DOCETAXEL KABI 160 mg/8 ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for theuser

DOCETAXEL KABI 160 mg/8 ml concentrate for solution for infusionEFG

docetaxel

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, pharmacist or nurse.
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack:

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

1. What is DOCETAXEL KABI and what is it used for

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

This medicine belongs to a group of anticancer medicines called taxoids

DOCETAXEL KABI 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 cancer or head and neck cancer:

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

in combination with cisplatin and 5-fluorouracil.

2. What you need to know before you use DOCETAXEL KABI Do not use DOCETAXEL KABI:

• • if you are allergic (hypersensitive) to docetaxel or to any of the other ingredients of DOCETAXEL KABI (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 DOCETAXEL KABI, you will have a blood test to check that you have a sufficient number of blood cells and sufficient liver function to receive DOCETAXEL KABI. In case of alterations in white blood cells, you may suffer from fever or associated infections.

Inform your doctor, hospital pharmacist or nurse immediately if you have abdominal pain or tenderness, diarrhea, rectal bleeding, blood in stools or fever. These symptoms could 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 have vision problems. In case of vision problems, particularly blurred vision, an eye examination and vision test must be performed immediately.

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

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

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

Your doctor will recommend that you take premedication, consisting of an oral corticosteroid such as dexamethasone, one day before administration of DOCETAXEL KABI and that you continue for one or two days after to minimize some side effects that may occur after infusion of DOCETAXEL KABI, in particular allergic reactions and fluid retention (swelling of hands, feet, legs or weight gain).

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

Severe skin reactions such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), acute generalized exanthematous pustulosis (AGEP) have been reported with DOCETAXEL KABI:

• SJS/TEN symptoms may include 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 those of the flu at the same time, such as fever, chills or muscle pain.
• AGEP symptoms may include a red, scaly and widespread rash with bumps under the inflamed skin (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 DOCETAXEL KABI if you have kidney problems or high blood levels of uric acid.

DOCETAXEL KABI contains alcohol. Consult your doctor if you suffer from alcohol dependence, epilepsy or liver failure. See also the section "DOCETAXEL KABI contains ethanol (alcohol)" below.

Use of DOCETAXEL KABI with other medicines

The amount of alcohol contained in this medicine may alter the effect of other medicines. Consult your doctor or pharmacist if you are taking other medicines.

Inform your doctor or hospital pharmacist if you are using, have recently used or might use any other medicines, including those obtained without a prescription. This is because DOCETAXEL KABI or the other medicine may not work as well as expected and you may be more likely to experience side effects.

Pregnancy, breastfeeding and fertility

Consult your doctor before taking any medicine.

DOCETAXEL KABI MUST NOT be administered if you are pregnant, unless clearly indicated by your doctor.

You must not become pregnant while being treated with this medicine and for 2 months after the end of treatment with this medicine. You must use an effective method of contraception during treatment and for 2 months after the end of treatment, as DOCETAXEL KABI may be harmful to the fetus. If you become pregnant during treatment, you must inform your doctor immediately.

DOCETAXEL KABI must not be used during breastfeeding.

If you are a man being treated with DOCETAXEL KABI, you must not father a child and must use an effective method of contraception during and for 4 months after treatment with this medicine. It is recommended that you be informed about sperm preservation before treatment, as docetaxel may affect male fertility.

Driving and using machines

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

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

DOCETAXEL KABI contains ethanol (alcohol)

This medicine contains 3.16 g of alcohol (ethanol) in each 8 ml, which is equivalent to 39.5% p/v. The amount in a 9 ml dose is equivalent to 88.9 ml of beer and 35.6 ml of wine.

The alcohol in this medicine may affect children. The effects that may appear are changes in behavior and drowsiness. It may also affect your ability to concentrate and perform physical activities.

If you suffer from epilepsy or liver problems, consult your doctor or pharmacist before taking this medicine.

If you have a history of alcohol dependence, consult your doctor or pharmacist before taking this medicine.

3. How to use DOCETAXEL KABI

DOCETAXEL KABI will be administered to you by a healthcare professional.

Usual dose

The dose will depend on your weight and general 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 KABI will be administered by infusion into one of your veins (intravenously). The infusion will last approximately one hour, during which you will be in the hospital.

Frequency of administration

You will usually receive treatment by intravenous infusion once every 3 weeks. Your doctor may change the dose and frequency of administration depending on your blood tests, your general condition and your response to DOCETAXEL KABI. In particular, inform your doctor if you experience diarrhea, mouth sores, numbness or tingling, fever and provide them with the results of your blood tests. This information will allow your doctor to decide whether a dose reduction is necessary. If you have any further questions on the use of this medicine, ask 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 these with you and explain the possible risks and benefits of your treatment.

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

The severity of the side effects of DOCETAXEL KABI may increase when DOCETAXEL KABI is administered in combination with other chemotherapeutic agents.

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

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

More serious 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 monitor you closely during treatment. Inform them immediately if you notice any of these effects.

Between infusions of DOCETAXEL KABI, the following may occur and the frequency may vary with the combinations of medicines you receive.

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

• infections, decrease in the number of red or white blood cells in the blood (which are important for fighting infections) and platelets
• fever: if this happens, you must inform your doctor immediately.
• allergic reactions as described above
• loss of appetite (anorexia)
• insomnia
• numbness, tingling or pain in the joints or muscles
• headache
• taste alteration
• eye inflammation or excessive tearing
• swelling caused by defective lymphatic drainage
• shortness of breath
• nasal discharge; inflammation of the throat and nose; cough
• nasal bleeding
• mouth sores
• stomach upset including nausea, vomiting and diarrhea; constipation
• abdominal pain
• indigestion
• hair loss: in most cases, your hair will grow back normally. 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 can cause skin peeling (this can also occur on arms, face or body)
• change in nail color, which can cause nail detachment
• muscle pain; back pain or bone pain
• changes or absence of menstrual period
• swelling of hands, feet, legs
• fatigue; or flu-like symptoms
• weight gain or loss
• upper respiratory tract infection.

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

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

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

• fainting
• skin reactions, phlebitis (inflammation of the vein) or swelling at the infusion site
• blood clot formation
• 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 people)

• inflammation of the colon, small intestine, which could be fatal (frequency not known); intestinal perforation.

Frequency not known(cannot be estimated from the available data)

• interstitial lung disease (inflammation of the lungs that produces cough and difficulty breathing. Lung inflammation can also occur when docetaxel treatment is used with radiotherapy)
• pneumonia (lung infection)
• pulmonary fibrosis (scarring and thickening in the lungs with difficulty breathing).
• blurred vision due to inflammation of the retina within the eye (cystoid macular edema)
• decrease in sodium, potassium, magnesium and/or calcium in your blood (electrolyte imbalance disorders). ventricular arrhythmia or ventricular tachycardia (which manifests as irregular and/or rapid heartbeats, severe shortness of breath, dizziness and/or fainting). Some of these symptoms may be severe. If this happens, 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 treatment with docetaxel and other anticancer treatments
• Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) (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 those of the flu at the same time, such as fever, chills or muscle pain
• acute generalized exanthematous pustulosis (AGEP) (red, scaly and widespread rash with bumps under the inflamed skin (including skin folds, trunk and upper limbs) and blisters accompanied by fever)
• tumor lysis syndrome, a serious condition that manifests as changes in blood tests, such as increased uric acid, potassium, phosphorus and decreased calcium levels; and results in symptoms such as seizures, kidney failure (reduced or darkened urine) and heart rhythm disturbances. If this happens, you must inform your doctor immediately.
• myositis (inflammation of the muscles - heat, redness and swelling - that causes muscle pain and weakness).

Reporting of side effects

If you experience side effects, consult your doctor, hospital pharmacist or nurse, even if they are not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of DOCETAXEL KABI

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

Do not use this medicine after the expiry date which is stated on the carton and on the label of the vial after Exp. The expiry date is the last day of the month shown.

Do not store above 25°C.

Store in the original packaging to protect from light.

Use the vial immediately after opening. If not used immediately, the in-use storage times and conditions are the responsibility of the user.

From a microbiological point of view, the reconstitution/dilution must be carried out under controlled and aseptic conditions.

Use the medicine immediately once added to the infusion bag. If not used immediately, the in-use storage times and conditions are the responsibility of the user and should not exceed 6 hours at less than 25°C, including the infusion time.

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

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Container Contents and Additional Information

DOCETAXEL KABI Contents

• The active ingredient is anhydrous docetaxel. Each ml of concentrate for solution for infusion contains 20 mg of docetaxel.

• The other components are polysorbate 80, anhydrous ethanol, and anhydrous citric acid (for pH adjustment).

Appearance of DOCETAXEL KABI and Container Contents

DOCETAXEL KABI concentrate for solution for infusion is a clear, colorless to pale yellow solution.

10 ml glass vials, transparent, colorless type I, closed with a flurotec stopper and a yellow aluminum flip-off sealing cap containing 8 ml of concentrate.

Each box contains one vial of 8 ml concentrate (160 mg of docetaxel).

Marketing Authorization Holder

Fresenius Kabi Deutschland GmbH Else-Kröner-Straße 1,

61352 Bad Homburg v.d.Höhe

Germany

Manufacturer

Fresenius Kabi Deutschland GmbH

Pfingstweide 53

61169 Friedberg

Germany

You can request more information about this medication by contacting the local representative of the marketing authorization holder:

Date of the Last Revision of this Prospectus:

This information is intended only for healthcare professionals:

PREPARATION GUIDE FOR THE USE OF DOCETAXEL KABI 160 mg/8 ml CONCENTRATE FOR SOLUTION FOR INFUSION EFG

Recommendations for Safe Handling

Docetaxel is an antineoplastic agent, and as with other potentially toxic compounds, caution should be exercised when handling and preparing solutions. The use of gloves is recommended.

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

Preparation for Intravenous Administration

Preparation of the Infusion Solution

DO NOT use other medications with docetaxel that contain 2 vials (concentrate and solvent) with this medication (DOCETAXEL KABI 160 mg/8 ml concentrate for solution for infusion, which contains only 1 vial).

DOCETAXEL KABI 160 mg/8 ml concentrate for solution for infusion DOES NOT require prior dilution with a solvent and is ready to be added to the infusion solution.

• Each vial is for single use and should be used immediately after opening. If not used immediately, the in-use storage times and conditions are the responsibility of the user. More than one vial of concentrate for solution for infusion may be necessary to obtain the required dose for the patient. For example, a dose of 140 mg of docetaxel would require 7 ml of docetaxel concentrate for solution.
• Asceptically extract the necessary amount of concentrate for solution for infusion with a calibrated syringe.

In each vial of DOCETAXEL KABI 160 mg/8 ml, the concentration of docetaxel is 20 mg/ml.

• Then, inject through a single injection (one puncture) into the 250 ml infusion bag or bottle containing either a 5% glucose solution or a 9 mg/ml (0.9%) sodium chloride solution for infusion. If a dose greater than 190 mg of docetaxel is required, use a larger volume of infusion vehicle so that the concentration of docetaxel does not exceed 0.74 mg/ml.
• Manually mix the infusion bag or bottle by performing a rotational movement.
• From a microbiological point of view, the reconstitution/dilution should take place under controlled and aseptic conditions, and the infusion solution should be used immediately. If not used immediately, the in-use storage times and conditions 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 at a temperature below 25°C. It should be used within 6 hours (including the infusion time of the intravenous administration).

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

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

Disposal

All materials used for dilution and administration should be discarded according to standard procedures. Medicines should not be disposed of via wastewater. Ask your pharmacist how to dispose of the packaging and medicines that are no longer needed. This will help protect the environment.