Paclitaxelum Accord

Leaflet accompanying the packaging: patient information

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

Paclitaxel

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• In case of any doubts, consult a doctor, pharmacist, or nurse.
• If the patient experiences any side effects, including any possible side effects not listed in this leaflet, they should inform their doctor, pharmacist, or nurse. See section 4.

The medicine is called "Paclitaxel Accord, 6 mg/ml, concentrate for solution for infusion", but in the rest of the leaflet, it will be referred to as "Paclitaxel Accord".

Table of contents of the leaflet:

• 1. What is Paclitaxel Accord and what is it used for
• 2. Important information before using Paclitaxel Accord
• 3. How to use Paclitaxel Accord
• 4. Possible side effects
• 5. How to store Paclitaxel Accord
• 6. Contents of the packaging and other information

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

Paclitaxel belongs to a group of anticancer medicines called "taxanes". These medicines slow down the growth of cancer cells. Paclitaxel Accord is used to treat the following cancers:

Ovarian cancer:

• as a first-line treatment (after previous surgery, in combination with a platinum-containing medicine, cisplatin).
• when other treatment methods have failed, using traditional platinum-containing medicines.

Breast cancer:

• as a first-line treatment for advanced disease or disease that has spread to other parts of the body (metastases). Paclitaxel Accord is used in combination with an anthracycline (e.g., doxorubicin) or a medicine called trastuzumab (in patients who cannot receive anthracycline treatment and have HER2 receptor protein on the surface of their cancer cells, see the trastuzumab patient leaflet).
• after previous surgery, as adjuvant therapy after anthracycline and cyclophosphamide (AC) treatment.
• as a second-line treatment for patients who have not responded to standard anthracycline treatment or for whom anthracycline treatment is not suitable.

Advanced non-small cell lung cancer:

• in combination with cisplatin in patients who are not eligible for surgical or radiotherapy treatment.

Kaposi's sarcoma in AIDS:

• in patients who have not responded to other treatment methods (e.g., liposomal anthracycline treatment).

2. Important information before using Paclitaxel Accord

When not to use Paclitaxel Accord

If the patient is allergic (hypersensitive) to paclitaxel or any of the other ingredients of this medicine, especially macrogolglycerol ricinoleate 35 (listed in section 6.1); during breastfeeding; in patients with a low white blood cell count. The doctor will perform a blood test to check if the patient has a sufficient number of blood cells; in cases of severe and uncontrolled infections, in patients receiving Paclitaxel Accord for the treatment of Kaposi's sarcoma. If the patient has any of the above conditions, they should inform their doctor before starting treatment with Paclitaxel Accord. It is not recommended to use Paclitaxel Accord in children (under 18 years of age).

Warnings and precautions

Before starting treatment with Paclitaxel Accord, the patient should discuss it with their doctor or pharmacist. To prevent allergic reactions, the patient will receive other medicines before starting therapy with Paclitaxel Accord. If the patient experiences severe allergic reactions (e.g., difficulty breathing, shortness of breath, chest tightness, low blood pressure, dizziness, fainting, skin reactions such as rash or swelling); if the patient experiences fever, severe chills, sore throat, or mouth ulcers (symptoms of bone marrow suppression); if the patient experiences numbness, tingling, or weakness in the hands and feet (symptoms of peripheral neuropathy); the dose of Paclitaxel Accord may need to be reduced; if the patient has severe liver function disorders; it is not recommended to use Paclitaxel Accord; if the patient has conduction disorders in the heart muscle; if the patient has severe or chronic diarrhea, accompanied by fever and abdominal pain. The patient should immediately inform their doctor if any of the above conditions occur. Paclitaxel Accord should only be administered intravenously. Intrarterial administration of Paclitaxel Accord can cause arterial inflammation, leading to pain, swelling, redness, and burning.

Paclitaxel Accord and other medicines

The patient should tell their doctor about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take, including over-the-counter medicines. This is because Paclitaxel Accord or another medicine may not work as expected or may increase the risk of side effects. Interaction means that different medicines can affect each other. The patient should be cautious and inform their doctor if they are taking the following medicines with paclitaxel:

• infection medicines (e.g., antibiotics such as erythromycin, etc.; if the patient is unsure whether their medicine is an antibiotic, they should consult their doctor, nurse, or pharmacist), including antifungal medicines (e.g., ketoconazole and other imidazole antifungals)
• medicines used to improve mood, sometimes called antidepressants (e.g., fluoxetine)
• medicines used to treat seizures (epilepsy) (e.g., carbamazepine, phenytoin)
• medicines used to lower blood lipid levels (e.g., gemfibrozil)
• medicines used to treat heartburn or stomach ulcers (e.g., cimetidine)
• medicines used to treat HIV and AIDS (e.g., ritonavir, saquinavir, indinavir, nelfinavir, efavirenz, nevirapine)
• the anti-clotting medicine called clopidogrel
• the antibiotic used to treat tuberculosis called rifampicin. It may be necessary to increase the dose of Paclitaxel Accord
• vaccines: if the patient has recently been vaccinated or plans to be vaccinated, they should inform their doctor. Using paclitaxel with certain vaccines can lead to serious complications.
• cisplatin (used to treat cancer): Paclitaxel Accord should be administered before cisplatin. More frequent kidney function checks may be necessary.
• doxorubicin (used to treat cancer): Paclitaxel Accord should be administered 24 hours after doxorubicin to avoid high levels of doxorubicin in the body.

Paclitaxel Accord with food, drink, and alcohol

Food and drink do not affect the use of Paclitaxel Accord.

Pregnancy, breastfeeding, and fertility

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a child, they should consult their doctor or pharmacist before using this medicine. It is not recommended to use Paclitaxel Accord during pregnancy, unless it is absolutely necessary. This medicine may cause birth defects, and women should not become pregnant during paclitaxel treatment. Men and women of childbearing age, as well as their partners, must use effective contraception during treatment and for at least 6 months after treatment. If a woman becomes pregnant during treatment or within 6 months after treatment, she should immediately inform her doctor. Men treated with Paclitaxel Accord should not attempt to father a child during treatment and for 6 months after treatment. Breastfeeding women should inform their doctor. Breastfeeding should be discontinued during treatment with Paclitaxel Accord. Breastfeeding should not be resumed until the doctor indicates it is safe to do so. Paclitaxel may have an irreversible effect on fertility. Before starting treatment, men should seek advice on sperm storage.

Driving and using machines

Paclitaxel Accord may cause side effects such as fatigue (very common) and dizziness (common), which may affect the ability to drive and use machines. If the patient experiences these symptoms, they should not drive or operate machines until they have resolved. If the patient is taking other medicines as part of their treatment, they should ask their doctor for advice on driving and using machines. The medicine contains alcohol. Therefore, it is not recommended to drive or operate machines immediately after a treatment course.

Important information about some ingredients of Paclitaxel Accord

Paclitaxel Accord contains castor oil (50% polyoxyethylated castor oil 35), which may cause severe allergic reactions. If the patient is allergic to castor oil, they should inform their doctor before starting treatment with Paclitaxel Accord.

Paclitaxel Accord contains alcohol

This medicine contains 391 mg of alcohol (ethanol) per ml. The amount of alcohol in the medicine (at the maximum dose of 220 mg/m²) is equivalent to 646 ml of beer or 258 ml of wine. The alcohol in this medicine may affect the action of other medicines. If the patient is taking other medicines, they should consult their doctor or pharmacist. If the patient is pregnant or breastfeeding, they should consult their doctor or pharmacist before using this medicine. If the patient is addicted to alcohol, they should consult their doctor or pharmacist before using this medicine.

3. How to use Paclitaxel Accord

• To minimize allergic reactions, the patient will receive other medicines before starting therapy with Paclitaxel Accord. These medicines can be administered orally or intravenously, or both.
• Paclitaxel Accord is administered as an intravenous infusion into one of the veins (using a filter provided in the kit). Paclitaxel Accord is administered by a healthcare professional. The healthcare professional will prepare the infusion solution before administration. The dose of the medicine will depend on the results of the patient's blood tests. Depending on the type and severity of the cancer, Paclitaxel Accord is used as monotherapy or in combination with another anticancer medicine.
• Paclitaxel Accord should always be administered into one of the veins over 3 or 24 hours. The medicine is usually administered every 2 or 3 weeks, unless the doctor indicates otherwise. The doctor will inform the patient about the number of treatment courses with Paclitaxel Accord that they need to receive.

If the patient has any further doubts about using the medicine, they should consult their doctor.

Using a higher dose of Paclitaxel Accord than recommended

There is no antidote in case of overdose with Paclitaxel Accord. The patient will receive symptomatic treatment.

4. Possible side effects

Like all medicines, Paclitaxel Accord can cause side effects, although not everybody gets them. The patient should immediately inform their doctor if they experience any symptoms of an allergic reaction, including one or more of the following:

• flushing,
• skin reactions,
• itching,
• chest tightness,
• shortness of breath or breathing difficulties,
• swelling. All of these reactions can be symptoms of severe side effects.

The patient should immediately inform their doctor:

• if they experience fever, severe chills, sore throat, or mouth ulcers (symptoms of bone marrow suppression);
• if they experience numbness or weakness in the hands and feet (symptoms of peripheral neuropathy); Neuropathy symptoms may persist for more than 6 months after treatment.
• if they experience severe or chronic diarrhea, accompanied by fever and abdominal pain.

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

• Mild allergic reactions such as flushing, rash, itching.
• Infections: mainly of the upper respiratory tract, urinary tract infections.
• Shortness of breath.
• Sore throat or mouth ulcers, pain or redness of the mouth, diarrhea, nausea, vomiting.
• Hair loss (most cases of hair loss occurred within a month of starting paclitaxel treatment. In most patients, hair loss was significant (more than 50%)).
• Muscle pain, cramps, joint pain.
• Fever, severe chills, headache, dizziness, fatigue, pale skin, bleeding, increased bruising.
• Numbness, tingling, or weakness in the hands and feet (all symptoms of peripheral neuropathy).
• Tests may indicate: decreased platelet count, white or red blood cell count, and low blood pressure.

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

• Transient, mild changes in the nails and skin disorders, reactions at the injection site (local swelling, pain, redness of the skin).
• Tests may indicate: decreased heart rate, significant increase in liver enzyme activity (alkaline phosphatase and aspartate aminotransferase).

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

• Septic shock (a life-threatening condition caused by a severe infection).
• Irregular heartbeat, heart disorders (atrioventricular block), rapid heartbeat, heart attack, respiratory failure.
• Fatigue, sweating, fainting, severe allergic reactions, blood clotting in the veins (thrombophlebitis), facial swelling, lip swelling, mouth swelling, tongue swelling, or throat swelling.
• Back pain, chest pain, pain in the hands and feet, chills, abdominal pain.
• Tests may indicate: significant increase in bilirubin levels (jaundice), high blood pressure, 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).
• Nerve disorders, including muscle weakness in the arms and legs (motor neuropathy).
• Shortness of breath, pulmonary embolism, pulmonary fibrosis, interstitial pneumonia, dyspnea, pleural effusion.
• Bowel obstruction, perforation of the bowel, ischemic colitis, pancreatitis.
• Itching, rash, skin redness (erythema).
• Blood infection (sepsis), peritonitis.
• Fever, dehydration, weakness, swelling, and malaise.
• Severe allergic reactions that can be life-threatening (anaphylactic reactions).
• Tests may indicate: increased creatinine levels in the blood, indicating kidney function disorders.
• Heart failure.

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

• Irregular, rapid heartbeat (atrial fibrillation, supraventricular tachycardia).
• Sudden disorders of blood cell production (acute myeloid leukemia, myelodysplastic syndrome).
• Eye disorders, such as thickening and swelling of the macula (macular edema), flashes of light (photopsia), and floaters, spots, or "cobwebs" in the visual field (vitreous opacities).
• Hearing loss (ototoxicity), tinnitus, dizziness of labyrinthine origin.
• Cough.
• Blood clots in the abdominal and intestinal veins (mesenteric thrombosis), colitis, sometimes with persistent severe diarrhea (pseudomembranous colitis, neutropenic colitis), ascites, esophagitis, constipation.
• Severe allergic reactions, including fever, skin redness, joint pain, and (or) eye inflammation (Stevens-Johnson syndrome), skin peeling (toxic epidermal necrolysis), skin redness with irregular red patches (erythema multiforme), skin inflammation with blisters and peeling (exfoliative dermatitis), hives, nail separation from the nail bed (patients undergoing treatment should use a sun-protective cream on their hands and feet).
• Loss of appetite (anorexia).
• Severe allergic reactions that can be life-threatening (anaphylactic shock).
• Liver function disorders (liver necrosis, hepatic encephalopathy [both cases have been reported with fatal outcomes]).
• Confusional state.

Unknown frequency of side effects (frequency cannot be estimated from available data):

• Skin thickening (scleroderma).
• Sudden constriction of the airway muscles (bronchospasm).
• Metabolic complications after cancer treatment (tumor lysis syndrome).
• Eye disorders, such as thickening and swelling of the macula (macular edema), flashes of light (photopsia), and floaters, spots, or "cobwebs" in the visual field (vitreous opacities).
• Phlebitis.
• Systemic lupus erythematosus.
• Disseminated intravascular coagulation (DIC) has been reported; it is a serious condition that causes bleeding or clotting, or both.
• Redness and swelling of the palms of the hands and soles of the feet, which can cause skin peeling.

The patient should inform their doctor if any of the side effects get worse or if they experience any side effects not listed in the leaflet.

Reporting side effects

If the patient experiences any side effects, including any possible side effects not listed in the leaflet, they should tell their doctor or pharmacist. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocides of the Office for Registration of Medicinal Products, Medical Devices, and Biocides, Al. Jerozolimskie 181C, 02-222 Warsaw, Tel: +48 22 49 21 301, Fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl. Side effects can also be reported to the marketing authorization holder. By reporting side effects, it is possible to gather more information on the safety of the medicine.

5. How to store Paclitaxel Accord

Keep out of sight and reach of children. Do not use this medicine after the expiry date stated on the carton after the expiry date (EXP). The expiry date refers to the last day of the month stated.

Before opening

Do not store above 25°C. Store the vial in the outer packaging to protect from light. Freezing does not affect the quality of the product.

After opening before dilution (description of conditions)

From a microbiological point of view, the product can be stored for a maximum of 28 days at 25°C after opening. The user is responsible for other conditions and storage time.

After dilution (description of conditions)

From a microbiological point of view, the diluted product should be used immediately. If the product is not used immediately, it should be stored in the refrigerator (2 to 8°C). The storage period should not exceed 24 hours, unless dilution is performed under controlled and validated aseptic conditions. For detailed information on stability after dilution, see the section intended for healthcare professionals. Do not use Paclitaxel Accord if visible signs of precipitation or a non-soluble sediment are observed. Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Paclitaxel Accord contains

The active substance is paclitaxel. Each milliliter of the concentrate for solution for infusion contains 6 mg of paclitaxel. Each vial contains 5, 16.7, 25, 50 ml, or 100 ml (corresponding to 30, 100, 150, 300 mg, and 600 mg of paclitaxel). The medicine also contains macrogolglycerol ricinoleate 35 and anhydrous ethanol.

What Paclitaxel Accord looks like and contents of the pack

Paclitaxel Accord is a clear, colorless, or slightly yellowish solution without visible particles. The medicine is available in vials of 5 ml, 16.7 ml, 25 ml, 50 ml, and 100 ml concentrate for solution for infusion. Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder

Accord Healthcare Polska Sp. z o.o. ul. Taśmowa 7 02-677 Warszawa Tel: + 48 22 577 28 00

Manufacturer/Importer

Accord Healthcare Polska Sp. z o.o. ul. Lutomierska 50 95-200 Pabianice Accord Healthcare Single Member S.A. 64th Km National Road Athens 32009 Lamia Greece

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

Date of last revision of the leaflet: January 2025

Information intended for healthcare professionals only:

Preparation of infusion solutions:

• Containers and infusion sets used with Paclitaxel Accord must not contain DEHP. This reduces the patient's exposure to DEHP [di-(2-ethylhexyl) phthalate], which can leach from containers or infusion sets made of PVC. The use of filter devices (e.g., IVEX-2) equipped with short inlet and (or) outlet tubing made of PVC did not have a significant impact on DEHP leaching.
• As with other anticancer medicines, caution should be exercised when handling Paclitaxel Accord. The patient should always wear appropriate protective gloves when handling vials containing paclitaxel. Dilution should be performed under sterile conditions by trained personnel in a designated area. In case of contact with the skin, the area should be washed with soap and water. In case of contact with the mucous membranes, they should be thoroughly flushed with water.
• Devices of the type "Chemo-Dispensing Pin" or similar devices should not be used to withdraw doses from the vial, as they can cause the vial stopper to be removed, resulting in loss of sterility.

Step 1: Dilution of the concentrate

Before administration, Paclitaxel Accord should be diluted in:

• 0.9% sodium chloride injection or
• 5% glucose injection or
• 5% glucose and 0.9% sodium chloride injection or
• 5% glucose in Ringer's injection

The final concentration of the paclitaxel solution should be between 0.3 and 1.2 mg/ml. Containers and infusion sets used with Paclitaxel Accord must not contain DEHP. After dilution, the solution may appear cloudy due to the solvent contained in the medicine, which is not removed by filtration. No significant loss of potency was observed after simulated administration of the solution through an intravenous infusion set with a filter.

Step 2: Administration of the infusion

Before administration, patients should receive corticosteroids, antihistamines, and H2 receptor antagonists. Paclitaxel Accord should not be administered again until the neutrophil count is ≥ 1500/mm³ (≥ 1000/mm³ in patients with Kaposi's sarcoma), and the platelet count is ≥ 100,000/mm³ (≥ 75,000/mm³ in patients with Kaposi's sarcoma). To limit the risk of precipitation of the infusion solution:

• it should be administered as soon as possible after dilution,
• excessive shaking, vibration, or agitation should be avoided,
• the infusion sets should be thoroughly flushed before use,
• the appearance of the solution should be regularly checked, and the infusion should be stopped in case of precipitation.

The diluted solution is chemically and physically stable at 5°C and 25°C for 7 days when diluted in 5% glucose and for 14 days when diluted in 0.9% sodium chloride injection. From a microbiological point of view, the diluted product should be used immediately or stored in the refrigerator (2 to 8°C) for no longer than 24 hours. Paclitaxel Accord should be administered through a suitable filter provided in the kit with a microporous membrane with a pore size of ≤ 0.2 micrometers. Containers and infusion sets used with Paclitaxel Accord must not contain DEHP. The use of filter devices equipped with short inlet and (or) outlet tubing made of PVC did not have a significant impact on DEHP leaching.

Step 3: Disposal

Any unused product or waste material should be disposed of in accordance with local regulations for cytotoxic medicines.

Dose:

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

Paclitaxel Accord should not be administered again until the neutrophil count is ≥ 1500/mm³ (≥ 1000/mm³ in patients with Kaposi's sarcoma), and the platelet count is ≥ 100,000/mm³ (≥ 75,000/mm³ in patients with Kaposi's sarcoma). In patients with severe neutropenia (neutrophil count <500>