Pharma code 1696

Y 93.130.701-I

TFW71

HOSPITALS

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

Below is a summary of information to assist in the administration of Paclitaxel. You should be experienced in the handling and use of cytotoxic agents and be familiar with the SPC of Paclitaxel. Reference should be made to guidelines on the safe handling of antineoplastic agents.

Handling: as with all antineoplastic agents, caution should be exercised when handling Paclitaxel. Pregnant women should not handle cytotoxic agents. Dilution should be carried out under aseptic conditions by trained personnel in a designated area. Adequate protective gloves should be worn. Precautions should be taken to avoid contact with the skin or mucous membranes. In the event of contact with the skin, the area should be washed with soap and water. Following topical exposure, tingling, burns and redness have been observed. In the event of contact with the mucous membranes, these should be flushed thoroughly with water. Upon inhalation, dyspnoea, chest pain, burning throat and nausea have been reported.

If unopened vials are refrigerated or frozen, a precipitation may form, that redissolves with little or no agitation upon reaching room temperature. Product quality is not affected. If the solution remains cloudy or if an insoluble precipitate is noted, the vial should be discarded.

Following multiple needle entries and product withdrawals, the vials maintain microbial, chemical and physical stability for up to 28 days at 25°C. Other in-use storage times and conditions are the responsibility of the user.

The ‘Chemo-Dispensing Pin' device or similar devices with spikes should not be used since they can cause the vial stopper to collapse, resulting in loss of sterile integrity.

Preparation for intravenous administration: prior to infusion, Paclitaxel must be diluted using aseptic techniques in 9 mg/ml (0.9%) sodium chloride solution for infusion, or 50 mg/ml (5%) glucose solution for infusion, or a mixture of 9 mg/ml (0.9%) sodium chloride solution for infusion and 50 mg/ml (5%) glucose solution for infusion, or Ringer's solution for infusion containing 50 mg/ml (5%) glucose, to a final concentration of 0.3 to 1.2 mg/ml.

Chemical and physical in-use stability of the solution prepared for infusion has been demonstrated for 27 hours at 25°C when diluted in a mixture of 9 mg/ml (0.9%) sodium chloride solution for infusion and 50 mg/ml (5%) glucose solution for infusion, or Ringer's solution for infusion containing 50 mg/ml (5%) glucose.

Chemical and physical in-use stability of the solution prepared for infusion has been demonstrated at 5°C and at 25°C for 14 days when diluted in 50 mg/ml (5%) glucose solution for infusion or in 9 mg/ml (0.9%) sodium chloride solution for infusion.

Microbiological in-use stability of the solution prepared for infusion has been demonstrated for 27 hours at 25°C. Other in-use storage times and conditions are the responsibility of the user.

Upon preparation, solutions may show some haziness, which is attributed to the formulation vehicle, and is not removed by filtration. Paclitaxel should be administered through an in-line filter with a microporous membrane < 0.22 pm. No significant losses in potency have been noted following simulated delivery of the solution through IV tubing containing an in-line filter.

There have been rare reports of precipitation during paclitaxel infusions, usually towards the end of a 24-hour infusion period. Although the cause of this precipitation has not been elucidated, it is probably linked to the supersaturation of the diluted solution. To reduce the precipitation risk, Paclitaxel should be used as soon as possible after dilution, and excessive agitation, vibration or shaking should be avoided. The infusion sets should be flushed thoroughly before use. During infusion, the appearance of the solution should be regularly inspected and the infusion should be stopped if precipitation is present.

To minimise patient exposure to DEHP [di-(2-ethylhexyl)phthalate] which may be leached from plasticised PVC infusion materials, diluted paclitaxel solutions should be stored in non-PVC bottles (glass, polypropylene) or plastic bags (polypropylene, polyolefin) and administered through polyethylene-lined administration sets. Use of filter devices which incorporate short inlet and/or outlet plasticised PVC tubing has not resulted in significant leaching of DEHP.

Disposal: all items used for the preparation, administration or otherwise coming into contact with Paclitaxel should undergo disposal according to local guidelines for the handling of cytotoxic compounds.

Administration and dosage

All patients should be premedicated with corticosteroids, antihistamines and H₂ antagonists prior to administration. The diluted Paclitaxel infusion should be administrated using non-PVC containing equipment through an in-line filter with a microporous membrane < 0.22 pm.

The recommended doses for the intravenous infusion of Paclitaxel are as follows:

First-line ovarian cancer:

Second-line ovarian or breast cancer: Adjuvant breast cancer:

First-line breast cancer:

Non-small cell lung cancer:

AIDs related Kaposi's sarcoma:

135 mg/m² over 24 hours, followed by cisplatin 75 mg/m²; or 175 mg/m² over 3 hours, followed by cisplatin 75 mg/m²;

175 mg/m² over 3 hours;

175 mg/m² over 3 hours; following anthracycline and cyclophosphamide (AC) therapy; 220 mg/m² over 24 hours, 24 hours after doxorubicin (50 mg/m²),

175 mg/m² over 3 hours, after trastuzumab (see trastuzumab SPC); 175 mg/m² over 3 hours, followed by cisplatin 80 mg/m²:

100 mg/m² over 3 hours.

PACKAGE LEAFLET: INFORMATION FOR THE USER

Paclitaxel®, 6 mg/ml, concentrate for solution for infusion

Paclitaxel

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, ask your doctor

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

What is in this leaflet:

1.    What Paclitaxel® is and what it is used for

2.    What you need to know before you use Paclitaxel®

3.    How to use Paclitaxel^®

4.    Possible side effects.

5.    How to store Paclitaxel^®

6.    Contents of the pack and other information

Paclitaxel® concentrate for solution for infusion is given only by healthcare personnel, who can reply to any questions which you may have after reading this package leaflet.

What Paclitaxel® is and what it is used for

Paclitaxel® is an antineoplastic or anticancer agent. It may stop cancer cells from dividing and growing.

Paclitaxel® is used to treat different types of cancer, i.e.:

Ovarian cancer (advanced or spreading ovarian cancer, residual tumour >1 cm after laparotomy)

Either as initial therapy in combination with platinum-containing medicine, cisplatin, or as a second-line treatment when other platinum-containing treatments have not worked.

Breast cancer (treatment of early breast cancer after surgical removal of the primary tumour, advanced or spreading breast cancer)

As adjuvant therapy following treatment with anthracycline and cyclophosphamide (AC).

As initial therapy either in combination with a medicine belonging to the group known as anthracyclines in patients for whom anthracyclines therapy is suitable, or with a medicine called trastuzumab.

On its own, in patients who have not responded to standard treatments using anthracyclines, or for whom such treatment should not be used.

A certain type of lung cancer (Non-small cell lung cancer)

In combination with cisplatin, in patients who are not candidates for potentially curative surgery and/or radiotherapy.

It is also used to treat a special AIDS-related form of cancer that develops in the connective tissue (Kaposi's sarcoma) where other treatments, i.e. liposomal anthracyclines, have not worked.

What you need to know before you use Paclitaxel^®

Do not use Paclitaxel®

•    if you are allergic (hypersensitive) to paclitaxel or any of the other ingredients of this medicine (listed in section 6), especially macrogolglycerol ricinoleate in Paclitaxel®

•    if you are breast-feeding

•    if your liver function is severely reduced

•    if your white blood cell count is too low (neutrophils). This will be measured by a healthcare personnel.

•    if you have concurrent, serious, uncontrolled infections, and are being treated for Kaposi's sarcoma.

Warnings and precautions

Talk to your doctor, pharmacist or nurse before using

Paclitaxel^®

•    if you notice marked allergic (hypersensitivity) reactions (e.g. shortness of breath, low blood pressure, facial swelling or rash)

•    because this medicinal product contains alcohol and macrogolglycerol ricinoleate (see section“Paclitaxel® contains alcohol and macrogolglycerol ricinoleate")

•    if you have a serious disorder in the composition of your blood; your physician will check your blood every time before treatment with Paclitaxel®

•    if you experience heart problems during Paclitaxel® treatment; your physician should check the functioning of your heart before the next treatment with Paclitaxel^®

•    if you experience continuing numbness, tingling or pain in hand and feet (peripheral neuropathy); it could be that the dose of Paclitaxel^® has to be reduced

•    if you experience diarrhoea during or shortly after treatment with Paclitaxel®; it could be that your intestine is inflamed (pseudomembranous colitis). Your physician should consider this option

•    when Paclitaxel® is given to you in combination with radiotherapy of the lung or with gemcitabine; it could be that you'll develop pneumonia (interstitial pneumonitis)

•    if you have severe inflammation of the mucous membrane (mucositis) occurs; it could be that the dose of Paclitaxel® has to be reduced.

•    male patients treated with Paclitaxel® should not father a child during and up to six months after treatment because this may cause birth defects

•    male patients should seek advice regarding sperm freezing prior to Paclitaxel® treatment because of the possibility of infertility.

•    women of childbearing age should use effective contraceptives during therapy and up to six months after treatment with Paclitaxel®

You will be premedicated with several different medicinal products (dexamethasone and diphenhydramine or chlorphenamine and cimetidine or ranitidine) before every treatment with Paclitaxel®. Premedication is necessary to decrease the risk of severe hypersensitive reactions (see section 4, Possible side effects, uncommon).

Other medicines and Paclitaxel^®

Please tell your doctor or healthcare personnel if you are taking or have recently taken or might take any other medicines.

Paclitaxel® should be given:

•    before cisplatin when used in combination; your renal function may need to be checked more frequently.

•    24 hours following administration of doxorubicin, to avoid high levels of doxorubicin in your body.

If you are treated with a combination of paclitaxel and doxorubicin or trastuzumab: your heart function will be checked both before and during treatment.

Caution should be exercised if you are receiving any of the following medicines:

•    A dose reduction of Paclitaxel® may be necessary if you are using for example: erythromycin (against bacterial infection), fluoxetine (against depression), some antifungals (imidazole antifungals) or gemfibrozil (lowing cholesterol).

•    A dose increase of Paclitaxel® may be necessary if you are using for example: rifampicin (against bacterial infection), carbamazepine, phenytoin or phenobarbital (against epilepsy), efavirenz or nevirapine (against infection).

•    Some medicines against HIV and AIDS, the so-called protease-inhibitors (e.g. nelfinavir, ritonavir). If you are treated concomitantly with Paclitaxel® and these medicines, a dose adjustment of Paclitaxel^® may be necessary.

Pregnancy and breast-feeding and fertility

If you are pregnanat or breast-feeding, think you may be pregnanat or are planning to have a baby, ask your doctor or pharmacist for advice before taking any medicine. Paclitaxel may cause foetal harm. Avoid becoming pregnant. Use effective contraceptives during therapy and up to 6 months after treatment with Paclitaxel®. If pregnancy occurs inform your doctor immediately.

Paclitaxel® must not be used when you are pregnant, unless clearly necessary.

Paclitaxel® must not be used when you are breast-feeding.

You have to interrupt breast feeding while you are being treated with Paclitaxel®.

Male patients should seek advice regarding cryoconservation of sperm prior to treatment with Paclitaxel® because of the possibility of infertility.

Male patients of fertile age should use contraceptions for at least 6 months after treatment with Paclitaxel®.

Driving and using machines

There is no reason why you cannot continue driving between courses of Paclitaxel® but you should remember that this medicine contains some alcohol and it may be unwise to drive immediately after a course of treatment. As in all cases, you should not drive if you feel dizzy or light headed.

Discuss with your doctor, nurse or pharmacist if you are unsure about anything.

Paclitaxel® contains alcohol and macrogolglycerol ricinoleate

Since this medicinal product contains 49.7% (volume) ethanol (alcohol), that is up to 20 g per dose, corresponding to 520 ml of beer per dose or 210 ml of wine per dose. This amount may be hazardous to patients suffering from alcoholism. This should also be taken into consideration with high risk patients as well as those with liver disorder or epilepsy.

The amount of ethanol in this medicinal product may change the effects of other medicinal products.

This medicinal product also contains macrogolglycerol ricinoleate, which can cause severe hypersensitivity (allergic) reactions.

How to use Paclitaxel^®

Your doctor has decided which dose and how many doses you will be given. Paclitaxel® will be given under supervision of a doctor, who can give you more information.

The amount (dose) of Paclitaxel^® you will be given is based on your body surface in square meters (m²). This is calculated from your height and weight. The dose you receive will also depend on results of your blood tests. Depending on the type and severity of the cancer you will receive Paclitaxel^® either alone or in combination with another anticancer agent (e.g. cisplatin, doxorubicin, trastuzumab). Paclitaxel® is given into a vein (intravenous use) from an intravenous drip over 3 or 24 hours. Paclitaxel® is usually given every 3 weeks (2 weeks in patients with Kaposi's sarcoma). The needle must remain in the vein while the drug is being given. If the needle comes out or becomes loose, or the solution is going into the tissue outside the vein (you may feel discomfort or pain) - tell the doctor or nurse immediately.

Use in children

Paclitaxel® is not recommended for use in children below 18 years due to lack of data on safety and effectiveness.

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

POSSIBLE SIDE EFFECTS

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

Tell your doctor immediately:

•    if you get serious hypersensitivity reaction with fever, red spots on the skin, joint pain and/or inflammation of the eye (Stevens-Johnson syndrome)

•    if you get serious, general and possibly life threatening hypersensitivity reactions with shock.

•    if you get local necrosis of the skin (epidermal necrolysis), rash with red (moist) irregular spots (erythema multiforme), nettle rash and formation of bumps (urticaria)

•    if you suffer from inflammation of the skin with blisters or peeling (exfoliative dermatitis),

PL 00289/0859

Storage

There are no special storage conditions. If refrigerated, a precipitate may form which redissolves with little or no agitation upon reaching room temperature. Product quality is not affected. If the solution remains cloudy, or should insoluble precipitate is noted, the vial should be discarded. Freezing does not adversely affect the product.

An expiry date is given on the outer carton and vial label of the product. It should not be used after this date.

10074-B

93.130.701-I

r

Pharma code: 370

The following information is intended for medical or healthcare professionals only: Below is a summary of information to assist in the administration of Paclitaxel. You should be experienced in the handling and use of cytotoxic agents and be familiar with the SPC of Paclitaxel. Reference should be made to guidelines on the safe handling of antineoplastic agents.

Handling: as with all antineoplastic agents, caution should be exercised when handling Paclitaxel. Pregnant women should not handle cytotoxic agents. Dilution should be carried out under aseptic conditions by trained personnel in a designated area. Adequate protective gloves should be worn. Precautions should be taken to avoid contact with the skin or mucous membranes. In the event of contact with the skin, the area should be washed with soap and water. Following topical exposure, tingling, burns and redness have been observed. In the event of contact with the mucous membranes, these should be flushed thoroughly with water. Upon inhalation, dyspnoea, chest pain, burning throat and nausea have been reported.

If unopened vials are refrigerated or frozen, a precipitation may form, that redissolves with little or no agitation upon reaching room temperature. Product quality is not affected. If the solution remains cloudy or if an insoluble precipitate is noted, the vial should be discarded.

Following multiple needle entries and product withdrawals, the vials maintain microbial, chemical and physical stability for up to 28 days at 25°C. Other in-use storage times and conditions are the responsibility of the user.

The ‘Chemo-Dispensing Pin' device or similar devices with spikes should not be used since they can cause the vial stopper to collapse, resulting in loss of sterile integrity.

Preparation for intravenous administration:

prior to infusion, Paclitaxel must be diluted using aseptic techniques in 9 mg/ml (0.9%) sodium chloride solution for infusion, or 50 mg/ml (5%) glucose solution for infusion, or a mixture of 9 mg/ml (0.9%) sodium chloride solution for infusion and 50 mg/ml (5%) glucose solution for infusion, or Ringer's solution for infusion containing 50 mg/ml (5%) glucose, to a final concentration of 0.3 to 1.2 mg/ml.

Chemical and physical in-use stability of the solution prepared for infusion has been demonstrated for 27 hours at 25°C when diluted in a mixture of 9 mg/ml (0.9%) sodium chloride solution for infusion and 50 mg/ml (5%) glucose solution for infusion, or Ringer's solution for infusion containing 50 mg/ml (5%) glucose. Chemical and physical in-use stability of the solution prepared for infusion has been demonstrated at 5°C and at 25°C for 14 days when diluted in 50 mg/ml (5%) glucose solution for infusion or in 9 mg/ml (0.9%) sodium chloride solution for infusion.

Microbiological in-use stability of the solution prepared for infusion has been demonstrated for 27 hours at 25°C. Other in-use storage times and conditions are the responsibility of the user.

Upon preparation, solutions may show some haziness, which is attributed to the formulation vehicle, and is not removed by filtration. Paclitaxel should be administered through an in-line filter with a microporous membrane < 0.22 pm. No significant losses in potency have been noted following simulated delivery of the solution through IV tubing containing an in-line filter.

There have been rare reports of precipitation during paclitaxel infusions, usually towards the end of a 24-hour infusion period. Although the cause of this precipitation has not been elucidated, it is probably linked to the supersaturation of the diluted solution. To reduce the precipitation risk, Paclitaxel should be used as soon as possible after dilution, and excessive agitation, vibration or shaking should be avoided. The infusion sets should be flushed thoroughly before use.

During infusion, the appearance of the solution should be regularly inspected and the infusion should be stopped if precipitation is present.

To minimise patient exposure to DEHP [di-(2-ethylhexyl)phthalate] which may be leached from plasticised PVC infusion materials, diluted paclitaxel solutions should be stored in non-PvC bottles (glass, polypropylene) or plastic bags

TFW71

HOSPITALS

PACKAGE LEAFLET: INFORMATION FOR THE USER

Paclitaxel®, 6 mg/ml, concentrate for solution for infusion

Paclitaxel

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, ask your doctor

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

What is in this leaflet:

1.    What Paclitaxel® is and what it is used for

2.    What you need to know before you use Paclitaxel®

3.    How to use Paclitaxel®

4.    Possible side effects.

5.    How to store Paclitaxel®

6.    Contents of the pack and other information Paclitaxel® concentrate for solution for infusion is given only by healthcare personnel, who can reply to any questions which you may have after reading this package leaflet.

What Paclitaxel® is and what it is used for

Paclitaxel® is an antineoplastic or anticancer agent. It may stop cancer cells from dividing and growing.

Paclitaxel® is used to treat different types of cancer, i.e.:

Ovarian cancer (advanced or spreading ovarian cancer, residual tumour >1 cm after laparotomy)

Either as initial therapy in combination with platinum-containing medicine, cisplatin, or as a second-line treatment when other platinum-containing treatments have not worked.

Breast cancer (treatment of early breast cancer after surgical removal of the primary tumour, advanced or spreading breast cancer)

As adjuvant therapy following treatment with anthracycline and cyclophosphamide (AC).

As initial therapy either in combination with a medicine belonging to the group known as anthracyclines in patients for whom anthracyclines therapy is suitable, or with a medicine called trastuzumab.

On its own, in patients who have not responded to standard treatments using anthracyclines, or for whom such treatment should not be used.

A certain type of lung cancer (Non-small cell lung cancer)

In combination with cisplatin, in patients who are not candidates for potentially curative surgery and/or radiotherapy.

It is also used to treat a special AIDS-related form of cancer that develops in the connective tissue (Kaposi's sarcoma) where other treatments, i.e. liposomal anthracyclines, have not worked.

What you need to know before you use Paclitaxel^®

Do not use Paclitaxel®

•    if you are allergic (hypersensitive) to paclitaxel or any of the other ingredients of this medicine (listed in section 6), especially macrogolglycerol ricinoleate in Paclitaxel®

•    if you are breast-feeding

•    if your liver function is severely reduced

•    if your white blood cell count is too low (neutrophils). This will be measured by a healthcare personnel.

•    if you have concurrent, serious, uncontrolled infections, and are being treated for Kaposi's sarcoma.

Warnings and precautions

Talk to your doctor, pharmacist or nurse before using

Paclitaxel®

•    if you notice marked allergic (hypersensitivity) reactions (e.g. shortness of breath, low blood pressure, facial swelling or rash)

•    because this medicinal product contains alcohol and macrogolglycerol ricinoleate (see section“Paclitaxel® contains alcohol and macrogolglycerol ricinoleate")

•    if you have a serious disorder in the composition of your blood; your physician will check your blood every time before treatment with Paclitaxel®

•    if you experience heart problems during Paclitaxel® treatment; your physician should check the functioning of your heart before the next treatment with Paclitaxel®

•    if you experience continuing numbness, tingling or pain in hand and feet (peripheral neuropathy); it could be that the dose of Paclitaxel® has to be reduced

•    if you experience diarrhoea during or shortly after treatment with Paclitaxel®; it could be that your intestine is inflamed (pseudomembranous colitis). Your physician should consider this option

•    when Paclitaxel® is given to you in combination with radiotherapy of the lung or with gemcitabine; it could be that you'll develop pneumonia (interstitial pneumonitis)

•    if you have severe inflammation of the mucous membrane (mucositis) occurs; it could be that the dose of Paclitaxel® has to be reduced.

•    male patients treated with Paclitaxel® should not father a child during and up to six months after treatment because this may cause birth defects

•    male patients should seek advice regarding sperm freezing prior to Paclitaxel® treatment because of the possibility of infertility.

•    women of childbearing age should use effective contraceptives during therapy and up to six months after treatment with Paclitaxel®

You will be premedicated with several different medicinal products (dexamethasone and diphenhydramine or chlorphenamine and cimetidine or ranitidine) before every treatment with Paclitaxel®. Premedication is necessary to decrease the risk of severe hypersensitive reactions (see section 4, Possible side effects, uncommon).

Other medicines and Paclitaxel®

Please tell your doctor or healthcare personnel if you are taking or have recently taken or might take any other medicines.

Paclitaxel® should be given:

•    before cisplatin when used in combination; your renal function may need to be checked more frequently.

•    24 hours following administration of doxorubicin, to avoid high levels of doxorubicin in your body.

If you are treated with a combination of paclitaxel and doxorubicin or trastuzumab: your heart function will be checked both before and during treatment.

Caution should be exercised if you are receiving any of the following medicines:

•    A dose reduction of Paclitaxel® may be necessary if you are using for example: erythromycin (against bacterial infection), fluoxetine (against depression), some antifungals (imidazole antifungals) or gemfibrozil (lowing cholesterol).

•    A dose increase of Paclitaxel® may be necessary if you are using for example: rifampicin (against bacterial infection), carbamazepine, phenytoin or phenobarbital (against epilepsy), efavirenz or nevirapine (against infection).

•    Some medicines against HIV and AIDS, the so-called protease-inhibitors (e.g. nelfinavir, ritonavir). If you are treated concomitantly with Paclitaxel^® and these medicines, a dose adjustment of Paclitaxel^® may be necessary.

Pregnancy and breast-feeding and fertility

If you are pregnanat or breast-feeding, think you may be pregnanat or are planning to have a baby, ask your doctor or pharmacist for advice before taking any medicine. Paclitaxel may cause foetal harm. Avoid becoming pregnant. Use effective contraceptives during therapy and up to 6 months after treatment with Paclitaxel®. If pregnancy occurs inform your doctor immediately.

Paclitaxel® must not be used when you are pregnant, unless clearly necessary.

Paclitaxel® must not be used when you are breast-feeding. You have to interrupt breast feeding while you are being treated with Paclitaxel^®.

Male patients should seek advice regarding cryoconservation of sperm prior to treatment with Paclitaxel^® because of the possibility of infertility.

Male patients of fertile age should use contraceptions for at least 6 months after treatment with Paclitaxel®.

Driving and using machines

There is no reason why you cannot continue driving between courses of Paclitaxel® but you should remember that this medicine contains some alcohol and it may be unwise to drive immediately after a course of treatment. As in all cases, you should not drive if you feel dizzy or light headed.

Discuss with your doctor, nurse or pharmacist if you are unsure about anything.

Paclitaxel® contains alcohol and macrogolglycerol ricinoleate

Since this medicinal product contains 49.7% (volume) ethanol (alcohol), that is up to 20 g per dose, corresponding to 520 ml of beer per dose or 210 ml of wine per dose. This amount may be hazardous to patients suffering from alcoholism. This should also be taken into consideration with high risk patients as well as those with liver disorder or epilepsy.

The amount of ethanol in this medicinal product may change the effects of other medicinal products.

This medicinal product also contains macrogolglycerol ricinoleate, which can cause severe hypersensitivity (allergic) reactions.

s How to use Paclitaxel®

Your doctor has decided which dose and how many doses you will be given. Paclitaxel^® will be given under supervision of a doctor, who can give you more information.

The amount (dose) of Paclitaxel^® you will be given is based on your body surface in square meters (m²). This is calculated from your height and weight. The dose you receive will also depend on results of your blood tests. Depending on the type and severity of the cancer you will receive Paclitaxel® either alone or in combination with another anticancer agent (e.g. cisplatin, doxorubicin, trastuzumab). Paclitaxel® is given into a vein (intravenous use) from an intravenous drip over 3 or 24 hours. Paclitaxel® is usually given every 3 weeks (2 weeks in patients with Kaposi's sarcoma). The needle must remain in the vein while the drug is being given. If the needle comes out or becomes loose, or the solution is going into the tissue outside the vein (you may feel discomfort or pain) - tell the doctor or nurse immediately.

Use in children

Paclitaxel® is not recommended for use in children below 18 years due to lack of data on safety and effectiveness.

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

POSSIBLE SIDE EFFECTS

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

Tell your doctor immediately:

•    if you get serious hypersensitivity reaction with fever, red spots on the skin, joint pain and/or inflammation of the eye (Stevens-Johnson syndrome)

•    if you get serious, general and possibly life threatening hypersensitivity reactions with shock.

•    if you get local necrosis of the skin (epidermal necrolysis), rash with red (moist) irregular spots (erythema multiforme), nettle rash and formation of bumps (urticaria)

Pharma code: 370

Pharma code: 370

•    if you suffer from inflammation of the skin with blisters or peeling (exfoliative dermatitis),

•    if you suffer from allergic condition which causes joint pain, skin rashes and fever (systemic lupus erythematosis).

•    if you get serious hypersensitivity reactions (angioedema) which make treatment necessary (for low blood pressure, swelling of tongue or lips, breathing problems or general rash, chills, back pain, chest pain, fast heart rhythm, stomach pain, pain in the hands and feet, sweating, and high blood pressure)

•    if you notice any abnormal bruising, bleeding or signs of infection such as sore throat or high temperature

•    if you get infection (mainly urinary tract and upper airways: inflammation of the nose mucous membrane characterized by a stuffed-up nose, sneezing and secretion (rhinitis) and inflammation of the throat (pharyngitis) and including herpes simplex, fungal infection of the mouth) with reported cases of fatal outcome

•    if you get mild hypersensitivity reactions (mainly flushing of the face and skin rash)

•    if you get severe infection

•    if you get (delayed) hypersensitivity

•    if you get abnormal accumulation of fluid in hands, feet and face (oedema)

•    if you have decreased heart rate (bradycardia), increased heart rate (tachycardia), palpitation

•    if you get irregular fast heart beat (atrial fibrillation)

•    if you have faster heart beat originating from a specific part of the heart (supraventricular tachycardia)

•    if you have disturbance in the heart conductance (AV block) sometimes with loss of consciousness

•    if you have sudden disorders of blood forming bone marrow cells (acute myeloid leukaemia, myelodysplastic syndrome)

•    if you suffer from blood disorder (shortage of white blood cells) accompanied with fever and increased sensitivity for infections (neutropenic fever)

•    if you suffer from bleeding nose

•    if you suffer from severe anaemia

•    if you get thrombosis, inflammation of the veins with the formation of a blood clot, which can often be felt as a painful, harsh strand with a red skin

•    if you get redness of the skin

•    if you suffer from skin rash, heavily itching rash (pruritus)

•    if you suffer from ringing in the ears (tinnitus)

•    if you suffer from shortage of blood platelets causing bruises and tendency to bleed (thrombocytopenia)

•    if you suffer from shortage of white blood cells attended with an increased sensitivity for infections and associated fever (severe leucopenia, severe neutropenia, febrile neutopenia), severe anaemia, bleeding

•    if you notice black and blood containing stools (melaena)

•    if you get mild reaction at the place of injection (swelling of ^u skin due to water retention (oedema), pain, redness

(erythema), hardening of skin (induration), tenderness, skin discolouration or swelling, extravasation (leaking of drug outside the vein) which can result in cellulitis (painful swelling and redness), scar formation (skin fibrosis) and death of skin tissue (skin necrosis)). The onset of injection site reactions can be delayed by a week to 10 days.

•    if you have serious lowering of the blood pressure by bacteria in the blood accompanied with paleness and restlessness, high heart rate and moist skin (septic shock)

•    if you suffer from myocardial infarction

•    if you suffer from insufficient pump function of the heart (congestive heart failure)

•    if you suffer from disorders of the heart muscle (cardiomyopathy)

•    if you suffer from disorders in the heart rhythm (fast heart beat: asymptomatic ventricular tachycardia, tachycardia with bigeminia)

•    if you get fever

•    if you suffer from loss of body fluids (dehydration)

•    if you suffer from (epileptic) fits, affection of the brain characterised by, for instance, convulsions and lowering of the consciousness (encephalopathy), coordination disturbances (ataxia)

•    if you have disturbed functioning of the liver (hepatic necrosis, hepatic encephalopathy) with reported cases of fatal outcome

•    if you lose nails (patients in therapy should wear sun protection on hands and feet)

•    if you suffer from inflammation of hair follicles (folliculitis)

•    if you suffer from inflammation of a vein (phlebitis)

•    if you have discoloration of the nails or nail beds

•    if you have severe blood poisoning (sepsis)

•    if you have inflammation of the lungs (pneumonia)

•    if you have affection of movement nerves causing muscle weakness of arms and feet (motor neuropathy)

•    if you have heart failure

•    if you have shortness of breath.

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

•    deviations in blood content because of suppression of the bone marrow (myelosuppression)

•    anorexia

•    sleepiness

•    paraesthesia

•    lowered blood pressure

•    nausea, vomiting, diarrhoea

•    inflammation of the mucous membrane (mucositis)

•    inflammation of the mucous membranes in the mouth (stomatitis), abdominal pain

•    hairloss/ baldness

•    muscle pain and joint pain

•    weakness

•    pain

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

•    flu syndrome

•    depression,

•    loss of consciousness

•    dilated blood vessel resulting in flushing

•    dry mouth, mouth ulceration

•    indigestion

•    dry skin, itch, acne, transient and mild nail and skin changes

•    bone pain

•    leg cramps, muscle weakness, back pain

•    uncomfortable urination

•    chest pain

•    chills

•    increase of certain enzymes in the blood (AST, SGOT).

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

•    weight loss, weight gain

•    dry eyes, lazy eye (amblyopia)

•    vision field disorder

•    disorders of the electrocardiogram

•    high blood pressure

•    increase in bilirubin (a waste product that results from the breakdown of red blood cells).

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

•    inflammation of the abdominal membrane (peritonitis)

•    pleural effusion, pneumonia (interstitial pneumonia)

•    lung fibrosis, airway occlusion (pulmonary embolism), breathing difficulties

•    pain in the stomach for instance caused by constipation or a hole in the intestine (intestinal obstruction/perforation)

•    inflammation of the pancreas, which causes severe pain in the abdomen and back (pancreatitis)

•    inflammation of the large intestine with possible serious continuous diarrhoea (ischaemic colitis)

•    general discomfort

•    increase in blood creatinine.

Very rare(may affect up to 1 in 10,000 people), including

isolated reports:

•    confusion, defect of certain nerves (autonomous neuropathy) which could result in paralysis of the intestine muscles (paralytic ileus) and a

•    sudden drop in blood pressure sometimes with dizziness caused by, for instance, fast rising from a seated or lying position (orthostatic hypotension)

•    headache

•    dizziness

•    disorders of the eye nerve and/or disorder of the vision (scotoma scintillans)

•    damage to the ears (ototoxicity), hearing loss, dizziness (vertigo)

•    shock

•    cough

•    high blood pressure in the lungs

•    inflammation of the large intestine with possible serious continuous diarrhoea (neutropenic colitis, pseudomembranous colitis, necrotising colitis)

•    blood clot in the abdominal membrane (mesenteric thrombosis)

•    inflammation of the gullet (oesophagitis)

•    accumulation of fluid in the abdominal cavity (ascites)

•    constipation

Not known (frequency cannot be estimated from the available

data):

•    complications caused by the break-down products of dying cancer cells (tumor lysis syndrome)

•    fluid accumulation in the eye (macular oedema), light flashes in the eye (photopsia), little dots or dust floating in your field of vision (vitrious floaters)

•    excessive deposits of collagen in the skin (scleroderma).

Reporting of side effects

If you get any side effects, talk to your doctor or 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 at: www.mhra.gov.uk/yellowcard.

By reporting side effects you can help provide more information on the safety of this medicine.

How to store Paclitaxel®

Keep out of the sight and reach of children.

Do not use this medicinal product after the expiry date which is stated on the vial and the outer carton after “do not use after" or “exp.". The first 2 numbers indicate the month, the last numbers indicate the year. The expiry date refers to the last day of the month.

No special storage temperature, store in the original carton. Freezing does not have harmful effects on the product.

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

Contents of the pack and other information

What Paclitaxel® contains

The active substance is paclitaxel.

Paclitaxel®, concentrate for solution for infusion contains 6 mg paclitaxel per ml.

The other ingredients are macrogolglycerol ricinoleate, anhydrous ethanol and citric acid.

What Paclitaxel® looks like and the contents of the pack

Paclitaxel® is a clear, colourless or slightly yellow, viscous solution. It is available in vials with 5 ml, 16.7 ml, 25 ml and 50 ml.

A 5 ml vial contains 30 mg paclitaxel.

A 16.7 ml vial contains 100 mg paclitaxel.

A 25 ml vial contains 150 mg paclitaxel.

A 50 ml vial contains 300 mg paclitaxel.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Manufacturer

Teva Pharmaceutical Works Private Limited Company Tancsics Mihaly ut 82 2100 Godollo Hungary

Marketing Authorisation Holder

TEVA UK Limited, Eastbourne, BN22 9AG

This leaflet was last approved in April 2016    10077 C

PL 00289/0859    3-29135030/C

r

(polypropylene, polyolefin) and administered through polyethylene-lined administration sets. Use of filter devices which incorporate short inlet and/or outlet plasticised PVC tubing has not resulted in significant leaching of DEHP

Disposal: all items used for the preparation, administration or otherwise coming into contact with Paclitaxel should undergo disposal according to local guidelines for the handling of cytotoxic compounds.

Administration and dosage

All patients should be premedicated with corticosteroids, antihistamines and H2 antagonists prior to administration. The diluted Paclitaxel infusion should be administrated using non-PVC containing equipment through an in-line filter with a microporous membrane < 0.22 pm.

The recommended doses for the intravenous infusion of Paclitaxel are as follows:

sarcoma:

Storage

There are no special storage conditions. If refrigerated, a precipitate may form which redissolves with little or no agitation upon reaching room temperature. Product quality is not affected. If the solution remains cloudy, or should insoluble precipitate is noted, the vial should be discarded.

Freezing does not adversely affect the product.

An expiry date is given on the outer carton and vial label of the product. It should not be used after this date.

10077-C

3-29135030/C

Pharma code: 370