PACLITAXEL AUROVITAS 6 mg/ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

Paclitaxel Aurovitas6 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 or pharmacist.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack:

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

Paclitaxel Aurovitas 6 mg/ml concentrate for solution for infusion EFG is administered only by a doctor or a nurse. They can answer any questions you may have after reading this leaflet.

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

Paclitaxel belongs to a group of anticancer medicines called taxanes. These agents inhibit the growth of cancer cells.

Paclitaxel is used to treat:

Ovarian cancer

• as first-line treatment (after initial surgery in combination with a platinum-based medicine called cisplatin).
• after treatment with platinum-based medicines has not worked.

Breast cancer

• as first-line treatment for advanced or metastatic cancer. Paclitaxel is combined with an anthracycline (e.g. doxorubicin) or with a medicine called trastuzumab (for patients for whom anthracyclines are not suitable or who have cancer cells with a protein on their surface called HER2; see the trastuzumab package leaflet).
• as additional treatment after initial surgery followed by treatment with an anthracycline and cyclophosphamide (AC).
• as second-line treatment for patients who have not responded to anthracycline-based treatments or who cannot use these treatments.

Advanced non-small cell lung cancer

• in combination with cisplatin, when surgery, radiotherapy or both are not suitable.

AIDS-related Kaposi's sarcoma

• after other treatment (e.g. liposomal anthracyclines) has not worked.

2. What you need to know before you use Paclitaxel Aurovitas

Do not use Paclitaxel Aurovitas

• if you are allergic to paclitaxel or any of the other ingredients of this medicine (listed in section 6), especially macrogolglycerol ricinoleate.
• if you have very low white blood cell counts. Your doctor will take blood samples to check this.
• if you are breastfeeding.
• if you have a severe and uncontrolled infection and paclitaxel is to be used to treat Kaposi's sarcoma.

If you are in any of these situations, talk to your doctor before starting treatment with paclitaxel.

Paclitaxel is not recommended for use in children and adolescents (under 18 years).

Warnings and precautions

Talk to your doctor before starting treatment with Paclitaxel Aurovitas.

Before starting treatment with paclitaxel, you will be given other medicines to minimize the risk of allergic reactions.

• If you experience severe allergic reactions (e.g. difficulty breathing, shortness of breath, chest tightness, low blood pressure, dizziness, drowsiness, skin reactions such as rash or inflammation).
• If you have fever, severe chills, sore throat or mouth ulcers (signs of bone marrow suppression).
• If you experience numbness or weakness in arms and legs (signs of peripheral neuropathy); a dose reduction of paclitaxel may be necessary.
• If you have severe liver problems; in this case, the use of paclitaxel is not recommended.
• If you have conduction disorders.
• If you develop severe or persistent diarrhea with fever and abdominal pain during treatment with paclitaxel or immediately after its administration. You may have colon inflammation (pseudomembranous colitis).
• If you have received previous radiotherapy in the chest (as it may increase the risk of lung inflammation).
• If you have mouth sores or redness (signs of mucositis) and are being treated for Kaposi's sarcoma. You may need a lower dose.

Tell your doctor immediately if any of these apply to you.

Paclitaxel must always be administered in the veins. Administration of paclitaxel in the arteries can cause inflammation of these and you may experience pain, inflammation, redness, and heat.

Other medicines and Paclitaxel Aurovitas

Tell your doctor if you are using, have recently used or might use any other medicines, including those obtained without a prescription. This is because paclitaxel or the other medicine may not work as well as expected, or you may be more likely to get a side effect.

Interaction means that different medicines can affect each other. Talk to your doctor when taking paclitaxel at the same time as:

• medicines to treat infections (i.e. antibiotics such as erythromycin, rifampicin, etc.; ask your doctor, nurse or pharmacist if you are not sure if the medicine you are taking is an antibiotic).
• medicines used to help you stabilize your mood, sometimes called antidepressants (e.g. fluoxetine).
• medicines used to treat seizures (epilepsy) (e.g. carbamazepine, phenytoin).
• medicines used to help lower blood lipid levels (e.g. gemfibrozil).
• medicines used for heartburn or stomach ulcers (e.g. cimetidine).
• medicines used to treat HIV or AIDS (e.g. ritonavir, saquinavir, indinavir, nelfinavir, efavirenz, nevirapine).
• a medicine called clopidogrel used to prevent blood clots.
• a medicine called rifampicin, an antibiotic used for tuberculosis. It may be necessary to increase the dose of paclitaxel.
• vaccines: if you have been vaccinated recently, or if you plan to be vaccinated, tell your doctor. The use of paclitaxel with some vaccines may lead to serious complications.
• cisplatin (to treat cancer): paclitaxel should be administered before cisplatin. It may be necessary to monitor your kidney function more frequently.
• doxorubicin (to treat cancer): paclitaxel should be administered 24 hours after doxorubicin, to avoid high levels of doxorubicin in your body.

Pregnancy and breastfeeding

Tell your doctor if you are pregnantor think you may be pregnant before receiving treatment with paclitaxel. If you may become pregnant, use a safe and effective contraceptive method during treatment. Paclitaxel should not be used during pregnancy, unless clearly necessary. Men and women of childbearing age, and/or their partners, should use contraceptive methods during and for at least 6 months after the end of treatment with paclitaxel.

Male patients should ask about sperm freezing before treatment with paclitaxel, due to the possibility of irreversible infertility.

If you are breastfeeding, tell your doctor. Stop breastfeeding if you are receiving paclitaxel. Do not restart breastfeeding until your doctor tells you to.

Driving and using machines

This medicine contains alcohol. Therefore, it may be unwise to drive immediately after a treatment cycle. In any case, do not drive if you feel dizzy or unsure of yourself.

Paclitaxel Aurovitas contains alcohol and macrogolglycerol ricinoleate

This medicine contains approximately 50% v/v ethanol, which corresponds to almost 20 g of ethanol per dose, equivalent to 500 ml of beer or a large glass (210 ml) of wine per dose.

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.

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

If you have epilepsy or liver problems, talk to your doctor or pharmacist before using this medicine.

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

If you are pregnant or breastfeeding, talk to your doctor or pharmacist before using this medicine.

If you are addicted to alcohol, talk to your doctor or pharmacist before using this medicine.

This medicine may cause severe allergic reactions because it contains macrogolglycerol ricinoleate.

3. How to use Paclitaxel Aurovitas

• To minimize the risk of allergic reactions, before starting treatment with paclitaxel, you will be given other medicines. These medicines may be administered in the form of tablets or intravenous infusion, or both.
• Paclitaxel will be administered to you through a drip in one of your veins (intravenous infusion), through an in-line filter. It will be administered by a healthcare professional who will prepare the infusion solution before administering it to you. The dose you receive will also depend on the results of your blood tests. Depending on the type and severity of the cancer, you will receive paclitaxel alone or in combination with another anticancer agent.
• Paclitaxel must always be administered in a vein over a period of 3 to 24 hours. It is usually administered every 2 or 3 weeks, unless your doctor indicates a different dosing schedule. Your doctor will tell you how many treatment cycles with paclitaxel you need to receive.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

If you have been administered more Paclitaxel Aurovitas than you should

There is no known antidote for paclitaxel overdose, so you will receive treatment for the symptoms.

In case of accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone 91 562 04 20, indicating the medicine and the amount administered.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Tell your doctor immediately if you notice any signs of an allergic reaction. You may experience one or more of the following signs:

• redness (flushing).
• skin reactions.
• itching (pruritus).
• chest tightness.
• shortness of breath or difficulty breathing.
• inflammation.

All of these can be signs of serious side effects.

Tell your doctor immediately:

• If you have fever, severe chills, sore throat or mouth ulcers (signs of bone marrow suppression).
• If you have numbness or weakness in arms and legs (symptoms of peripheral neuropathy).
• If you develop severe or persistent diarrhea, with fever and abdominal pain.

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

• Mild allergic reactions, such as redness, rash, itching.
• Infections: mainly upper respiratory tract infections, urinary tract infections.
• Shortness of breath.
• Sore throat or mouth ulcers, mouth sores and redness, diarrhea, discomfort (nausea, vomiting).
• Hair loss (in most cases of hair loss, it occurred less than a month after starting paclitaxel. When it happens, it is a pronounced hair loss (more than 50%) in most patients).
• Muscle pain, cramps, joint pain.
• Fever, severe chills, headache, dizziness, fatigue, pallor, bleeding, easy bruising.
• Numbness, tingling or weakness in arms and legs (all symptoms of peripheral neuropathy, which may persist for more than 6 months after stopping treatment with paclitaxel).
• Lab tests may show: decreased platelet count, decreased white blood cell count or red blood cell count, low blood pressure.

Common side effects (may affect up to 1 in 10 people)

• Mild and transient changes in nails and skin, reactions at the injection site (local inflammation, pain and redness of the skin).
• Lab tests may show: slowing of heart rate, severe elevation of liver enzymes (alkaline phosphatase and AST-SGOT).

Uncommon side effects (may affect up to 1 in 100 people)

• Shock due to infection (known as "septic shock").
• Palpitations, heart failure (AV block), rapid heartbeat, infarction, respiratory problems.
• Fatigue, sweating, fainting, significant allergic reactions, inflammation of a vein caused by a blood clot (thrombophlebitis), swelling of the face, lips, mouth, tongue or throat.
• Back pain, chest pain, pain in hands and feet, chills, abdominal pain (abdominal).
• Lab tests may show: significant elevation of bilirubin (jaundice), high blood pressure and blood clots.

Rare side effects (may affect up to 1 in 1,000 people)

• Decreased white blood cell count, with fever and increased risk of infection (febrile neutropenia).
• Affecting the nerves, with a feeling of weakness in the muscles of the arms and legs (motor neuropathy).
• Shortness of breath, pulmonary embolism, pulmonary fibrosis, interstitial pneumonia, dyspnea, pleural effusion.
• Intestinal obstruction, intestinal perforation, colon inflammation (ischemic colitis), pancreatitis.
• Itching, rash, redness of the skin (erythema).
• Blood infection (septicemia), peritonitis.
• Fever, dehydration, asthenia, edema, discomfort.
• Severe and potentially life-threatening hypersensitivity reactions (anaphylactic reactions).
• Lab tests may show: increased creatinine in blood, indicating kidney dysfunction.

Very rare side effects (may affect up to 1 in 10,000 people)

• Rapid and irregular heartbeat (atrial fibrillation, supraventricular tachycardia).
• Sudden disorder in the hematopoietic cells (acute myeloid leukemia, myelodysplastic syndrome).
• Visual and/or optic nerve disorders (scintillating scotoma).
• Hearing loss (ototoxicity), ringing in the ears (tinnitus), vertigo.
• Cough.
• Blood clot in a blood vessel in the abdomen and intestine (mesenteric thrombosis), colon inflammation, sometimes with severe persistent diarrhea (pseudomembranous colitis, neutropenic colitis), fluid retention in the abdomen (ascites), esophagitis, constipation.
• Severe hypersensitivity reactions, such as fever, skin redness, joint pain and/or eye inflammation (Stevens-Johnson syndrome), local skin peeling (necrotizing epidermolysis), redness with irregular red spots (erythema multiforme), skin inflammation, with blisters and peeling (exfoliative dermatitis), hives, nail detachment (patients under treatment should wear sun protection on hands and feet).
• Loss of appetite (anorexia)
• Severe and potentially life-threatening hypersensitivity reactions with shock (anaphylactic reactions).
• Alteration of liver function (liver necrosis, hepatic encephalopathy [both with reported fatal outcomes]).
• Confusional state.

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

• Disseminated intravascular coagulation or "DIC" has been reported. This is a serious condition that causes easier bleeding, blood clots or both.
• Hardening/thickening of the skin (scleroderma).
• Metabolic complications after cancer treatment (tumor lysis syndrome).
• Eye disorders, such as thickened and swollen macula (macular edema), flashes in the eyes (photopsia), small spots or particles floating in the visual field (vitreous floaters).
• Inflammation of the veins (phlebitis).
• Autoimmune disease with multiple symptoms such as red and scaly patches on the skin, joint pain or fatigue (systemic lupus erythematosus).

Redness and swelling of the palms of the hands and the soles of the feet that can cause skin peeling.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist, even if it is 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 Paclitaxel Aurovitas

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

Store the vial in the outer packaging to protect it from light.

Do not use this medicine after the expiry date stated on the carton, after EXP. The expiry date is the last day of the month indicated.

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

6. Package Contents and Additional Information

Composition of Paclitaxel Aurovitas

• The active ingredient is paclitaxel.
• 1 ml of concentrate for solution for infusion contains 6 mg of paclitaxel.
• The other ingredients are: citric acid, macrogolglycerol ricinoleate, and anhydrous ethanol.

Appearance of the Product and Package Contents

Paclitaxel Aurovitas 6 mg/ml concentrate for solution for infusion is a clear, colorless or pale yellow, slightly viscous solution, and is packaged in glass vials.

Package sizes:

1 vial of 5 ml (30 mg/5 ml)

1 vial of 16.7 ml (100 mg/16.7 ml)

1 vial of 25 ml (150 mg/25 ml)

1 vial of 50 ml (300 mg/50 ml)

Not all package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

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 medicine, please contact the local representative of the marketing authorization holder:

Aurovitas Spain, S.A.U.

Avda. de Burgos, 16-D

28036 Madrid

Spain

This medicine is authorized in the Member States of the European Economic Area under the following names:

Germany: Paclitaxel Aurobindo 6 mg/ml Konzentrat zur Herstellung einer Infusionslösung

Belgium: Paclitaxel AB 6 mg/ml

Spain: Paclitaxel Aurovitas 6 mg/ml concentrate for solution for infusion EFG

France: Paclitaxel Arrow 6mg/ml, solution à diluer pour perfusion

Netherlands: Paclitaxel Aurobindo 6 mg/ml, concentraat voor oplossing voor infusie

Italy: Paclitaxel Aurobindo

Portugal: Paclitaxel Aurovitas

Date of the last revision of this leaflet:December 2020

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/).

This information is intended only for healthcare professionals:

Instructions for Use

CYTOSTATIC AGENT

Handling of Paclitaxel Aurovitas

As with all cytotoxic agents, Paclitaxel Aurovitas should be handled with caution. Dilutions should be carried out by experienced personnel, under aseptic conditions, and in a designated area. Precautions should be taken to avoid skin and mucous membrane contact. After topical exposure, tingling, burning sensation, and redness have been described. In case of inhalation, difficulty breathing (dyspnea), chest pain, throat burning, and nausea have been reported.

Protection instructions for the preparation of Paclitaxel Aurovitas 6 mg/ml concentrate for solution for infusion:

1. A protective hood, as well as protective gloves and gown, should be used. If a protective hood is not available, goggles and a mask should be used.
2. Open containers, such as injection vials, infusion bottles, and cannulas, syringes, catheters, and tubes used, as well as cytostatic residues, should be considered hazardous waste and disposed of in accordance with local regulations for the handling of HAZARDOUS WASTE.
3. In case of spillage, follow these instructions:
   • protective clothing should be used
   • broken glass should be collected and thrown into a HAZARDOUS WASTE container
   • contaminated surfaces should be washed thoroughly with a large amount of cold water
   • washed surfaces should be completely dried and materials used should be eliminated as HAZARDOUS WASTE
4. If paclitaxel comes into contact with the skin, wash the affected area with a large amount of running water, and then wash with water and soap. In case of contact with mucous membranes, wash the area thoroughly with water. If you experience any discomfort, contact a doctor.
5. If paclitaxel comes into contact with the eyes, rinse them thoroughly with a large amount of cold water. Contact an ophthalmologist immediately.

Preparation of the Infusion Solution

Closed systems of the type "Chemo-Dispensing Pin" or similar devices should not be used, as they may cause the collapse of the vial's elastomer, resulting in the loss of sterility.

Preparation, storage, and administration should not be performed in equipment containing PVC (see "Incompatibilities" section below).

Before proceeding to infusion, Paclitaxel Aurovitas 6 mg/ml concentrate for solution for infusion should be diluted using aseptic techniques. For dilution, the following infusion solutions can be used: sodium chloride 0.9% infusion solution, or glucose 5% infusion solution, or a mixture of glucose 5% and sodium chloride 0.9% solution, or Ringer's solution for infusion with glucose 5%, up to a final concentration of 0.3 to 1.2 mg/ml.

Rare cases of precipitation have been reported during paclitaxel infusions, usually towards the end of the 24-hour infusion period. Although the cause of this precipitation has not been established, it is likely related to the supersaturation of the diluted solution. To reduce the risk of precipitation, paclitaxel should be administered as soon as possible after dilution, and excessive agitation, vibration, or shaking should be avoided.

After preparation, these solutions may present a slightly turbid appearance, which is attributed to the excipient of the preparation and is not eliminated by filtration. To reduce the risk of precipitation, the infusion of Paclitaxel Aurovitas diluted should be used as soon as possible after dilution.

Infusion Technique

The infusion solution of Paclitaxel Aurovitas should be administered as an intravenous infusion over 3 or 24 hours.

Paclitaxel Aurovitas should be administered through an in-line filter with a microporous membrane ≤ 0.22 μm. (No significant loss of potency has been observed after simulated release of the solution through IV infusion equipment with an in-line filter).

Infusion equipment should be thoroughly washed before use. During infusion, the appearance of the solution should be regularly examined, and if precipitation is observed, the infusion should be interrupted.

Stability and Storage Conditions

Store the vial in the original packaging to protect it from light. If stored in a refrigerator, a precipitate may form, which dissolves again by gently shaking or without shaking when it reaches room temperature. This does not affect the quality of the product. If the solution remains turbid or if an insoluble precipitate is observed, the vial should be discarded. The expiry date is stated on the carton and on the label of the vial. Do not use after this date.

After opening: from a microbiological point of view, once the package is opened, the product should be stored for a maximum of 28 days at 25°C. Storage under other conditions will be the responsibility of the user.

The prepared infusion solutions are chemically and physically stable for 7 days at 5°C and 25°C when diluted in a glucose 5% solution and glucose 5% in injectable Ringer's solution, and for 14 days when diluted in sodium chloride 0.9% injection solution. From a microbiological point of view, the product should be used immediately. If not used immediately, the in-use storage conditions and times will be the responsibility of the user and should not exceed 24 hours at 2-8°C, unless the dilution is performed under validated and controlled aseptic conditions.

After dilution, the solution is for single use.

Incompatibilities

To minimize patient exposure to DEHP (di-2-ethylhexyl phthalate), which may be formed by leaching of PVC-plasticized infusion bags, infusion equipment, or other medical devices, diluted paclitaxel solutions should be stored in containers that do not contain PVC (glass, polypropylene), or in plastic bags (polypropylene, polyolefin), and administered with polyethylene administration equipment. No significant release of DEHP has been observed with the use of filter models that incorporate a short PVC-plasticized inlet/outlet tube (e.g., IVEX-2?).

This medicine should not be mixed with other medicines except those mentioned above in the "Preparation of the Infusion Solution" section.

Elimination

All materials used for the preparation, administration, or that come into contact with paclitaxel should be eliminated according to local regulations for the handling of cytotoxic compounds.