DOCETAXEL SEACROSS 20 mg/mL CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

Docetaxel Seacross 20 mg/ml concentrate for solution for infusion EFG

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

Contents of the pack

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

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

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

Docetaxel belongs to a group of anticancer medicines called taxoids.

Docetaxel 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 Seacross

Docetaxel Seacross must not be administered:

• if you are allergic (hypersensitive) to docetaxel or to any of the other ingredients of this medicine (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, you will have a blood test to check that you have a sufficient number of blood cells and sufficient liver function to receive this medicine. 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 sensitivity, 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 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 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 the administration of Docetaxel and that you continue for one or two days after to minimize some side effects that may occur after the infusion of Docetaxel, particularly allergic reactions and fluid retention (swelling of the hands, feet, legs, or weight gain).

During treatment, you may receive other medicines to maintain the number of your blood cells.

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

• 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 a rash. You may also have flu-like symptoms 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 if you have kidney problems or high levels of uric acid in your blood.

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

Using Docetaxel Seacross with other medicines

Please 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.

The reason is that Docetaxel or the other medicine may not work as well as expected, and you may have a greater chance of experiencing 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 Seacross 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 contraceptive method during treatment and for 2 months after the end of treatment, as Docetaxel may be harmful to the fetus. If you become pregnant during treatment, you must inform your doctor immediately.

Docetaxel Seacross must not be used during breastfeeding.

If you are a man being treated with Docetaxel, you must not father a child and must use an effective contraceptive method during treatment and for 4 months after the end of 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 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 hospital pharmacist.

Docetaxel Seacross contains ethanol (alcohol)

This medicine contains 50% v/v ethanol, i.e., 395 mg (0.5 ml) of ethanol per 1 ml fill volume, equivalent to 10 ml of beer or 4 ml of wine per 1 ml vial, 1.58 g (2 ml) of ethanol per 4 ml fill volume, equivalent to 40 ml of beer or 17 ml of wine per 4 ml vial, or 3.16 g (4 ml) of ethanol per 8 ml fill volume, equivalent to 80 ml of beer or 33 ml of wine per 8 ml vial.

This medicine is harmful to individuals with alcohol dependence. If you have a history of alcohol dependence, consult your doctor or pharmacist before taking this medicine.

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

The amount of alcohol contained in this medicine may affect your ability to drive and use machines because it may alter your judgment and reaction time.

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.

3. How to use Docetaxel Seacross

Docetaxel 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 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 this medicine. In particular, inform your doctor in case of diarrhea, mouth sores, numbness or tingling, fever, and provide 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 the possible risks and benefits of your treatment with you.

The most frequently reported side effects of docetaxel when administered alone are: decrease in the number of red or white blood cells, alopecia, 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.

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 condition during treatment. If you notice any of these effects, inform them immediately.

Between one infusion and another of Docetaxel, the following may occur, and their frequency may vary depending on the combination of medicines 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 as described above
• loss of appetite (anorexia)
• insomnia
• numbness or tingling, or pain in the joints or muscles
• headache
• altered taste
• 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 may cause skin peeling (this may also occur on the arms, face, or body)
• change in nail color, which may 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
• upper respiratory tract infection.

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

• 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)
• increased blood sugar levels (diabetes)
• decrease in potassium, calcium, and/or phosphate in your blood.

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

• fainting
• skin reactions, phlebitis (inflammation of the vein), or swelling at the injection 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 (frequency not known); intestinal perforation.

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

• interstitial lung disease (inflammation of the lungs that causes cough and difficulty breathing. Lung inflammation may 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 within the eye (cystoid macular edema)
• decrease in sodium and/or magnesium in your blood (electrolyte imbalance disorders)
• ventricular arrhythmia or ventricular tachycardia (which may manifest 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's lymphoma (a cancer that affects the immune system) and other types of cancer may occur in patients receiving treatment with docetaxel in combination with 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 a rash. You may also have flu-like symptoms 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 cardiac arrhythmias. 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 any side effects, talk to your doctor, pharmacist, or nurse, even if it is possible that they are not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Docetaxel Seacross

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 CAD. The expiry date is the last day of the month indicated.

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 should be reconstituted/diluted under controlled aseptic conditions.

The medicine should be used immediately once 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 8 hours in an infusion bottle or 6 hours in an infusion bag 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°C 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 throw away medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.

6. Package Contents and Additional Information

Composition ofDocetaxel Seacross

• The active substance is docetaxel.
• Each ml of concentrate for solution for infusion contains 20 mg of docetaxel.
• The other ingredients are polysorbate 80, anhydrous ethanol (see section 2), and citric acid.

Appearance and Package Contents of the Product

Docetaxel Seacross concentrate for solution for infusion is a clear, viscous, colorless to yellow-brown sterile solution.

The concentrate is supplied in a 2 ml colorless glass vial with a green flip-off cap. Each pack contains one 1 ml vial of concentrate (20 mg of docetaxel).

The concentrate is supplied in a 6 ml colorless glass vial with an orange flip-off cap. Each pack contains one 4 ml vial of concentrate (80 mg of docetaxel).

The concentrate is supplied in a 15 ml colorless glass vial with a red flip-off cap. Each pack contains one 8 ml vial of concentrate (160 mg of docetaxel).

Marketing Authorization Holder and Manufacturer

Seacross Pharma (Europe) Limited

POD 13, The Old Station House

15A Main Street, Blackrock

Dublin, A94 T8P8

Ireland

Date of the Last Revision of this Leaflet:July 2023

Detailed information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

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This information is intended only for healthcare professionals:

PREPARATION GUIDE FOR THE USE OFDOCETAXEL SEACROSS20 mg/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 concentrate or infusion solution comes into contact with the skin, wash the skin immediately and thoroughly with water and soap. If it comes into contact with the mucous membranes, rinse immediately and thoroughly with water.

Preparation for Intravenous Administration

Preparation of the Infusion Solution

DO NOT USE this medicine (Docetaxel Seacross 20 mg/ml concentrate for solution for infusion, in a single vial) with other medicines that contain docetaxel in2vials (concentrate and solvent).

Docetaxel Seacross 20 mg/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. It may be necessary to use more than one vial of 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 needed.
• 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 Seacross 20 mg/ml is 20 mg/ml.

• Then, inject it in a single injection into a 250 ml infusion bag or bottle containing either a 5% glucose solution or a 9 mg/ml (0.9%) sodium chloride infusion 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 or bottle by rotating it.
• From a microbiological point of view, it should be reconstituted/diluted under controlled 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 (PP) or bottle (PE) as recommended, the docetaxel infusion solution is stable for 8 hours in an infusion bottle or 6 hours in an infusion bag if stored below 25°C. It should be used within this 6-8 hour period (including the infusion time to the patient).

Additionally, the physical and chemical stability of the prepared infusion solution as recommended is demonstrated for up to 48 hours if stored between 2°C 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 precipitate formation should be discarded.

Disposal

Disposal of unused medicine and all materials that have come into contact with it should be carried out in accordance with local regulations. Do not throw away medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.