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PHARMORUBICIN SOLUTION FOR INJECTION 2MG/ML

Active substance(s): EPIRUBICIN HYDROCHLORIDE

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DRUK FM PAM658

Item Code

PFIZER (PERTH) PTY LIMITED, AUSTRALIA
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Pharmorubicin® Solution for Injection 2 mg/ml

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DRAFT# 2

17 OCT 2014

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44009038

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PAR-2014-0025324

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A GUIDE FOR HOSPITAL STAFF
®

Pharmorubicin

2 mg/ml Solution for Injection
Solution for Injection or Infusion
epirubicin hydrochloride
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IMPORTANT: Refer to Summary of Product Characteristics before prescribing.

Presentation:

Sterile, red, mobile solution containing 10 mg, 20 mg, 50 mg and 200 mg of epirubicin
hydrochloride as a 2 mg/ml solution in 0.9% sodium chloride solution.

Uses:

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Pharmorubicin has produced responses in a wide range of neoplastic conditions including
breast, ovarian, gastric, lung and colorectal carcinomas, malignant lymphomas, leukaemias
and multiple myeloma.
Intravesical administration of epirubicin has been found to be beneficial in the treatment
of superficial bladder cancer, carcinoma-in-situ and the prophylaxis of recurrences after
transurethral resection.

Dosage and administration:

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Intravenous administration:
Pharmorubicin is not active when given orally and should not be injected intramuscularly or intrathecally.
Pharmorubicin solution should be administered only under the supervision of a qualified physician experienced in antiblastic and
cytotoxic therapy. Treatment with high dose Pharmorubicin in particular requires the availability of facilities for the care of possible
clinical complications due to profound myelosuppression.
It is advisable to give the drug via a freely-running i.v. saline infusion after checking that the needle is well placed in the vein. This
method minimises the risk of drug extravasation and makes sure that the vein is flushed with saline after the administration of the
drug. Extravasation of Pharmorubicin from the vein during injection may give rise to severe tissue lesions, even necrosis. Venous
sclerosis may result from injection into small vessels or repeated injections into the same vein.
Conventional doses:
When Pharmorubicin is used as a single agent, the recommended dosage in adults is 60-90 mg/m² body area; the drug should be
injected i.v. over 3-5 minutes and, depending on the patient’s haematomedullary status, the dose should be repeated at 21-day
intervals.
Dose modification (reduction) following signs of toxicity (specifically severe neutropaenia/neutropaenic fever and
thrombocytopaenia, which could persist on Day 21 after the first dose) could be required or the following dose could be delayed, as
in cases of liver impairment.
High doses:
Pharmorubicin as a single agent for the treatment of lung cancer at high doses should be administered according to the following
regimens:
• small cell lung cancer (previously untreated): 120 mg/m² day 1, every 3 weeks.
• non-small cell lung cancer (squamous, large cell, and adenocarcinoma previously untreated): 135 mg/m² day 1 or 45mg/m²
days 1, 2, 3, every 3 weeks.
• 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.
The drug should be given as an i.v. bolus over 3-5 minutes or as an infusion up to 30 minutes. Lower doses (60-75 mg/m² for
conventional treatment and 105-120 mg/m² for high dose schedules) are recommended for patients whose bone marrow function
has already been impaired by previous chemotherapy or radiotherapy, by age, or neoplastic bone marrow infiltration. The total
dosage per cycle may be divided over 2-3 successive days.
When the drug is used in combination with other antitumour agents, the doses need to be adequately reduced. Since the major
route of elimination of Pharmorubicin is the hepatobiliary system, the dosage should be reduced in patients with impaired liver
function, in order to avoid an increase in overall toxicity. Moderate liver impairment (bilirubin: 1.4-3 mg/100 ml) requires a 50%
reduction of dose, while severe impairment (bilirubin >3 mg/100 ml) necessitates a dose reduction of 75%.
Moderate renal impairment does not appear to require a dose reduction in view of the limited amount of Pharmorubicin excreted
by this route.
Intravesical administration:
Pharmorubicin may be given by intravesical administration for the treatment of superficial bladder cancer and carcinoma-in-situ.
It should not be used in this way for the treatment of invasive tumours which have penetrated the bladder wall where systemic
therapy or surgery is more appropriate. Epirubicin has also been successfully used intravesically as a prophylactic agent after
transurethral resection of superficial bladder tumours in order to prevent recurrences.
While many regimens have been used, the following may be helpful as a guide: for therapy, 8 x weekly instillations of 50 mg/50 ml
(diluted with saline or distilled sterile water). In the case of local toxicity (chemical cystitis), a dose reduction to 30 mg/50 ml
is advised. For carcinoma-in-situ, depending on the individual tolerability of the patient, the dose may be increased up to
80 mg/50 ml. For prophylaxis, 4 x weekly administrations of 50 mg/50 ml followed by 11 x monthly instillations at the same
dosage, is the schedule most commonly used.
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 instillation, the patient should be rotated occasionally and should be
instructed to void at the end of the instillation time.

Contraindications:

Hypersensitivity to epirubicin or any other component of the product, other anthracyclines or anthracenediones.
• Lactation
Intravenous use:
• persistent myelosuppression
• severe hepatic impairment
• severe myocardial insufficiency
• recent myocardial infarction
• severe arrhythmias
• previous treatments with maximum cumulative doses of epirubicin and/or other anthracyclines and anthracenediones (see
section 4.4)
• patients with acute systemic infections
• unstable angina pectoris
• myocardiopathy
Intravesical use:
• urinary tract infections
• inflammation of the bladder
• haematuria
• invasive tumours penetrating the bladder
• catheterisation problems

Patient leaflet: Information for the user

Warnings & Precautions

(refer to the SPC, section 4.4 - special warnings & precautions for use, for further information)

General

Epirubicin should be administered only under the supervision of qualified physicians experienced in the use of cytotoxic therapy.
Patients should recover from acute toxicities (such as stomatitis, neutropenia, thrombocytopenia, and generalized infections) of prior
cytotoxic treatment before beginning treatment with epirubicin.
While treatment with high doses of epirubicin (e.g., ≥ 90 mg/m² every 3 to 4 weeks) causes adverse events generally similar to
those seen at standard doses (< 90 mg/m² every 3 to 4 weeks), the severity of the neutropenia and stomatitis/mucositis may be
increased. Treatment with high doses of epirubicin does require special attention for possible clinical complications due to profound
myelosuppression.
Cardiac function - Cardiotoxicity is a risk of anthracycline treatment that may be manifested by early (i.e., acute) or late (i.e., delayed)
events.
The risk of developing CHF increases rapidly with increasing total cumulative doses of epirubicin in excess of 900 mg/m²; this
cumulative dose should only be exceeded with extreme caution (see section 5.1 - pharmacodynamic properties, clinical studies).
Cardiac function should be assessed before patients undergo treatment with epirubicin and must be monitored throughout therapy to
minimize the risk of incurring severe cardiac impairment.
Given the risk of cardiomyopathy, a cumulative dose of 900 mg/m² epirubicin should be exceeded only with extreme caution.
Heart failure (New York Heart Association [NYHA] class II-IV) has been observed in patients receiving trastuzumab therapy alone or in
combination with anthracyclines such as epirubicin. This may be moderate to severe and has been associated with death.
Trastuzumab and anthracyclines such as epirubicin should not be used currently in combination except in a well-controlled clinical
trial setting with cardiac monitoring. Patients who have previously received anthracyclines are also at risk of cardiotoxicity with
trastuzumab treatment, although the risk is lower than with concurrent use of traztuzumab and anthracyclines.
Because the reported half-life of trastuzumab is approximately 28-38 days, trastuzumab may persist in the circulation for up to 27
weeks after stopping trastuzumab treatment. Patients who receive anthracyclines such as epirubicin after stopping trastuzumab may
possibly be at increased risk of cardiotoxicity. If possible, physicians should avoid anthracycline-based therapy for up to 27 weeks
after stopping trastuzumab. If anthracyclines such as epirubicin are used, the patient’s cardiac function should be monitored carefully
(see Interactions).
If symptomatic cardiac failure develops during trastuzumab therapy after epirubicin therapy, it should be treated with the standard
medications for this purpose.
(Please refer to the SPC, section 4.4 - special warnings & precautions for use, for further information)
Haematologic toxicity - As with other cytotoxic agents, epirubicin may produce myelosuppression. Haematologic profiles should be
assessed before and during each cycle of therapy with epirubicin, including differential white blood cell (WBC) counts.
Secondary leukaemia - Secondary leukaemia, with or without a preleukaemic phase, has been reported in patients treated with
anthracyclines, including epirubicin.
Gastrointestinal - Epirubicin is emetigenic. Mucositis/stomatitis generally appears early after drug administration and, if severe, may
progress over a few days to mucosal ulcerations.
Liver function - The major route of elimination of epirubicin is the hepatobiliary system. Serum total bilirubin and AST levels should
be evaluated before and during treatment with epirubicin. Lower doses of epirubicin are recommended in patients with elevated
bilirubin or AST levels.
Renal function - Serum creatinine should be assessed before and during therapy.
Dosage adjustment is necessary in patients with serum creatinine >5 mg/dL.
Effects at site of injection - Phlebosclerosis may result from an injection into a small vessel or from repeated injections into the
same vein. Following the recommended administration procedures may minimize the risk of phlebitis/thrombophlebitis at the injection
site (see section 4.2).
Extravasation - Extravasation of epirubicin during intravenous injection may produce local pain, severe tissue lesions (vesication,
severe cellulitis) and necrosis. The adverse effect of extravastation of anthracyclines may be prevented or reduced by immediate use
of a specific treatment e.g. dexrazoxane (please refer to relevant labels for use). The patient’s pain may be relieved by cooling down
the area and keeping it cool, using hyaluronic acid and DMSO. If extravasation occurs the patient should be monitored closely during
the subsequent period of time, as tissue necrosis at the extravasation site may occur after several weeks from the extravasation
episode.
Other - As with other cytotoxic agents, thrombophlebitis and thromboembolic phenomena, including pulmonary embolism (in some
cases fatal), have been coincidentally reported with the use of epirubicin.
Tumour-lysis syndrome - Epirubicin may induce hyperuricemia because of the extensive purine catabolism that accompanies rapid
drug-induced lysis of neoplastic cells (tumour-lysis syndrome).
Immunosuppressant effects/increased susceptibility to infections - Administration of live or live-attenuated vaccines in patients
immunocompromised by chemotherapeutic agents including epirubicin, may result in serious or fatal infections (see section 4.5).
Vaccination with a live vaccine should be avoided in patients receiving epirubicin. Killed or inactivated vaccines may be administered;
however, the response to such vaccines may be diminished.
Reproductive system - Epirubicin can cause genotoxicity. Men and women treated with epirubicin should adopt appropriate
contraceptives.
Intravesical administration of epirubicin may produce symptoms of chemical cystitis (such as dysuria, polyuria, nocturia, stranguria,
haematuria, bladder discomfort, necrosis of the bladder wall) and bladder constriction.
Intra-arterial administration of epirubicin (transcatheter arterial embolization for the localized or regional therapies of primary
hepatocellular carcinoma or liver metastases) may produce (in addition to systemic toxicity qualitatively similar to that observed
following intravenous administration of epirubicin) localized or regional events which include gastro-duodenal ulcers (probably due
to reflux of the drugs into the gastric artery) and narrowing of bile ducts due to drug-induced sclerosing cholangitis. This route of
administration can lead to widespread necrosis of the perfused tissue.
For additional warnings and precautions for other routes of administration refer to the SPC section 4.4 – special warnings &
precautions for use.

Interactions:

Epirubicin is mainly used in combination with other cytotoxic drugs. Additive toxicity may occur especially with regard to bone
marrow/haematologic and gastro-intestinal effects (see section 4.4). The use of epirubicin in combination chemotherapy with other
potentially cardiotoxic drugs, as well as the concomitant use of other cardioactive compounds (e.g., calcium channel blockers),
requires monitoring of cardiac function throughout treatment.
Epirubicin is extensively metabolized by the liver. Changes in hepatic function induced by concomitant therapies may affect epirubicin
metabolism, pharmacokinetics, therapeutic efficacy and/or toxicity (see section 4.4).
Anthracyclines including epirubicin should not be administered in combination with other cardiotoxic agents unless the patient’s
cardiac function is closely monitored.
Vaccination with a live vaccine should be avoided in patients receiving epirubicin. Killed or inactivated vaccines may be administered;
however, the response to such vaccines may be diminished.
Cimetidine increased the AUC of epirubicin by 50% and should be discontinued during treatment with epirubicin.
When given prior to epirubicin, paclitaxel can cause increased plasma concentrations of unchanged epirubicin and its metabolites, the
latter being, however, neither toxic nor active.
Increase of myelosuppression may occur in patients receiving combination therapy of anthracycline and dexrazoxane.
Refer to the SPC, section 4.5 – interaction with other medicinal products and other forms of interaction, for further
information.

Adverse reactions:

The undesirable effects in the table below have been observed and reported during treatment with epirubicin with the following
frequencies: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000);
very rare (<1/10,000), not known (cannot be estimated from the available data).
More than 10% of treated patients can expect to develop undesirable effects. The most common undesirable effects are
myelosuppression, gastrointestinal side effects, anorexia, alopecia, infection.

®

Pharmorubicin

2 mg/ml Solution for Injection or Infusion
Epirubicin hydrochloride
Read all of 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, please ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them,
even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible
side effects not listed in this leaflet. See section 4.

What is in this leaflet:
1.
2.
3.
4.
5.
6.

What Pharmorubicin is and what it is used for
What you need to know before you use Pharmorubicin
How to use Pharmorubicin
Possible side effects
How to store Pharmorubicin
Contents of the pack and other information

1. What Pharmorubicin is and what it is used for
• Pharmorubicin is an injection that contains epirubicin hydrochloride. It belongs to a group of medicines
called cytotoxics used for chemotherapy. Pharmorubicin causes cells that are actively growing, such as
cancer cells, to slow or stop their growth and increases the likelihood that they die. This medicine helps
to selectively kill the cancer tissue rather than normal, healthy tissue.
• Pharmorubicin is used to treat a variety of cancers, either alone or in combination with other drugs. The
way in which it is used depends upon the type of cancer that is being treated.
• It has been found to be particularly useful in the treatment of cancers of the breast, ovaries, stomach,
bowel and lung. In addition, this medicine can be given to treat cancers of the blood forming tissues such
as malignant lymphomas, leukaemias and multiple myeloma.
• Pharmorubicin can also be put directly into the bladder through a tube. This is sometimes used to treat
abnormal cells or cancers of the bladder wall. It can be used after other treatments to try and prevent
such cells from growing again.
You must talk to a doctor if you do not feel better or if you feel worse.

2. What you need to know before you use Pharmorubicin
Do not use Pharmorubicin:
• if you are allergic to epirubicin or any of the other ingredients of this medicine (listed in section 6) or
similar chemotherapy drugs (anthracyclines or anthracenediones)
• if you have infections affecting multiple organs
• If you have urine infection
• if you have inflammation of the bladder
• if you have invasive tumours penetrating the bladder
• if you have catheterisation problems (your doctor has problems inserting a catheter (tube) into your
bladder)
• if you have presence of blood in urine
• if you have decreased ability to produce blood cells leading to low blood cell counts, as it can lower them
further
• if you have previously been treated with Pharmorubicin or similar chemotherapy drugs, as previous
treatment with these medicines can increase the risk of side effects
• if you have suffered from recent heart attack, poor functioning of the heart muscle, severe irregular
heartbeat pattern, sudden pain in the chest, non-inflammatory disease of the heart muscle or any other
severe heart trouble in the past, or are presently receiving treatment for this
• if you have severe liver disease
• if you are pregnant or breast-feeding

Warnings and precautions
Talk to your doctor, pharmacist or nurse before using Pharmorubicin:
• if your liver or kidneys are not working properly
• if you have had or you are due to have any vaccination
• if you are currently suffering from acute toxicities such as
inflammation of the mouth
° acute
white blood cell count
° low
platelet count or
° low
infections in general
°
This will help your doctor decide if this medicine is suitable for you.

FRONT

• Cimetidine (a drug usually used to treat stomach ulcers and heartburn). Cimetidine can make the
effects of Pharmorubicin stronger
• Calcium channel blockers (medicines for the heart)
• Quinine (antimalaria drug)
• Antibiotics such as sulphonamide and chloramphenicol
• Antiretroviral (drugs used to treat infection by HIV)
• Diphenylhydantoin (a drug used to treat epilepsy)
• Painkillers such as amidopyrine derivate
• Trastuzumab therapy for treatment of cancer. Your doctor should avoid using pharmorubicin for up to
27 weeks after stopping trastuzumab when possible. If pharmorubicin is used before this time, careful
monitoring of cardiac function is recommended
• Vaccination with a live vaccine should be avoided in patients receiving epirubicin
• Paclitaxel or docetaxel (drugs used to treat cancer). When paclitaxel is given prior to epirubicin, it
may increase concentration of epirubicin in blood. However when paclitaxel and docetaxel are given
together and given after epirubicin, they did not affect concentration of epirubicin
• Dexverapamil (used to treat some heart conditions)
• Dexrazoxane (used to prevent chronic cumulative cardiotoxicity caused by epirubicin).
• Interferon Ơ2b (used to treat cancers)

Pregnancy, breast-feeding and fertility
Pregnancy
If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for advice
before being given this medicine. Avoid becoming pregnant while you or your partner is being treated with
this medicine. If you are sexually active, you are advised to use effective birth control to prevent pregnancy
during treatment, whether you are male or female. It may cause birth defects, so it is important to tell your
doctor if you think you are pregnant.

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
There are no special precautions, as long as you feel fully recovered following your hospital treatment and
you have discussed this with your doctor.

Pharmorubicin contains sodium
This medicinal product contains less than 1mmol sodium (23 mg) per dose, i.e. essentially sodium free.

3. How to use Pharmorubicin
If you are prescribed Pharmorubicin it will only be given to you by doctors or nurses experienced in giving
chemotherapy.
This medicine 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’ treatment you will receive depending
on 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.
Pharmorubicin 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 Pharmorubicin treatment
During treatment your doctor will be making regular checks of your:
• Blood - to check for low blood cell counts that may need treatment
• Heart function - heart damage can occur when high doses of Pharmorubicin are given. This may not
be detected for several weeks, so regular tests may be required during this period
• Liver - using blood tests to check that this medicine is not affecting the way it functions in a harmful
way
• Blood uric acid levels - Pharmorubicin may increase uric acid levels in the blood, which might cause
gout. Another medicine may be given if your uric acid levels are too high

If you receive high doses of Pharmorubicin
High doses can worsen side effects like sores in the mouth or may decrease the number of white blood
cells (which fight infection) and platelets (these help the blood to clot) in the blood. Should this happen,
you may need antibiotics or blood transfusions. Mouth ulcers can be treated to make them less
uncomfortable as they heal.
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

Other medicines and Pharmorubicin:
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2/PAR 2014-0025324
CK
17 Oct 2014

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Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, even
those obtained without a prescription, particularly the following:

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DRUK FM PAM658

Item Code

PFIZER (PERTH) PTY LIMITED, AUSTRALIA

PAR-2014-0025324

DRAFT# 2

17 OCT 2014

BACK

4. Possible side effects

6. Contents of the pack and other information

System organ class

Like all medicines, this medicine can cause side effects, although not everybody gets them.

What Pharmorubicin contains

Infections and infestations

Please contact your doctor or nurse immediately if you notice any of the following
side effects.
Although they are rare (may affect up to 1 in 1,000 people), these symptoms can be serious:
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)
• Gasping for air, shortness of breath, swelling of abdomen, legs or ankles, fluid in lungs (signs of
congestive heart failure)
• Insufficient tissue level of oxygen; low blood pressure, rapid heartbeat, confusion or loss of
consciousness may follow (shock)
• Blood clots, including a clot in the lungs which causes chest pain and breathlessness

The active substance is epirubicin hydrochloride. The other ingredients are hydrochloric acid, sodium
chloride and water for injections.

What Pharmorubicin looks like and contents of the pack
Pharmorubicin is a red solution for injection or infusion containing 10 mg, 20 mg, 50 mg or 200 mg of
epirubicin hydrochloride as a 2 mg/ml solution in single glass or plastic vials. Not all pack sizes may be
marketed.

• White blood cell counts (which fight infection) can drop, which increases the chance of infections and
fever
• A low red blood cell count (anaemia) that can leave you feeling tired and lethargic
• Hair loss - may be quite severe. Beard growth may stop in men. Hair normally re-grows when your
treatment course ends
• Red discolouration of urine (which is normal and related to the colour of the medicine). You should
inform your doctor if it does not stop in a few days or you think there is blood in your urine

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

Myelosuppression (leucopenia, granucytopenia and neutropenia,
anaemia and febrile neutropenia)

Uncommon

Thrombocytopenia

10 mg, 20 mg, 50 mg and 200 mg vials for intravenous or intravesicular use.

Not known

Haemorrhage and tissue hypoxia as result of myelosoppression.

Rare

Anaphylaxis

Common

Anorexia, dehydration

Rare

Hyperuricaemia (see section 4.4 )

Nervous system disorders

Rare

Dizziness

Eye disorders

Not known

Conjunctivitis, keratitis

Cardiac disorders

Rare

Congestive heart failure (dyspnoea, oedema, hepatomegaly, ascites,
pulmonary oedema, pleural effusions, gallop rhythm), cardiotoxicity
(e.g. ECG abnormalities, arrhythmias, cardiomyopathy), ventricular
tachycardia, bradycardia, AV block, bundle-branch block

Vascular disorders

For further information please contact Medical Information at Pfizer Limited in Walton Oaks, Tadworth,
Surrey, KT20 7NS. Tel: 01304 616161.
This leaflet was last revised in 06/2014
Document Reference: United Kingdom PMA 11_0

Gastrointestinal disorders
Skin and subcutaneous tissue disorders

Renal and urinary disorders

Common

Hot flashes, hot flushes

Uncommon

Phlebitis, thrombophlebitis

Not known

Shock, thromboembolism, including pulmonary emboli

Common

Alopecia
Urticaria

Not known

Local toxicity, rash, itch, skin changes, erythema, flushes, skin
and nail hyperpigmentation, photosensitivity, hypersensitivity to
irradiated skin (radiation-recall reaction)

Very common

Red colouration of urine for 1 to 2 days after administration

Rare

General disorders and administration site
conditions

Common

Infusion site erythema

Rare

Malaise, asthenia, fever, chills

Rare
Not known

Injury, poisoning and procedural complications Common

POM
PL 0032/0275
This leaflet was prepared in 06/2014
Further information is available to the medical and allied professions on request from:
Medical Information at Pfizer Limited, Walton Oaks, Tadworth, Surrey, KT20 7NS, UK.
Tel: 01304 616161.

Mucositis, esophagitis, stomatitis, vomiting, diarrhoea, nausea

Very common
Rare

Reproductive system and breast disorders

Investigations

Amenorrhoea, azoospermia

Changes in transaminase levels
Asymptomatic drops in left ventricular ejection fraction
Chemical cystitis, sometimes haemorrhagic, has been observed
following intravesical administration (see section 4.4)

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the
benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the
Yellow Card Scheme at www.mhra.gov.uk/yellowcard.

Uncommon: (may affect up to 1 in 100 people)
• Platelets (cells that help the blood to clot) can be affected which could make you bruise or bleed more
easily. It is important to seek medical advice if this happens
• Inflammation of veins at site of infusion, swelling, redness, leg pain, which can be associated with
blood clots

Impairment of fertility

Epirubicin could induce chromosomal damage in human spermatozoa.
Epirubicin may cause amenorrhoea or premature menopause in premenopausal women.

Pregnancy

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

Experimental data, however, suggest that epirubicin may harm the foetus.
If epirubicin is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the
potential hazard to the foetus.
There are no studies in pregnant women. Epirubicin should be used during pregnancy only if the potential benefit justifies the
potential risk to the foetus.

• When given in combination with other anti-cancer drugs, some patients have developed a rare
leukaemia (cancer of white blood cells) after completing treatment
• Tiredness, weakness, fever and feeling cold
• Low sperm count
• Absence of menstruation
• ECG abnormalities, irregular heartbeat, heart muscle disease, increase or decrease of heart rate
• Changes in liver enzyme transaminase levels
• Increase uric acid levels in the blood which might cause gout
• A skin rash commonly known as hives (urticaria)
• Dizziness

Lactation

It is not known whether epirubicin is excreted in human milk. Because many drugs, including other anthracyclines, are excreted in
human milk and because of the potential for serious adverse reactions in nursing infants from epirubicin, mothers should discontinue
nursing prior to taking this drug.
Refer to SPC section 4.6 - pregnancy and lactation, for further information.

Effects on ability to drive and use machines

There have been no reports of particular adverse events relating to effects on ability to drive and to use machines.

Overdosage:

Acute overdosage with epirubicin will result in severe myelosuppression (mainly leucopoenia and thrombocytopenia), gastrointestinal
toxic effects (mainly mucositis) and acute cardiac complications. Latent cardiac failure has been observed with anthracyclines several
months to years after completion of treatment (see section 4.4). Patients must be carefully monitored. If signs of cardiac failure occur,
patients should be treated according to conventional guidelines.

Not known: (frequency cannot be estimated from the available data)
Pneumonia
Internal bleeding and lack of oxygen to tissues due to bone marrow suppression
Inflammation to the eye (conjunctivitis and keratitis)
Discolouration of skin and nails
Sensitive to light
Rash, itch, skin changes
Redness of the skin (erythema)
Sensitive to skin treated with radiation

Treatment:

Symptomatic. Epirubicin cannot be removed by dialysis.

Pharmaceutical precautions:

The following protective recommendations are given due to the toxic nature of this substance:
• Personnel should be trained in good technique for handling.
• Pregnant staff should be excluded from working with this drug.
• Personnel handling Pharmorubicin Solution should wear protective clothing: goggles, gowns, and disposable gloves and masks.
• All items used for administration or cleaning, including gloves, should be placed in high-risk waste-disposal bags for hightemperature 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. Accidental contact with the skin or eyes should be treated
immediately by copious lavage with water, or soap and water, or sodium bicarbonate solution; medical attention should be sought.
Discard any unused solution.

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects
not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme website:
www.mhra.gov.uk/yellowcard. By reporting side effects you can help provide more information on the
safety of this medicine.

Incompatibilities

Prolonged contact with any solution of an alkaline pH should be avoided as it will result in hydrolysis of the drug. Pharmorubicin
should not be mixed with heparin due to chemical incompatibility which may lead to precipitation when the drugs are in certain
proportions.
Pharmorubicin can be used in combination with other antitumour agents, but it is not recommended that it be mixed with other drugs.

5. How to store Pharmorubicin

2/PAR 2014-0025324
CK
17 Oct 2014

Very common

Company contact address:

Infections
Loss of appetite
Feeling thirsty (dehydration)
Hot flushes
Heartburn, nausea (feeling sick), vomiting (being sick) or diarrhoea
Inflammation of the gullet (esophagitis)
Pain, redness, burning or stinging sensation at injection site
Inflammation or irritation of the bladder, sometimes with bleeding. Frequent urination or burning may
occur after local administration the bladder wall
• Painful inflammation and ulceration of the mucous membranes lining the digestive tract (mucositis)

• The unopened vials should be stored in the original container until ready for use. Store at 2° to 8°C (in
a refrigerator).
• Keep out of the sight and reach of children.
• This medicine should not be used after the expiry date printed on the box and on the vial label after
EXP. The expiry date refers to the last day of that month. The pharmacist will check this when your
medicine is prepared for you. If the solution is cloudy after preparation, the pharmacist will dispose of it
safely.

Package quantities:

Blood and the lymphatic system disorders

Metabolism and nutrition disorders



















From a microbiological point of view, the product should be used immediately after first penetration of the rubber stopper. If not
used immediately, in use storage times and conditions are the responsibility of the user.
Vials are for single use only and any unused portion must be discarded after use.

Acute lymphocytic leukaemia, acute myelogenous leukaemia

Marketing Authorisation Holder:

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

Shelf life after first opening the container

Neoplasms benign, malignant and unspecified Rare
(incl cysts and polyps)

Marketing Authorisation Holder and Manufacturer
Pharmacia Limited
Ramsgate Road, Sandwich, Kent, CT13 9NJ, UK
Pfizer Service Company BVBA,
10 Hoge Wei, 1930 Zaventem,
Belgium. (plastic vials)
Actavis Italy S.p.A 10 Viale Pasteur
20014 Nerviano (MI)
Italy. (glass vials)

Undesirable effects
Infection
Septic shock, sepsis, pneumonia

Immune system disorders

Manufacturer:

Frequency
Common
Not known

Shelf life

Glass vials – three years from time of manufacture.
Polypropylene Cytosafe® vials – three years from time of manufacture.

Storage

The vials should be stored at between 2°C - 8°C (in the refrigerator).
Keep the container in outer carton.
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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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