers during this treatment. Drinking plenty of fluids, and cleaning your teeth regularly and gently with a soft toothbrush, can help to reduce the risk of this happening.

Tell your nurse or doctor if you have any of these problems, as special mouthwashes and medicines to prevent or clear any mouth infection can be prescribed.

Taste changes

You may notice that your food tastes different. Normal taste will usually come back after the treatment finishes.

Discoloured urine

Your urine may become a pink-red colour. This may last for up to a day after you have had the epirubicin, and is due to the colour of the drug. It is quite normal.

Skin changes

Epirubicin can cause a rash, which may be itchy. Your doctor can prescribe medicine to help with this. Areas which have previously been treated with radiotherapy may become red and sore. Let your doctor know if this happens. The skin over the vein used for the injection may become discoloured. Your skin may darken, due to excess production of pigment. The darkening usually returns to normal a few months after the treatment has finished.

Tiredness and feeling weak

You may feel very tired. It is important to allow yourself plenty of time to rest.

Less common side effects

Changes in the way your heart works

Higher doses of epirubicin may cause changes in the muscle of the heart. This can affect how the heart works. The effect on the heart depends on the dose given. It is very unusual for the heart to be affected if you have standard doses. Tests to see how well your heart is working like an ECHO or a MUGA scan may sometimes be carried out before the drug is given.

Diarrhoea

This can usually be controlled easily with medicines such as loperamide or codeine, but let your doctor know if it is severe or if it continues. It is important to drink plenty of fluids if you have diarrhoea.

Changes to nails

Your nails may become darker. White lines may appear on them. These changes grow out over a few months once the treatment has finished.

Additional information

Some people have hot flushes when this drug is being given.

Leakage into the tissue

If epirubicin leaks into the tissue around the vein it can damage the tissue in that area. If you notice any stinging or burning around the vein while the drug is being given, or any leakage of fluid from the cannula site, it is very important that you tell your doctor or nurse.

If the area around the injection site becomes red or swollen at any time you should either tell the doctor or nurse on the ward, or if you are at home, ring the clinic or ward and ask to speak to the doctor or nurse.

Risk of blood clots

Cancer can increase your risk of developing a blood clot (thrombosis), and having chemotherapy may increase this risk further. A blood clot may cause symptoms such as pain, redness and swelling in a leg, or breathlessness and chest pain. Blood clots can be very serious so it is important to tell your doctor straightaway if you have any of these symptoms. However, most clots can usually be successfully treated with drugs to thin the blood. Your doctor or nurse can give you more information.

Other medicines

Some medicines can be harmful to take when you are having chemotherapy. Let your doctor know about any medications you are taking, including non-prescribed drugs such as complementary therapies and herbal drugs.

Fertility

Your ability to become pregnant or father a child may be affected by taking this drug. It is important to discuss fertility with your doctor before starting treatment.

Contraception

It is not advisable to become pregnant or father a child while taking epirubicin, as the developing foetus may be harmed. It is important to use effective contraception while taking this drug, and for at least a few months afterwards. Again, discuss this with your doctor.

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Additional Information For Healthcare Professionals

ADVERSE REACTIONS SIGNIFICANT

Percentages reported as part of combination chemotherapy regimens.

>10%:

• Central nervous system: Lethargy (1% to 46%)
• Dermatologic: Alopecia (69% to 96%)
• Endocrine & metabolic: Amenorrhea (69% to 72%), hot flashes (5% to 39%)
• Gastrointestinal: Nausea/vomiting (83% to 92%), mucositis (9% to 59%), diarrhea (7% to 25%)
• Hematologic: Leukopenia (50% to 80%; grades 3/4: 2% to 59%), neutropenia (54% to 80%; grades 3/4: 11% to 67%; nadir: 10-14 days; recovery: 21 days), anemia (13% to 72%; grades 3/4: 6%), thrombocytopenia (5% to 49%; grades 3/4: 5%)
• Local: Injection site reactions (3% to 20%)
• Ocular: Conjunctivitis (1% to 15%)
• Miscellaneous: Infection (15% to 21%)

1% to 10%:

• Cardiovascular: CHF (0.4% to 1.5%), decreased LVEF (asymptomatic) (1% to 2%); recommended maximum cumulative dose: 900 mg/m2
• Central nervous system: Fever (1% to 5%)
• Dermatologic: Rash (1% to 9%), skin changes (1% to 5%)
• Gastrointestinal: Anorexia (2% to 3%)
• Hematologic: Neutropenic fever (grades 3/4: 6%)

<1%, postmarketing, case reports, and/or frequency not defined:

Acute lymphoid leukemia; acute myelogenous leukemia (0.3% at 3 years, 0.5% at 5 years, 0.6% at 8 years); anaphylaxis, atrioventricular block, bradycardia, bundle-branch block, cardiomyopathy, ECG abnormalities, hypersensitivity, myelodysplastic syndrome, photosensitivity, premature menopause, premature ventricular contractions, pulmonary embolism, radiation recall, sinus tachycardia, skin and nail hyperpigmentation, ST-T wave changes (nonspecific), tachyarrhythmias, thromboembolism, thrombophlebitis, transaminases increased, urticaria, ventricular tachycardia

MECHANISM OF ACTION

Epirubicin is an anthracycline antibiotic; known to inhibit DNA and RNA synthesis by steric obstruction after intercalating between DNA base pairs; active throughout entire cell cycle. Intercalation triggers DNA cleavage by topoisomerase II, resulting in cytocidal activity. Also inhibits DNA helicase, and generates cytotoxic free radicals.

PHARMACODYNAMICS / KINETICS

• Distribution: Vss: 21-27 L/kg
• Protein binding: 77% to albumin
• Metabolism: Extensively via hepatic and extrahepatic (including RBCs) routes
• Half-life elimination: Triphasic; Mean terminal: 33 hours
• Excretion: Faeces (34% to 35%); urine (20% to 27%)