Docetaxel Ratiopharm Italia

Patient Information Leaflet: Information for the User

DOCETAXEL RATIOPHARM ITALIA 20 mg/ml concentrate for solution for infusion

docetaxel
Read this entire leaflet carefully before using this medicine, as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, hospital pharmacist, or nurse.
• If you experience any side effects, including those not listed in this leaflet, inform your doctor, hospital pharmacist, or nurse. See section 4.

Contents of this leaflet:

1. What DOCETAXEL RATIOPHARM ITALIA is and what it is used for
2. What you need to know before using DOCETAXEL RATIOPHARM ITALIA
3. How to use DOCETAXEL RATIOPHARM ITALIA
4. Possible side effects
5. How to store DOCETAXEL RATIOPHARM ITALIA
6. Contents of the pack and other information

1. What DOCETAXEL RATIOPHARM ITALIA is and what it is used for

The name of this medicine is DOCETAXEL RATIOPHARM ITALIA. The name of the active substance is
docetaxel. Docetaxel is a substance derived from the needle-like leaves of the yew tree.
Docetaxel belongs to a group of anticancer drugs known as taxanes.
DOCETAXEL RATIOPHARM ITALIA has been prescribed by your doctor for the treatment of
breast cancer, certain types of lung cancer (non-small cell lung cancer), prostate cancer,
gastric adenocarcinoma, or head and neck cancer:

• for the treatment of advanced breast cancer, DOCETAXEL RATIOPHARM ITALIA may be given alone or in combination with doxorubicin, or trastuzumab, or capecitabine.
• for the treatment of early-stage breast cancer with or without lymph node involvement, DOCETAXEL RATIOPHARM ITALIA may be given in combination with doxorubicin and cyclophosphamide.
• for the treatment of lung cancer, DOCETAXEL RATIOPHARM ITALIA may be given alone or in combination with cisplatin.
• for the treatment of prostate cancer, DOCETAXEL RATIOPHARM ITALIA is given in combination with prednisone or prednisolone.
• for the treatment of metastatic gastric adenocarcinoma, DOCETAXEL RATIOPHARM ITALIA is given in combination with cisplatin and 5-fluorouracil.
• for the treatment of head and neck cancer, DOCETAXEL RATIOPHARM ITALIA is given in combination with cisplatin and 5-fluorouracil.

2. What you need to know before taking DOCETAXEL RATIOPHARM ITALIA

Do not take DOCETAXEL RATIOPHARM ITALIA if
you are allergic to docetaxel or to any of the other ingredients of this medicine (listed in section 6);
your white blood cell count is too low;
you have severe liver problems.

Warnings and precautions
Before each treatment with DOCETAXEL RATIOPHARM ITALIA, blood tests must be performed to ensure that your blood cells are sufficiently numerous and that your liver function is adequate for receiving DOCETAXEL RATIOPHARM ITALIA. If abnormalities in white blood cells occur, you may also experience fever or infections.
Immediately inform your doctor, hospital pharmacist, or nurse if you experience abdominal pain or tenderness, diarrhoea, rectal bleeding, blood in the stools, or fever. These symptoms may be the first signs of severe gastrointestinal toxicity, which can be fatal. Your doctor will address this immediately.
Inform your doctor, hospital pharmacist, or nurse if you have vision problems. If you experience vision problems, particularly blurred vision, you must have your eyes and vision checked immediately.
Inform your doctor, hospital pharmacist, or nurse if you have had an allergic reaction to previous treatment with paclitaxel.
Inform your doctor, hospital pharmacist, or nurse if you have heart problems.
If you develop acute lung problems or if your existing symptoms worsen (fever, shortness of breath, or cough), inform your doctor, hospital pharmacist, or nurse immediately. Your doctor may immediately discontinue treatment.
You will be asked to take preventive treatment with oral corticosteroids such as dexamethasone one day before administration of DOCETAXEL RATIOPHARM ITALIA and to continue for one or two days afterwards, in order to reduce certain adverse effects that may occur following infusion of DOCETAXEL RATIOPHARM ITALIA, particularly allergic reactions and fluid retention (swelling of hands, feet, legs, or weight gain).
During treatment, you may need additional medicines to maintain your blood cell counts.
Severe skin reactions have been reported with DOCETAXEL RATIOPHARM ITALIA, including Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), and Acute Generalized Exanthematous Pustulosis (AGEP).

• Symptoms of SJS/TEN may include blisters, peeling or bleeding of the skin (including lips, eyes, mouth, nose, genitals, hands and feet), with or without redness. You may also have flu-like symptoms such as fever, chills, or muscle pain at the same time.
• Symptoms of AGEP may include a widespread, scaly, red rash with swollen bumps under the skin (including skin folds, trunk, and upper extremities) and blisters, accompanied by fever. If you develop severe skin reactions or any of the reactions listed above, contact your doctor or a healthcare professional immediately.

Before starting DOCETAXEL RATIOPHARM ITALIA, inform your doctor, hospital pharmacist, or nurse if you have kidney problems or high levels of uric acid in your blood.
DOCETAXEL RATIOPHARM ITALIA contains alcohol. Inform your doctor if you are alcohol-dependent. See also the section “DOCETAXEL RATIOPHARM ITALIA contains ethanol (alcohol)” below.

Other medicines and DOCETAXEL RATIOPHARM ITALIA
Inform your doctor or hospital pharmacist if you are taking, have recently taken, or might take any other medicines, including those not requiring a prescription. This is because DOCETAXEL RATIOPHARM ITALIA or the other medicines may not work as expected, and you may be more likely to experience adverse effects.
The amount of alcohol in this medicine may alter the effects of other medicines.

Pregnancy, breast-feeding and fertility
Ask your doctor for advice before receiving any medicine.
DOCETAXEL RATIOPHARM ITALIA must not be administered during pregnancy unless clearly indicated by your doctor.
You must not become pregnant during treatment with this medicine and should use adequate contraception during therapy, as DOCETAXEL RATIOPHARM ITALIA may be harmful to the unborn baby. If you become pregnant during treatment, inform your doctor immediately.
You must not breast-feed during treatment with DOCETAXEL RATIOPHARM ITALIA.
If you are a man being treated with DOCETAXEL RATIOPHARM ITALIA, you are advised not to father a child during treatment and for 6 months after treatment ends. You should also discuss sperm preservation before starting treatment, as docetaxel may impair male fertility.

Driving and using machines
The amount of alcohol in this medicine may impair your ability to drive or operate machinery. You may experience side effects from this medicine that could affect your ability to drive, use equipment, or operate machinery (see section 4 “Possible side effects”). If this occurs, do not drive or use any equipment or machinery until you have discussed it with your doctor, nurse, or hospital pharmacist.

DOCETAXEL RATIOPHARM ITALIA contains ethanol (alcohol)
This medicine contains 400 mg of alcohol (ethanol) in each 1 ml vial, equivalent to 40% p/v. The amount in one vial of this medicine is equivalent to less than 10 ml of beer or 4 ml of wine.
This medicine contains 1600 mg of alcohol (ethanol) in each 4 ml vial, equivalent to 40% p/v. The amount in one vial of this medicine is equivalent to less than 40 ml of beer or 16 ml of wine.
This medicine contains 2800 mg of alcohol (ethanol) in each 7 ml vial, equivalent to 40% p/v. The amount in one vial of this medicine is equivalent to less than 70 ml of beer or 28 ml of wine.
This medicine contains 3200 mg of alcohol (ethanol) in each 8 ml vial, equivalent to 40% p/v. The amount in one vial of this medicine is equivalent to less than 80 ml of beer or 32 ml of wine.
The amount of alcohol in this medicine does not appear to have an effect on adults and adolescents, and its effects in children are not evident. However, some effects may occur in very young children, for example, feeling drowsy.
The alcohol in this medicine may alter the effects of other medicines. Talk to your doctor or pharmacist if you are taking other medicines.
If you are pregnant or breast-feeding, talk to your doctor or pharmacist before taking this medicine.
If you are alcohol-dependent, talk to your doctor or pharmacist before taking this medicine.
The amount of alcohol in this medicine may have effects on the central nervous system (the part of the nervous system that includes the brain and spinal cord).

3. How to take DOCETAXEL RATIOPHARM ITALIA

DOCETAXEL RATIOPHARM ITALIA will be administered to you by a healthcare professional.
Recommended dose
The dose will depend on your body weight and general health condition. Your doctor will calculate your body surface area in square meters (m²) and determine the dose you should receive.
Method and route of administration
DOCETAXEL RATIOPHARM ITALIA will be administered by infusion into one of your veins (intravenous use). The infusion will last approximately 1 hour, during which you will remain in the hospital.
Frequency of administration
The infusion is normally administered once every 3 weeks.
Your doctor may adjust the dose and frequency of administration based on blood test results, your general condition, and your response to DOCETAXEL RATIOPHARM ITALIA. In particular, inform your doctor if you experience diarrhea, mouth inflammation, numbness, tingling, fever, and show him or her the results of your blood tests. This information will help the doctor decide whether a dose reduction is necessary. If you have any doubts about the use of this medicine, consult your doctor or hospital pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Your doctor will discuss this with you and explain the potential risks and benefits of the treatment.
The most commonly reported adverse reactions with DOCETAXEL RATIOPHARM ITALIA used alone are:
reduction in the number of red or white blood cells, hair loss, nausea, vomiting, mouth inflammation,
diarrhea, and fatigue.
If you are administered DOCETAXEL RATIOPHARM ITALIA in combination with other chemotherapeutic
agents, the severity of adverse events may increase.
During the infusion in hospital, the following allergic reactions may occur (may affect more than 1 in 10
people):
hot flushes, skin reactions, itching,
feeling of tightness in the chest, difficulty breathing,
fever or chills,
back pain,
low blood pressure.
More severe reactions may also occur.
If you have had an allergic reaction to paclitaxel, you may also develop an allergic reaction to
docetaxel, which could be more severe.
During treatment, your condition will be closely monitored by the hospital staff.
Inform the hospital staff immediately if you notice any of these effects.
Between two infusions of DOCETAXEL RATIOPHARM ITALIA, the following undesirable effects may
occur, and their frequency may vary depending on the associated medicines you are taking:

Very common (may affect more than 1 in 10 people)
infections, decreased number of red blood cells (anaemia) or white blood cells (the latter are important
in fighting infections) and platelets
fever: if this occurs, you must inform your doctor immediately
allergic reactions as described above
loss of appetite (anorexia)
insomnia
numbness, tingling sensation, or pain in joints or muscles
headache
change in taste sensation
inflammation of the eye or increased eye tearing
swelling due to insufficient lymphatic drainage
difficulty breathing
nasal discharge; inflammation of the throat and nose; cough
nosebleeds
mouth inflammation
stomach disorders including nausea, vomiting, and diarrhea, constipation
abdominal pain
indigestion
hair loss (in most cases, hair regrowth returns to normal). In some cases (frequency not known),
permanent hair loss has been observed
redness and swelling of the palms of the hands or soles of the feet, which may lead to skin peeling
(this may also occur on arms, face or body)
changes in nail colour, which may lead to nail loss
muscle pain; back pain or bone pain
changes or absence of menstrual periods
swelling of hands, feet, legs
tiredness or flu-like symptoms
weight gain or weight loss
upper respiratory tract infection.

Common (may affect up to 1 in 10 people)
oral candidiasis
dehydration
dizziness
hearing disturbances
decreased blood pressure; irregular or rapid heartbeat
heart failure
oesophagitis
dry mouth
difficulty or pain when swallowing
bleeding
increased liver enzymes (requiring regular blood tests)
increased blood sugar levels (diabetes)
reduction in potassium, calcium and/or phosphate levels in the blood.

Uncommon (may affect up to 1 in 100 people)
fainting
skin reactions at injection site, phlebitis (vein inflammation) or swelling
blood clot formation
acute myeloid leukaemia and myelodysplastic syndrome (types of blood cancer) may occur in
patients treated with docetaxel in combination with certain other anticancer treatments.

Rare (may affect up to 1 in 1,000 people):
inflammation of the colon or small intestine, which may be fatal (frequency not known);
intestinal perforation.

Frequency not known: (cannot be estimated from the available data):
interstitial lung disease (lung inflammation that may cause cough and difficulty breathing).
Lung inflammation may also develop when docetaxel treatment is administered concurrently with
radiotherapy.
pneumonia (lung infections)
pulmonary fibrosis (scarring and thickening in the lungs causing shortness of breath)
a "burn-like" appearance at the injection site may appear several days after the last dose
blurred vision due to swelling of the retina inside the eye (cystoid macular edema)
decreased sodium and/or magnesium levels in the blood (electrolyte imbalance)
ventricular arrhythmia or ventricular tachycardia (manifesting as rapid or irregular heartbeat, severe
shortness of breath, dizziness and/or fainting). Some of these symptoms may be serious. If this
occurs, you must inform a doctor immediately
injection site reactions at a previous reaction site
non-Hodgkin's lymphoma (a cancer affecting the immune system) and other tumours may occur in
patients treated with docetaxel in combination with certain other anticancer treatments.
Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) (blisters, peeling or
bleeding of the skin (including lips, eyes, mouth, nose, genitals, hands or feet), with or without
redness. You may also have flu-like symptoms such as fever, chills or muscle pain at the same time)
Acute Generalized Exanthematous Pustulosis (AGEP) (widespread, scaly, red rash with raised
bumps under the skin (including skin folds, trunk and upper limbs) and blisters, accompanied by
fever).

Tumour lysis syndrome is a serious condition revealed by changes in blood tests, such as increased
levels of uric acid, potassium and phosphate, and decreased calcium levels, and causes symptoms such
as seizures, kidney failure (reduced urine output or dark urine) and heart rhythm disturbances. In such
cases, it is necessary to inform your doctor immediately.
Myositis (muscle inflammation – warmth, redness and swelling – causing muscle pain and weakness).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, hospital
pharmacist or nurse. You can also report side effects directly via the national reporting system at
www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide
more information on the safety of this medicine.

5. How to store DOCETAXEL RATIOPHARM ITALIA

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the outer carton and on the label of the vial after "Exp.". The expiry date refers to the last day of that month.
Store below 25°C.
Keep in the original packaging to protect the medicine from light.
Do not refrigerate or freeze.

6. Package contents and other information

What DOCETAXEL RATIOPHARM ITALIA contains

• The active substance is docetaxel. Each ml of docetaxel solution contains 20 mg of docetaxel.
• The excipients are citric acid, povidone, absolute ethanol (see section 2), and polysorbate 80.

Description of the appearance of DOCETAXEL RATIOPHARM ITALIA and contents of the pack
DOCETAXEL RATIOPHARM ITALIA concentrate for solution for infusion is a clear, light yellow solution.
Pack sizes:
1 single-dose vial of 1 ml
1 single-dose vial of 4 ml
1 single-dose vial of 7 ml
1 single-dose vial of 8 ml
Not all pack sizes may be marketed.

Marketing Authorization Holder
Teva BV
Swensweg 5
2031 GA Haarlem
The Netherlands

Manufacturer
S. C. Sindan-Pharma S.R.L.
11 Ion Mihalache Blvd
011171 Bucharest, Romania
Actavis Italy S.p.A.
Viale Pasteur 10
20014 Nerviano (MI)
Italy
Merckle GmbH
Ludwig-Merckle-Straße 3
89143 Blaubeuren-Weiler
Germany

This patient information leaflet was last approved on:

The following information is intended for healthcare professionals only:
Docetaxel ratiopharm Italia 20 mg/ml concentrate for solution for infusion
Instructions for use
Safety handling recommendations
Docetaxel is an antineoplastic medicinal product and, as with other potentially toxic agents, care must be taken when handling and preparing solutions. The use of gloves is recommended.
If concentrated DOCETAXEL RATIOPHARM ITALIA or the infusion solution comes into contact with the skin, wash immediately and thoroughly with water and soap. If contact occurs with mucous membranes, wash immediately and thoroughly with water.

Preparation of the infusion solution
Each vial is for single use only and must be used immediately after opening. If not used immediately, the storage times and conditions prior to use are the responsibility of the user.
More than one vial of concentrate for solution for infusion may be required to achieve the patient's required dose.
For example, to administer a 140 mg dose of docetaxel, 7 ml of concentrate for solution for infusion should be withdrawn.
Aseptically withdraw the required amount of concentrate for solution for infusion using a graduated syringe with a needle.
Then, inject in a single injection ("one shot") into a 250 ml infusion bag or bottle containing 5% glucose solution or 9 mg/ml (0.9%) sodium chloride solution for infusion.
If a docetaxel dose exceeding 190 mg is required, use a larger volume of infusion solution so that the docetaxel concentration does not exceed 0.74 mg/ml.
Gently mix the infusion bag or bottle by inverting it several times.
The diluted solution must be administered under aseptic conditions as a 1-hour infusion at room temperature and under normal lighting conditions.
As with all parenteral medicinal products, the infusion solution should be inspected visually before use; any solutions containing precipitates must be discarded.

Storage after dilution
Chemical and physical in-use stability of the diluted solution (0.74 mg/ml) in the recommended infusion solutions (glucose 50 mg/ml (5%) for infusion or sodium chloride 9 mg/ml (0.9%) for infusion) has been demonstrated for 3 days when stored at 2–8°C protected from light, and for 8 hours in non-PVC bags when stored at temperatures below 25°C under normal lighting conditions.
From a microbiological standpoint, the product should be used immediately. If not used immediately, the storage times and conditions prior to use are the responsibility of the user and normally should not exceed 24 hours at 2–8°C, unless dilution has been performed under controlled and validated aseptic conditions.

Docetaxel infusion solution is supersaturated and may crystallize over time. If crystals form, the solution must no longer be used and must be discarded.

Disposal
Unused medicine or waste materials must be disposed of in accordance with local regulations.