Prospect: information for the user

Paclitaxel Kabi 6mg/ml concentrated solution for EFG infusion

The name of your medicine is ‘Paclitaxel Kabi 6 mg/ml concentrated solution for EFG infusion’ but in the rest of the prospectus it will be called ‘Paclitaxel Kabi’.

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

• Keep this prospectus, as you may need to read it again.
• If you have any doubts, consult your doctor or nurse.
• If you experience any adverse effects, consult your doctor or nurse, even if they are not listed in this prospectus. See section 4.

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

2.What you need to know before starting to use Paclitaxel Kabi

3.How Paclitaxel Kabi is administered

4.Possible adverse effects

5Storage of Paclitaxel Kabi

6.Contents of the package and additional information

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

Paclitaxel Kabi is used to treat:

Ovarian cancer

• as first-line treatment (after initial surgery in combination with a platinum-based drug called cisplatin)
• after treatment with reference drugs containing platinum has not worked.

Breast cancer

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

Kaposi's sarcoma associated with AIDS

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

Do not administer Paclitaxel Kabi

• if you areallergicto paclitaxel, or to any of the other components of this medication (listed in section 6), especially, to polyoxylated castor oil (ricinoleate of macrogolglycerol).

• if you are breastfeeding
• if you have very low white blood cell counts(a baseline neutrophil count of <1.5 x 109/l or <1.0 x 109/l for patients with Kaposi's sarcoma; your doctor will inform you about this aspect). Your doctor will take a blood sample to check it.
• if you have a severe and uncontrolled infection(or in the case of using Paclitaxel Kabi to treat Kaposi's sarcoma).

If you are in any of the above circumstances, talk to your doctor before starting treatment with Paclitaxel Kabi.

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

Warnings and precautions

Consult your doctor before starting to use Paclitaxel Kabi.

Before starting treatment with Paclitaxel Kabi, you will be given other medicationsto minimize the risk of allergic reactions.

-if you experience allergic reactions(such as difficulty breathing, shortness of breath, chest tightness, low blood pressure, dizziness, sensation of dizziness, skin reactions such as exanthema or inflammation).

• if you have fever, intense chills, sore throat, or mouth ulcers(signs of bone marrow suppression),

• if you experiencenumbness, tingling,pinching sensations in the skin, sensitivity to touch, or weaknessin arms and legs(signs of peripheral neuropathy); you may need a reduction in the dose of Paclitaxel Kabi
• if you havesevere liver problemsin this case, the use of Paclitaxel Kabi is not recommended

• if you have cardiac conduction disorders

• if you developsevere or persistent diarrheawith fever and stomach pain, during treatment with Paclitaxel Kabi or immediately after its administration. You may have inflammation of the colon (pseudomembranous colitis).

• if you have previously received radiation therapy in the chest(as it may increase the risk of pulmonary inflammation)
• if you havemouth sores or redness(signs of mucositis)and are being treated forKaposi's sarcoma.You may need a lower dose.

Due to the possibility of extravasation, it is recommended to strictly control the infusion site in case of a possible infiltration during the administration of the medication.

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

Paclitaxel Kabi must be administered always through a vein. Administration of Paclitaxel Kabi through an artery may cause inflammation of these and you may experience pain, inflammation, redness, and heat.

Use of Paclitaxel Kabi with other medications

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), including medications to treat fungal infections (e.g., ketoconazole)
• medications used to help stabilize your mood, sometimes called antidepressants (e.g., fluoxetine)
• medications used to treat seizures (epilepsy) (e.g., carbamazepine, phenytoin)
• medications used to help 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.

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

Pregnancy, breastfeeding, and fertility

Pregnancy

Before receiving treatment with Paclitaxel,inform your doctor if you are pregnantor think you may be. If there is a possibility that you may become pregnant,use a safe and effective contraceptive method during treatment. Paclitaxel should not be used during pregnancy, unless it is 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.

Breastfeeding

If you are breastfeeding, inform your doctor.It is unknown whether paclitaxel is excreted in breast milk. Given the possibility of causing harm to the infant, stop breastfeeding if you are receiving Paclitaxel Kabi. Do not resume breastfeeding until your doctor tells you to.

Driving and operating machinery

You should not drive or operate machinery if you experience dizziness or vertigo.Paclitaxel Kabi contains castor oil, which may cause allergic reactions. If you are allergic to castor oil, consult your doctor before receiving Paclitaxel Kabi.

The amount of alcohol in this medication may affect your ability to drive or operate machinery. This is because it may affect your judgment and the speed with which you react.

Paclitaxel Kabi contains castor oil (ricinoleate of macrogolglycerol) and alcohol.

Paclitaxel Kabi contains castor oil and may cause severe allergic reactions. If you are allergic to castor oil, consult your doctor before receiving Paclitaxel Kabi.

This medication contains 393mg of alcohol (ethanol) per 1 ml, which is equivalent to 39.3% v/v. The amount in 52.5 ml of this medication is equivalent to 515.8 ml of beer or 206.3 ml of wine.

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

If you are addicted to alcohol, consult your doctor or pharmacist before taking this medication.

• To minimize the risk of allergic reactions,before starting treatment with Paclitaxel Kabi, you will be given other medications. These medications may be administered in the form of tablets or intravenous infusion, or in both forms.
• Paclitaxel Kabi will be administered through a slow intravenous infusioninto 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 Kabi alone or in combination with another antineoplastic agent.
• Paclitaxel Kabi must be administered always through 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 Kabi that you need to receive.

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

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

If you consider you are experiencing any sign of allergic reaction, inform your doctor immediately.You may experience one or more of the following signs:

• Redness (rubefaction)

• Skin reactions

• Itching (pruritus)

• Chest tightness

• Shortness of breath or difficulty breathing

• Inflammation

All of them can be signs of severe side effects.

Inform your doctor immediately if you experience:

• Fever, intense chills, sore throat, or mouth ulcers(signs of bone marrow suppression).
• Numbness or weakness in arms and legs(symptoms of peripheral neuropathy).
• Severe or persistent diarrhea, with fever and stomach pain.

Very common side effects: can affect more than 1 in 10 people

• Mild allergic reactions, such as redness (rubefaction), rash (exanthema), itching (pruritus)
• Infections: mainly upper respiratory tract infections, urinary tract infections
• 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
• Numbness, tingling, or weakness in arms and legs (symptoms of peripheral neuropathy) *
• *May persist for more than 6 months after stopping treatment with paclitaxel

• Laboratory tests may show: decreased platelets that can cause bleeding or the appearance of bruises with increased ease, decreased white blood cells or red blood cells, low blood pressure

Common side effects: can 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: slowed heart rate, severe elevation of liver enzymes (alkaline phosphatase and AST-SGOT)

Rare side effects: can affect up to 1 in 100 people

• Shockdue to infections (known as "septic shock")
• Palpitations, heart dysfunction (AV block, cardiomyopathy), rapid heartbeat, infarction, respiratory distress
• Fatigue, sweating, syncope, significant allergic reactions, phlebitis (inflammation of a vein), facial swelling, lip, mouth, tongue, or throat swelling
• Chest pain, back pain, hand and foot pain, chills, abdominal pain (stomach)
• Laboratory tests may show: significant elevation of bilirubin (jaundice), high blood pressure, and clots

Very rare side effects: can affect up to 1 in 10,000 people.

• Decreased white blood cells, with fever and increased risk of infection (febrile neutropenia)
• Affecting nerves, with sensation of weakness in arm and leg muscles (motor neuropathy)
• Heart failure (cardiac insufficiency)
• Shortness of breath, narrowing and blockage of blood vessels in the lungs that can cause shortness of breath (pulmonary embolism), inflammatory reaction of lung tissue with changes and hardening of tissue (pulmonary fibrosis), interstitial pneumonia, difficulty breathing, lung injuries, and fluid around the lungs (pleural effusion)
• Intestinal obstruction, intestinal perforation, inflammation of the colon (ischemic colitis), inflammation of the pancreas (pancreatitis)
• Itching (pruritus), rashes (exanthema), skin redness (erythema)
• Blood infection (septicemia), peritonitis (inflammation of the peritoneum), pneumonia
• Fever (pyrexia), dehydration, weakness (asthenia), accumulation of fluid in body tissues (edema), discomfort
• Severe and potentially life-threatening allergic reactions (anaphylactic reactions)
• Laboratory tests may show: increased creatinine in blood, indicating kidney dysfunction

Side effects of unknown frequency: the frequency cannot be estimated from available data

• Sudden disruption of hematopoietic cells (acute myeloid leukemia, myelodysplastic syndrome)
• Visual and/or optic nerve alterations (scintillating scotoma)
• Loss of hearing (ototoxicity), ringing in the ears (tinnitus), vertigo
• Cough
• Thrombosis of a blood vessel in the abdomen and intestine (mesenteric thrombosis), inflammation of the colon, sometimes with severe and persistent diarrhea (pseudomembranous colitis, neutropenic colitis), ascites (fluid retention in the abdomen), esophagitis (inflammation of the esophagus), constipation
• Severe allergic reactions, such as fever, skin redness, joint pain, and/or eye inflammation (Stevens-Johnson syndrome), localized skin exfoliation (epidermal necrosis), redness with irregular, exudative patches (erythema multiforme), skin inflammation, with blisters and peeling (exfoliative dermatitis), urticaria, onycholysis (patients on treatment should wear sun protection on hands and feet)
• Loss of appetite (anorexia)
• Severe and potentially life-threatening allergic reactions withshock(anaphylactic reactions)
• Liver function alterations (hepatic necrosis, hepatic encephalopathy [both with reported fatal outcomes])
• Confusion
• Grand mal seizures, autonomic nervous system disorders (neuropathy, alteration of involuntary body functions, which can cause ileus and low blood pressure), seizures, brain disease (encephalopathy), dizziness, headache, coordination problems (ataxia)

Side effects of unknown frequency: the frequency cannot be estimated from available data

• Rapid destruction of tumor cells (tumor lysis syndrome)
• Accumulation of fluid in the eyes (macular edema), flashes in the eyes (photopsia), small points or particles floating in the visual field (vitreous floaters)
• Phlebitis (inflammation of veins)
• Narrowing and hardening of skin, blood vessels, and internal organs (scleroderma)
• "Butterfly rash" (systemic lupus erythematosus)
• Coagulation disorders.Disseminated intravascular coagulation (DIC) has been reported. It is a serious condition that causes bleeding with increased ease, blood clots, or both).
• Redness and swelling of the palms of the hands and soles of the feet that can cause skin peeling

Reporting of side effects:

If you experience any type of side effect, consult your doctor, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the Spanish System of Pharmacovigilance of Medicines for Human Use: https://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.

Do not store at a temperature above25°C.

Store the vial in the outer packagingto protect it from light.

Do not use this medication after the expiration date that appears on the packaging after CAD.The expiration date is the last day of the month indicated.

Do not usethis medicationif a cloudy solution or insoluble precipitate is observed.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and unused medications. In this way, you will help protect the environment.

Composition ofPaclitaxel Kabi

• The active ingredient is paclitaxel

Each ml of concentrate for solution for infusion contains 6 mg of paclitaxel.

A vial of 5 ml contains 30 mg of paclitaxel

A vial of 16.7 ml contains 100 mg of paclitaxel

A vial of 25 ml contains 150 mg of paclitaxel

A vial of 50 ml contains 300 mg of paclitaxel

A vial of 100 ml contains 600 mg of paclitaxel.

• The other components are anhydrous ethanol, ricinoleate of macrogolglycerol, and anhydrous citric acid (to adjust the pH).

Appearance of the product and contents of the package

Concentrate for solution for infusion

Paclitaxel is a transparent, slightly yellowish solution.

Paclitaxel is available in glass vials.The glass vials are closed with chlorobutyl or bromobutyl rubber stoppers with aluminum seal and a removable plastic cap.

Package sizes:packages containing 1 or 5 glass vials.

Only some package sizes may be commercially available.

Holder of the marketing authorizationauthorization

Fresenius Kabi España S.A.U.

C/ Marina 16-18

08005 Barcelona (Spain)

Responsible for manufacturing

Fresenius Kabi Deutschland GmbH

Pfingstweide 53

61169 Friedberg

Germany

Or

Corden Pharma Latina S.P.A.

Via del Murillo, KM 2,800

04013 – Sermoneta (LT) -Italy

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

Last review date of this prospectus March 2021

The detailed and updated information on this medicinal product is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/.

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This information is intended solely for healthcare professionals:

Handling

As with all antineoplastics, paclitaxel should be handled with caution. Dilutions should be carried out in aseptic conditions by experienced personnel in a designated area. They should wear suitable protective gloves. Precautions should be taken to avoid all contact with the skin and mucous membranes. In case of skin contact, the affected area should be washed with water and soap. After topical exposure, tingling, burning sensation, and redness have been described. In case of contact with mucous membranes, they should be thoroughly washed with plenty of water. Inhalation has been described as causing dyspnea, chest pain, burning sensation in the throat, and nausea.

If the vials are refrigerated without opening, a precipitate may form that redissolves with little or no agitation upon reaching room temperature. This does not affect the quality of the product. If the solution remains turbid or a precipitate is observed, the vial should be discarded.

After several needle punctures and product extractions, the vials maintain their microbiological, chemical, and physical stability for a maximum of 28 days at 25°C. Other times and conditions of conservation are the responsibility of the user.

The "Chemo-Dispensing Pin" or similar devices with pins should not be used, as they may cause the collapse of the vial stopper, resulting in loss of sterility.

Preparation for intravenous administration

Before infusion, Paclitaxel Kabi must be diluted using aseptic techniquesin 5% glucose solution or 0.9% sodium chloride solution, 5% glucose solution in Ringer's solution, and 5% glucose solution/0.9% sodium chloride solution to a final concentration of0.3 to 1.2mg/ml.

The chemical and physical stability during the use of the prepared infusion solution has been demonstrated at 25°C for 24 hours when diluted in 5% glucose solution, 0.9% sodium chloride solution, 5% glucose solution in Ringer's solution, and 5% glucose solution/0.9% sodium chloride solution.

From a microbiological point of view, the product should be used immediately. If not used immediately, the times and conditions of conservation before use are the responsibility of the user and, in general, should not exceed 24 hours at 2-8°C, unless the dilution has been carried out in controlled and validated aseptic conditions.

After dilution, the solution is for single use only.

The prepared solutions may exhibit a slight turbidity that is attributed to the vehicle of the formulation, andwhich does not disappear by filtration. Paclitaxel Kabimust be administered witha filter in line with a microporous membrane ≤ 0.22 μm.No significant lossesin potencyhave been observedafter simulated administration of the solution through IV equipment provided with a filter in line.

Isolated casesof precipitation have been reportedduring 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 Kabishould be administered as soon as possible after dilution, and excessive agitation, vibration, or shaking should be avoided. The infusion equipment should be thoroughly cleaned before use. During infusion, the appearance of the solution should be regularly examined, and in case of precipitation, the infusion should be interrupted.

To minimize the patient's exposure to DEHP that may leach from PVC bags, infusion equipment, or other medical instruments, the diluted solutions ofPaclitaxel Kabishould be stored in non-PVC containers (glass, polypropylene) or plastic bags (polypropylene, polyolefin) and administered with a polyethylene-coated administration equipment. The use of filter devices(e.g., IVEX-2®)with a short PVC-plasticized outlet/inlet tube has not produced significant DEHP leaching.

Instructions for protection during preparation of the paclitaxel solution for infusion

1.A protective cabinet and protective gloves, as well as a laboratory coat, should be used. If a protective cabinet is not available, a suitable face mask and safety glasses should be used.

2.The product should not be handled by pregnant women or women who may become pregnant.

3.Opened containers, as well as injection vials and infusion bottles, cannulas, syringes, catheters, and tubes used, and cytostatic substance residues should be considered hazardous waste and disposed of in accordance with local regulations for the handling of HAZARDOUS WASTE.

4.In case of spillage, follow the instructions below: - Wear protective clothing. Broken glass should be collected and placed in the HAZARDOUS WASTE container. Contaminated surfaces should be thoroughly washed with plenty of cold water; subsequently, the washed surfaces should be thoroughly cleaned and the material used for cleaning should be disposed of as HAZARDOUS WASTE.

5.In case of contact of the paclitaxel concentrate for infusion solution with the skin, the area should be washed with plenty of running water and, subsequently, washed with water and soap. In case of contact with mucous membranes, the affected area should be thoroughly washed with plenty of water. If any discomfort occurs, consult a doctor.

6.In case of contact of the paclitaxel concentrate for infusion solution with the eyes, they should be thoroughly washed with plenty of cold water. Consult an ophthalmologist immediately.

Disposal

The disposal of unused medicinal product and all materials that have been in contact with it will be carried out in accordance with local regulations.