PACLITAXEL ACCORD 6 mg/ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

Paclitaxel Accord 6 mg/ml concentrate for solution for infusion EFG

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• 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 Paclitaxel Accord and what is it used for
2. What you need to know before you use Paclitaxel Accord
3. How to use Paclitaxel Accord
4. Possible side effects
5. Storage of Paclitaxel Accord
6. Contents of the pack and other information

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

Paclitaxel belongs to a group of medicines called taxanes, which are used to treat cancer. These agents inhibit the growth of cancer cells.

Paclitaxel Accord is used to treat:

Ovarian cancer

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

Breast cancer

• as first-line treatment for advanced or metastatic cancer. Paclitaxel Accord is combined with an anthracycline(e.g., doxorubicin) or with a drug called trastuzumab(for patients for whom anthracyclines are not indicated or who have cancer cells with a protein on their surface called HER2; see the trastuzumab package leaflet).
• after initial surgery following treatment with anthracycline and cyclophosphamide (AC) as additional treatment.
• 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 indicated.

AIDS-related Kaposi's sarcoma

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

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

Do not use Paclitaxel Accord

• if you are allergic(hypersensitive) to paclitaxel or any of the other ingredients of this medicine (listed in section 6), especially polyoxyethylated castor oil 35 (macrogolglycerol ricinoleate 35).
• if you are breastfeeding.
• if you have very low white blood cell countsin your blood. Your doctor will take a blood sample to check.
• if you have a severe and uncontrolled infectionand Paclitaxel Accord is used to treat Kaposi's sarcoma.

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

Paclitaxel Accord is not recommended for use in childrenand adolescents(under 18 years of age).

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before starting treatment with Paclitaxel Accord.

Before starting treatment with Paclitaxel Accord, 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, feeling of dizziness, 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, tingling, prickling sensations in the skin, sensitivity to touch, or weakness in arms and legs(signs of peripheral neuropathy); a dose reduction of Paclitaxel Accord may be necessary.
• if you have severe liver problems; in this case, the use of Paclitaxel Accord is not recommended.
• if you have conduction disorders.
• if you develop severe or persistent diarrhea, with fever and stomach pain, during treatment with Paclitaxel Accord or immediately after its administration. You may have inflammation of the colon (pseudomembranous colitis).
• if you have previously received radiotherapy to 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 you are in any of the above situations.

Paclitaxel Accord must always be administered into a vein. Administration of Paclitaxel Accord into an artery can cause inflammation of the artery, and you may experience pain, inflammation, redness, and heat.

Paclitaxel Accord and other medicines

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 have a higher chance of getting a side effect.

Interaction means that different medicines can affect each other.

Ask your doctor when using Abraxane at the same time as any of the following:

• medicines to treat infections (i.e., antibiotics such as erythromycin, etc.; if in doubt about whether the medicine you are taking is an antibiotic, ask your doctor, nurse, or pharmacist), and medicines to treat fungal infections (e.g., ketoconazole, other imidazole antifungals)
• medicines used to help stabilize mood, also called antidepressants (e.g., fluoxetine)
• medicines used to treat seizure disorders (epilepsy) (e.g., carbamazepine, phenytoin)
• medicines used to help lower blood lipid levels (e.g., gemfibrozil)
• medicines used to treat stomach acid or stomach ulcers (e.g., cimetidine)
• medicines used to treat HIV and AIDS (e.g., ritonavir, saquinavir, indinavir, nelfinavir, efavirenz, nevirapine)
• a medicine called clopidogrel, which is 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 are planning to be vaccinated, inform your doctor. The use of paclitaxel in combination with certain 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 a high level of doxorubicin in your body.

Using Paclitaxel Accord with food, drinks, and alcohol

Paclitaxel Accord is not affected by food and drink intake.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine. Paclitaxel Accord should not be used during pregnancy, unless clearly advised by your doctor. This medicine may cause birth defects; therefore, you should not become pregnant during treatment with paclitaxel and you and/or your partner should use an effective contraceptive method while receiving treatment with paclitaxel and for 6 months after the end of treatment. If you become pregnant during treatment or within 6 months after the end of treatment, inform your doctor immediately.

Male patients treated with paclitaxel should not father a child during and up to 6 months after treatment.

If you are breastfeeding, inform your doctor. Stop breastfeeding if you are receiving Paclitaxel Accord. Do not restart breastfeeding until your doctor tells you to.

Paclitaxel may cause irreversible infertility. Male patients should ask about sperm freezing before treatment with paclitaxel.

Driving and using machines

Paclitaxel Accord may cause side effects such as fatigue (very common) and dizziness (common) that may affect your ability to drive and use machines. If you experience these symptoms, do not drive or use machines until the symptoms have completely disappeared. If you are given other medicines as part of your treatment, ask your doctor if you can drive and use machines.

This medicine contains alcohol. Therefore, it may not be prudent to drive immediately after receiving a treatment cycle.

Important information about some of the ingredients of Paclitaxel Accord

Paclitaxel Accord contains macrogolglycerol ricinoleate(50% polyoxyethylated castor oil) which may cause severe allergic reactions. If you are allergic to castor oil, talk to your doctor before using Paclitaxel Accord.

Paclitaxel Accord contains alcohol

This medicine contains 391 mg of alcohol (ethanol) per ml. The amount of alcohol in this medicine (at the maximum dose of 220 mg/m2) is equivalent to 646 ml of beer or 258 ml of wine.

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

If you are pregnant or breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.

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

3. How to use Paclitaxel Accord

• Before starting treatment with Paclitaxel Accord, you will be given other medicines to minimize the risk of allergic reactions. These medicines may be administered in the form of tablets or intravenous infusion, or both.
• Paclitaxel Accord will be administered to you through a dripin 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 Accord alone or in combination with another anticancer agent.
• Paclitaxel Accord should always be administered into 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 Accord that you need to receive.

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

If you receive more Paclitaxel Accord than you should

There is no known antidote for overdose with Paclitaxel Accord. You will receive treatment for your symptoms.

4. Possible Adverse Effects

Like all medicines, this medicine may cause adverse effects, although not all people suffer from them.

If you consider that you are suffering from any sign of an 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 these can be signs of serious adverse effects.

Inform your doctor immediately:

• If you have a fever, severe chills, sore throat, or mouth ulcers (signs of bone marrow suppression).
• If you experience numbness or weakness in your arms and legs (symptoms of peripheral neuropathy). These neuropathy symptoms can persist for more than 6 months after discontinuation of paclitaxel treatment.
• If you develop severe or persistent diarrhea, with fever and stomach pain.

Very Common Adverse Effects (may 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
• 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 occurs, hair loss is pronounced (more than 50%) in most patients)
• Muscle pain, cramps, joint pain
• Fever, severe chills, headache, dizziness, fatigue, paleness, bleeding, more frequent bruising than usual
• Numbness, tingling, or weakness in arms and legs (all symptoms of peripheral neuropathy)*
• Lab tests may show: decreased platelets, white blood cells, or red blood cells, low blood pressure

Common Adverse Effects (may affect less than 1 in 10 people):

• Mild and transient nail and skin changes, injection site reactions (localized inflammation, pain, and redness of the skin)
• Lab tests may show: slowed heart rate, severe elevation of liver enzymes (alkaline phosphatase and AST-SGOT)

Uncommon Adverse Effects (may affect less than 1 in 100 people):

• Shockdue to infections (known as "septic shock")
• Palpitations, heart failure (AV block), rapid heartbeat, infarction, respiratory distress
• 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 (belly pain)
• Lab tests may show: considerable elevation of bilirubin (jaundice), high blood pressure, and blood clots

Rare Adverse Effects (may affect more than 1 in 10,000 but less than 1 in 1,000 people):

• Decrease in white blood cells, 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, 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), inflammation of the lungs (interstitial pneumonia), difficulty breathing, lung damage, 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), redness of the skin (erythema)
• Blood infection (septicemia), inflammation of the peritoneum (peritonitis)
• Fever (pyrexia), dehydration, weakness (asthenia), accumulation of fluid in body tissues (edema), discomfort
• Severe and potentially life-threatening hypersensitivity reactions (anaphylactic reactions)
• Lab tests may show: increased creatinine in blood, indicating kidney dysfunction
• Heart failure

Very Rare Adverse Effects (may affect less than 1 in 10,000 people):

• Rapid and irregular heartbeat (atrial fibrillation, supraventricular tachycardia)
• Sudden disorder in 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), inflammation of the colon, sometimes with severe persistent diarrhea (pseudomembranous colitis, neutropenic colitis), fluid retention in the abdomen (ascites), inflammation of the esophagus (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 patches (erythema multiforme), skin inflammation with blisters and peeling (exfoliative dermatitis), hives, onycholysis (patients undergoing treatment should wear sun protection on hands and feet)
• Loss of appetite (anorexia)
• Severe and potentially life-threatening hypersensitivity reactions with shock(anaphylactic reactions)
• Alterations in liver function (liver necrosis, hepatic encephalopathy [both with reported fatal outcomes])
• State of confusion

Adverse Effects of Unknown Frequency (frequency cannot be estimated from available data):

• Hardening/thickening of the skin (scleroderma)
• Sudden constriction of the muscles in the bronchiole walls (bronchospasm)
• Metabolic complications after cancer treatment (Tumor Lysis Syndrome)
• Eye disorders, such as thickening and inflammation of the macula (macular edema), flashes of light (photopsia), and spots, floaters, and "cobwebs" floating in the visual field (vitreous floaters)
• Inflammation of the veins (phlebitis)
• Systemic lupus erythematosus
• Severe disease that causes people to bleed too easily, clot too easily, or both (disseminated intravascular coagulation, DIC). This is a serious condition that causes people to bleed very easily, also get blood clots, or both.

Skin disorders such as red and scaly patches on the skin and scalp, ulcerative lesions.

If any of the adverse effects worsen, or if you notice any adverse effect not mentioned in this leaflet, please inform your doctor.

Reporting of Adverse Effects:

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

5. Storage of Paclitaxel Accord

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

Do not use this medicine after the expiration date stated on the packaging after CAD. The expiration date is the last day of the month indicated.

Before Opening

Do not store above 25°C. Keep the vial in the outer packaging to protect it from light.

Freezing does not negatively affect the product.

Once Opened and Before Dilution (description of conditions)

From a microbiological point of view, once opened, the product can be stored for a maximum of 28 days at 25°C.

If other periods and conditions of storage are used during the use of the medicine, the responsibility will be that of the user.

After Dilution (description of conditions)

From a microbiological point of view, the diluted product should be used immediately. If not used immediately, it must be stored in a refrigerator (between 2°C and 8°C) for a maximum period of 24 hours, unless the dilution was performed under controlled and validated aseptic conditions. If you want more information about stability after dilution, consult the section intended for healthcare professionals.

Do not use this medicine if a turbid solution or an insoluble precipitate is observed.

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. Container Contents and Additional Information

Composition of Paclitaxel Accord

The active ingredient is paclitaxel.

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

Each vial contains 5, 16.7, 25, 50 or 100 ml (equivalent to 30, 100, 150, 300 or 600 mg of paclitaxel, respectively).

The other components are polyoxyethylated castor oil 35 (macrogolglycerol ricinoleate 35) and anhydrous ethanol.

Appearance of the Product and Container Contents

Paclitaxel Accord is a clear, colorless or slightly yellowish solution free of visible particles.

It is available in vials containing 5 ml, 16.7 ml, 25 ml, 50 ml or 100 ml of concentrate for solution for infusion.

Only some pack sizes may be marketed.

Marketing Authorization Holder

Accord Healthcare S.L.U.

World Trade Center

Moll de Barcelona, s/n

Edifici Est, 6ª planta

08039 Barcelona

Manufacturer

Accord Healthcare Polska Sp.z o.o.,

ul. Lutomierska 50,95-200 Pabianice, Poland

or

Accord Healthcare Single Member S.A.

64th Km National Road Athens, Lamia, 32009,

Greece

This Medicinal Product is Authorized in the Member States of the European Economic Area under the Following Names

Date of Last Revision of this Leaflet:August 2023.

Detailed and updated 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

Preparation of Infusion Solutions

• The containers and infusion equipment used with Paclitaxel Accord must notcontain DEHP. This will minimize patient exposure to DEHP [di-(2-ethylhexyl)phthalate], which may be formed by leaching of PVC present in containers or equipment. The use of filter models (e.g., IVEX-2) that incorporate a short PVC plastic inlet and/or outlet tube does not result in significant leaching of DEHP.
• Handle Paclitaxel Accord with care, as with all other cytotoxic agents. Always wear suitable protective gloves when handling vials containing paclitaxel. Dilution should be carried out under aseptic conditions, by trained personnel, and in a designated area. In case of skin contact, wash the affected area with water and soap. In case of contact with mucous membranes, rinse with plenty of water.
• Do not use "Chemo-Dispensing Pin" devices or similar, as they may cause the vial cap to fall off, resulting in loss of sterility.

Step 1: Dilute the Concentrate

Prior to administration, Paclitaxel Accord must be diluted using:

• Sodium chloride 0.9% solution for infusion

• Dextrose 5% solution for infusion
• Dextrose 0.5% and sodium chloride 0.9% solution for infusion
• Sodium chloride composed solution for infusion with dextrose 5%

The final infusion concentration of paclitaxel should be between 0.3 mg/ml and 1.2 mg/ml.

DEHP-free containers and infusion equipment should be used

Once diluted, the solutions may appear cloudy, which is attributed to the formulation vehicle and does not disappear with filtration. No significant loss of potency has been observed after simulated administration of the solution through a drip system with an in-line filter.

Step 2: Administer the Infusion

Administer corticosteroids, antihistamines, and H2 antagonists to all patients prior to administration of Paclitaxel Accord.

Do not re-administer Paclitaxel Accord until the neutrophil count is ≥ 1,500/mm3 (≥ 1,000/mm3 for patients with Kaposi's sarcoma) and the platelet count is ≥ 100,000/mm3 (≥ 75,000/mm3 for patients with Kaposi's sarcoma).

Avoid precipitation of the infusion solution:

• Use immediately after dilution
• Do not remove, shake, or agitate excessively
• Wash infusion equipment thoroughly before use.
• Regularly check the appearance of the solution and interrupt the infusion if precipitation is observed.

The chemical and physical stability of the diluted solution has been demonstrated at 5°C and 25°C for 7 days when diluted in 5% dextrose solution and for 14 days when diluted in 0.9% sodium chloride solution. From a microbiological point of view, the diluted product should be used immediately or stored at a temperature between 2°C and 8°C for a maximum of 24 hours.

Paclitaxel Accord should be administered through a suitable in-line filter with a microporous membrane of ≤ 0.2 microns. DEHP-free infusion containers and administration equipment should be used. The use of filter models that incorporate a short PVC plastic inlet and/or outlet tube does not result in significant leaching of DEHP.

Step 3: Disposal

Unused products or waste materials derived from them should be disposed of in accordance with local regulations for the handling of cytotoxic compounds.

Dose:

The recommended doses for intravenous infusion of Paclitaxel Accord are as follows:

Do not re-administer Paclitaxel Accord until the neutrophil count is ≥ 1,500/mm3 (≥ 1,000/mm3 for patients with Kaposi's sarcoma) and the platelet count is ≥ 100,000/mm3 (≥ 75,000/mm3 for patients with Kaposi's sarcoma).

Patient who experience severe neutropenia (neutrophil count <500>

There are insufficient data to recommend dose modifications in patients with mild to moderate hepatic impairment. Patients with severe hepatic impairment should not be treated with Paclitaxel Accord (see the Summary of Product Characteristics).

Paclitaxel Accord is not recommended for use in children and adolescents under 18 years due to the lack of data on safety and efficacy.