PAZENIR 5 mg/ml POWDER FOR DISPERSION FOR INFUSION

Introduction

Package Leaflet: Information for the User

Pazenir 5 mg/ml powder for dispersion for infusion EFG

paclitaxel

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 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 or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What is Pazenir and what is it used for
2. What you need to know before you are given Pazenir
3. How to use Pazenir
4. Possible side effects
5. Storage of Pazenir
6. Contents of the pack and other information

1. What is Pazenir and what is it used for

What is Pazenir

Pazenir contains the active substance paclitaxel bound to human albumin, in the form of tiny particles called nanoparticles. Paclitaxel belongs to a group of medicines called “taxanes” used in cancer.

• Paclitaxel is the part of the medicine that affects cancer, it works by preventing cancer cells from dividing, which means they die.
• Albumin is the part of the medicine that helps paclitaxel dissolve in the blood and cross the walls of blood vessels to reach the tumor. This means that other chemical agents that can cause life-threatening side effects are not needed. Such side effects occur much less frequently with Pazenir.

What is Pazenir used for

Pazenir is used to treat the following types of cancer:

Breast cancer

• Breast cancer that has spread to other parts of the body (this is called “metastatic” breast cancer).
• Pazenir is used in metastatic breast cancer when at least one other therapy has been tried but has not worked and your case is not suitable for treatment with a group of medicines called “anthracyclines”.
• People with metastatic breast cancer who received paclitaxel bound to human albumin when another treatment had failed, were more likely to experience a reduction in tumor size, and lived longer than people who received an alternative treatment.

Pancreatic cancer

• Pazenir is used together with a medicine called gemcitabine if you have metastatic pancreatic cancer. People with metastatic pancreatic cancer (pancreatic cancer that has spread to other parts of the body) who received paclitaxel bound to human albumin with gemcitabine in a clinical trial lived longer than people who only received gemcitabine.

Lung cancer

• Pazenir is also used together with a medicine called carboplatin if you have the most common type of lung cancer, called “non-small cell lung cancer”.
• Pazenir is used in non-small cell lung cancer when surgery or radiotherapy are not suitable to treat the disease.

2. What you need to know before you are given Pazenir

Do not use Pazenir

• if you are allergic (hypersensitive) to paclitaxel or any of the other ingredients of Pazenir (listed in section 6);
• if you are breast-feeding;
• if you have a low white blood cell count (neutrophil count <1,500 cells/mm3 before starting treatment. Your doctor will advise you about this).

Warnings and precautions

Talk to your doctor or nurse before starting treatment with Pazenir

• if you have reduced kidney function;
• if you have severe liver disease;
• if you have heart disease.

If you experience any of these disorders while receiving treatment with Pazenir, talk to your doctor or nurse. Your doctor may decide to interrupt treatment or reduce the dose:

• if you experience any unusual bruising, bleeding or signs of infection such as sore throat or fever;
• if you experience numbness, tingling, pinching, sensitivity to touch or muscle weakness;
• if you experience respiratory problems, such as difficulty breathing or dry cough.

Children and adolescents

This medicine is only intended for adults and must not be given to children or adolescents under 18 years.

Other medicines and Pazenir

Tell your doctor if you are taking or have recently taken any other medicines. This includes medicines that you buy without a prescription, including herbal medicines. This is because Pazenir may affect the way some medicines work. Similarly, some medicines may affect the way Pazenir works.

Be careful and talk to your doctor when using Pazenir at the same time as any of the following:

• medicines to treat infections (i.e. antibiotics such as erythromycin, rifampicin, 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)
• 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 lipid levels in the blood (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)
• the medicine called clopidogrel, which is used to prevent blood clots.

Pregnancy, breast-feeding and fertility

Paclitaxel may cause serious birth defects, so it must not be used if you are pregnant. Your doctor will ask for a pregnancy test before starting treatment with Pazenir.

Women of childbearing age must use effective contraceptive methods during and up to one month after finishing treatment with Pazenir.

Pazenir must not be used during breast-feeding as it is not known whether the active substance paclitaxel passes into breast milk.

Men treated with Pazenir are advised to use effective contraceptive methods and avoid fathering children during treatment and for six months after finishing treatment, as well as to be informed about the possibility of preserving their sperm before starting treatment, given the possibility that treatment with Pazenir may cause irreversible infertility.

Talk to your doctor before using this medicine.

Driving and using machines

Some people may feel tired or dizzy after receiving Pazenir. If this happens to you, do not drive or use any tools or machines.

If you are taking other medicines as part of your treatment, talk to your doctor about your ability to drive and use machines.

Pazenir contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per 100 mg; this is essentially “sodium-free”.

3. How to use Pazenir

A doctor or nurse will give you Pazenir into a vein through an intravenous infusion system. The dose you receive will be calculated based on your body surface area and blood test results. The usual dose for breast cancer is 260 mg/m2 of body surface area, given over 30 minutes. The usual dose for advanced pancreatic cancer is 125 mg/m2 of body surface area, given over 30 minutes. The usual dose for non-small cell lung cancer is 100 mg/m2 of body surface area, given over 30 minutes.

How often will you be given Pazenir?

For the treatment of metastatic breast cancer, Pazenir is usually given once every three weeks (on day 1 of a 21-day cycle).

For the treatment of metastatic pancreatic cancer, Pazenir is given on days 1, 8, and 15 of each 28-day cycle, with gemcitabine given immediately after Pazenir.

For the treatment of non-small cell lung cancer, Pazenir is given once a week (i.e. on days 1, 8, and 15 of a 21-day cycle), with carboplatin given once every three weeks (i.e. only on day 1 of each 21-day cycle), immediately after the Pazenir dose.

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

4. Possible side effects

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

The very commonside effects may affect more than 1 in 10 people:

• Hair loss (most cases of hair loss occurred within a month of starting treatment with paclitaxel. When it occurs, hair loss is pronounced (more than 50%) in most patients)
• Rash
• Abnormal decrease in the number of some types of white blood cells (neutrophils, lymphocytes or leucocytes) in the blood Decrease in red blood cells
• Decrease in the number of platelets in the blood
• Effect on peripheral nerves (pain, numbness, tingling or loss of sensitivity)
• Pain in one or more joints
• Muscle pain
• Nausea, diarrhea, constipation, mouth pain, loss of appetite
• Vomiting
• Weakness and fatigue, fever
• Dehydration, altered taste, weight loss
• Low potassium levels in the blood
• Depression, sleep problems
• Headache
• Chills
• Difficulty breathing
• Dizziness
• Swelling of the mucous membranes and soft tissues
• Increased liver values in liver function tests
• Pain in the limbs
• Cough
• Abdominal pain
• Nosebleeds

The commonside effects may affect up to 1 in 10 people:

• Itching, dry skin, nail disorders
• Infection, fever with a decrease in the number of a type of white blood cell (neutrophils) in the blood, flushing, mouth ulcers, severe blood infection that can be due to a reduction in white blood cells
• Reduction in all blood cell values
• Chest pain or throat pain
• Indigestion, abdominal discomfort
• Nasal congestion
• Back pain, bone pain
• Decrease in muscle coordination or difficulty reading, increased or decreased tears, loss of eyelashes
• Changes in heart rate or rhythm, heart failure
• Low or high blood pressure
• Redness or swelling at the injection site
• Anxiety
• Lung infection
• Urinary tract infection
• Intestinal obstruction, inflammation of the large intestine, inflammation of the bile duct
• Acute kidney failure
• Increased bilirubin in the blood
• Coughing up blood
• Dry mouth, difficulty swallowing
• Muscle weakness
• Blurred vision

The uncommonside effects may affect up to 1 in 100 people:

• Weight gain, increased lactate dehydrogenase in the blood, altered kidney function, increased glucose in the blood, increased phosphorus in the blood

• Decreased or absent reflexes, involuntary movements, pain along a nerve, fainting, dizziness when standing, tremors, paralysis of the facial nerves
• Irritated eyes, eye pain, red eyes, itching eyes, double vision, reduced vision, or flashing lights, blurred vision due to inflammation of the retina (cystoid macular edema)
• Ear pain, ringing in the ears
• Coughing up mucus, shortness of breath when walking or climbing stairs, runny nose or dry nose, decreased breath sounds, fluid in the lungs, loss of voice, blood clots in the lungs, dry throat
• Gas, stomach cramps, gum pain, rectal bleeding
• Pain when urinating, need to urinate more often than usual, blood in the urine, involuntary loss of urine (incontinence)
• Pain in the nails, discomfort in the nails, loss of nails, hives, skin pain, photosensitivity reaction, skin pigmentation disorders, increased sweating, night sweats, white patches on the skin, sores, swelling of the face
• Decreased phosphorus in the blood, fluid retention, low albumin in the blood, increased thirst, decreased calcium in the blood, decreased sugar in the blood, decreased sodium in the blood
• Pain and swelling in the nose, skin infections, catheter-related infections
• Bruising
• Pain and swelling at the tumor site, tumor necrosis
• Decrease in blood pressure when standing, coldness in hands and feet
• Difficulty walking, swelling
• Allergic reaction
• Decreased liver function, increased liver size
• Chest pain
• Nervousness
• Small bleeding spots on the skin due to blood clots
• A condition that involves the destruction of red blood cells and acute kidney failure

The rareside effects may affect up to 1 in 1,000 people:

• Skin reaction to another agent or lung inflammation after radiation
• Blood clots
• Very slow pulse, heart attack
• Medicine leak outside the vein
• Disorder of the heart's electrical conduction system (atrioventricular block)

The very rareside effects may affect up to 1 in 10,000 people:

• Severe skin and mucous membrane inflammation (Stevens-Johnson syndrome, toxic epidermal necrolysis)

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

• Hardening/thickening of the skin (scleroderma).

Reporting of side effects

If you experience any side effects, talk to your doctor or nurse, even if it is possible that the side effects are not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Pazenir

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

Do not use this medicine after the expiry date which is stated on the carton and on the vial after EXP. The expiry date is the last day of the month stated.

Unopened vial: store the container in the outer packaging until use to protect it from light.

After the first reconstitution, it must be used immediately. If not used immediately, the dispersion can be stored in the refrigerator (2°C - 8°C) for a maximum of 24 hours in the vial if stored in its outer packaging to protect it from light.

The reconstituted dispersion in the infusion bag can be stored for a maximum of 24 hours at 2°C - 8°C, protected from light, and then for 4 hours at 15°C - 25°C.

Your doctor or pharmacist is responsible for the proper disposal of any unused Pazenir.

6. Container Contents and Additional Information

Pazenir Composition

The active ingredient is paclitaxel.

Each vial contains 100 mg of paclitaxel bound to albumin in a nanoparticle formulation.

After reconstitution, each ml of dispersion contains 5 mg of paclitaxel bound to albumin in a nanoparticle formulation.

The other component is human albumin (containing sodium caprylate and N-acetyl-DL-tryptophan), see section 2 "Pazenir contains sodium".

Product Appearance and Container Contents

Pazenir is a powder for dispersion for infusion, white to yellow in color. Pazenir is available in glass vials containing 100 mg of paclitaxel bound to albumin in a nanoparticle formulation.

Each container contains 1 vial.

Marketing Authorization Holder

ratiopharm GmbH

Graf-Arco-Straße

89079 Ulm

Germany

Manufacturer

Merckle GmbH

Ludwig-Merckle-Straße 3

89143 Blaubeuren

Germany

Pharmachemie B.V.

Swensweg 5

Haarlem

2031 GA

Netherlands

Teva Pharma B.V.

Swensweg 5

2031 GA Haarlem

Netherlands

Teva Nederland B.V.

Swensweg 5

2031 GA Haarlem

Netherlands

For further information on this medicinal product, please contact the local representative of the marketing authorization holder:

Date of Last Revision of this Leaflet: March 2022

Detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu.

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Healthcare Professionals

This information is intended for healthcare professionals only:

Instructions for Use, Preparation, and Disposal

Precautions for Preparation and Administration

Paclitaxel is a cytotoxic antineoplastic agent, so Pazenir should be handled with caution, as with other potentially toxic agents. Gloves, safety glasses, and protective clothing should be used. In case of contact of the Pazenir dispersion with the skin, the affected area should be washed immediately and thoroughly with water and soap. In case of contact of Pazenir with mucous membranes, they should be rinsed thoroughly with plenty of water. Pazenir should only be prepared and administered by personnel experienced in handling cytotoxic agents. Pregnant women should not handle Pazenir.

Due to the possibility of extravasation, it is advisable to closely monitor the infusion site in case it occurs during administration of the medicinal product. Limiting the infusion time of Pazenir to 30 minutes, according to the instructions, reduces the likelihood of infusion-related reactions.

Reconstitution of the Medicinal Product and Administration

Pazenir should be administered under the supervision of a qualified oncologist, in units specialized in the administration of cytotoxic agents.

Pazenir is presented as a sterile lyophilized powder for reconstitution prior to use. After reconstitution, each ml of dispersion contains 5 mg of paclitaxel bound to albumin in a nanoparticle formulation. The reconstituted Pazenir dispersion should be administered intravenously using an infusion set that incorporates a 15 μm filter.

Reconstitution of 100 mg

Using a sterile syringe, 20 ml of 9 mg/ml (0.9%) sodium chloride injection solution should be slowly injected into the 100 mg Pazenir vial over at least 1 minute.

The solution should be directed at the inner walls of the vial. The solution should not be injected directly onto the powder as this will cause foaming.

Once the solution has been added, the vial should be allowed to stand for at least 5 minutes to ensure adequate wetting of the solute. The vial should then be gently agitated and/or inverted for at least 2 minutes to complete the redispersion of the powder. Foaming should be avoided. If foaming or clumping occurs, the dispersion should be allowed to stand for at least 15 minutes until the foam has disappeared.

The reconstituted dispersion should have a milky and homogeneous appearance without visible precipitates.

A certain sedimentation of the reconstituted dispersion may occur. If there are signs of precipitate or sedimentation, the vial should be gently inverted again to achieve complete redispersion before use.

Inspect the dispersion in the vial for particles. Do not administer the reconstituted dispersion if particles are observed in the vial.

The exact total volume of 5 mg/ml dispersion required for the patient should be calculated and the appropriate amount of reconstituted Pazenir should be injected into an empty, sterile intravenous infusion bag made of PVC or non-PVC material.

The use of medical products containing silicone oil as a lubricant (i.e., syringes and IV bags) to reconstitute and administer Pazenir may result in the formation of protein filaments. Pazenir should be administered through an infusion set that incorporates a 15 μm filter to prevent the administration of these filaments. The use of a 15 μm filter removes the filaments and does not alter the physical or chemical properties of the reconstituted medicinal product.

The use of filters with a pore size smaller than 15 μm may result in filter blockage.

There is no need for the use of DEHP-free infusion bags or administration sets to prepare or administer Pazenir infusions.

After administration, it is recommended to flush the intravenous line with 9 mg/ml (0.9%) sodium chloride injection solution to ensure complete administration of the dose.

Disposal of unused medicinal product and all materials that have come into contact with it should be done in accordance with local regulations.

Stability

Unopened Pazenir vials remain stable until the expiry date stated on the container, provided they are stored in the outer packaging to protect them from light. Freezing or refrigeration does not adversely affect the stability of the medicinal product. This medicinal product does not require any special storage temperature.

Stability of the Reconstituted Dispersion in the Vial

After the first reconstitution, the dispersion should be immediately transferred to an infusion bag. However, the chemical and physical stability in-use has been demonstrated for 8 hours at 2°C-8°C in the original container and protected from intense light.

Stability of the Reconstituted Dispersion in the Infusion Bag

After reconstitution, the reconstituted dispersion in the infusion bag should be used immediately. However, the chemical and physical stability in-use has been demonstrated for 24 hours at 2°C-8°C, protected from light, and then for 4 hours at 15°C-25°C.