Leaflet: information for the user

Paclitaxel Accord 6 mg/ml concentrate for infusion solution EFG

Read the entire leaflet carefully before starting to use the medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any doubts, consult your doctor, pharmacist or nurse.
• This medicine has been prescribed only for you, and you must not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor, pharmacist or nurse, even if they are not listed in this leaflet. See section 4.

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

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

3.How to use Paclitaxel Accord

4.Possible side effects

5.Storage of Paclitaxel Accord

6.Contents of the pack and additional information

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 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 Accord works well with ananthracycline(for example, doxorubicin) or with a medicine calledtrastuzumab(for patients in whom an anthracycline is not indicated or who have a cancer whose cells have a protein on their surface called HER2; see the trastuzumab package leaflet).
• after initial surgery following treatment with an anthracycline and cyclophosphamide (AC) as additional treatment.
• 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.

No use Paclitaxel Accord

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

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

PaclitaxelAccordis not recommended for use in childrenand adolescents(under 18 years).

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to use Paclitaxel Accord.

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

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

Inform your doctor immediately if you are in any of the cases mentioned.

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

Paclitaxel Accord and other medications

Inform your doctor if you are using, have used recently, or may need to use any other medicationincluding those acquired without a prescription. This is because paclitaxel or the other medication may not work as well as expected, or you may be more likely to experience a side effect.

Interaction means that different medications can influence each other.

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

• medications to treat infections (e.g., antibiotics such as erythromycin, etc.; in case of doubt about whether the medication you are taking is an antibiotic, ask your doctor, nurse, or pharmacist), and medications to treat fungal infections (e.g., ketoconazole, other imidazolic antifungals)
• medications used to help stabilize mood, also called antidepressants (e.g., fluoxetine)
• medications used to treat seizures (epilepsy) (e.g., carbamazepine, phenytoin)
• medications used to help reduce lipid levels in the blood (e.g., gemfibrozil)
• medications used to treat stomach acid or ulcers (e.g., cimetidine)
• medications used to treat HIV and AIDS (e.g., ritonavir, saquinavir, indinavir, nelfinavir, efavirenz, nevirapina)
• the 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 in combination with certain vaccines may lead to severe complications.
• cisplatin (to treat cancer): paclitaxel must be administered before cisplatin. You may need to have your renal function monitored more frequently.
• doxorubicin(to treat cancer): paclitaxel must be administered 24 hours after doxorubicin to avoid a high level of doxorubicin in your body.

Use of Paclitaxel Accord with food, drinks, and alcohol

Paclitaxel Accord is not altered by the consumption of food and drinks.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or intend to become pregnant, consult your doctor or pharmacist before using this medication. Paclitaxel Accord should not be used during pregnancy, unless it has been clearly advised. This medication may cause birth defects, so 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.

It is recommended that male patients treated with paclitaxel not father a child during and for 6 months after treatment.

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

Paclitaxel may cause infertility that could be irreversible. Male patients should ask about sperm cryopreservation before treatment with paclitaxel.

Driving and operating machinery

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

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

Important information about some of the components of Paclitaxel Accord

Paclitaxel Accord contains ricinoleate of macrogolglycerol(50% polioxyethylated ricin oil) which may cause severe allergic reactions. If you are allergic to ricin oil, consult your doctor before using Paclitaxel Accord.

PaclitaxelAccordcontains alcohol

This medication contains 391 mg of alcohol (ethanol) in each ml. The amount of alcohol in this medication (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 medication may alter the effects of other medications. Talk to your doctor or pharmacist if you are taking other medications.

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

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

• Before starting treatment with Paclitaxel Accord, you will be given other medicationsto minimize the risk of allergic reactions. These medications may be administered in the form of tablets or intravenous infusion, or both.
• PaclitaxelAccordwill 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 depend on the results of your blood tests. Depending on the type and severity of cancer, you will receive Paclitaxel Accord alone or in combination with another antineoplastic agent.
• Paclitaxel Accord must be administered always in a vein over a period of3 to24 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 other questions about the use of this product, ask your doctor.

If you receive more Paclitaxel Accord than you should

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

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

If you consider that you are experiencing 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
• Lack of breath or difficulty breathing
• Inflammation

All of these can be signs of severe side effects.

Inform your doctor immediately:

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

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

• Minor allergic reactions, such as redness (rubefaction), rash (exanthema), itching (pruritus)
• Infections: mainly upper respiratory tract infections, urinary tract infections
• Lack 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, the hair loss is pronounced (more than 50%) in most patients)
• Muscle pain, cramps, joint pain
• Fever, intense chills, headache, dizziness, fatigue, paleness, bleeding, frequent bruising
• Numbness, tingling, or weakness in arms and legs (all symptoms of peripheral neuropathy)*
• Laboratory tests may show: decreased platelets, white blood cells, or red blood cells, low blood pressure

Common side effects (may affect less than 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 (may affect less than 1 in 100 people):

• Shockdue to infections (known as "septic shock")
• Palpitations, cardiac dysfunction (AV block), rapid heartbeat, infarction, respiratory distress
• Fatigue, sweating, syncope, significant allergic reactions, inflammation of a vein caused by a blood clot (thrombophlebitis), facial swelling, lip, mouth, tongue, or throat swelling
• 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

Very rare side effects (may affect less than 1 in 10,000 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)
• Lack of breath, narrowing and blockage of blood vessels in the lungs that can cause shortness of breath (pulmonary embolism), inflammatory lung tissue changes and hardening (pulmonary fibrosis), interstitial lung inflammation (pneumonitis), difficulty breathing, lung injuries, and fluid around the lungs (pleural effusion)
• Intestinal obstruction, intestinal perforation, ischemic colitis, pancreatitis
• Itching (pruritus), rashes (exanthema), skin redness (erythema)
• Blood infection (septicemia), peritonitis
• Fever (pyrexia), dehydration, weakness (asthenia), fluid accumulation in body tissues (edema), discomfort
• Severe and potentially life-threatening allergic reactions (anaphylactic reactions)
• Laboratory tests may show: increased creatinine in the blood, indicating kidney dysfunction
• Heart failure

Very rare side effects (may affect less than 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)
• Hearing loss (ototoxicity), ear ringing (tinnitus), dizziness
• Cough
• Thrombosis of a blood vessel in the abdomen and intestine (mesenteric thrombosis), inflammatory bowel disease, sometimes with persistent severe diarrhea (pseudomembranous colitis, neutropenic colitis), ascites, esophagitis, constipation
• Severe hypersensitivity reactions, such as fever, skin redness, joint pain, and/or eye inflammation (Stevens-Johnson syndrome), localized skin exfoliation (epidermal necrosis), red skin patches (exudative) irregular (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 hypersensitivity reactions withshock(anaphylactic reactions)
• Liver function changes (hepatic necrosis, hepatic encephalopathy [both with reported fatal outcomes])
• Confusion

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

• Thickening or thickening of the skin (scleroderma)
• Sudden constriction of bronchiolar muscle walls (bronchospasm)
• Metabolic complications after cancer treatment (tumor lysis syndrome)
• Eye disorders, such as macular thickening and inflammation (macular edema), flashes of light (photopsia), and spots, motes, and "cobwebs" floating in your field of vision (floaters in the vitreous)
• Phlebitis
• SLE (lupus erythematosus)
• A serious condition that makes people bleed too easily, clot too easily, or both (disseminated intravascular coagulation, DIC). It is a serious condition that makes people bleed very easily, form clots, or both.

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

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

Reporting 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: 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 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.

Before opening

Do not store above25 °C.Store 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 at25 °C.

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

After dilution (description of conditions)

From a microbiological point of view, the diluted product must be used immediately.If not used immediately, it must be stored in a refrigerator (between2 °Cand8 °C) for a maximum period of 24 hours, unless the dilution was performed in controlled and validated aseptic conditions.If youwish tomore information on stability after dilution, consult the section intended for healthcare professionals.

Do not use this medication if 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 packaging and unused medications. In this way, you will help protect the environment.

Composition of Paclitaxel Accord

The active ingredient is paclitaxel.

Each milliliter 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 polioxietilated ricin oil 35 (ricinoleate of macrogolglycerol 35) and anhydrous ethanol.

Appearance of the product and contents of the package

Paclitaxel Accord is a transparent, 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 sizes of packaging may be commercially available.

Marketing Authorization Holder

Accord Healthcare S.L.U.

World Trade Center

Moll de Barcelona, s/n

Edifici Est, 6th floor

08039 Barcelona

Responsible for manufacturing

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 with the following names

Last review date of this leaflet:August 2023.

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/.

This information is intended solely for healthcare professionals

Preparation of infusion solutions

• The containers and infusion equipment used with Paclitaxel Accordmust not contain DEHP. This will minimize the patient's exposure to DEHP [di-(2-ethylhexyl)phthalate], which may be formed by leaching of PVC present in containers or equipment. The use of models of filters (e.g. IVEX-2) that incorporate a short plastic PVC tube for entry and/or exit does not result in significant DEHP leaching.
• Be careful when handling Paclitaxel Accord, as with all other antineoplastic agents. Always use suitable protective gloves when handling vials containing paclitaxel. The dilution will be carried out in aseptic conditions, by experienced personnel, in a specific area. In case of skin contact, wash the affected area with water and soap. In case of mucous membrane contact, rinse with plenty of water.
• Do not use "Chemo-Dispensing Pin" or similar devices, as they may cause the vial cap to fall off, resulting in the loss of the product's sterility.

Step 1: Dilute the concentrate

Before 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
• Composed sodium chloride solution for infusion with dextrose 5%

The final concentration for infusion of paclitaxel must range from 0.3 mg/ml to 1.2 mg/ml.

Use containers and infusion equipment free of DEHP

Once diluted, the solutions may have a turbid appearance, which is attributed to the vehicle of the formulation, and which does not disappear by filtration. No significant potency losses have been observed after simulated administration of the solution via a drip set with a filter in line.

Step 2: Administer the infusion

Administer corticosteroids, antihistamines, and H2 antagonists to all patients before administering Paclitaxel Accord.

Do not administer Paclitaxel Accord again 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 precipitating the infusion solution:

• Use immediately after dilution
• Do not remove, shake, or agitate excessively
• Wash the 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 dextrose 5% solution, and for 14 days when diluted in sodium chloride 0.9% solution. From a microbiological point of view, the diluted product must be used immediately or stored at a temperature between 2°C and 8°C for a maximum of 24 hours.

Paclitaxel Accord must be administered through an appropriate in-line filter, with a microporous membrane of ≤ 0.2 micrometers. Containers and infusion equipment for administration that do not contain DEHP must be used. The use of filter models that incorporate a short plastic PVC tube for entry and/or exit does not result in significant DEHP leaching.

Step 3: Elimination

The unused products or residues derived from them will be disposed of in accordance with local regulations for the handling of cytotoxic compounds.

Dose:

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

Do not administer Paclitaxel Accord again 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).

Patients who experience severe neutropenia (neutrophil count < 500/mm3 for 1 week or more) or severe peripheral neuropathy should have their dose reduced by 20% in subsequent cycles (25% for patients with Kaposi's sarcoma) (see Product Characteristics).

No dose adjustments are recommended for patients with mild to moderate hepatic impairment. Patients with severe hepatic impairment should not be treated with Paclitaxel Accord (see Product Characteristics).

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