BUGVI 5 mg/ml POWDER FOR DISPERSION FOR INFUSION

Introduction

Package Leaflet: Information for the User

Bugvi 5mg/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 experience any side effects, talk to your doctor or nurse, even if you think they are not serious. See section 4.

Contents of the package leaflet

1. What is Bugvi and what is it used for
2. What you need to know before you use Bugvi
3. How to use Bugvi
4. Possible side effects
5. Storage of Bugvi

1. Contents of the pack and further information

1. What is Bugvi and what is it used for

What is Bugvi

Bugvi contains, as an 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 this medicine.

What Bugvi is used for

This medicine 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).
• This medicine 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 this medicine when another treatment had failed had a higher chance of experiencing a reduction in tumor size and lived longer than people who received an alternative treatment.

Pancreatic cancer

• This medicine 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 with gemcitabine in a clinical trial lived longer than people who only received gemcitabine.

Lung cancer

• This medicine 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".
• This medicine 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 use Bugvi

Do not use Bugvi

• if you are allergic (hypersensitive) to paclitaxel or any of the other ingredients of this medicine (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 this medicine

• 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 this medicine, inform 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 should not be given to children or adolescents under 18 years of age.

Other medicines and Bugvi

Tell your doctor if you are using or have recently used any other medicines, including those obtained without a prescription, including herbal medicines. This is because this medicine may affect how some medicines work. Similarly, some medicines may affect how this medicine works.

Be careful and consult your doctor when using this medicine 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 blood lipid levels (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, breastfeeding, and fertility

Paclitaxel may cause serious birth defects, so it should not be used if you are pregnant. Your doctor will request a pregnancy test before starting treatment with this medicine.

Women of childbearing age should use effective contraceptive methods during and up to one month after finishing treatment with this medicine.

This medicine should not be used during breastfeeding, as it is not known whether the active substance paclitaxel passes into breast milk.

Men treated with this medicine are advised to use effective contraceptive methods and avoid having children during treatment and for six months after finishing it, as well as to inform themselves about the possibility of preserving their sperm before starting treatment, given the possibility that treatment with this medicine 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 this medicine. 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, consult your doctor about your ability to drive and use machines.

Bugvi contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per ml of solution for infusion; this is essentially "sodium-free".

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3. How to use Bugvi

A doctor or nurse will give you this medicine in 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, 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 you be given Bugvi?

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

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

For the treatment of non-small cell lung cancer, this medicine 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 dose of this medicine.

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.

Very commonside effects may affect more than 1 in 10 people

• hair loss (most cases of hair loss occurred within a month after starting treatment with paclitaxel. When it occurs, hair loss is pronounced (more than 50%) in most patients)
• skin rash
• abnormal decrease in the number of some types of white blood cells (neutrophils, lymphocytes, or leukocytes) in the blood
• decrease in red blood cells
• decrease in platelet count in 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 blood
• depression, sleep problems
• headache
• chills
• difficulty breathing
• dizziness
• swelling of the mucous membranes and soft tissues
• increase in liver values in liver function tests
• pain in the limbs
• cough
• abdominal pain
• nasal bleeding

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, redness, mouth sores, severe blood infection that may 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 tearing, 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
• increase in bilirubin in the blood
• coughing up blood
• dry mouth, difficulty swallowing
• muscle weakness
• blurred vision

Uncommonside effects may affect up to 1 in 100 people

• weight gain, increase in lactate dehydrogenase in blood, alteration of renal function, increase in blood glucose, increase in blood phosphorus
• decrease or absence of reflexes, involuntary movements, nerve pain, fainting, dizziness when standing, tremors, paralysis of the facial nerves
• irritated eyes, eye pain, red eyes, itching in the 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 or dry nose, decreased respiratory sounds, fluid in the lung, loss of voice, blood clots in the lungs, dry throat
• gas, stomach cramps, gum pain, rectal bleeding
• painful urination (dysuria), need to urinate more often than normal (frequent urination), blood in the urine, involuntary loss of urine (urinary incontinence)
• nail pain, nail discomfort, nail loss, hives, skin pain, photosensitivity reaction, skin pigmentation disorders, increased sweating, night sweats, white spots on the skin, sores, facial swelling
• low phosphorus in blood, fluid retention, low albumin in blood, increased thirst, low calcium in blood, low blood sugar, low sodium in blood
• nose pain and swelling, skin infections, catheter-related infections
• bruising
• pain and swelling at the tumor site, tumor necrosis
• decrease in blood pressure when standing, cold extremities
• difficulty walking, swelling
• allergic reaction
• decrease in liver function, increase in 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

Rareside effects may affect up to 1 in 1,000 people

• skin reaction to another agent or radiation pneumonitis
• blood clots
• very slow pulse, heart attack
• leakage of the medicine outside the vein
• disorder of the heart's electrical conduction system (atrioventricular block)

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)

• skin hardening/thickening (scleroderma).

Reporting of side effects

If you experience any side effects, talk to your doctor or nurse, even if you think they are not serious. You can also report side effects 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 Bugvi

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 vial after EXP. The expiry date is the last day of the month shown.

Unopened vials: Store the vial in the outer packaging to protect it from light.

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

The reconstituted dispersion in the infusion bag can be stored in the refrigerator (2°C-8°C) for a maximum of 24 hours, protected from light.

The total storage time for the reconstituted medicine, combining the time in the vial and in the infusion bag when refrigerated and protected from light, is 24 hours. After this, it can be stored in the infusion bag for 4 hours below 25°C.

Your doctor or pharmacist is responsible for disposing of any unused medicine correctly.

6. Container Contents and Additional Information

Bugvi 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 (contains sodium caprylate and N-acetyl-L-tryptophan).

Product Appearance and Container Contents

Bugvi is a powder for dispersion for infusion, white to yellow in color.

Bugvi 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 and Manufacturer

Marketing Authorization Holder

Laboratory STADA, S.L.

Frederic Mompou, 5

08960 Sant Just Desvern (Barcelona)

Spain

info@stada.es

Manufacturer

STADA Arzneimittel AG

Stadastrasse 2-18

61118 Bad Vilbel

Germany

or

STADA Arzneimittel GmbH

Muthgasse 36/2

1190 Vienna

Austria

Date of Last Revision of this Leaflet:April 2024

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

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Doctors or Healthcare Professionals

This information is intended solely for doctors or healthcare professionals:

Instructions for Use, Preparation, and Disposal

Precautions for Preparation and Administration

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

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 this medicinal product to 30 minutes, according to the instructions, reduces the likelihood of infusion-related reactions.

Reconstitution and Administration of the Medicinal Product

This medicinal product should be administered under the supervision of a qualified oncologist in specialized units for the administration of cytotoxic agents.

This medicinal product 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 dispersion of this medicinal product is administered intravenously using an infusion set that incorporates a 15 µm filter.

Reconstitution of 100 mg

With a sterile syringe, slowly inject 20 ml of sodium chloride 9 mg/ml (0.9%) solution for infusion into the vial of 100 mg of this medicinal product over a minimum of 1 minute.

The solution should be directed towards the inner wall of the vial. The solution should not be injected directly into the powder, as this would cause foaming.

After adding the solution, the vial should be allowed to stand for a minimum of 5 minutes to ensure proper wetting of the solute. Then, it should be gently agitated and/or slowly inverted for at least 2 minutes until the powder is completely redispersed. Foaming should be avoided. If foaming or clumping occurs, the dispersion should be allowed to stand for at least 15 minutes until the foam disappears.

The reconstituted dispersion should have a milky and homogeneous appearance without visible precipitates. Some 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 this reconstituted medicinal product should be injected 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 (i.e., syringes and IV bags) to reconstitute and administer this medicinal product may result in the formation of protein filaments. This medicinal product should be administered using an infusion set that incorporates a 15 µm filter to prevent the administration of these filaments. The use of a 15 µm filter eliminates 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 to use DEHP-free infusion bags or administration sets to prepare or administer infusions of this medicinal product.

After administration, it is recommended to thoroughly flush the intravenous line with sodium chloride 9 mg/ml (0.9%) 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 carried out in accordance with local regulations.

Stability

Unopened vials of this medicinal product remain stable until the expiry date stated on the label if stored in the outer packaging to protect from light. Freezing or refrigeration does not negatively 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

Chemical and physical stability has been demonstrated for 24 hours at 2°C-8°C in the original container, protected from light.

Stability of the Reconstituted Dispersion in the Infusion Bag

Chemical and physical stability has been demonstrated for 24 hours at 2°C-8°C followed by 4 hours at 25°C, protected from light.

However, from a microbiological point of view, unless the method of reconstitution and filling of the infusion bags precludes the risk of microbial contamination, the product should be used immediately after reconstitution and filling of the infusion bags.

If not used immediately, the in-use storage times and conditions of the product are the responsibility of the user.

The total storage time for the reconstituted medicinal product in the vial and in the infusion bag when refrigerated and protected from light is 24 hours. After this, it can be stored in the infusion bag for 4 hours at a temperature below 25°C.