Pazenir 5 mg/ml powder for dispersion for infusion EFG

Patient Information Leaflet

Introduction

Patient Information Leaflet

Pazenir 5 mg/ml powder for concentrate for solution for infusion EFG

paclitaxel

Please read all of this leaflet carefully before you start using this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor or nurse.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any side effects, talk to your doctor or nurse, even if the side effect is not listed in this leaflet. See section 4.

Contents of this leaflet

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

1. What Pazenir is and what it is used for

What Pazenir is

Pazenir contains, as its active substance, paclitaxel bound to human protein albumin, in the form of tiny particles called nanoparticles. Paclitaxel belongs to a group of medicines known as "taxanes" used in cancer treatment.

• Paclitaxel is the part of the medicine that acts against cancer; it works by preventing cancer cells from dividing, causing them to 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 it is not necessary to use other chemical agents that may cause adverse reactions potentially life-threatening. Such adverse reactions occur much less frequently with Pazenir.

What Pazenir is 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 was ineffective, and when your condition is not suitable for treatment with a group of medicines called "anthracyclines".
• People with metastatic breast cancer who received paclitaxel bound to human protein albumin after another treatment had failed had a higher likelihood of experiencing tumor shrinkage and lived longer than those who received an alternative treatment.

Pancreatic cancer

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

Lung cancer

• Pazenir is also used in combination 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 for treating the disease.

2. What you need to know before Pazenir is administered to you

Do not use Pazenir

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

Warnings and precautions

Talk to your doctor or nurse before starting treatment with Pazenir

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

If you experience any of the following conditions while receiving Pazenir treatment, consult your doctor or nurse. Your doctor may decide to interrupt treatment or reduce the dose:

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

Children and adolescents

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

Other medicines and Pazenir

Inform your doctor if you are taking or have recently taken any other medicines. This includes medicines obtained without a prescription, including herbal medicines. This is because Pazenir may affect how some medicines work. Likewise, some medicines may affect how Pazenir works.

Be cautious and consult 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 you are unsure 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 stabilize mood, also called antidepressants (e.g.: fluoxetine);
• medicines used to treat seizures (epilepsy) (e.g.: carbamazepine, phenytoin);
• medicines used to help lower lipid levels in the blood (e.g.: gemfibrozil);
• medicines used for stomach acidity 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, breastfeeding and fertility

Paclitaxel may cause severe birth defects and therefore must not be used if you are pregnant. Your doctor will request a pregnancy test before starting treatment with Pazenir.

Women of childbearing potential must use effective contraceptive methods during treatment and for one month after completion of Pazenir treatment.

Pazenir must not be used during breastfeeding, as it is unknown whether the active substance paclitaxel passes into breast milk.

Men treated with Pazenir are advised to use effective contraception and to avoid fathering children during treatment and for six months after treatment ends. Men should also be informed about the possibility of preserving sperm before starting treatment, due to the risk that Pazenir treatment may cause irreversible infertility.

Consult 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 operate any tools or machinery.

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

Pazenir contains sodium

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

3. How to use Pazenir

A doctor or nurse will administer Pazenir into a vein through an intravenous infusion system. The dose you receive is 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, administered over 30 minutes. The usual dose for advanced pancreatic cancer is 125 mg/m² of body surface area, administered over 30 minutes. The usual dose for non-small cell lung cancer is 100 mg/m² of body surface area, administered over 30 minutes.

How often will Pazenir be administered?

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 administered 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 administered 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 about the use of this medicine, ask your doctor or nurse.

4. Possible adverse effects

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

Very common adverse effects may affect more than 1 in 10 people:

• Hair loss (most cases of hair loss occurred within less than one month after starting treatment with paclitaxel. When it occurs, hair loss is marked (more than 50%) in most patients)
• Rash
• Abnormally low levels of certain types of white blood cells (neutrophils, lymphocytes, or leukocytes) in the blood
• Decrease in red blood cells
• Decreased platelet count in blood
• Peripheral nerve effects (pain, numbness, tingling, or loss of sensation)
• 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 blood potassium levels
• Depression, sleep disturbances
• Headache
• Chills
• Difficulty breathing
• Dizziness
• Swelling of mucous membranes and soft tissues
• Increased liver enzyme values in liver function tests
• Pain in limbs
• Cough
• Abdominal pain
• Nosebleeds

Common adverse effects may affect up to 1 in 10 people:

• Itching, dry skin, nail disorders
• Infection, fever with low levels of a type of white blood cell (neutrophils) in blood, flushing, mouth ulcers, severe blood infection possibly due to reduced white blood cells
• Reduction in all blood cell counts
• Chest or throat pain
• Indigestion, abdominal discomfort
• Nasal congestion
• Back pain, bone pain
• Reduced muscle coordination or difficulty reading, increased or decreased tear production, eyelash loss
• Changes in heart rate or rhythm, heart failure
• Low or high blood pressure
• Redness or swelling at the site of needle insertion
• Anxiety
• Lung infection
• Urinary tract infection
• Intestinal obstruction, inflammation of the large intestine, bile duct inflammation
• Acute kidney failure
• Increased bilirubin in blood
• Coughing up blood
• Dry mouth, difficulty swallowing
• Muscle weakness
• Blurred vision

Uncommon adverse effects may affect up to 1 in 100 people:

• Weight gain, increased blood lactate dehydrogenase, kidney function impairment, increased blood glucose, increased blood phosphorus

• Decreased or absent reflexes, involuntary movements, nerve pain, fainting, dizziness when standing, tremors, facial nerve paralysis

• Irritated eyes, eye pain, red eyes, itchy eyes, double vision, reduced vision, flashing lights, blurred vision due to retinal inflammation (cystoid macular edema)

• Ear pain, ringing in the ears

• Cough with phlegm, shortness of breath when walking or climbing stairs, runny or dry nose, decreased breath sounds, fluid in the lungs, loss of voice, blood clot in the lungs, dry throat

• Gas, stomach cramps, gum pain, rectal bleeding

• Painful urination, increased frequency of urination, blood in urine, involuntary loss of urine (incontinence)

• Nail pain, nail discomfort, nail loss, hives, skin pain, photosensitivity reaction, pigmentation disorders, increased sweating, night sweats, white patches on the skin, sores, facial swelling

• Low blood phosphorus, fluid retention, low blood albumin, increased thirst, low blood calcium, low blood sugar, low blood sodium

• Nasal pain and swelling, skin infections, catheter-related infection

• Bruising

• Tumor site pain, tumor necrosis

• Drop in blood pressure upon standing, cold hands and feet

• Difficulty walking, swelling

• Allergic reaction

• Decreased liver function, enlarged liver

• Chest pain

• Nervousness

• Small skin bleeds due to blood clots

• A condition involving destruction of red blood cells and acute kidney failure

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

• Skin reaction to another agent or lung inflammation following radiation
• Blood clot
• Very slow pulse, heart attack
• Leakage of medicine from the vein
• Heart electrical conduction system disorder (atrioventricular block)

Very rare adverse effects may affect up to 1 in 10,000 people:

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

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

• Hardening/thickening of the skin (scleroderma)

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor or nurse, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through the national reporting system detailed in Appendix V. By reporting adverse 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 stated on the carton and vial after EXP. The expiry date refers to the last day of the month indicated.

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

After first reconstitution, the dispersion should be used immediately. If not used immediately, the dispersion may be stored in the refrigerator (2 °C - 8 °C) for up to 24 hours in the vial, provided it is kept within its outer packaging to protect it from light.

The reconstituted dispersion in the infusion bag may be stored for up to 24 hours at 2 °C - 8 °C, protected from light, and subsequently for up to 4 hours at 15 °C - 25 °C.

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

6. Contents of the pack and other information

Composition of Pazenir

The active substance 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 caprylate sodium and N-acetyl-DL-tryptophan); see section 2 “Pazenir contains sodium”.

Appearance of the product and contents of the pack

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

Each pack contains 1 vial.

Marketing Authorization Holder

ratiopharm GmbH
Graf-Arco-Straße
89079 Ulm
Germany

Manufacturer responsible

Merckle GmbH
Ludwig-Merckle-Straße 3
89143 Blaubeuren
Germany

Pharmachemie B.V.
Swensweg 5
Haarlem
2031 GA
The Netherlands

Teva Pharma B.V.
Swensweg 5
2031 GA Haarlem
The Netherlands

Teva Nederland B.V.
Swensweg 5
2031 GA Haarlem
The Netherlands

Further information on this medicinal product is available upon request to the local representative of the Marketing Authorization Holder:

Date of the most recent review of this summary: March 2022

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

For physicians or healthcare professionals

This information is intended for physicians or healthcare professionals only:

Instructions for use, preparation and disposal

Precautions for preparation and administration

Paclitaxel is a cytotoxic antineoplastic agent; therefore, Pazenir must be handled with care, as with other potentially toxic drugs. Gloves, safety goggles, and protective clothing must be used. If Pazenir comes into contact with the skin, the affected area must be washed immediately and thoroughly with soap and water. In case of mucosal contact, the area must be thoroughly rinsed with abundant water. Pazenir must only be prepared and administered by personnel experienced in handling cytotoxic agents. Pregnant women must not handle Pazenir.

Due to the possibility of extravasation, close monitoring of the infusion site is recommended to detect any occurrence during drug administration. Limiting the infusion time of Pazenir to 30 minutes, as per instructions, reduces the likelihood of infusion-related reactions.

Reconstitution of the medicinal product and administration

Pazenir must be administered under the supervision of a qualified oncologist in specialized units for cytotoxic drug administration.

Pazenir is supplied 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 must be administered intravenously using an infusion set incorporating a 15 μm filter.

Reconstitution of 100 mg

Using a sterile syringe, slowly inject 20 mL of 9 mg/mL (0.9%) sodium chloride solution for infusion into the 100 mg vial of Pazenir over a period of at least 1 minute.

The solution should be directed toward the inner walls of the vial. The solution must not be injected directly onto the powder, as this may cause foaming.

After adding the solution, allow the vial to stand for at least 5 minutes to ensure adequate wetting of the solute. Then gently and slowly shake and/or invert the vial for at least 2 minutes until complete redispersion of the powder is achieved. Foaming should be avoided. If foam or clumps form, allow the dispersion to stand for at least 15 minutes until the foam disappears.

The reconstituted dispersion should appear milky and homogeneous, without visible precipitates.

Some sedimentation of the reconstituted dispersion may occur. If precipitate or sedimentation is observed, gently invert the vial 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.

Calculate the exact total volume of 5 mg/mL dispersion required for the patient and transfer the appropriate amount of reconstituted Pazenir into an empty, sterile intravenous infusion bag made of PVC or non-PVC material.

The use of medical devices containing silicone oil as a lubricant (e.g., syringes and IV administration bags) for reconstituting and administering Pazenir may lead to the formation of protein filaments. Pazenir must be administered using an infusion set incorporating a 15 μm filter to prevent administration of these filaments. The use of a 15 μm filter removes filaments without altering the physical or chemical properties of the reconstituted drug.

Using filters with a pore size smaller than 15 μm may result in filter blockage.

There is no requirement for DEHP-free containers or administration sets when preparing or administering Pazenir infusions.

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

Any unused medicine and materials that have come into contact with it must be disposed of in accordance with local regulations.

Stability

Unopened vials of Pazenir remain stable until the date indicated on the packaging when stored in the outer carton to protect from light. Freezing or refrigeration does not adversely affect the stability of the medicinal product. This medicine does not require special storage temperature conditions.

Stability of the reconstituted dispersion in the vial

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

Stability of the reconstituted dispersion in the infusion bag

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