DOCETAXEL AUROVITAS 20 mg/ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

Docetaxel Aurovitas 20 mg/ml concentrate for solution for infusion

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

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

The name of this medicine is Docetaxel Aurovitas. Its common name is docetaxel. Docetaxel is a substance derived from the needles 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, special forms of lung cancer (non-small cell lung cancer), prostate cancer, stomach cancer or head and neck cancer:

• For the treatment of advanced breast cancer, docetaxel can 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 can be administered in combination with doxorubicin and cyclophosphamide.
• For the treatment of lung cancer, docetaxel can 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 stomach 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 Aurovitas

Docetaxel Aurovitas should not be administered to you

• 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, blood tests will be carried out to check that you have enough blood cells and that your liver is working sufficiently to be treated with docetaxel. In case of alteration in white blood cells, you may experience fever or associated infections.

Tell 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 a severe gastrointestinal toxicity, which can be fatal. Your doctor must address this immediately.

Tell your doctor, pharmacist or nurse if you have vision problems. In case of vision problems, particularly blurred vision, an eye and vision examination should be carried out immediately.

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

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

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

You will be asked to take an oral corticosteroid such as dexamethasone, one day before the administration of docetaxel and will continue for one or two days after, in order to reduce certain side effects that may occur after the infusion of docetaxel, especially allergic reactions and fluid retention (swelling of the hands, feet, legs or weight gain).

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

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

• SSJ/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 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.

Docetaxel Aurovitas contains alcohol. If you have epilepsy or liver problems, ask your doctor or pharmacist before using this medicine. If you are an alcoholic, ask your doctor or pharmacist before using this medicine. See also the section "Docetaxel Aurovitas contains ethanol (alcohol)" below.

Other medicines and Docetaxel Aurovitas

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including those obtained without a prescription. The reason is that it is possible that docetaxel or the other medicine may not have the expected effect and that you may have more chances of suffering a side effect.

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

Ask your doctor or pharmacist if you are taking other medicines.

Pregnancy, breast-feeding and fertility

Consult your doctor before you are given any medicine.

Pregnancy

Docetaxel MUST NOT be administered during pregnancy unless it is specifically indicated by your doctor.

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

Breast-feeding

You MUST NOT breast-feed during treatment with docetaxel.

If you are pregnant or breast-feeding, ask your doctor or pharmacist for advice before using this medicine.

Fertility

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

Driving and using machines

The alcohol content of this medicine may alter your ability to drive and use machines. You may experience side effects of this medicine that could 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 Aurovitas contains ethanol (alcohol)

This medicine contains 51% ethanol (alcohol), which corresponds to 400 mg per 1 ml vial, equivalent to 10 ml of beer or 4.16 ml of wine.

This medicine contains 51% ethanol (alcohol), which corresponds to 1600 mg per 4 ml vial, equivalent to 40 ml of beer or 16.67 ml of wine.

This medicine contains 51% ethanol (alcohol), which corresponds to 2800 mg per 7 ml vial, equivalent to 70 ml of beer or 29.17 ml of wine.

This medicine contains 51% ethanol (alcohol), which corresponds to 3200 mg per 8 ml vial, equivalent to 80 ml of beer or 33.33 ml of wine.

This medicine is harmful to individuals with alcoholism.

The alcohol content must be taken into account in pregnant or breast-feeding women, children and high-risk groups, such as patients with liver disease or epilepsy.

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

3. How to use Docetaxel Aurovitas

Docetaxel should be administered by a healthcare professional.

Normal dose

The dose depends on your weight and general state of 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

Docetaxel will be administered by infusion into a vein (intravenously). The infusion will last approximately one hour, during which you will have to stay in the hospital.

Frequency of administration

Normally, an infusion is administered every 3 weeks.

Your doctor may change the dose and frequency of administration based on the results of your blood tests, your general state and your response to docetaxel. Inform your doctor especially in case of diarrhea, mouth sores, sensation of numbness or tingling or pain in the joints or muscles, fever and the results of your blood tests. This information will allow your doctor to decide whether a dose reduction is necessary. If you have any other questions about the use of this medicine, ask your doctor or 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 frequently reported side effects of docetaxel 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 be increased when docetaxel 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.

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 infusion and another of docetaxel, the following effects may occur, and the frequency may vary depending on the combinations of medicines you have received:

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

• infections, decrease in the number of red or white blood cells and platelets.
• fever: in case it appears, you must inform your doctor immediately.
• allergic reactions as described above.
• loss of appetite (anorexia).
• insomnia.
• sensation of numbness or tingling or pain in the joints or muscles.
• headache.
• alteration of taste.
• inflammation of the eyes or increased tearing of the eyes.
• swelling due to lack of lymphatic drainage.
• shortness of breath.
• runny nose, inflammation of the nose and throat, cough.
• nasal bleeding.
• mouth sores.
• discomfort in the stomach, including nausea, vomiting and diarrhea, constipation.
• abdominal pain.
• indigestion.
• hair loss (in most cases, normal hair growth returns). 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 lead to nail detachment.
• muscle pain, back pain or bone pain.
• change or absence of menstrual period.
• swelling of the 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.
• hearing loss.
• decrease in blood pressure; rapid or irregular heartbeat.
• heart failure.
• esophagitis.
• dry mouth.
• difficulty or pain when swallowing.
• bleeding.
• increase in liver enzymes (for which regular blood tests are necessary).
• increase in blood sugar levels (diabetes).
• decrease in potassium, calcium and/or phosphate in the blood.

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

• fainting.
• at the injection site, skin reactions, phlebitis (inflammation of the vein) or swelling.
• 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 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 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 retinal swelling (Cystoid Macular Edema).
• decrease in sodium and/or magnesium in the 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 serious. 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 who receive treatment with docetaxel in combination with other anticancer treatments.
• Stevens-Johnson syndrome (SSJ) 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 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 heart rhythm disorders. If this happens, 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 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 Spanish Pharmacovigilance System for Human Use Medicines: www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Docetaxel Aurovitas

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 vial.

Store below 25°C.

Store in the original packaging to protect from light.

Do not refrigerate or freeze.

After opening the vial:

Each vial is for single use and must be used immediately after opening. If not used immediately, the in-use storage times and conditions are the responsibility of the user.

Once added to the infusion bag:

The diluted solution must be used immediately after preparation. If not used immediately, the in-use storage times and conditions are the responsibility of the user and should not normally exceed 3 days if stored between 2 and 8°C protected from light or 8 hours at room temperature (below 25°C) including the time for infusion.

The disposal of unused medicine and all materials that have come into contact with it will be carried out in accordance with local regulations.

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

Composition ofDocetaxel Aurovitas

• The active ingredient is docetaxel. Each milliliter of docetaxel solution contains 20 mg of anhydrous docetaxel.
• The other components are anhydrous citric acid, povidone, absolute ethanol, and polysorbate 80.

Appearance of theproductand container contents:

Docetaxel Aurovitas concentrated solution for infusion is a clear, pale yellow solution.

Docetaxel Aurovitas is supplied in a transparent glass vial with a rubber stopper and an aluminum flip-off cap with a polypropylene disc. The vial may be packaged with or without a protective plastic wrapper.

Container 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

Only some container sizes may be marketed.

Marketing authorization holder

Eugia Pharma (Malta) Limited

Vault 14, Level 2, Valletta Waterfront

Floriana, FRN 1914

Malta

Manufacturer

APL Swift Services (Malta) Limited

HF26, Hal Far Industrial Estate, Hal Far

Birzebbugia, BBG 3000

Malta

Or

Generis Farmacêutica, S.A.

Rua João de Deus, nº 19, Venda Nova

2700-487 Amadora

Portugal

For further information on this medicinal product, please contact the local representative of the marketing authorization holder:

Aurovitas Spain, S.A.U.

Avda. de Burgos, 16-D

28036 Madrid

Spain

Date of last revision of this leaflet: November 2023

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

This information is intended only for healthcare professionals:

Docetaxel Aurovitas 20 mg/ml concentrated solution for infusion

Instructions for use

Docetaxel is a cytotoxic agent, and as with other potentially toxic compounds, precautions should be taken during handling and preparation of docetaxel solutions. This type of preparation should only be prepared and handled by personnel qualified in the safe handling of cytotoxic agents. Female personnel who are pregnant should not handle cytotoxic agents. Before starting, local recommendations on cytotoxics should be consulted. The use of gloves is recommended. In the event of skin contact with the concentrated or infusion solution of docetaxel, wash immediately and thoroughly with water and soap. In the event of contact with the mucous membranes of the concentrated or infusion solution of docetaxel, wash immediately and thoroughly with water. In the event of a spill, qualified personnel, with appropriate personal protective equipment, should remove as much material as possible using a cytotoxic drug spill kit or designated absorbent materials. The area should be washed with a large amount of water. All contaminated cleaning materials should be disposed of in accordance with local regulations.

Preparation of the infusion solution

More than one vial of docetaxel 20 mg/ml concentrated solution for infusion may be needed to obtain the required dose for a given patient. Using graduated syringes with a needle, aseptically withdraw from the necessary vials the volume of docetaxel 20 mg/ml corresponding to the dose required for the patient expressed in mg. For example, a dose of 140 mg of docetaxel would require 7 ml of Docetaxel Aurovitas 20 mg/ml concentrated solution for infusion.

For doses less than 192 mg of docetaxel, inject the necessary volume of docetaxel 20 mg/ml concentrated solution for infusion into a 250 ml infusion bag or bottle containing either 250 ml of glucose 50 mg/ml (5%) infusion solution or sodium chloride 9 mg/ml (0.9%) infusion solution. For doses greater than 192 mg of docetaxel, more than 250 ml of infusion solution is needed, since the maximum concentration of docetaxel is 0.74 mg per ml of infusion solution.

Manually mix the infusion bag or bottle by shaking. The diluted solution should be used within 8 hours, and should be administered aseptically as a 1-hour infusion at room temperature and under normal light conditions.

As with all parenteral products, this medicinal product should be inspected visually before use, and solutions that present a precipitate should be rejected.

The disposal of unused medicinal products and all materials that have come into contact with them should be carried out in accordance with local regulations.

Storage after opening

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.

Storage after dilution

From a microbiological point of view, the reconstitution/dilution should be carried out under controlled aseptic conditions and the medicinal product 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 8 hours if stored below 25°C in non-PVC bags. It should be used within this 8-hour period (including the 1-hour infusion administration time).

Additionally, the physical and chemical stability of the infusion solution, prepared as recommended, has been demonstrated for 3 days if stored between 2 and 8°C protected from light.

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.

Disposal

The disposal of unused medicinal products and all materials that have come into contact with them should be carried out in accordance with local regulations.