PACLITAXEL 6MG/ML CONCENTRATE FOR SOLUTION FOR INFUSION

Active substance: PACLITAXEL

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PACKAGE LEAFLET: INFORMATION FOR THE USER
Paclitaxel®, 6 mg/ml, concentrate for solution for 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, ask your doctor
This medicine has been prescribed for you. Do not pass it on to others. It may harm them,
even if their symptoms ate 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.
IN THIS LEAFLET:
1. What Paclitaxel® is and what it is used for
2. Before you use Paclitaxel®
3. How to use Paclitaxel®
4. Possible side effects.
5. How to store Paclitaxel®
6. Further 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.
1. 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.

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2. BEFORE YOU USE PACLITAXEL
Do not use Paclitaxel
- if you are hypersensitive (allergic) to paclitaxel or any of the other ingredients, 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.
Take special care with 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 “Important information about some of the ingredients of Paclitaxel ”)
- 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.
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).
Taking other medicines
Please tell your doctor or healthcare personnel if you are taking or have recently taken any
other medicines, including medicines obtained without a prescription.
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.

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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
Ask your doctor or pharmacist for advice before taking any medicine. Avoid becoming
pregnant while you are given 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 .
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.
Important information about some of the ingredients of Paclitaxel®
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 hepatic 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.
3. 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.

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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.
4. POSSIBLE SIDE EFFECTS
Like all medicines, Paclitaxel® can cause side effects, although not everybody gets them.
The following side effects may occur amongst others:
Very common: occurs with more than 1 of 10 of the users
Common: occurs with more than 1 of 100, but less than 1 of 10 of the users
Uncommon: occurs with more than 1 of 1,000, but less than 1 of 100 of the users
Rare: occurs with more than 1 of 10,000, but less than 1 of 1,000 of the users
Very rare: occurs with less than 1of 10,000 of the users
Unknown: the frequency cannot be determined based on the available data
Tell your doctor immediately:
if you notice any abnormal bruising, bleeding or signs of infection such as sore throat
or high temperature.
Very common:
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
deviations in blood content because of suppression of the bone marrow
(myelosuppression)
shortage of blood platelets causing bruises and tendency to bleed (thrombocytopenia)
shortage of white blood cells attended with an increased sensitivity for infections
(severe leucopenia, severe neutropenia), anaemia, bleeding
mild hypersensitivity reactions (mainly flushing of the face and skin rash)
anorexia
neuropathy, mainly constant numbness, tingling or pain in hands and feet (peripheral
neuropathy)
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

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muscle pain and joint pain
weakness
pain
abnormal accumulation of fluid in hands, feet and face (oedema)
Common:
flu syndrome
blood disorder (shortage of white blood cells) accompanied with fever and increased
sensitivity for infections (neutropenic fever)
depression,
severe form of neuropathy, mainly resulting in constant numbness, tingling or pain in
hands and feet (peripheral neuropathy), nervousness, sleeplessness, abnormal thinking,
taste perversion, abnormal walking, movement disorder (hypokinesia), decreased
sense of touch (hypoaesthesia)
decreased heart rate (bradycardia), increased heart rate (tachycardia), palpitation
loss of consciousness
dilated blood vessel resulting in flushing
bleeding nose
dry mouth, mouth ulceration
black and blood containing stools (melaena)
indigestion
dry skin, itch, acne, transient and mild nail and skin changes
bone pain
leg cramps, muscle weakness, back pain
uncomfortable urination
mild reaction at the place of injection (swelling of 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.
chest pain
chills
increase of certain enzymes in the blood (AST, SGOT).
Uncommon:
severe infection
serious lowering of the blood pressure by bacteria in the blood accompanied with
paleness and restlessness, high heart rate and moist skin (septic shock)
severe anaemia
(delayed) hypersensitivity
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)
weight loss, weight gain
dry eyes, lazy eye (amblyopia)
vision field disorder

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myocardial infarction
insufficient pump function of the heart (congestive heart failure)
disorders of the heart muscle (cardiomyopathy)
disorders in the heart rhythm (fast heart beat: asymptomatic ventricular tachycardia,
tachycardia with bigeminia)
disturbance in the heart conductance (AV block) sometimes with loss of consciousness
disorders of the electrocardiogram
high blood pressure
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
discoloration of the nails or nail beds
increase in bilirubin (a waste product that results from the breakdown of red blood
cells).
Rare:
severe blood poisoning (sepsis)
inflammation of the lungs (pneumonia)
inflammation of the abdominal membrane (peritonitis)
fever associated with a low number of specific white blood cells which are needed to
fight an infection (febrile neutropenia)
serious general and possibly life threatening hypersensitivity reactions (anaphylactic
reactions)
affection of movement nerves causing muscle weakness of arms and feet (motor
neuropathy)
heart failure
shortness of breath
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)
redness of the skin
skin rash, heavily itching rash (pruritus)
fever
loss of body fluids (dehydration)
water retention (oedema)
general discomfort
increase in blood creatinine.
Very rare, including isolated reports:
sudden disorders of blood forming bone marrow cells (acute myeloid leukaemia,
myelodysplastic syndrome)
serious, general and possibly life threatening hypersensitivity reactions with shock
confusion, defect of certain nerves (autonomous neuropathy) which could result in
paralysis of the intestine muscles (paralytic ileus) and a

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sudden drop in blood pressure sometimes with dizziness caused by, for instance, fast
rising from a seated or lying position (orthostatic hypotension)
(epileptic) fits, affection of the brain characterised by, for instance, convulsions and
lowering of the consciousness (encephalopathy), coordination disturbances (ataxia)
headache
dizziness
disorders of the eye nerve and/or disorder of the vision (scotoma scintillans)
damage to the ears (ototoxicity), hearing loss, dizziness (vertigo)
ringing in the ears (tinnitus)
irregular fast heart beat (atrial fibrillation)
faster heart beat originating from a specific part of the heart (supraventricular
tachycardia)
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
disturbed functioning of the liver (hepatic necrosis, hepatic encephalopathy) with
reported cases of fatal outcome
serious hypersensitivity reaction with fever, red spots on the skin, joint pain and/or
inflammation of the eye (Stevens-Johnson syndrome)
local necrosis of the skin (epidermal necrolysis), rash with red (moist) irregular spots
(erythema multiforme), nettle rash and formation of bumps (urticaria)
losing nails (patients in therapy should wear sun protection on hands and feet)
inflammation of hair follicles (folliculitis)
inflammation of the skin with blisters or peeling (exfoliative dermatitis),
Not known:
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)
inflammation of a vein (phlebitis)
excessive deposits of collagen in the skin (scleroderma)
allergic condition which causes joint pain, skin rashes and fever (systemic lupus
erythematosis).
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.
5. HOW TO STORE PACLITAXEL
Keep out of reach and sight of children.

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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.

6. FURTHER 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.
Manufacturer
Pharmachemie B.V.
Swensweg 5
P.O. Box 552,
2003 RN Haarlem, The Netherlands
OR*
Teva Pharmaceutical Works Private Limited Company
Táncsics Mihály út 82
2100 Gödöllö
Hungary
Marketing Authorisation Holder
TEVA UK Limited, Eastbourne, BN22 9AG

This leaflet was last approved in December 2011
PL 00289/0859
*

Only the paragraph containing the details of the current batch release site will be included in the printed version of the PIL

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

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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 µm. 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

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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 nonPVC 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 nonPVC containing equipment through an in-line filter with a microporous membrane 0.22 µm.
The recommended doses for the intravenous infusion of Paclitaxel are as follows:
First-line ovarian cancer:
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;
Second-line ovarian or breast cancer:
175 mg/m2 over 3 hours;
Adjuvant breast cancer:
175 mg/m2 over 3 hours; following anthracycline
and cyclophosphamide (AC) therapy;
First-line breast cancer:
220 mg/m2 over 24 hours, 24 hours after
doxorubicin (50 mg/m2),
175 mg/m2 over 3 hours, after trastuzumab (see
trastuzumab SPC);
Non-small cell lung cancer:
175 mg/m2 over 3 hours, followed by cisplatin
80 mg/m2:
AIDs related Kaposi‟s sarcoma:
100 mg/m2 over 3 hours.
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.

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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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