Prospecto: information for the user

Paclitaxel Aurovitas6 mg/ml concentrate for infusion solution EFG

Read this prospect carefully before starting to use this medicine, because it contains important information for you.

-Keep this prospect, as you may need to read it again.

-If you have any questions, consult your doctor.

-If you experience any adverse effects, consult your doctor, even if they are not listed in this prospect. See section 4.

1.What isPaclitaxel Aurovitasand for what it is used

2.What you need to know before starting to usePaclitaxel Aurovitas

3.How to usePaclitaxel Aurovitas

4.Possible adverse effects

5.Storage ofPaclitaxel Aurovitas

6.Contents of the package and additional information

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

Paclitaxel belongs to a group of cancer medications 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 medication called cisplatin).

•after treatment with reference medications containing platinum has not been effective.

Breast Cancer

•as first-line treatment for advanced cancer or cancer that has spread to other parts of the body (metastatic cancer). Paclitaxel is combined with ananthracycline(for example, doxorubicin) or with a medication calledtrastuzumab(for patients in whom an anthracycline is not suitable or who have cancer whose cells have a protein on their surface called HER2; see the trastuzumab package insert).

•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 reference treatments based on anthracyclines or who cannot use these treatments.

Advanced Non-Small Cell Lung Cancer

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

Kaposi's Sarcoma associated with AIDS

•after another treatment (for example, liposomal anthracyclines) has not been effective.

No use Paclitaxel Aurovitas

-if you are allergic to paclitaxel or any of the other components of this medication (listed in section 6), especiallymacrogolglycerol ricinoleate.

-if you have very low white blood cell counts in your blood. Your doctor will take a blood sample to check this.

-if you are breastfeeding.

-ifyou have a severe and uncontrolled infectionand paclitaxel is to be used to treat Kaposi's sarcoma.

If you are in any of the above circumstances, speak with your doctor before starting treatment with paclitaxel.

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

Warnings and Precautions

Consult your doctor before starting to use Paclitaxel Aurovitas.

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

•If you experiencesevere allergic reactions(such as difficulty breathing, shortness of breath, chest tightness, low blood pressure, dizziness, feeling of dizziness, skin reactions such as exanthema or inflammation).

•If you havefever, intense chills, sore throat, or mouth ulcers(signs of bone marrow suppression).

•If you experiencenumbness or weakness in arms and legs(signs of peripheral neuropathy); a reduction in paclitaxel dose may be necessary.

•If you havesevere liver problems; in this case, the use of paclitaxel is not recommended.

•If you haveheart conduction disorders.

•If you developsevere or persistent diarrheawith fever and stomach pain during treatment with paclitaxel or immediately after its administration. You may have pseudomembranous colitis.

•If you have receivedprevious radiation therapy to the chest(as it may increase the risk of pulmonary inflammation).

•If you havemouth sores or redness(signs of mucositis) and are being treated for Kaposi's sarcoma. You may need a lower dose.

Inform your doctor immediately if any of these cases apply to you.

Paclitaxelmust be administered always through a vein. Administration of paclitaxel through arteries may cause inflammation of these and you may experience pain, inflammation, redness, and heat.

Other Medications andPaclitaxel Aurovitas

Informyour doctor if you are using, have used recently, or may need to use any other medication, even those purchased without a prescription. This is because it is possible that paclitaxel or the other medication may not work as expected, or it is more likely to have a side effect.

Interaction means that different medications can influence each other. Consult your doctor when taking paclitaxel at the same time as:

•medications to treat infections (such as antibiotics like erythromycin, rifampicin, etc.; ask your doctor, nurse, or pharmacist if you are not sure if the medication you are taking is an antibiotic).

•medications used to help you stabilize your mood, sometimes called antidepressants (e.g., fluoxetine).

•medications used to treat seizures (epilepsy) (e.g., carbamazepine, phenytoin).

•medications used to help you lower your blood lipid levels (e.g., gemfibrozil).

•medications used to treat heartburn or stomach ulcers (e.g., cimetidine).

•medications used to treat HIV or AIDS (e.g., ritonavir, saquinavir, indinavir, nelfinavir, efavirenz, nevirapina).

•a medication called clopidogrel used to prevent blood clots.

•a medication called rifampicin, an antibiotic used to treat tuberculosis. You may need to increase the dose of paclitaxel.

•vaccines: if you have been vaccinated recently, or if you are planning to be vaccinated, inform your doctor. The use of paclitaxel with some vaccines may lead to serious complications.

•cisplatin (to treat cancer): paclitaxel should be administered before cisplatin. You may need to monitor your renal 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

Inform your doctor if you are pregnantor think you may bebefore receiving treatment with paclitaxel. If there is a possibility that you may become pregnant,use a safe and effective contraceptive method during treatment. Paclitaxel should notbe used during pregnancy, except when clearly necessary. Males and females of childbearing age, and/or their partners,should use contraceptive methods during at least the 6 months following the completion of treatment with paclitaxel.

Male patients should request information on sperm cryopreservation before treatment with paclitaxel, due to the possibility of irreversible infertility.

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

Driving and Operating Machines

This medication 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 medication contains approximately 50% v/v ofethanol, which corresponds to a quantity of 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 contained in this medication 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 contained in this medication may affect your ability to drive and operate machines due to the fact that it may alter your judgment and reaction time.

If you have epilepsy or liver problems, consult your doctor or pharmacist before using this medication.

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

If you are pregnant or breastfeeding, consult your doctor or pharmacist before using this medication.

If you have a history of alcohol addiction, consult your doctor or pharmacist before using this medication.

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

•To minimize the risk of allergic reactions, before starting treatment with paclitaxel, you will be given other medications. These medications may be administered in the form of tablets or intravenous infusion, or in both forms.

•Paclitaxel will be administered through a slow intravenous infusionin 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 cancer, you will receive paclitaxel alone or in combination with another antineoplastic agent.

•Paclitaxel must be administered always 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 inform you of the number of treatment cycles with paclitaxel that you need to receive.

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

If you have been given more Paclitaxel Aurovitas than you should

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

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

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

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

•Redness (rubor).

•Skin reactions.

•Itching (pruritus).

•Chest tightness.

•Shortness of breath or difficulty breathing.

•Inflammation.

All of these can be signs of serious side effects.

Inform your doctor immediately:

•If you havefever, intense chills, sore throat, or mouth ulcers(signs of bone marrow suppression).

•If you havenumbness or weakness in arms and legs(symptoms of peripheral neuropathy).

•If you developsevere or persistent diarrhea, with fever and stomach pain.

Side effectsvery common (may affect more than 1 in 10 people)

•Mild allergic reactions, such as redness, skin 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 (most cases of hair loss occurred less than a month after starting paclitaxel. When it happens, it is a pronounced hair loss (over 50%) in most patients).

•Muscle pain, cramps, joint pain.

•Fever, intense chills, headache, dizziness, fatigue, pallor, hemorrhages, appearance of hematomas with increased ease.

•Numbness, tingling or weakness in arms and legs (symptoms of peripheral neuropathy, which may persist for more than 6 months after stopping treatment with paclitaxel).

•Laboratory tests may show: decreased platelets, decreased white blood cells or red blood cells, low blood pressure.

Side effectscommon (may affect up to 1 in 10 people)

•Mild and transient changes in nails and skin, reactions at the injection site (localized inflammation, pain, and redness of the skin).

•Laboratory tests may show: bradycardia, severe elevation of liver enzymes (alkaline phosphatase and AST-SGOT).

Side effectsuncommon (may affect up to 1 in 100 people)

•Shockdue to infections (known as "septic shock").

•Palpitations, cardiac dysfunction (AV block), rapid heart rate, myocardial infarction, respiratory problems.

•Fatigue, sweating, syncope, significant allergic reactions, localized inflammation of a vein caused by a blood clot (thrombophlebitis), facial swelling, lip, mouth, tongue, or throat.

•Back pain, chest pain, hand and foot pain, chills, abdominal pain.

•Laboratory tests may show: significant elevation of bilirubin (jaundice), high blood pressure, and clots.

Side effectsrare (may affect up to 1 in 1,000 people)

•Decreased white blood cells, with fever and increased risk of infection (febrile neutropenia).

•Nerve damage, with muscle weakness in arms and legs (motor neuropathy).

•Shortness of breath, pulmonary embolism, pulmonary fibrosis, interstitial pneumonia, dyspnea, pleural effusion.

•Intestinal obstruction, intestinal perforation, ischemic colitis, pancreatitis.

•Itching, skin rash, skin redness (erythema).

•Blood infection (septicemia), peritonitis.

•Fever, dehydration, asthenia, edema, discomfort.

•Severe and potentially life-threatening allergic reactions (anaphylactic reactions).

•Laboratory tests may show: increased creatinine in blood, indicating renal dysfunction.

Side effectsvery rare (may affect up to 1 in 10,000 people)

•Rapid and irregular heart rate (atrial fibrillation, supraventricular tachycardia).

•Sudden changes in hematopoietic cells (acute myeloid leukemia, myelodysplastic syndrome).

•Visual and optic nerve changes (scintillating scotoma).

•Loss of hearing (ototoxicity), ear ringing (tinnitus), vertigo.

•Cough.

•Clot in a blood vessel in the abdomen and intestine (mesenteric thrombosis), intestinal inflammation, sometimes with persistent and severe diarrhea (pseudomembranous colitis, neutropenic colitis), ascites, esophagitis, constipation.

•Severe and potentially life-threatening allergic reactions, such as fever, skin redness, joint pain, and/or eye inflammation (Stevens-Johnson syndrome), local skin exfoliation (necrolytic epidermal necrosis), erythema multiforme, skin inflammation with blisters and peeling (exfoliative dermatitis), urticaria, nail detachment (patients on treatment should wear sun protection on hands and feet).

•Loss of appetite (anorexia)

•Severe and potentially life-threatening allergic reactions with shock (anaphylactic reactions).

•Liver function changes (hepatic necrosis, hepatic encephalopathy [both with reported fatal outcomes]).

•Confusion.

Frequency not known (cannot be estimated from available data)

•Disseminated intravascular coagulation or "DIC" has been reported. This is a serious condition that causes increased bleeding, clots, or both.

•Hardening/thickening of the skin (scleroderma).

•Metabolic complications after cancer treatment (tumor lysis syndrome).

•Eye changes, such as thickened and swollen macula (macular edema), eye flashes (photopsia), small dots or particles floating in the field of vision (vitreous floaters).

•Vein inflammation (phlebitis).

•Autoimmune disease with multiple symptoms such as red and scaly skin patches, joint pain, or fatigue (systemic lupus erythematosus).

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

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Use:www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

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

Do not use this medication after the expiration date shown on the case, after CAD. The expiration date is the last day of the month indicated.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medicines you no longer need. This will help protect the environment.

Composition of Paclitaxel Aurovitas

-The active ingredient is paclitaxel.

-1 ml of concentrate for infusion solution contains 6 mg of paclitaxel.

-The other components are: citric acid, ricinoleate of macrogolglycerol, and anhydrous ethanol.

Aspect of the product and content of the packaging

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

Packaging 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)

Only some packaging sizes may be commercially available.

Marketing authorization holder and manufacturer responsible

Marketing authorization holder

Eugia Pharma (Malta) Limited

Vault 14, Level 2, Valletta Waterfront

Floriana, FRN 1914

Malta

Manufacturer responsible

APL Swift Services (Malta) Limited

HF26, Hal Far Industrial Estate, Hal Far

Birzebbugia, BBG 3000

Malta

O

Generis Farmacêutica, S.A.

Rua João de Deus, no 19, Venda Nova

2700-487 Amadora

Portugal

For more information about this medication, please contact the local representative of the marketing authorization holder:

Aurovitas Spain, S.A.U.

Avda. de Burgos, 16-D

28036 Madrid

Spain

This medicinal product is authorized in the Member States of the European Economic Area with the following names:

Germany:PaclitaxelAurobindo6 mg/ml Concentrate for the preparation of an infusion solution

Belgium:Paclitaxel AB 6 mg/ml

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

France:Paclitaxel Arrow 6mg/ml, solution to be diluted for infusion

Netherlands:PaclitaxelAurobindo6 mg/ml, concentrate for infusion solution

Italy:PaclitaxelAurobindo

Portugal:PaclitaxelAurovitas

Last review date of this leaflet:December 2020

For detailed information about this medicinal product, please visit the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) (http://www.aemps.gob.es/).

This information is intended for healthcare professionals only:

Instructions for use

CYTOSTATIC AGENT

Handling of Paclitaxel Aurovitas

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

Instructions for protection for the preparation of Paclitaxel Aurovitas 6 mg/ml concentrate for infusion solution:

1.A protective hood, as well as protective gloves and gown, must be used. If a protective hood is not available, glasses and a mask must be used.

2.Open containers, such as injection vials, infusion bags, and cannulas, syringes, catheters, and tubes used, as well as cytostatic residues must be considered as hazardous waste and disposed of in accordance with local regulations for the handling of HAZARDOUS WASTE.

3.In case of spill, follow these instructions:

-Protective clothing must be used

-The broken glass must be collected and disposed of in a HAZARDOUS WASTE container

-The contaminated surfaces must be thoroughly washed with large amounts of cold water

-The washed surfaces must be completely dried and the materials used must be disposed of as HAZARDOUS WASTE

4.If paclitaxel comes into contact with the skin, the affected area must be rinsed with large amounts of running water, and then washed with water and soap. In case of contact with mucous membranes, the area must be thoroughly rinsed with water. If you experience any discomfort, contact a doctor.

5.In case paclitaxel comes into contact with the eyes, they must be thoroughly rinsed with large amounts of cold water. Contact an ophthalmologist immediately.

Preparation of the infusion solution

The infusion solution of Paclitaxel Aurovitas must not be used with closed systems of the type "Chemo-Dispensing Pin" or similar, as they may cause the collapse of the elastomer of the vial, resulting in the loss of the integrity of the sterility.

The preparation, storage, and administration must not be carried out in equipment containing PVC (see section "Incompatibilities", below).

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

Cases of rare 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 over-saturation of the diluted solution. To reduce the risk of precipitation, paclitaxel must be administered as soon as possible after dilution, and excessive agitation, vibration, or shaking must be avoided.

After preparation, these solutions may present a slight turbidity, 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 must be used as soon as possible after dilution.

Infusion technique

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

Paclitaxel Aurovitas must be administered through a filter in line with a microporous membrane ≤0.22 μm. (No significant losses of potency have been observed after simulated release of the solution through IV infusion equipment provided with a filter in line).

Infusion equipment must be thoroughly washed before use. During infusion, the appearance of the solution must be regularly examined, and in case of precipitation, infusion must be interrupted.

Stability and storage conditions

Store the vial in the original packaging to protect it from light. If stored in the refrigerator, a precipitate may form, which dissolves again when agitated slightly or not at all, when the ambient temperature is reached. This does not affect the quality of the product. If the solution remains turbid or a precipitate is noted, the vial must be discarded. The expiration date is indicated on the box and on the label of the vial of the product. Do not use after that date.

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

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

After dilution, the solution is for single use.

Incompatibilities

To minimize the patient's exposure to DEHP (di-2-ethylhexyl phthalate), which may be formed by leaching of PVC plastified from infusion bags, infusion equipment, or other medical instruments, paclitaxel diluted solutions must 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 models of filters that incorporate a short PVC plastified outlet/entry tube (e.g. IVEX-2?).

This medicinal product must not be mixed with other medicinal products except those mentioned in the section "Preparation of the infusion solution" above.

Elimination

All materials used for preparation, administration, or coming into contact with paclitaxel must be disposed of in accordance with local regulations for the handling of cytotoxic compounds.