PATIENT INFORMATION LEAFLET

Paclitaxel Hospira 6 mg/ml Concentrate for Solution for Infusion EFG

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

2.What you need to know before you start using Paclitaxel Hospira

3.How to use Paclitaxel Hospira

4.Possible side effects

1. Storage of Paclitaxel Hospira
2. Contents of the pack and additional information

Paclitaxel Hospira is a medication that belongs to a group of compounds called taxanes, which are used for cancer treatment. These agents inhibit the growth of cancer cells.

Paclitaxel Hospira is used to treat:

-Ovarian cancer

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

-Breast cancer:

• as first treatment for advanced or extended disease to other parts of the body (metastatic disease), paclitaxel is combined with other cancer medications.
• as additional treatment after initial surgery followed by treatment with anthracycline and cyclophosphamide (AC).
• as second-line treatment in patients in whom the reference treatment using anthracyclines has not worked or who cannot use these treatments.

-Non-small cell lung canceradvanced, in combination with cisplatin,when surgery and/or radiation therapy are not indicated.

-Kaposi's sarcomaadvancedassociated with AIDS, after other treatments (e.g. liposomal anthracyclines) that have been tried have not worked.

Laboratory tests (such as blood tests) must be performed to ensure that you can be treated with this medication. Some patients may need heart tests.

Do not use Paclitaxel Hospira:

• If you are allergic to paclitaxel, or to polyoxylated castor oil (ricinoleate of macrogolglycerol) or to any of the other components of this medication (listed in section 6)
• If you are pregnant or breastfeeding
• If your white blood cell or platelet count is very low (this will be checked with a blood test)
• If you have severe and uncontrolled infections in patients with Kaposi's sarcoma

Warnings and precautions

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

• If you experience a marked allergic reaction that can cause difficulty breathing, dizziness (caused by low blood pressure), facial swelling, or rash. Some of these allergic reactions can be fatal
• If you have heart problems or severe liver problems (if liver damage is severe, paclitaxel should not be administered to you)
• If your blood cell counts are abnormal
• If you experience irregular heartbeats, dizziness, or fainting during treatment
• If you experience tingling, burning, or numbness in your fingers and/or toes
• If this product is given to you along with radiation therapy (radiation) to the lungs (see 4. Possible side effects)
• If diarrhea occurs during or shortly after treatment with this product, the colon may be inflamed
• If you have Kaposi's sarcoma and experience mouth pain or inflammation
• If you experience visual disturbances*
• If you have alcoholism

*Patients with vision deterioration during paclitaxel treatment should undergo a complete ophthalmological examination immediately.

Children and adolescents

This product is not recommended for use in children under 18 years old

Use of Paclitaxel Hospira with other medications

Consult your doctor when taking paclitaxel at the same time as any of the following medications:

• Medications to treat infections (such as antibiotics like erythromycin, rifampicin, trimethoprim, etc.; ask your doctor, nurse, or pharmacist if you are unsure 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, nevirapine);
• A medication called clopidogrel, used to prevent blood clots
• Medications used to remove excess iron from the body (also known as iron overload) (e.g., deferasirox);
• Medications or preparations containing St. John's Wort orHypericum(Hypericum perforatum), a medicinal plant used to treat depression and anxiety.

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication.

Use of Paclitaxel Hospira with food, drinks, and alcohol

Paclitaxel is not affected by the consumption of food and drinks.

Pregnancy, breastfeeding, and fertility

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

Paclitaxel concentrate for infusion solution should not be administered if you are pregnant. This medication may cause birth defects, therefore, do 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 six months after completing treatment. If pregnancy occurs during treatment or within six months after completing treatment, inform your doctor immediately.

Paclitaxel Hospira concentrate for infusion solution is contraindicated during breastfeeding.

Paclitaxel may cause infertility, which may be irreversible. Therefore, male patients are advised to seek advice on sperm conservation before treatment.

Driving and operating machinery:

Paclitaxel has not been shown to interfere with the ability to drive or operate machinery. However, it should be noted that this medication contains alcohol and may therefore reduce reaction time, so caution should be exercised when driving and operating hazardous machinery.

Paclitaxel Hospira contains polyoxylated castor oil (ricinoleate of macrogolglycerol) and ethanol.

This medication may produce severe allergic reactions because it contains ricinoleate of macrogolglycerol (polyoxylated castor oil)

This medication contains 49.7% ethanol (alcohol), which corresponds to a quantity of 21 g per dose, equivalent to 740 ml of beer or 190 ml of wine. This medication is harmful to individuals with alcoholism.

The alcohol content should be taken into account in the case of pregnant women, breastfeeding women, children, and high-risk groups, such as patients with liver disease or epilepsy.

The amount of alcohol in this medication may alter the effects of other medications.

The amount of alcohol in this medication may reduce the ability to drive or operate machinery

Follow exactly the administration instructions for this medication as indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

Your doctor will determine the daily dose of paclitaxel based on body surface area and the dosing will be subject to changes as deemed necessary by your doctor.

If you receive more Paclitaxel Hospira than you should

If you believe you have received more paclitaxel than you should, consult your doctor immediately or go to the nearest hospital.

In case of overdose or accidental ingestion, consult the Toxicological Information Service, phone 91 562 04 20.

There is no known antidote for paclitaxel overdose. It is expected that the first complications resulting from overdose will be related to bone marrow suppression, as well as peripheral nerve alterations and mucous membrane inflammation.

If you forgot to use Paclitaxel Hospira

If you forget to administer a dose, do not administer a double dose to compensate for the missed one. Always follow your doctor's recommendations.

If you interrupt treatment with Paclitaxel Hospira

Your doctor will decide when to interrupt treatment with paclitaxel.

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

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

If you experience any of the following side effects, inform your doctor immediately as they may be serious, requiring urgent medical attention or hospitalization.

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

• Infection - usually of the urinary tract or upper respiratory tract. This may be associated with a low blood cell count resulting from paclitaxel treatment. This can sometimes be fatal
• Bone marrow suppression, which can lead to a decrease in blood cell counts and may cause infections, anemia, weakness, bruising, and bleeding
• Mild allergic reactions, including redness and rashes on the skin
• Tickling and pinching sensations in the hands and feet (peripheral neuropathy)*
• Low blood pressure that can make you feel dizzy, especially when standing up
• Nausea and vomiting
• Mild diarrhea
• Hair loss
• Muscle weakness or joint pain, pain, or numbness in the extremities. These usually decrease or disappear several months after paclitaxel treatment is stopped
• Mouth or tongue pain
• Hair loss(most cases of hair loss occurred less than a month after paclitaxel initiation. When it occurs, it is a pronounced hair loss (greater than 50%)in most patients)

Common:may affect up to 1 in 10 people

• Slow heart rate
• Mild temporary changes in nails and skin
• Reactions at the injection site, such as local swelling, pain, redness, hardening of tissues, skin tissue death, extravasation (medication leakage outside the vein) resulting in cellulitis (painful inflammation and redness)
• Changes in liver function, increased liver enzymes (shown in blood tests)

Uncommon:may affect up to 1 in 100 people

• Severe allergic reactions that cause low or high blood pressure, chest pain, difficulty breathing, rapid heart rate (pulse), abdominal or limb pain, sweating, itching, and/or back pain. This can be fatal
• Severe chest pain that may radiate to the jaw or arm, sweating, difficulty breathing, and nausea (heart attack)
• Chest pain caused by heart disease
• Muscle or heart weakness (cardiac degeneration)
• Abnormal heart rhythm
• Fainting
• High blood pressure (may cause headaches)
• Vein blood clots (thrombosis) and inflammation of veins associated with blood clot formation (thrombophlebitis) - this may present as pain and/or swelling in your arms or legs or vein inflammation
• Yellow color in the white part of the eyes and skin
• Severe infections, such as sepsis (blood poisoning) with shock
• Chills

Rare: may affectup to 1 in 1,000 people

• Pneumonia
• Generalized infection (sepsis)
• Peritonitis (inflammation of the membrane surrounding the stomach and intestines), with symptoms of abdominal pain, constipation, vomiting, and fever
• Fever
• Fever due to a decrease in neutrophil count (neutropenic fever)
• Severe allergic reaction (anaphylactic reaction): you may experience a skin rash with sudden itching (urticaria), swelling of the hands, feet, ankles, face, lips, mouth, or throat (which may cause difficulty swallowing or breathing), and may feel dizzy
• Dehydration

• Effect on nerves controlling muscles, resulting in muscle weakness in the arms and legs (motor neuropathy)

• Heart problems that may cause shortness of breath or inflammation of the ankles. Difficulty breathing, coughing, coughing with blood, or chest or shoulder pain. Some of these effects may not occur immediately (pulmonary fibrosis)
• Abdominal pain caused by intestinal inflammation, intestinal obstruction, or intestinal wall perforation
• Ischemic colitis (inflammation of the colon due to obstruction or constriction of blood vessels)
• Itching, skin rashes, redness
• Fluid accumulation throughout the body (edema)
• Loss of energy
• Pancreatitis (inflammation of the pancreas)
• Edema (inflammation)
• Discomfort
• Elevated creatinine in the blood

Very rare: may affectup to 1 in 10,000 people

• Severe diarrhea with blood in the stool (pseudomembranous colitis)
• Acute leukemia (blood cancer) or related condition (myelodysplastic syndrome)
• Potentially fatal anaphylactic shock
• Loss of appetite
• Confusion
• Muscle weakness, cramps, severe abdominal or intestinal pain (paralytic ileus) or dizziness when standing up (orthostatic hypotension) that may be caused by a nervous system disease
• Seizures ("attacks")
• Brain damage (encephalopathy)
• Balance problems
• Dizziness
• Headache
• Visual disturbances
• Loss of hearing
• Tinnitus (ringing in the ears)
• Dizziness
• Increased heart rate
• Persistent diarrhea
• Shock
• Coughing
• Abdominal pain that may be caused by fluid accumulation in the abdomen (ascites), intestinal inflammation, or blood clot in the intestinal blood vessels
• Constipation
• Stomach burning, nausea, and/or vomiting that may be caused by esophagitis (inflammation of the throat)
• Severe liver damage that may be fatal (hepatic necrosis). This may affect brain function (hepatic encephalopathy)
• Generalized rash with blisters and skin peeling, particularly around the mouth, nose, eyes, and genitals (Stevens-Johnson syndrome), causing widespread skin peeling (more than 30% of the body surface) (epidermal necrosis)
• Rapid onset of a rash followed by the appearance of skin lesions on the soles of the feet and palms of the hands and mouth ulcers (erythema multiforme).
• Severe skin peeling (exfoliative dermatitis)
• Urticaria
• Nail loss from the fingers (recommended to use protection on hands and feet when exposed to the sun)

Frequency not known(cannot be estimated from available data)

• Difficulty breathing (bronchospasm)
• A condition called tumor lysis syndrome that may cause high sodium or potassium levels or low calcium levels in the blood
• Posterior eye swelling (macular edema)
• Visual disturbances such as seeing flashes of light (photopsia) or floaters
• Vein inflammation
• Connective tissue diseases (scleroderma)
• An autoimmune disorder that may affect the skin, joints, kidneys, brain, and other organs (systemic lupus erythematosus)
• Disseminated intravascular coagulation (CID) has been reported. This is a serious condition that causes excessive bleeding, blood clots, or both
• Wheezing has been reported, but the frequency is unknown
• Redness and swelling of the palms of the hands and soles of the feet that may cause skin peeling (erythema palmoplantar syndrome)

*May persist for more than 6 months after paclitaxel treatment is stopped

Reporting side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect not listed in this prospectus. You can also report them directly through the Spanish System for 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 usethis medicationafter the expiration date that appears onthe label and on the boxafter CAD. The expiration date is the last day of the month indicated.

Do not store at temperatures above 25°C. Store in the original packaging to protect it from light.

Do not use if you detect a cloudy solution or an insoluble precipitate.

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

Paclitaxel Hospira Composition

The active ingredient is paclitaxel. Each milliliter of concentrate contains 6 mg of paclitaxel.

The other components are polyoxylated ricinoleate (macrogolglycerol ricinoleate), anhydrous ethanol, and anhydrous citric acid.

Product Appearance and Packaging Contents

Paclitaxel Hospira is a clear, colorless, or slightly yellowish solution.

This medication is a sterile concentrate solution. This means that the concentrated solution in the vial must be diluted before use. Once diluted, it is administered as a slow intravenous injection.

Paclitaxel Hospira is presented in Type I glass vials: 30 mg/5 ml or 100 mg/16.7 ml or 150 mg/25 ml or 300 mg/50 ml. Each package contains 1 vial.

Only some package sizes may be commercially available.

Marketing Authorization Holder and Responsible Manufacturer

Marketing Authorization Holder

HOSPIRA INVICTA, S.A.

Avda. de Europa 20-B

Parque Empresarial La Moraleja

28108 Alcobendas (Madrid)

Spain

Responsible Manufacturer

Pfizer Service Company BV

Hoge Wei 10,

Zaventem 1930,

Belgium

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

Pfizer, S.L.

Avda. de Europa, 20-B

Parque Empresarial La Moraleja

28108, Alcobendas (Madrid)

Spain

Last review date of this leaflet: April 2021

For detailed and updated information about this medication, please visit 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

In addition to the information provided in section 3, this section provides practical information on the preparation and handling of the medication.

Instructions for use, handling, and disposal

Handling:As with all cytostatic drugs, paclitaxel should be handled with caution. Dilutions should be carried out in aseptic conditions by experienced personnel in a designated area. Gloves should be worn. Precautions should be taken to avoid contact with the skin and mucous membranes. Pregnant women should avoid contact with cytostatics.

In the event 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 the event of mucous membrane contact, they should be thoroughly washed with plenty of water. After inhalation, dyspnea, chest pain, throat burning, and nausea have been described.

If closed vials are refrigerated, a precipitate may form that redissolves when agitated gently when the ambient temperature is reached. This does not affect the quality of the product. If the solution remains turbid or a precipitate remains insoluble, the vial should be discarded.

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

Preparation for IV administration: Before proceeding with the infusion, Paclitaxel Hospira must be diluted to a final concentration of0.3 to1.2 mg/ml using aseptic techniques. The dilution should be carried out using:

• sodium chloride 0.9% solution (9 mg/ml),
• dextrose 5% solution (50 mg/ml)
• a mixture of dextrose 5% (50 mg/ml) and sodium chloride 0.9% solution (9 mg/ml)
• Ringer's injection solution with dextrose 5% (50 mg/ml)

Once diluted, the prepared solution is for single use only.

For the conservation of prepared solutions for infusion:

After opening the vial, before dilution:

After multiple needle insertions and withdrawals, the physical and chemical stability of the prepared solutions for infusion has been demonstrated for 28 days at25°C, protected from light.

From a microbiological point of view, once the package is opened, the sterile concentrate solution for infusion remains stable for a maximum of 28 days at temperatures below25°C. The storage conditions will be the responsibility of the user.

After dilution:

The chemical and physical stability of the prepared solutions for infusion has been demonstrated for 72 hours at25°C, under normal lighting conditions. The diluted solution should not be frozen.

From a microbiological point of view, the diluted solution should be used immediately. If not, the storage and use conditions before use will be the responsibility of the user and should not exceed 24 hours at2 to8°C, unless the reconstitution/dilution was carried out in controlled and validated aseptic conditions.

The prepared infusion solution should be visually inspected for particles and coloration after preparation.

After preparation, these solutions may present a slight turbidity that is attributed to the excipient of the preparation and which does not disappear by filtration. Paclitaxel should be administered with an appropriate infusion device equipped with a microporous filter membrane with pores?0.22 μm. No significant losses of potency have been observed after simulated release of the solution through IV infusion equipment provided with a filter in series.

Isolated cases of precipitation have been reported during paclitaxel infusions, usually towards the end of the 24-hour infusion period. Although the cause of this precipitation has not been established, it is likely related to the supersaturation of the diluted solution. To reduce the risk of precipitation, paclitaxel should be administered as soon as possible after dilution, and excessive agitation, vibration, or shaking should be avoided. Infusion equipment should be thoroughly washed before use. During infusion, the appearance of the solution should be regularly examined, and in the event of precipitation, the infusion should be interrupted.

To minimize the patient's exposure to DEHP that may be leached from PVC plastic present in bags, infusion equipment, or other medical instruments, diluted paclitaxel solutions should be stored in non-PVC containers (glass, polypropylene), or plastic bags (polypropylene, polyolefin), and administered with a polyethylene device. The use of filter models with a short plastic PVC outlet/entry tube (e.g. IVEX-2®), is not significant because the amount of DEHP that may be released is not significant.

Disposal: All elements used in preparation and administration, and those that may have come into contact with paclitaxel, must comply with local regulations for the handling of cytotoxic products.