Pazenir

Package leaflet: Information for the user

Pazenir 5 mg/mL powder for dispersion for infusion

paclitaxel
Please 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 questions, ask your doctor or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, because it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of this leaflet

1. What Pazenir is and what it is used for
2. What you need to know before being 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 the active substance, paclitaxel bound to albumin, a human protein, in the form of tiny particles known as nanoparticles. Paclitaxel belongs to a group of medicines called taxanes, which are used in cancer therapy.

• Paclitaxel is the part of the medicine that acts on the tumour by stopping tumour 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 tumour. This means that additional chemical substances, which may cause life-threatening side effects, are not required. Such side effects are much less frequent 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 after at least one other therapy has been tried but proved ineffective, and in patients who are not suitable for treatments containing a group of medicines called “anthracyclines”.
• Patients with metastatic breast cancer who received paclitaxel bound to albumin, a human protein, when previous therapies had failed, had a greater chance of experiencing tumour shrinkage and lived longer compared to patients who received alternative therapy.

Pancreatic cancer

• Pazenir is used in combination with a medicine called gemcitabine for metastatic pancreatic cancer. Patients with metastatic pancreatic cancer (pancreatic cancer that has spread to other parts of the body) treated with paclitaxel bound to albumin, a human protein, and gemcitabine in a clinical study lived longer than those who received gemcitabine alone.

Lung cancer

• Pazenir is used in combination with a medicine called carboplatin for the treatment of 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 you are given Pazenir

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 (baseline neutrophil count < 1,500 cells/mm³ – your doctor will provide information on this).

Warnings and precautions
Talk to your doctor or nurse before using Pazenir

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

Contact your doctor or nurse if you develop any of the following during treatment with Pazenir; your doctor may decide to stop treatment or reduce the dose:

• unusual bruising, bleeding, or signs of infection such as sore throat or fever;
• numbness, tingling, prickling sensations, sensitivity to touch, or muscle weakness;
• breathing problems, such as shortness of breath or dry cough.

Children and adolescents
This medicine is intended for adults only and must not be used in children and adolescents under 18 years of age.
Other medicines and Pazenir
Inform your doctor if you are taking, have recently taken, or might take any other medicines, including those obtained without a prescription and herbal medicines. This is because Pazenir may affect the action of other medicines, and other medicines may affect the action of Pazenir.
Be cautious and consult your doctor when taking Pazenir together with any of the following:

• medicines used to treat infections (i.e. antibiotics, such as erythromycin, rifampicin, etc.; ask your doctor, nurse, or pharmacist for confirmation if you are unsure whether your medicine is an antibiotic), including medicines used to treat fungal infections (e.g. ketoconazole);
• medicines used to stabilize mood, sometimes also called antidepressants (e.g. fluoxetine);
• medicines used to treat epileptic seizures (epilepsy) (e.g. carbamazepine, phenytoin);
• medicines used to lower lipid levels in the blood (e.g. gemfibrozil);
• medicines used for heartburn or stomach ulcers (e.g. cimetidine);
• medicines used to treat HIV and AIDS (e.g. ritonavir, saquinavir, indinavir, nelfinavir, efavirenz, nevirapine);
• a medicine called clopidogrel used to prevent blood clots.

Pregnancy, breastfeeding and fertility
Paclitaxel may cause severe birth defects and therefore must not be used during pregnancy. Your doctor will perform a pregnancy test before starting treatment with Pazenir.
Women of childbearing potential must use effective contraception during treatment with Pazenir and for 1 month after stopping treatment.
Do not breastfeed during treatment with Pazenir, as it is not known whether the active substance paclitaxel passes into breast milk.
Male patients are advised to use effective contraception and to avoid fathering a child during treatment and for six months after stopping treatment. You should also consider sperm preservation before treatment due to the possibility that Pazenir therapy may cause permanent infertility.
Ask your doctor for advice before taking this medicine.
Driving and using machines
Some people may experience fatigue or dizziness after administration of Pazenir. If this occurs, do not drive or operate tools or machinery.
If other medicines are prescribed as part of your treatment, consult your doctor regarding your ability to drive and use machinery.
Pazenir contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per 100 mg, i.e. essentially ‘sodium-free’.

3. How to use Pazenir

Pazenir will be administered intravenously by infusion under the supervision of a doctor or nurse.
The amount administered depends on 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 is Pazenir administered?
For the treatment of metastatic breast cancer, Pazenir is usually administered once every three weeks (on day 1 of a 21-day cycle).
For the treatment of advanced pancreatic cancer, Pazenir is administered on days 1, 8, and 15 of each 28-day treatment cycle, with gemcitabine administered immediately after Pazenir.
For the treatment of non-small cell lung cancer, Pazenir is administered once weekly (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 administration of Pazenir.

If you have any doubts about how to use this medicine, consult your doctor or nurse.

4. Possible side effects

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

Very common side 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 (over 50%) in most patients)
• Skin rash
• Abnormally low levels of certain types of white blood cells (neutrophils, lymphocytes or leukocytes) in the blood
• Deficiency of red blood cells (erythrocytes)
• Reduced number of platelets in the blood
• Effects on peripheral nerves (pain, numbness, tingling or loss of sensation)
• Pain in one or more joints
• Muscle pain
• Nausea, diarrhoea, constipation, mouth irritation, loss of appetite
• Vomiting
• Weakness and fatigue, fever
• Dehydration, altered taste, weight loss
• Low levels of potassium in the blood
• Depression, sleep disorders
• Headache
• Chills
• Difficulty breathing
• Dizziness
• Swelling of mucous membranes and soft tissues
• Increased liver function test values
• Pain in extremities
• Cough
• Abdominal pain
• Nosebleed

Common side effects (may affect up to 1 in 10 people):

• Itching, dry skin, nail changes
• Infection, fever with reduced number of a type of white blood cells (neutrophils) in the blood, hot flushes, oral candidiasis, severe blood infection that may be caused by reduced white blood cells
• Reduced number of all types of blood cells
• Chest pain or sore throat
• Indigestion, abdominal problems
• Stuffy nose
• Back pain, bone pain
• Reduced muscle coordination or difficulty reading, increased or decreased tear production, loss of eyelashes
• Changes in heart rate or rhythm, heart failure
• Decreased or increased 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

Uncommon side effects (may affect up to 1 in 100 people):

• Weight gain, increased lactate dehydrogenase in the blood, reduced kidney function, increased blood sugar, increased blood phosphorus
• Reduced or absent reflexes, involuntary movements, neuralgia, fainting, dizziness upon standing, tremor, facial nerve paralysis
• Eye irritation, eye pain, eye redness, eye itching, double vision, reduced visual acuity or seeing flashing lights, blurred vision due to swelling of the retina (cystoid macular edema)
• Ear pain, ringing in the ears
• Cough with mucus, shortness of breath when walking or climbing stairs, runny or dry nose, decreased breath sounds, fluid in the lungs, hoarseness, blood clot in the lung, dry throat
• Intestinal gas, stomach cramps, gum pain or irritation, rectal bleeding
• Painful urination, frequent urination, blood in the urine, urinary incontinence
• Nail pain, painful sensitivity of nails, nail loss, hives, skin pain, photosensitivity reaction, pigmentation disorders, increased sweating, night sweats, white spots on the skin, skin lesions, facial swelling
• Decreased blood phosphorus, fluid retention, low albumin levels in the blood, increased thirst, decreased blood calcium, low blood sugar, decreased blood sodium
• Nasal pain and congestion, skin infections, catheter-related infection
• Bruising
• Pain at the site of the tumour, tumour necrosis
• Decreased blood pressure when standing, cold extremities (hands and feet)
• Difficulty walking, swelling
• Allergic reaction
• Decreased liver function, enlarged liver
• Chest pain
• Restlessness
• Small skin hemorrhages due to blood clots
• A condition involving destruction of red blood cells and acute kidney failure

Rare side effects (may affect up to 1 in 1,000 people):

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

Very rare side effects (may affect up to 1 in 10,000 people):

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

Not known side effects (frequency cannot be estimated from the available data):

• Hardening/thickening of the skin (scleroderma)

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor or nurse. You can also report side effects directly through the national reporting system referred to in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store 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 that month.
Closed vials: keep the container in the outer packaging until use to protect the
medicine from light.
After first reconstitution, the dispersion should be used immediately. If not used immediately, the dispersion can be stored in a refrigerator (2 °C - 8 °C) for up to 24 hours in the vial kept in the outer packaging to protect the medicine from light.
Reconstituted intravenous infusion dispersion can be stored for up to 24 hours at 2 - 8 °C, protected from light, followed by 4 hours at 15-25 °C.
Your doctor or pharmacist is responsible for the proper disposal of unused Pazenir.

6. Package Contents and Other Information

What Pazenir Contains
The active substance is paclitaxel.
Each vial contains 100 mg of paclitaxel bound to albumin formulated as nanoparticles.
After reconstitution, each mL of dispersion contains 5 mg of paclitaxel bound to albumin formulated as nanoparticles.
The other component is human albumin (containing sodium caprylate and N-acetyl-DL-tryptophan); see section 2, “Pazenir contains sodium”.

Description of the Appearance of Pazenir and Contents of the Pack
Pazenir is a white to yellow powder for infusion dispersion. Pazenir is available in glass vials containing 100 mg of paclitaxel bound to albumin formulated as nanoparticles. Each pack contains 1 vial.

Marketing Authorization Holder
ratiopharm GmbH
Graf-Arco-Straße 3
89079 Ulm
Germany

Manufacturer
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

For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

België/Belgique/Belgien Lietuva
Teva Pharma Belgium N.V./S.A./AG UAB Teva Baltics
Tél/Tel: +32 38207373 Tel: +370 52660203

България Luxembourg/Luxemburg
Тева Фарма ЕАД Teva Pharma Belgium N.V./S.A./AG
Тел: +359 24899585 Belgique/Belgien
Tél/Tel: +32 38207373

Česká republika Malta
Teva Pharmaceuticals CR, s.r.o. Teva Pharmaceuticals Ireland
Tel: +420 251007111 L-Irlanda
Τel: +44 2075407117

Danmark Nederland
Teva Denmark A/S Teva Nederland B.V.
Tlf: +45 44985511 Tel: +31 8000228400

Deutschland Norge
ratiopharm GmbH Teva Norway AS
Tel: +49 73140202 Tlf: +47 66775590

Ελλάδα Österreich
TEVA HELLAS Α.Ε. ratiopharm Arzneimittel Vertriebs-GmbH
Τηλ: +30 2118805000 Tel: +43 1970070

España Polska
Teva Pharma, S.L.U. Teva Pharmaceuticals Polska Sp. z o.o.
Tel: +34 913873280 Tel: +48 223459300

France Portugal
Teva Santé Teva Pharma - Produtos Farmacêuticos,
Tél: +33 155917800 Lda.
Tel: +351 214767550

Hrvatska România
Pliva Hrvatska d.o.o. Teva Pharmaceuticals S.R.L.
Tel: +385 13720000 Tel: +40 212306524

Ireland Slovenija
Teva Pharmaceuticals Ireland Pliva Ljubljana d.o.o.
Tel: +44 2075407117 Tel: +386 15890390

Ísland Slovenská republika
Teva Pharma Iceland ehf. TEVA Pharmaceuticals Slovakia s.r.o.
Sími: +354 5503300 Tel: +421 257267911

Italia Suomi/Finland
Teva Italia S.r.l. Teva Finland Oy
Tel: +39 028917981 Puh/Tel: +358 201805900

Κύπρος Sverige
TEVA HELLAS Α.Ε. Teva Sweden AB
Ελλάδα Tel: +46 42121100
Τηλ: +30 2118805000

Latvija United Kingdom (Northern Ireland)
UAB Teva Baltics filiāle Latvijā Teva Pharmaceuticals Ireland
Tel: +371 67323666 Ireland
Tel: +44 2075407117

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

For Healthcare Professionals

The following information is intended exclusively for physicians and healthcare professionals:

Instructions for Use, Handling, and Disposal

Precautions for Preparation and Administration
Paclitaxel is a cytotoxic antineoplastic medicinal product. As with other potentially toxic compounds, certain precautions should be taken when handling Pazenir. Wear gloves, eye protection, and protective clothing. If the Pazenir dispersion comes into contact with the skin, wash the skin immediately and thoroughly with soap and water. If contact with mucous membranes occurs, rinse thoroughly with copious amounts of water. Pazenir must be prepared and administered only by personnel adequately trained in handling cytotoxic agents. Pazenir should not be handled by pregnant women.

Due to the risk of extravasation, the infusion site should be closely monitored for signs of infiltration during administration. Limiting the infusion duration of Pazenir to 30 minutes, as indicated, reduces the likelihood of infusion-related reactions.

Reconstitution and Administration of the Medicinal Product

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

Pazenir is supplied as a sterile lyophilized powder and must be reconstituted before use. After reconstitution, each mL of dispersion contains 5 mg of paclitaxel bound to albumin formulated as nanoparticles. The reconstituted Pazenir dispersion is administered intravenously using an infusion set equipped with a 15-micron 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 Pazenir vial over at least 1 minute.
The solution should be directed against the inner wall 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 complete wetting of the powder. Then gently and slowly rotate and/or invert the vial for at least 2 minutes until the powder is completely redispersed. Avoid foaming. 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 precipitate. Sediment may occur in the reconstituted dispersion. If precipitates or sediment are visible, gently invert the vial again to ensure complete redispersion before use.

Inspect the dispersion in the vial for the presence of precipitate. Do not administer the reconstituted dispersion if precipitates are observed in the vial.

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

The use of medical devices containing silicone lubricant (e.g., syringes and intravenous bags) for reconstituting and administering Pazenir may lead to the formation of proteinaceous filaments. Administer Pazenir using an infusion set equipped with a 15-micron filter to prevent administration of these filaments. The use of a 15-micron filter removes filaments and does not alter the physical or chemical properties of the reconstituted product.

Filters with pore diameters smaller than 15 microns may become blocked.

No special DEHP-free containers or administration sets are required for the preparation and administration of Pazenir infusions.

After administration, the infusion line should be flushed with 9 mg/mL (0.9%) sodium chloride solution for injection to ensure complete delivery of the dose.

Unused medicinal product and waste materials must be disposed of in accordance with local regulations.

Stability
Unopened vials of Pazenir are stable until the expiry date indicated on the packaging, provided the vial is stored in the outer carton to protect from light. Freezing and refrigeration do not adversely affect the stability of the medicinal product. This medicinal product does not require any specific storage temperature.

Stability of the Reconstituted Dispersion in the Vial
After initial reconstitution, the dispersion should be transferred immediately into an infusion bag. However, the medicinal product has been shown to be chemically and physically stable for 24 hours at 2 °C – 8 °C in the original packaging and 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, the medicinal product has been shown to be chemically and physically stable for 24 hours at 2–8 °C, protected from light, followed by 4 hours at 15–25 °C.