PACLITAXEL HOSPIRA 6 mg/ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

PATIENT INFORMATION LEAFLET

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

Contents of the pack:

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

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

1. How to use Paclitaxel Hospira
2. Possible side effects
   1. Storage of Paclitaxel Hospira
   2. Contents of the pack and other information

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

Paclitaxel Hospira is a medicine that belongs to a group of compounds called taxanes, which are used to treat cancer. 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 failure of platinum-based reference treatment.

• Breast cancer:
  • as first treatment for advanced or metastatic disease, paclitaxel is combined with other cancer medicines.
  • as additional treatment after initial surgery followed by treatment with anthracycline and cyclophosphamide (AC).
  • as second-line treatment in patients who have not responded to anthracycline-based reference treatment or who cannot use these treatments.

• Advanced non-small cell lung cancer, in combination with cisplatin, when surgery and/or radiotherapy are not indicated.

• Advanced Kaposi's sarcoma associated with AIDS, after other treatments (e.g. liposomal anthracyclines) have failed.

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

Lab tests (e.g. blood tests) must be performed to ensure that you can be treated with this medicine. Some patients may need heart tests.

Do not use Paclitaxel Hospira:

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

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting treatment with Paclitaxel Hospira.

• If you notice a marked allergic reaction that can cause difficulty breathing, dizziness (caused by low blood pressure), swelling of the face 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)
• 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 treatment (radiotherapy) of 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 have a painful or inflamed mouth
• If you experience visual disturbances*
• In case of alcoholism

• Patient with vision impairment during treatment with paclitaxel should undergo a complete ophthalmological examination immediately.

Children and adolescents

This product is not recommended for use in children under 18 years of age.

Using Paclitaxel Hospira with other medicines

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

• medicines to treat infections (i.e. antibiotics such as erythromycin, rifampicin, trimethoprim, etc.; ask your doctor, nurse, or pharmacist if you are not sure if the medicine you are taking is an antibiotic), including medicines to treat fungal infections (e.g. ketoconazole);
• medicines used to help stabilize your mood, sometimes called antidepressants (e.g. fluoxetine);
• medicines used to treat seizures (epilepsy) (e.g. carbamazepine, phenytoin);
• medicines used to help lower blood lipid levels (e.g. gemfibrozil);
• medicines used for heartburn or stomach ulcers (e.g. cimetidine);
• medicines used to treat HIV or AIDS (e.g. ritonavir, saquinavir, indinavir, nelfinavir, efavirenz, nevirapine);
• a medicine called clopidogrel, which is used to prevent blood clots.
• medicines used to remove excess iron from the body (also called iron overload) (e.g. deferasirox);
• medicines or preparations containing St. John's Wort or Hipérico(Hypericum perforatum), a medicinal plant used for depression and anxiety.

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

Using Paclitaxel Hospira with food, drinks, and alcohol

Paclitaxel is not affected by food and drink intake.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Paclitaxel concentrate for solution for infusion should not be administered if you are pregnant. 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 you are receiving treatment with paclitaxel and for six months after treatment has stopped. If you become pregnant during treatment or within six months after treatment has stopped, inform your doctor immediately.

Paclitaxel Hospira concentrate for solution for infusion is contraindicated during breastfeeding.

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

Driving and using machines:

It has not been shown that paclitaxel interferes with your ability to drive or use machines. However, it should be taken into account that this medicine contains alcohol and therefore may impair your reaction ability, so caution is advised when driving and operating hazardous machinery.

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

This medicine may cause severe allergic reactions because it contains macrogolglycerol ricinoleate (polyoxyethylated castor oil)

This medicine contains 49.7% ethanol (alcohol), which corresponds to an amount of 21 g per dose, equivalent to 740 ml of beer or 190 ml of wine. This medicine is harmful to people with alcoholism.

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

The amount of alcohol in this medicine may alter the effects of other medicines.

The amount of alcohol in this medicine may impair your ability to drive or use machines

3. How to use Paclitaxel Hospira

Follow exactly the administration instructions of this medicine given 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 your body surface area and the dosage will be subject to the changes that the doctor deems appropriate.

If you receive more Paclitaxel Hospira than you should

If you think 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 Toxicology Information Service, phone 91 562 04 20.

There is no known antidote for paclitaxel overdose. The first complications of overdose are expected to be related to bone marrow suppression, as well as peripheral nerve and mucosal inflammation.

If you forget to use Paclitaxel Hospira

If a dose is missed, a double dose will not be given to make up for the missed dose. Always follow the recommendations of your doctor.

If you stop treatment with Paclitaxel Hospira

Your doctor will decide when to stop treatment with paclitaxel.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

If you experience any of the following side effects, tell your doctor immediately, as they can be serious and require 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 receiving paclitaxel. This can sometimes be fatal
• Bone marrow suppression, which can lead to a decrease in blood cell counts and may result in infections, anemia, weakness, bruising, and bleeding
• Mild allergic reactions, including redness and skin rash
• Tingling and numbness in 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 or joint weakness, pain, or loss of sensation in the limbs. These usually decrease or disappear several months after stopping treatment with paclitaxel
• Mouth or tongue pain
• Hair loss (most cases of hair loss occurred less than a month after starting paclitaxel. When it happens, it is a pronounced hair loss (more 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 necrosis, extravasation (leakage of the medicine 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 can cause low or high blood pressure, chest pain, difficulty breathing, rapid heartbeat (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 that may be caused by heart disease
• Pain or weakness in the heart muscle (cardiac degeneration)
• Abnormal heart rhythms
• Fainting
• High blood pressure (may cause headaches)
• Blood clots in the veins (thrombosis) and inflammation of the veins associated with blood clot formation (thrombophlebitis) - this can present as pain and/or swelling in your arms or legs or vein inflammation
• Yellow color in the white of the eyes and skin
• Severe infections, such as sepsis (blood poisoning) with shock
• Chills

Rare: may affect up to 1 in 1,000 people

• Pneumonia
• Generalized infection (sepsis)
• Inflammation of the membrane (peritoneum) that surrounds the stomach and intestines, whose symptoms are abdominal pain, constipation, vomiting, and fever
• Fever
• Fever due to a decrease in the number of neutrophils (febrile neutropenia)
• 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 can cause difficulty swallowing or breathing), and may give a feeling of fainting
• Dehydration

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

• Heart problems that can cause shortness of breath or ankle swelling. Difficulty breathing, cough, coughing up blood, or chest pain or shoulder pain. Some of these effects may not occur immediately (pulmonary fibrosis)
• Abdominal pain caused by inflammation in the intestine, intestinal obstruction, or perforation of the intestinal wall
• Inflammation of the colon due to obstruction or constriction of blood vessels (ischemic colitis)
• Itching, skin rash, redness
• Fluid accumulation throughout the body (edema)
• Loss of energy
• Inflammation of the pancreas (pancreatitis)
• Inflammation (edema)
• Discomfort
• Elevated creatinine levels in the blood

Very rare: may affect up 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 allergic reaction (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 ("fits")
• Effect on the brain (encephalopathy)
• Balance problems
• Dizziness
• Headache
• Visual disturbances
• Hearing loss
• Ringing in the ears
• Vertigo
• Increased heart rate
• Persistent diarrhea
• Shock
• Cough
• Abdominal pain that may be caused by fluid accumulation in the abdomen (ascites), inflammation in the intestine, or blood clot in the intestinal blood vessels
• Constipation
• Heartburn, nausea, and/or vomiting that may be caused by inflammation of the throat (esophagitis)
• Liver damage that can be severe (liver necrosis). This can have an effect on brain function (hepatic encephalopathy). This can sometimes be fatal
• Widespread 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) (toxic epidermal necrolysis)
• Rapid onset of a rash followed by the appearance of skin lesions on the soles of the feet and palms of the hands and ulcers in the mouth (erythema multiforme).
• Severe skin peeling (exfoliative dermatitis)
• Hives
• Loss of fingernails (it is recommended to use protection on hands and feet when exposed to the sun)

Frequency not known(cannot be estimated from the available data)

• Difficulty breathing (bronchospasm)
• A condition called tumor lysis syndrome that can cause high sodium or potassium levels or low calcium levels in the blood
• Swelling of the back of the eye (macular edema)
• Visual disturbances such as seeing flashes of light (photopsia) or floaters
• Inflammation of the veins
• Diseases of the connective tissue (scleroderma)
• An autoimmune disorder that can affect the skin, joints, kidneys, brain, and other organs (systemic lupus erythematosus)
• Disseminated intravascular coagulation or "DIC" has been reported. This is a serious condition that causes excessive bleeding, blood clots, or both
• Cases of wheezing when breathing (wheezing) have been reported, but the frequency is unknown
• Redness and swelling of the palms of the hands and soles of the feet that can cause skin peeling (palmar-plantar erythrodysesthesia syndrome)

*May persist for more than 6 months after stopping treatment with paclitaxel

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist, even if it is possible side effects 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 side effects, you can help provide more information on the safety of this medicine.

5. Storage of Paclitaxel Hospira

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

Do not use this medicine after the expiration date that appears on the label and on the box after CAD. The expiration date is the last day of the month indicated.

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

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

Medicines should not be thrown down the drain or into the trash. Ask your pharmacist how to dispose of the packaging and medicines you no longer need. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Paclitaxel Hospira

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

The other components are polyoxyethylated castor oil (macrogolglycerol ricinoleate), anhydrous ethanol, and anhydrous citric acid.

Appearance of the Product and Package Contents

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

This medicine is a concentrate for solution (sterile concentrate). This means that the concentrated solution in the vial must be diluted before use. Once diluted, it is administered as a slow injection into a vein.

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 marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

HOSPIRA INVICTA, S.A.

Avda. de Europa 20-B

Parque Empresarial La Moraleja

28108 Alcobendas (Madrid)

Spain

Manufacturer

Pfizer Service Company BV

Hoge Wei 10,

Zaventem 1930,

Belgium

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Pfizer, S.L.

Avda. de Europa, 20-B

Parque Empresarial La Moraleja

28108, Alcobendas (Madrid)

Spain

Date of the Last Revision of this Prospectus: April 2021

Detailed and updated information about this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es

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This information is intended only for healthcare professionals

In addition to the information collected in section 3, practical information on the preparation/handling of the medicine is provided here.

Instructions for Use, Handling, and Disposal

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

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. After inhalation, dyspnea, chest pain, throat burning, and nausea have been described.

If the closed vials are refrigerated, a precipitate may form that redissolves when gently shaken when it reaches room temperature. This does not affect the quality of the product. If the solution remains turbid or if an insoluble precipitate remains, the vial should be discarded.

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

Preparation for IV Administration: Before proceeding to perfusion, Paclitaxel Hospira should be diluted to a final concentration of 0.3 to 1.2 mg/ml using aseptic techniques. The dilution should be performed using:

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

Once diluted, the prepared solution is for single use.

For the storage of prepared solutions for perfusion:

After opening the vial, before dilution:

After multiple needle insertions and withdrawals, the physical and chemical stability of the prepared perfusion solutions has been demonstrated for 28 days at 25°C, protected from light.

From a microbiological point of view, once the package is opened, the concentrate for solution for perfusion remains stable for up to 28 days at temperatures below 25°C. The user will be responsible for storage under other conditions.

After dilution:

The chemical and physical stability of the prepared perfusion solutions has been demonstrated for 72 hours at 25°C, stored under normal light 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 at 2-8°C, unless the reconstitution/dilution has been carried out under controlled and validated aseptic conditions.

The perfusion solution, once prepared, should be visually inspected for particles and coloration.

After preparation, these solutions may present a slightly turbid appearance attributed to the excipient of the preparation and which is not eliminated by filtration. Paclitaxel should be administered with a suitable perfusion apparatus 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 perfusion equipment provided with a filter in series.

Isolated cases of precipitation during paclitaxel perfusions have been reported, usually towards the end of the 24-hour perfusion period. Although the cause of this precipitation has not been established, it is probably 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. Perfusion equipment should be thoroughly washed before use. During perfusion, the appearance of the solution should be regularly examined, and if precipitation is observed, perfusion should be interrupted.

To minimize patient exposure to DEHP that may be formed by leaching of PVC plastic present in bags, perfusion equipment, or other medical devices, diluted paclitaxel solutions should be stored in non-PVC containers (glass, polypropylene) or plastic bags (polypropylene, polyolefin) and administered with a polyethylene equipment. The use of filter models that have a short PVC plastic inlet/outlet 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 the preparation and administration, and those that may have come into contact with paclitaxel, must comply with local regulations regarding the handling of cytotoxic products.