DOCETAXEL ACCORD 160 mg/8 ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

Docetaxel Accord 20 mg/1 ml concentrate for solution for infusion EFG

Docetaxel Accord 80 mg/4 ml concentrate for solution for infusion EFG

Docetaxel Accord 160 mg/8 ml concentrate for solution for infusion EFG

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.

• 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 Accord and what is it used for
2. What you need to know before you use Docetaxel Accord
3. How to use Docetaxel Accord
4. Possible side effects
5. Storage of Docetaxel Accord
6. Contents of the pack and further information

1. What is Docetaxel Accord and what is it used for

The name of this medicine is Docetaxel Accord. Its common name is docetaxel. The

docetaxel is a substance derived from the needles (leaves) of the yew tree.

Docetaxel belongs to a group of anticancer drugs called taxoids.

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

2. What you need to know before you use Docetaxel Accord

Docetaxel Accord should not be administered:

• if you are allergic (hypersensitive) to docetaxel or to any of the other ingredients of Docetaxel Accord(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 Accord, you will have a blood test to check that you have a sufficient number of blood cells and sufficient liver function to receive Docetaxel Accord. If you have altered white blood cell counts, you may suffer from fever or associated infections.

Inform your doctor, pharmacist, or nurse immediately if you have abdominal pain or tenderness, diarrhea, rectal bleeding, blood in your 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, 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, pharmacist, or nurse if you have previously experienced allergic reactions to paclitaxel.

Inform your doctor, 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, 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 the administration of Docetaxel Accord and that you continue for one or two days after to minimize some side effects that may occur after the infusion of Docetaxel Accord, in particular 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.

Docetaxel Accord contains alcohol. Consult your doctor if you have a history of alcohol dependence or liver disorders. See also the section below "Docetaxel Accord contains ethanol (alcohol)".

Use of Docetaxel Accord with other medicines

Please tell your doctor or pharmacist if you are using or have recently used any other medicines, including those obtained without a prescription. The reason is that Docetaxel Accord or the other medicine may not work as well as expected, and you may have more chances of suffering a side effect.

The alcohol content of this medicine may alter the effects of other medicines.

Pregnancy, breastfeeding, and fertility

Consult your doctor before using any medicine.

Docetaxel Accord should 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 must use an effective contraceptive method during therapy, as docetaxel may be harmful to the fetus. If you become pregnant during treatment, you must inform your doctor immediately.

You must not breastfeed while being treated with docetaxel.

If you are a man being treated with docetaxel, you are advised not to father a child during treatment and for up to 6 months after treatment, as well as to inform about sperm preservation before treatment, as docetaxel may alter 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 may alter 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 pharmacist.

Docetaxel Accord contains ethanol (alcohol)

Docetaxel Accord 20 ml/1 ml contains 50% v/v anhydrous ethanol (alcohol), which corresponds to 395 mg anhydrous ethanol per vial, equivalent to 10 ml of beer or 4 ml of wine.

Docetaxel Accord 80 ml/4 ml contains 50% v/v anhydrous ethanol (alcohol) which corresponds to 1.58 g anhydrous ethanol per vial, equivalent to 40 ml of beer or 17 ml of wine.

Docetaxel Accord 160 ml/8 ml contains 50% v/v anhydrous ethanol (alcohol) which corresponds to 3.16 g anhydrous ethanol per vial, equivalent to 80 ml of beer or 33 ml of wine.

This medicine is harmful to people with alcohol dependence.

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

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 use Docetaxel Accord

Docetaxel Accord will be administered to you by a healthcare professional.

Recommended 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.

Form and route of administration

Docetaxel Accord 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 receive the treatment, by intravenous infusion, once every 3 weeks.

Your doctor may change the dose and frequency of administration depending on your blood tests, general condition, and response to Docetaxel Accord. In particular, inform your doctor if you have diarrhea, mouth sores, numbness or tingling, fever, and provide the results of your blood tests. This information will allow your doctor to decide if a dose reduction is necessary. If you have any further questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, Docetaxel 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, when administered 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 the side effects of Docetaxel may increase when 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 patients):

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

Other 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 closely monitor your health status during treatment. If you notice any of these effects, inform them immediately.

Between one docetaxel infusion and another, 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, decrease in the number of red or white blood cells, and platelets
• fever: if this happens, you must inform your doctor immediately.
• allergic reactions like those described above
• loss of appetite (anorexia)
• insomnia
• numbness or tingling, or pain in the joints
• headache
• taste alteration
• eye inflammation or excessive tearing
• swelling caused by defective lymphatic drainage
• shortness of breath
• nasal discharge; throat and nose inflammation; 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 the 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 cold-like symptoms
• weight gain or loss.

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

• oral candidiasis
• dehydration
• dizziness
• hearing impairment
• 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).

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

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

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

• 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):

• pulmonary interstitial disease (inflammation of the lungs that causes cough and difficulty breathing. Lung inflammation can also occur when treatment with docetaxel 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 inside 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 can be severe. If this happens, inform your doctor immediately

• reactions at the injection site, at the site of a previous reaction.
• lymphoma (cancer that affects the immune system) and other cancers may occur in patients treated with docetaxel in combination with certain anticancer treatments.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects 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 Accord

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 outer packaging 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, it must be diluted under controlled aseptic conditions.

The medicine must be used immediately after it has been added to the infusion bag. If not used immediately, the in-use storage times and conditions are the responsibility of the user and normally 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 has been demonstrated for up to 48 hours if stored between 2 and 8°C in non-PVC bags.

Prepare the infusion solution as recommended. Do not connect the infusion solution to the infusion set for more than 6 hours when stored at 25°C.

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

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.

6. Container Contents and Additional Information

What Docetaxel Accord contains

• The active substance is docetaxel. Each ml of concentrate for solution for infusion contains

20 mg of docetaxel.

A 1 ml vial of concentrate contains 20 mg of docetaxel.

A 4 ml vial of concentrate contains 80 mg of docetaxel.

A 8 ml vial of concentrate contains 160 mg of docetaxel.

• The other ingredients are polysorbate 80, anhydrous ethanol (see section 2), and anhydrous citric acid.

Appearance of Docetaxel Accord and Container Contents

Docetaxel Accordconcentrate for solution for infusion is a clear, pale yellow to yellow-brown solution.

Docetaxel Accord 20 mg/1 ml is provided in a 5 ml clear glass vial with a fluorotec plus rubber stopper, an aluminum seal, and an orange flip-off cap.

Docetaxel Accord 80 mg/4 ml is provided in a 5 ml clear glass vial with a fluorotec plus rubber stopper, an aluminum seal, and a red flip-off cap.

Docetaxel Accord 160 mg/8 ml is provided in a 10 ml clear glass vial with a fluorotec plus rubber stopper, an aluminum seal, and a red flip-off cap.

Container Size:

Each container contains a 1 ml vial of concentrate.

Each container contains a 4 ml vial of concentrate.

Each container contains an 8 ml vial of concentrate.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Accord Healthcare S.L.U.

World Trade Center, Moll de Barcelona, s/n,

Edifici Est 6ª planta,

08039 Barcelona,

Spain

Manufacturer

Accord Healthcare Limited

Sage House

319, Pinner Road

North Harrow, Middlesex HA1 4HF

United Kingdom

Accord Healthcare Polska Sp.z o.o.,

ul. Lutomierska 50, 95-200 Pabianice, Poland

Date of the Last Revision of this Leaflet:

Other Sources of Information

Detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu.

This information is intended solely for healthcare professionals:

PREPARATION GUIDE FOR THE USE OF DOCETAXEL ACCORD

CONCENTRATE FOR SOLUTION FOR INFUSION

Recommendations for Safe Handling

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

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

Preparation for Intravenous Administration

Preparation of the Infusion Solution

DO NOT USE this medicinal product (Docetaxel Accord 20 mg/1 ml concentrate for solution for infusion, in a single vial) with other medicinal products containing docetaxel in 2 vials (concentrate and solvent).

DO NOT USE this medicinal product (Docetaxel Accord 80 mg/4 ml concentrate for solution for infusion, in a single vial) with other medicinal products containing docetaxel in 2 vials (concentrate and solvent).

DO NOT USE this medicinal product (Docetaxel Accord 160 mg/8 ml concentrate for solution for infusion, in a single vial) with other medicinal products containing docetaxel in 2 vials (concentrate and solvent).

Docetaxel Accord 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 time and conditions of storage are the responsibility of the user. It may be necessary to use more than 1 vial of docetaxel 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.
• Aseptically withdraw the required amount of concentrate for solution for infusion using a calibrated syringe with a 21G needle.

The concentration of docetaxel in the vial of Docetaxel Accord is 20 mg/ml.

• Then, inject it in a single injection into a 250 ml infusion bag containing either a 5% glucose solution or a 9 mg/ml (0.9%) sodium chloride solution. If a dose greater than 190 mg of docetaxel is required, use a larger volume of infusion fluid to avoid exceeding a concentration of 0.74 mg/ml of docetaxel.
• Manually mix the infusion bag by rotating it.
• From a microbiological point of view, it should be diluted under controlled aseptic conditions and the medicinal product 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 infusion administration time).

Additionally, 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 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 with visible precipitates should be discarded.

Disposal

Disposal of unused medicinal products and all materials that have come into contact with them should be carried out in accordance with local regulations. Do not dispose of medicinal products via wastewater. Ask your pharmacist how to dispose of medicinal products that are no longer needed. This will help protect the environment.