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Pharmorubicin®

Solution for Injection 2 mg/ml Solution for Injection or Infusion

epirubicin hydrochloride

_Pharmacia

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/mi solution in

0,9% sodium chloride solution,

Uses:

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:

Intravenous administration:

Pharmorubicin is not active when given orally and should not be injected intramuscularly or intrathecaily,

Pharmorubicin solution should be administered only under the supervision of a qualified physician experienced in antibiastic 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 myeiosuppression.

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 haematomeduilary 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 ceil lung cancer (previously untreated): 120 mg/mday 1, every 3 weeks.

*    non-smaii ceil lung cancer (squamous, large ceil, and adenocarcinoma previously untreated): 135 mg/m2 day 1 or 45 mg/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-fluorouraci! 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 mi) 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 intravesica I ly 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 mi 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 mi followed by 11 x monthly instillations at the same dosage, is the schedule most commonly used.

The solution should be retained intravesica I ly 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 myeiosuppression

*    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

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 myeiosuppression.

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 ll-IV) has been observed in patients receiving trastuzamab 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 weli-controlied 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 half-life of trastuzumab is approximately 4-5 weeks, trastuzumab may persist in the circulation for up to 20-25 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 25 weeks after stopping trastuzumab. If anthracyclines such as epirubicin are used, the patient’s cardiac function should be monitored carefully,

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)

Haematoiogic toxicity- As with other cytotoxic agents, epirubicin may produce myeiosuppression, Haematoiogic 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 preieukaemic 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- Phieboscierosis 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 phiebitis/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 extravasation 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 ceils (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).


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FRONT

PATIENT INFORMATION LEAFLET_ PlIMlMAClA

Pharmorubicin*

Solution for Injection 2 mg/ml Solution for Injection or Infusion



Read all of this leaflet carefully before you start using this medicine.

•    Keep this leaflet. You may need to read it again.

•    If you have any further questions, please ask your doctor or pharmacist.

•    This medicine has been prescribed for you personally and you should not pass it on to others. It may harm them, even if their symptoms are the same as yours.

•    If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

In this leaflet:

1.    What Pharmorubicin is and what it is used for

2.    Before you are given Pharmorubicin

3.    How Pharmorubicin is given to you

4.    Possible side effects

5.    How to store Pharmorubicin

6.    Further 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.

2. Before you are given Pharmorubicin

Do not use Pharmorubicin if you have:

•    an allergy (hypersensitivity) to epirubicin or any of the other ingredients of Pharmorubicin (a list of ingredients can be found in Section 6)

•    low blood cell counts, as it can lower them further

•    previously been treated with Pharmorubicin or similar chemotherapy drugs as previous treatment with these medicines can increase the risk of side effects

•    suffered from severe heart trouble in the past, or are presently receiving treatment for this.

Take special care with Pharmorubicin Tell your doctor if:

•    your liver or kidneys are not working properly

•    you have had or you are due to have any vaccination.

This will help your doctor decide if this medicine is suitable for you.

Taking other medicines:

Please tell your doctor or pharmacist if you have recently taken any other medicines, even those not prescribed, particularly the following:

•    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.

•    Trastuzamab therapy for treatment of cancer

•    Dexrazoxane (used to prevent chronic cumulative cardiotoxicity caused by epirubicin).

Pregnancy

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.

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

Driving and using machinery

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

Important information about some of the ingredients of Pharmorubicin

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

3. How Pharmorubicin is given to you

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.


PFIZER (PERTH) PTY LIMITED, AUSTRALIA


Item Code

PAM658PE

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090177e183a9ec5b\Final\Final On: 15-Oct-2012 11:34


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.

4. Possible side effects

Like all medicines Pharmorubicin can have side effects, although not everybody gets them.

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

Although they are rare (these may affect between 1 in 10,000 and 1 in 1,000 people), these symptoms can be serious:

•    Feeling dizzy, feverish, short of breath with a tight chest or throat or have an itchy rash. This type of allergic reaction can be very serious.

Very common possible side effects (these may affect at least 1 in 10 people)

•    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 possible side effects (these may affect between 1 in 100 and 1 in 10 people)

•    Infections.

•    Loss of appetite.

•    Feeling thirsty (dehydration).

•    Hot flushes.

•    Soreness or ulcers in the mouth, which may not appear until 3-10 days after treatment.

•    Heartburn, nausea (feeling sick), vomiting (being sick) or diarrhoea.

•    Pain, redness, burning or stinging sensation at injection site.

•    Irritation of the bladder or damage to the bladder wall (called necrosis).

Uncommon possible side effects (these may affect between 1 in 1,000 and 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.

•    Swelling, redness, leg pain, which can be associated with blood clots.

Rare possible side effects (these may affect between 1 in 10,000 and 1 in 1,000 people)

•    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 and feeling cold.

•    Low sperm count.

•    Absence of menstruation.

•    Gasping for air, shortness of breath, swelling of abdomen, legs or ankles, fluid in lungs (signs of congestive heart failure).

•    ECG abnormalities, irregular heartbeat, heart muscle disease.

•    Changes in liver enzyme levels.

•    Increase uric acid levels in the blood which might cause gout.

Not known (cannot be estimated from the available data)

•    Blood infection.

•    Pneumonia.

•    Internal bleeding.

•    Inflammation to the eye (conjunctivitis and keratitis).

•    Shock.

•    Discolouration of skin and nails.

•    Sensitive to light.

•    Blood clots, including a clot in the lungs which causes chest pain and breathlessness.

If you get any of the above side effects, or notice any other unusual side effects not listed in this leaflet, tell your doctor at once.

5.    How to store Pharmorubicin

•    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 reach and sight of children.

•    This medicine should not be used after the expiry date printed on the box and on the vial. 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.

6.    Further information

What Pharmorubicin contains

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 contains 10 mg, 20 mg,

50 mg or 200 mg of the active ingredient, epirubicin hydrochloride in single glass or plastic vials.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder:

Pharmacia Limited Ramsgate Road, Sandwich,

Kent, CT13 9NJ, UK

Manufacturer:

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)

Company contact address:

If you have any comments on the way this leaflet is written, please contact Medical Information at Pfizer Limited in Walton Oaks, Tadworth, Surrey.

Tel: 01304 616161.

This leaflet was last approved 10/2012. Document Reference: United Kingdom PM 10_1

PAM658PE

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.

Epirubicin, powder for solution for injection, contains methyl parahydroxybenzoate. This may cause allergic reactions (which may occur after treatment), and in rare cases, respiratory difficulties.

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.


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.

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.

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 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. 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.

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.

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.

Shelf life after first opening the container

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.

Package quantities:

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


Impairment of fertility

Epirubicin could induce chromosomal damage in human spermatozoa.

Epirubicin may cause amenorrhoea or premature menopause in premenopausal women.


Pregnancy

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.


PL 0032/0275

This leaflet was prepared in 10/2012.

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.    PAM658PE


System oraan class

Frequency

Undesirable effects

Infections and infestations

Common

Infection

Not known

Septic shock, sepsis, pneumonia

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

Rare

Acute lymphocytic leukaemia, acute myelogenous leukaemia

Blood and the lymphatic system disorders

Very common

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

Uncommon

Thrombocytopenia

Not known

Haemorrhaae and tissue hypoxia as result of myelosoppression.

Immune system disorders

Rare

Anaphylaxis

Metabolism and nutrition disorders

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, arrythmias, cardiomyopathy), ventricular tachycardia, bradycardia, AV block, bundle-branch block

Vascular disorders

Common

Hot flashes, hot flushes

Uncommon

Phlebitis, thrombophlebitis

Not known

Shock, thromboembolism, including pulmonary emboli

Gastrointestinal disorders

Common

Mucositis, esophaaitis, stomatitis, vomitina, diarrhoea, nausea

Skin and subcutaneous tissue disorders

Very common

Alopecia

Rare

Urticaria

Not known

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

Renal and urinary disorders

Very common

Red colouration of urine for 1 to 2 days after administration

Reproductive system and breast disorders

Rare

Amenorrhoea, azoospermia

General disorders and administration site conditions

Common

Infusion site erythema

Rare

Malaise, asthenia, fever, chills

Investigations

Rare

Changes in transaminase levels

Not known

Asymptomatic drops in left ventricular ejection fraction

Injury, poisoning and procedural complications

Common

Chemical cystitis, sometimes haemorrhagic, has been observed following intravesical administration (see section 4.4)


POM