Label: information for the user

TAXOTERE 80mg/4 ml concentrate for infusion solution

Docetaxel

Read this label carefully before starting to use this medicine, because it contains important information for you.

• Keep this label, as you may need to read it again.
• If you have any doubts, consult your doctor, hospital pharmacist or nurse.
• If you experience any adverse effects, consult your doctor, hospital pharmacist or nurse, even if they are not listed in this label. See section 4.

Label content:

1. What TAXOTERE is and for what it is used
2. What you need to know before starting to use TAXOTERE
3. How to use TAXOTERE
4. Possible adverse effects
5. Storage of TAXOTERE
6. Contents of the package and additional information

The name of this medication is TAXOTERE. Its common name is docetaxel. Docetaxel is a substance derived from the needles (leaves) of the yew tree.

Docetaxel belongs to the group of anticancer medications called taxoids.

TAXOTERE has been prescribed by your doctor for the treatment of breast cancer, certain types of lung cancer (non-small cell lung cancer), prostate cancer, stomach cancer, or head and neck cancer:

- For the treatment of advanced breast cancer, TAXOTERE may be administered either alone or in combination with doxorubicina, trastuzumab, or capecitabina.

You should not receive TAXOTERE:

• if you are allergic (hypersensitive) to docetaxel or any of the other components of TAXOTERE (listed in section 6).
• if your white blood cell count is too low.
• if you have severe liver disease.

Warnings and precautions

Before each treatment with TAXOTERE, a blood test will be performed to ensure that you have a sufficient number of blood cells and sufficient liver function to receive TAXOTERE. If you have abnormalities in your white blood cells, you may be at risk of fever or associated infections.

Inform your doctor, hospital pharmacist or nurse immediately if you experience abdominal pain or tenderness, diarrhea, rectal bleeding, bloody stools or fever. These symptoms may be the first signs of severe gastrointestinal toxicity, which can be fatal. Your doctor must address this immediately.

Inform your doctor, hospital pharmacist or nurse if you experience vision problems. In the case of vision problems, particularly blurred vision, an eye and vision examination must be performed immediately.

Inform your doctor, hospital pharmacist or nurse if you have heart problems.

Inform your doctor, hospital pharmacist or nurse if you have previously experienced allergic reactions to paclitaxel.

If you develop acute problems or worsening of the lungs (fever, difficulty breathing, cough), inform your doctor, hospital pharmacist or nurse immediately. Your doctor may immediately stop your treatment.

Your doctor will recommend taking premedication, consisting of an oral corticosteroid such as dexamethasone, one day before the administration of TAXOTERE and continuing for one or two days afterwards to minimize some adverse effects that may occur after the infusion of TAXOTERE, particularly allergic reactions and fluid retention (swelling of the hands, feet, legs or weight gain).

During treatment, you may receive other medications to maintain your blood cell count.

Severe skin problems such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), acute generalized pustular psoriasis (PGEP) have been reported with TAXOTERE:

-The symptoms of SJS/TEN may include blisters, peeling or bleeding on any part of your skin (including lips, eyes, mouth, nose, genitals, hands or feet) with or without a rash. You may also have symptoms similar to the flu at the same time, such as fever, chills or muscle pain.

-The symptoms of PGEP may include a red, scaly and widespread rash with inflamed skin lumps (including skin folds, trunk and upper limbs) and blisters accompanied by fever.

If you develop severe skin reactions or any of the reactions mentioned above, contact your doctor or healthcare professional immediately.

Inform your doctor, hospital pharmacist or nurse before starting TAXOTERE if you have kidney problems or high blood levels of uric acid.

TAXOTERE contains alcohol. Consult your doctor if you are dependent on alcohol, have epilepsy or liver disorders. See also the section “TAXOTERE contains ethanol (alcohol)” below.

Use of TAXOTERE with other medications

Please inform your doctor or hospital pharmacist if you are using or have recently used another medication, even those purchased without a prescription. This is because TAXOTERE or the other medication may not work as expected and you may be at a higher risk of an adverse effect.

The alcohol content of this medication may alter the effects of other medications.

Pregnancy, breastfeeding and fertility

Consult your doctor before using any medication.

TAXOTERESHOULD NOTbe administered if you are pregnant, unless clearly indicated by your doctor.

You should not become pregnant while receiving treatment and for 2 months after completing treatment with this medication. You must use an effective contraceptive method during treatment and for 2 months after completing treatment, as TAXOTERE may be harmful to the fetus. If you become pregnant during your treatment, you must inform your doctor immediately.

TAXOTERE should not be used during breastfeeding.

If you are a man receiving TAXOTERE, you should not father a child and must use an effective contraceptive method during treatment and for 4 months after completing treatment with this medication. It is recommended that you inform your doctor about sperm conservation before treatment, as docetaxel may affect male fertility.

Driving and operating machinery

The alcohol content of this medication may affect your ability to drive and use machines.

You may experience adverse effects of this medication that may impair your ability to drive, use tools or operate machinery (see section 4 Possible adverse effects). If this happens, do not drive or use any tools or machinery before consulting your doctor, nurse or hospital pharmacist.

TAXOTERE contains ethanol (alcohol)

This medication contains 50% volume of anhydrous ethanol (alcohol), which corresponds to 1.58 g of anhydrous ethanol per vial, equivalent to 40 ml of beer or 17 ml of wine.

This medication is harmful to people with alcoholism.

The alcohol content must be taken into account in the case of pregnant women, breastfeeding women, children and high-risk populations, such as patients with liver disease or epilepsy.

The alcohol content of this medication may have effects on the central nervous system (part of the nervous system that includes the brain and spinal cord).

TAXOTERE will be administered by a healthcare professional.

Usual dose

The dose will depend on your weight and overall health. Your doctor will calculate your body surface area in square meters (m2) and determine the dose you should receive.

Form and route of administration

TAXOTERE will be administered through infusion into one of your veins (intravenous route). The infusion will last approximately one hour during which you will be in the hospital.

Administration frequency

You will receive the treatment, through intravenous infusion, once every 3 weeks.

Your doctor may change the dose and administration frequency based on your blood test results, overall health, and response to TAXOTERE. In particular, inform your doctor if you experience diarrhea, mouth sores, numbness or tingling, fever, and provide your blood test results. This information will allow your doctor to decide if a dose reduction is necessary. If you have any other questions about the use of this medication, ask your doctor or the hospital pharmacist.

Like all medicines, TAXOTERE can cause side effects, although not everyone will experience them.

Your doctor will discuss them with you and explain the possible risks and benefits of your treatment.

The most common side effects of TAXOTERE, when given alone, are: a decrease in the number of red or white blood cells, hair loss, nausea, vomiting, mouth sores, diarrhea, and fatigue.

The severity of TAXOTERE side effects may increase when given in combination with other chemotherapy agents.

During hospital infusion, the following allergic reactions may occur (may affect more than 1 in 10 patients):

• hives, skin reactions, itching,
• chest tightness, difficulty breathing,
• fever or chills,
• back pain,
• low blood pressure.

Other more severe reactions may occur.

If you had an allergic reaction to paclitaxel, you may also experience an allergic reaction to docetaxel, which may be more severe.

The hospital staff will closely monitor your health status during treatment. If you notice any of these side effects, report them immediately.

Between TAXOTERE infusions, the following may occur and their frequency may vary depending on the combination of medications you receive:

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

• infections, a decrease in red or white blood cells (important for 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 or tingling or pain in the joints
• headache
• alteration of taste
• inflammation of the eye or excessive tearing
• swelling caused by defective lymphatic drainage
• shortness of breath
• nasal secretion; inflammation of the throat and nose; cough
• nosebleed
• mouth sores
• stomach discomfort including nausea, vomiting, and diarrhea, constipation
• abdominal pain
• indigestion
• hair loss (in most cases, your hair will regrow normally). In some cases (unknown frequency), permanent hair loss has been observed
• redness and swelling of the palms of the hands or soles of the feet, which may cause skin peeling (this can also occur on arms, face, or body)
• change in nail color, which may fall off
• muscle pain; back or bone pain
• changes or absence of menstrual period
• swelling of hands, feet, legs
• fatigue; or catarrhal symptoms
• weight gain or loss
• upper respiratory tract infection.

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

• oral candidiasis
• dehydration
• dizziness
• hearing loss
• decreased blood pressure, irregular or rapid heartbeats
• heart failure
• esophagitis
• dry mouth
• difficulty or pain swallowing
• bleeding
• elevation of liver enzymes (hence the need for regular blood tests)
• increased blood sugar levels (diabetes)
• decreased potassium, calcium, and/or phosphate in your blood.

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

• syncope
• skin reactions, phlebitis (inflammation of the vein) or swelling at the infusion site
• blood clots
• acute myeloid leukemia and myelodysplastic syndrome (types of blood cancer) may occur in patients treated with docetaxel in combination with other anticancer treatments.

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

• inflammation of the colon, small intestine, which could be fatal (unknown frequency); intestinal perforation.

Unknown frequency(cannot be estimated from available data):

• interstitial lung disease (inflammation of the lungs that produces cough and difficulty breathing. Lung inflammation may also occur when docetaxel treatment is used with radiation therapy)
• lung infection (pneumonia)
• pulmonary fibrosis (scarring and thickening of the lungs with difficulty breathing)
• blurred vision due to inflammation of the retina inside the eye (cystoid macular edema)
• decreased sodium and/or magnesium in your blood (electrolyte imbalance)
• ventricular arrhythmia or ventricular tachycardia (manifesting as irregular or rapid heartbeats, severe shortness of breath, dizziness, or fainting). Some of these symptoms may be severe. If this occurs, inform your doctor immediately
• reactions at the injection site, at the site of a previous reaction
• non-Hodgkin lymphoma (a cancer that affects the immune system) and other types of cancer may occur in patients receiving docetaxel treatment in combination with other anticancer treatments
• Stevens-Johnson syndrome (SSJ) and toxic epidermal necrolysis (NET) (blisters, peeling, or bleeding on any part of your skin (including lips, eyes, mouth, nose, genitals, hands, or feet) with or without rash. You may also have symptoms similar to the flu at the same time, such as fever, chills, or muscle pain
• generalized acute pustular psoriasis (PEGA) (red, scaly, and generalized rash with inflamed skin bumps (including skin folds, trunk, and upper limbs) and blisters accompanied by fever)
• tumor lysis syndrome, a serious condition that manifests by changes in blood tests, such as increased levels of uric acid, potassium, phosphate, and decreased levels of calcium; and results in symptoms such as seizures, kidney failure (reduced or dark urine) and cardiac arrhythmias. If this occurs, you must inform your doctor immediately.
• myositis (inflammation of the muscles -heat, redness, and swelling- that produces muscle pain and weakness).

Reporting of side effects

If you experience any type of side effect, consult your doctor, hospital pharmacist, or nurse, even if it is a possible side effect not listed in this prospectus.You can also report them directly through thenational notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information on the safety of this medication.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the outer packaging and on the vial label after CAD. The expiration date is the last day of the month indicated.

Do not store above 25°C.

Store in the original packaging to protect it from light.

Use the vial immediately after opening. If not used immediately, the user is responsible for the storage time and conditions.

From a microbiological standpoint, reconstitute/dilute in controlled, aseptic conditions.

The medication should be used immediately once added to the infusion bag. If not used immediately, the user is responsible for the storage time and conditions, and typically should not exceed 6 hours below 25°C, including the infusion time to the patient.

The physical and chemical stability of the prepared infusion solution as recommended is demonstrated for up to 48 hours if stored between 2 and 8°C in non-PVC bags.

The docetaxel infusion solution is supersaturated, and therefore may crystallize over time. If crystals appear, the solution should not be used and should be discarded.

Do not dispose of medications through the drains. Ask your pharmacist where to dispose of unused medications. This will help protect the environment.

What TAXOTERE contains

- The active substance is docetaxel (as trihydrate). Each milliliter of concentrate for solution for infusion contains 20 mg of docetaxel.

- The other components are polisorbate 80, anhydrous ethanol (see section 2) and citric acid.

Appearance of TAXOTERE and contents of the container

TAXOTERE concentrate for solution for infusion is a yellow to yellow-brown solution.

The concentrate is provided in a 7 ml transparent and colourless glass vial, with a purple aluminium seal and a magenta plastic flip-off cap.

Each pack contains a vial of 4 ml concentrate (80 mg of docetaxel).

Marketing authorisation holder

Sanofi Winthrop Industrie

82 Avenue Raspail

94250 Gentilly

France

Manufacturer(s)

Sanofi-Aventis Deutschland GmbH

Industriepark Höchst

65926 Frankfurt am Main

Germany

or

Sanofi-aventis Zrt.

(Harbor Park) 1, Campona utca

Budapest 1225

Hungary

You can request more information about this medicine by contacting the local representative of the marketing authorisation holder.

Last update of this leaflet:

Other sources of information

The detailed information on this medicine is available on the website of the European Medicines Agency:http://www.ema.europa.eu/.

This information is intended solely for healthcare professionals:

GUIDE FOR PREPARATION FOR USE OF TAXOTERE 80 mg/4 ml CONCENTRATE FOR SOLUTION FOR INFUSION

Please read carefully the contents of this guide before preparing the infusion solution of TAXOTERE.

Recommendations for safe handling

Docetaxel is an antineoplastic agent and, as with other potentially toxic compounds, it should be handled with caution when manipulating and preparing TAXOTERE solutions. It is recommended to use gloves.

If the TAXOTERE concentrate or the infusion solution comes into contact with the skin, the skin should be washed immediately and thoroughly with water and soap. If the TAXOTERE concentrate or the infusion solution enters the mucous membranes, it should be washed immediately and thoroughly with water.

Preparation for intravenous administration

Preparation of the infusion solution

DO NOT USE this medicine (TAXOTERE 80 mg/4 ml concentrate for solution for infusion, in a single vial) with other medicines that contain docetaxel in 2 vials (concentrate and solvent).

TAXOTERE 80 mg/4 ml concentrate for solution for infusion DOES NOT require a prior dilution with a solvent and is ready to be added to the infusion solution.

• Each vial is for single use and must be used immediately after opening. If not used immediately, the periods of time and conditions of storage are the responsibility of the user. It may be necessary to use more than 1 vial of TAXOTERE concentrate for solution for infusion to obtain the required dose for the patient. For example, for a dose of 140 mg of docetaxel, 7 ml of docetaxel concentrate for solution would be required.

• Extract the required amount of TAXOTERE concentrate for solution for infusion aseptically using a calibrated syringe with a 21G needle.

The concentration of docetaxel in the vial of TAXOTERE 80 mg/4 ml is 20 mg/ml.

• Then, inject it once (with a single injection) into a 250 ml infusion bag or bottle, which contains either a 5% glucose solution or a 0.9% sodium chloride solution. If a dose greater than 190 mg of docetaxel is required, use a larger volume of infusion solution, in order not to exceed the concentration of 0.74 mg/ml of docetaxel.
• Mix the infusion bag or bottle manually by rotating it.
• From a microbiological point of view, it should be reconstituted/diluted in controlled aseptic conditions and the medicine should be used immediately. If not used immediately, the periods and conditions of storage are the responsibility of the user.

Once added to the infusion bag as recommended, the docetaxel infusion solution is stable for 6 hours if stored below 25°C. It should be used within this 6-hour period (including the hour of intravenous infusion).

Furthermore, the physical and chemical stability of the prepared infusion solution is demonstrated for up to 48 hours if stored between 2 and 8°C in non-PVC bags.

The docetaxel infusion solution is supersaturated, and it may crystallize over time. If crystals appear, the solution should not be used and should be discarded.

• As with all parenteral products, the docetaxel infusion solution should be visually inspected before use; solutions with precipitate should be discarded.

Disposal

The unused medicine and all materials that have come into contact with it should be disposed of in accordance with local regulations. Do not dispose of medicines in the sewage. Ask your pharmacist where to dispose of medicines that are no longer needed. This will help protect the environment.