BORTEZOMIB AUROVITAS 3.5 mg POWDER FOR INJECTABLE SOLUTION

Introduction

Package Leaflet: Information for the User

Bortezomib Aurovitas 3.5 mg powder for solution for injection EFG

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 pharmacist.

• 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 pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is Bortezomib Aurovitas and what is it used for

Bortezomib Aurovitas contains the active substance bortezomib, a “proteasome inhibitor”. Proteasomes play an important role in controlling cell function and growth. Bortezomib can kill cancer cells by interfering with their function.

Bortezomib is used to treat multiple myeloma (a type of bone marrow cancer) in patients aged 18 years and over:

• Alone or with the medicines doxorubicin liposomal pegylated or dexamethasone, for patients whose disease is getting worse (in progression) after receiving at least one prior treatment and for those patients whose blood stem cell transplant did not work or is not suitable.
• In combination with the medicines melphalan and prednisone, for patients who have not been treated before and are not suitable for high-dose chemotherapy before a blood stem cell transplant.
• In combination with the medicines dexamethasone or dexamethasone plus thalidomide, in patients who have not been treated before and are receiving high-dose chemotherapy before a blood stem cell transplant (induction treatment).

Bortezomib is used to treat mantle cell lymphoma (a type of cancer that affects the lymph nodes) in patients aged 18 years and over in combination with the medicines rituximab, cyclophosphamide, doxorubicin, and prednisone, in patients who have not been treated before and for those patients for whom a blood stem cell transplant is not considered appropriate.

2. What you need to know before you use Bortezomib Aurovitas

Do not use Bortezomib Aurovitas

• If you are allergic to bortezomib, boron or any of the other ingredients of this medicine (listed in section 6).
• If you have certain severe lung or heart problems.

Warnings and precautions

Tell your doctor if you have:

• A low number of red blood cells or white blood cells.
• Bleeding problems and/or a low number of platelets in the blood.
• Diarrhea, constipation, nausea, or vomiting.
• A history of fainting, dizziness, or lightheadedness.
• Kidney problems.
• Moderate to severe liver problems.
• Numbness, tingling, or pain in your hands or feet (neuropathy) in the past.
• Heart problems or high blood pressure.
• Difficulty breathing or coughing.
• Seizures.
• Shingles (localized including around the eyes or spread across the body).
• Symptoms of tumor lysis syndrome, such as muscle cramps, muscle weakness, confusion, vision loss, or difficulty breathing.
• Memory loss, thought disturbances, difficulty walking, or vision loss. These may be signs of a serious brain infection and your doctor may advise further tests and follow-up.

You will need to have regular blood tests before and during treatment with bortezomib to check your blood cell count regularly.

You must tell your doctor if you have mantle cell lymphoma and are given rituximab together with bortezomib:

• If you think you have or have had hepatitis infection in the past. In a few cases, patients who have had hepatitis B can have repeated attacks of hepatitis, which can be fatal. If you have a history of hepatitis B infection, you will be closely monitored by your doctor for signs of active hepatitis B.

Before starting treatment with bortezomib, you should read the package leaflets of all the medicines you have to take in combination with bortezomib to see the information about these medicines.

When using thalidomide, special attention should be paid to pregnancy testing and prevention measures (see Pregnancy and breastfeeding in this section).

Children and adolescents

Bortezomib should not be used in children and adolescents because it is not known how they will be affected by the medicine.

Other medicines and Bortezomib Aurovitas

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

In particular, tell your doctor if you are using medicines that contain any of the following active substances:

• Ketoconazole, to treat fungal infections.
• Ritonavir, to treat HIV infection.
• Rifampicin, an antibiotic to treat bacterial infections.
• Carbamazepine, phenytoin, or phenobarbital, used to treat epilepsy.
• St. John's Wort (Hypericum perforatum), used for depression or other problems.
• Oral antidiabetics.

Pregnancy and breastfeeding

You should not use bortezomib if you are pregnant unless it is clearly necessary.

Women of childbearing age must use effective contraception during treatment and for up to 8 months after finishing treatment. Talk to your doctor if you want to freeze your eggs before starting treatment.

Men should not father a child while using bortezomib and must use effective contraception during treatment and for up to 5 months after finishing treatment. Talk to your doctor if you want to preserve your sperm before starting treatment.

You should not breastfeed while using bortezomib. Ask your doctor when it is safe to restart breastfeeding after finishing your treatment.

Thalidomide causes birth defects and fetal death. When bortezomib is given in combination with thalidomide, you should follow the thalidomide pregnancy prevention program (see the thalidomide package leaflet).

Driving and using machines

Bortezomib can cause fatigue, dizziness, fainting, or blurred vision. Do not drive or use tools or machines if you experience these side effects; even if you do not experience them, you should still be cautious.

3. How to use Bortezomib Aurovitas

Your doctor will tell you the dose of bortezomib based on your height and weight (body surface area). The usual starting dose of bortezomib is 1.3 mg/m2 of body surface area twice a week.

Your doctor may change the dose and the total number of treatment cycles depending on your response to treatment, the occurrence of certain side effects, and your underlying condition (e.g., liver problems).

Progressive multiple myeloma

When bortezomib is given alone, you will receive 4 doses of bortezomib by intravenous or subcutaneous injection on days 1, 4, 8, and 11, followed by a 10-day “rest” period without treatment. This 21-day period (3 weeks) is one treatment cycle. You may receive up to 8 cycles (24 weeks).

You may also receive bortezomib with the medicines doxorubicin liposomal pegylated or dexamethasone.

When bortezomib is given with doxorubicin liposomal pegylated, you will receive bortezomib by intravenous or subcutaneous injection in a 21-day treatment cycle and 30 mg/m2 of doxorubicin liposomal pegylated administered on day 4 of the 21-day bortezomib treatment cycle, by intravenous infusion after bortezomib injection. You may receive up to 8 cycles (24 weeks).

When bortezomib is given with dexamethasone, you will receive bortezomib by intravenous or subcutaneous injection in a 21-day treatment cycle and 20 mg of dexamethasone administered orally on days 1, 2, 4, 5, 8, 9, 11, and 12 of the 21-day bortezomib treatment cycle. You may receive up to 8 cycles (24 weeks).

Previously untreated multiple myeloma

If you have not been treated for multiple myeloma before and are not a candidate for a blood stem cell transplant, you will receive bortezomib with the medicines melphalan and prednisone.

In this case, the duration of one treatment cycle is 42 days (6 weeks). You will receive 9 cycles (54 weeks).

• In cycles 1 to 4, bortezomib is administered twice a week on days 1, 4, 8, 11, 22, 25, 29, and 32.
• In cycles 5 to 9, bortezomib is administered once a week on days 1, 8, 22, and 29. Melphalan (9 mg/m2) and prednisone (60 mg/m2) are administered orally during days 1, 2, 3, and 4 of the first week of each cycle.

If you have not received any previous treatment for multiple myeloma and are a candidate for a blood stem cell transplant, you will receive bortezomib by intravenous or subcutaneous injection with the medicines dexamethasone, or dexamethasone and thalidomide, as induction treatment.

When bortezomib is given with dexamethasone, you will receive bortezomib by intravenous or subcutaneous injection in a 21-day treatment cycle and dexamethasone administered orally at a dose of 40 mg on days 1, 2, 3, 4, 8, 9, 10, and 11 of the 21-day bortezomib treatment cycle. You will receive 4 cycles (12 weeks).

When bortezomib is given with thalidomide and dexamethasone, the duration of one treatment cycle is 28 days (4 weeks).

Dexamethasone 40 mg is administered orally on days 1, 2, 3, 4, 8, 9, 10, and 11 of the 28-day bortezomib treatment cycle and thalidomide is administered orally once daily at a dose of 50 mg up to day 14 of the first cycle and, if tolerated, the thalidomide dose is increased to 100 mg on days 15-28 and from the second cycle onwards may be increased further to 200 mg daily. You may receive up to 6 cycles (24 weeks).

Previously untreated mantle cell lymphoma

If you have not been treated for mantle cell lymphoma before, you will receive bortezomib by intravenous or subcutaneous injection with the medicines rituximab, cyclophosphamide, doxorubicin, and prednisone.

Bortezomib is administered by intravenous or subcutaneous injection on days 1, 4, 8, and 11, followed by a “rest” period without treatment. The duration of one treatment cycle is 21 days (3 weeks). You may receive up to 8 cycles (24 weeks).

The following medicines are administered by intravenous infusion on day 1 of the 21-day bortezomib treatment cycle:

Rituximab at a dose of 375 mg/m2, cyclophosphamide at a dose of 750 mg/m2, and doxorubicin at a dose of 50 mg/m2.

Prednisone is administered orally at a dose of 100 mg/m2 on days 1, 2, 3, 4, and 5 of the bortezomib treatment cycle.

How bortezomib is administered

This medicine is administered by intravenous or subcutaneous injection. You will be given bortezomib by a healthcare professional who is experienced in the use of cytotoxic medicines.

The bortezomib powder must be dissolved before administration. This will be done by a healthcare professional. The reconstituted solution is then injected into a vein or under the skin. The injection into a vein is rapid, lasting between 3 and 5 seconds. The injection under the skin is administered into the thighs or abdomen.

If you receive more Bortezomib Aurovitas than you should

This medicine will be administered by your doctor or nurse, so it is unlikely that you will receive too much. In the unlikely event of an overdose, your doctor will monitor you for side effects.

In case of overdose or accidental ingestion, contact your doctor or pharmacist immediately or call the Toxicology Information Service, telephone 91 562 04 20, stating the medicine and the amount administered.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them. Some of these effects can be serious.

If you are administered bortezomib for multiple myeloma or mantle cell lymphoma, report immediately to your doctor if you observe any of the following symptoms:

• Muscle cramps, muscle weakness.
• Confusion, loss or alteration of vision, blindness, convulsions, headaches.
• Difficulty breathing, swelling of the feet or alterations in heart rhythm, high blood pressure, fatigue, fainting.
• Cough and difficulty breathing or oppression in the chest.

Treatment with bortezomib can very frequently cause a decrease in the number of red and white blood cells and platelets in the blood. Therefore, you will need to have regular blood tests before and during treatment with bortezomib to regularly check your blood cell count. You may experience a reduction in the number of:

• Platelets, which can make you more prone to bruising (bruises) or bleeding without apparent injury (e.g., intestinal, stomach, mouth, and gum bleeding or brain or liver bleeding).
• Red blood cells, which can cause anemia, with symptoms such as fatigue and paleness.
• White blood cells, which can make you more prone to infections or symptoms similar to those of the flu.

If you are administered bortezomib for the treatment of multiple myeloma, the adverse effects you may experience are included below:

Very Common Adverse Effects (may affect more than 1 in 10 people)

• Sensitivity, numbness, tingling, or burning sensation in the skin or pain in hands or feet due to nerve damage.
• Decrease in the number of red and/or white blood cells (see above).
• Fever.
• Feeling of discomfort (nausea) or vomiting, loss of appetite.
• Constipation with or without swelling (can be severe).
• Diarrhea: if it appears, it is important to drink more water than usual. Your doctor may give you another medicine to control diarrhea.
• Exhaustion (fatigue), feeling of weakness.
• Muscle pain, bone pain.

Common Adverse Effects (may affect up to 1 in 10 people)

• Low blood pressure, sudden drop in blood pressure when standing, which could lead to fainting.
• High blood pressure.
• Decreased kidney function.
• Headache.
• Feeling of general discomfort, pain, dizziness, drowsiness, feeling of weakness or loss of consciousness.
• Chills.
• Infections, including pneumonia, respiratory infections, bronchitis, fungal infections, cough with phlegm, flu-like illness.
• Herpes zoster (localized, including around the eyes or spread throughout the body).
• Chest pain or difficulty breathing when exercising.
• Various types of rashes.
• Itching of the skin, skin lumps, or dry skin.
• Facial flushing or rupture of small blood vessels.
• Redness of the skin.
• Dehydration.
• Heartburn, swelling, belching, flatulence, stomach pain, intestinal or stomach bleeding.
• Alteration of liver function.
• Sores in the mouth or lip, dry mouth, mouth ulcers, or sore throat.
• Weight loss, loss of taste.
• Muscle cramps, muscle spasms, muscle weakness, pain in the limbs.
• Blurred vision.
• Infection of the outer layer of the eye and the inner surface of the eyelids (conjunctivitis).
• Nosebleeds.
• Difficulty or problems sleeping, sweating, anxiety, mood changes, depressed mood, restlessness or agitation, changes in mental state, disorientation.
• Swelling of the body, including around the eyes and in other parts of the body.

Uncommon Adverse Effects (may affect up to 1 in 100 people)

• Heart problems, including heart attack, angina pectoris.
• Kidney failure.
• Inflammation of a vein, blood clots in the veins and lungs.
• Blood coagulation problems.
• Insufficient circulation.
• Inflammation of the heart lining or fluid around the heart.
• Infections, including urinary tract infections, flu, herpes virus infection, ear infection, and cellulitis.
• Bleeding in the digestive tract or bleeding in the mucous membranes, for example, in the mouth or vagina.
• Cerebrovascular disorders.
• Paralysis, convulsions, falls, movement disorders, alterations or changes in sensitivity (touch, hearing, taste, smell), attention disorders, tremors, shaking.
• Arthritis, including inflammation of the joints of the fingers and toes and of the jaw.
• Disorders that affect the lungs, preventing the body from receiving enough oxygen. Some of these are difficulty breathing, shortness of breath, shortness of breath without exercise, shallow, difficult, or stopped breathing, panting breathing.
• Hiccup, speech disorders.
• Increased or decreased urine production (due to kidney damage), pain when urinating, or blood/protein in the urine, fluid retention.
• Alteration of the level of consciousness, confusion, alteration or loss of memory.
• Hypersensitivity.
• Hearing loss, deafness, or ringing in the ears, ear discomfort.
• Hormonal changes that can affect salt and water absorption.
• Overactivity of the thyroid gland.
• Inability to produce enough insulin or resistance to normal insulin levels.
• Eye irritation or inflammation, watery eyes, eye pain, dry eyes, eye infections, eyelid cyst (chalazion), reddened and swollen eyelids, tearing, abnormal vision, eye bleeding.
• Swelling of lymph nodes.
• Stiffness of the joints or muscles, feeling of heaviness, pain in the groin.
• Hair loss and abnormal hair texture.
• Allergic reactions.
• Redness or pain at the injection site.
• Mouth pain.
• Infections or inflammation of the mouth, mouth ulcers, esophagus, stomach, and intestine, sometimes associated with pain or bleeding, scant bowel movement (including obstruction), abdominal or esophageal discomfort, difficulty swallowing, vomiting blood.
• Skin infections.
• Bacterial and viral infections.
• Dental infections.
• Pancreatitis, obstruction of the bile ducts.
• Genital pain, difficulty achieving an erection.
• Weight gain.
• Thirst.
• Hepatitis.
• Disorders at the injection site or related to the injection device.
• Skin reactions and disorders (which can be severe and life-threatening), skin ulcers.
• Bruises, falls, and injuries.
• Inflammation or bleeding of blood vessels that can appear as small red or purple spots (usually on the legs) to large patches resembling bruises under the skin or tissue.
• Benign cysts.
• A severe and reversible disorder in the brain that includes convulsions, high blood pressure, headaches, fatigue, confusion, blindness, or other vision problems.

Rare Adverse Effects (may affect up to 1 in 1,000 people)

• Heart problems, including heart attack, angina pectoris.
• Severe nerve inflammation, which can cause paralysis and breathing difficulties (Guillain-Barré syndrome).
• Flushing.
• Discoloration of the veins.
• Inflammation of the spinal nerves.
• Ear problems, ear bleeding.
• Underactivity of the thyroid gland.
• Budd-Chiari syndrome (clinical symptoms caused by obstruction of the hepatic veins).
• Changes or anomalies in intestinal function.
• Cerebral hemorrhage.
• Yellowing of the eyes and skin (jaundice).
• Severe allergic reaction (anaphylactic shock), whose signs can be difficulty breathing, pain or oppression in the chest and/or feeling of dizziness/fainting, intense itching of the skin or lumps on the skin, swelling of the face, lips, tongue, and/or throat, which can cause difficulty swallowing, collapse.
• Breast disorders.
• Vaginal tear.
• Genital inflammation.
• Inability to tolerate alcohol consumption.
• Emaciation or loss of body mass.
• Increased appetite.
• Fistula.
• Joint effusion.
• Cysts in the joint lining (synovial cysts).
• Fracture.
• Breakdown of muscle fibers that causes other complications.
• Swelling of the liver, liver bleeding.
• Kidney cancer.
• Skin disease similar to psoriasis.
• Skin cancer.
• Pallor of the skin.
• Increased platelets or plasma cells (a type of white blood cell) in the blood.
• Blood clot in small blood vessels (thrombotic microangiopathy).
• Abnormal reaction to blood transfusions.
• Partial or total loss of vision.
• Loss of libido.
• Drooling.
• Bulging eyes.
• Sensitivity to light.
• Rapid breathing.
• Rectal pain.
• Gallstones.
• Hernia.
• Wounds.
• Weak or brittle nails.
• Abnormal protein deposits in vital organs.
• Coma.
• Intestinal ulcers.
• Multi-organ failure.
• Death.

The following adverse effects may occur if you are administered bortezomib along with other medicines for the treatment of mantle cell lymphoma:

Very Common Adverse Effects (may affect more than 1 in 10 people)

• Pneumonia.
• Loss of appetite.
• Sensitivity, numbness, tingling, or burning sensation in the skin or pain in hands or feet due to nerve damage.
• Nausea or vomiting.
• Diarrhea.
• Mouth ulcers.
• Constipation.
• Muscle pain, bone pain.
• Hair loss and abnormal hair texture.
• Exhaustion, feeling of weakness.
• Fever.

Common Adverse Effects (may affect up to 1 in 10 people)

• Herpes zoster (localized, including around the eyes or spread throughout the body).
• Herpes virus infection.
• Bacterial and viral infections.
• Respiratory infections, bronchitis, cough with phlegm, flu-like illness.
• Fungal infections.
• Hypersensitivity (allergic reaction).
• Inability to produce enough insulin or resistance to normal insulin levels.
• Fluid retention.
• Difficulty or problems sleeping.
• Loss of consciousness.
• Alteration of the level of consciousness, confusion.
• Feeling of dizziness.
• Increased heart rate, high blood pressure, sweating.
• Abnormal vision, blurred vision.
• Heart failure, heart attack, chest pain, chest discomfort, increased or decreased heart rate.
• High or low blood pressure.
• Sudden drop in blood pressure when standing, which could lead to fainting.
• Difficulty breathing when exercising.
• Cough.
• Hiccup.
• Ringing in the ears, ear discomfort.
• Intestinal or stomach bleeding.
• Heartburn.
• Stomach pain, swelling.
• Difficulty swallowing.
• Infection or inflammation of the stomach and intestine.
• Stomach pain.
• Sores in the mouth or lip, sore throat.
• Alteration of liver function.
• Itching of the skin.
• Redness of the skin.
• Rash.
• Muscle spasms.
• Urinary tract infections.
• Pain in the limbs.
• Swelling of the body, including around the eyes and in other parts of the body.
• Chills.
• Redness and pain at the injection site.
• Feeling of general discomfort.
• Weight loss.
• Weight gain.

Uncommon Adverse Effects (may affect up to 1 in 100 people)

• Hepatitis.
• Severe allergic reaction (anaphylactic reaction), whose signs can be difficulty breathing, pain or oppression in the chest and/or feeling of dizziness/fainting, intense itching of the skin or lumps on the skin, swelling of the face, lips, tongue, and/or throat, which can cause difficulty swallowing, collapse.
• Movement disorders, paralysis, shaking.
• Dizziness.
• Hearing loss, deafness.
• Disorders that affect the lungs, preventing the body from receiving enough oxygen. Some of these are difficulty breathing, shortness of breath, shortness of breath without exercise, shallow, difficult, or stopped breathing, panting breathing.
• Blood clots in the lungs.
• Yellowing of the eyes and skin (jaundice).
• Cyst in the eyelid (chalazion), reddened and swollen eyelids.

Rare Adverse Effects (may affect up to 1 in 1,000 people)

• Blood clot in small blood vessels (thrombotic microangiopathy).
• Severe nerve inflammation, which can cause paralysis and breathing difficulties (Guillain-Barré syndrome).

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect that is not listed in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Conservation of Bortezomib Aurovitas

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

Do not use this medicine after the expiration date that appears on the vial and on the packaging after CAD.

Keep the vial in the outer packaging to protect it from light.

Intravenous administration:

Solution after reconstitution of 1 mg/ml.

Do not refrigerate.

Chemical and physical stability has been demonstrated for 7 days at 25°C.

From a microbiological point of view, the medicine should be used immediately unless the opening/reconstitution/dilution method prevents the risk of microbiological contamination.

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

Subcutaneous administration:

Solution after reconstitution of 2.5 mg/ml.

Do not refrigerate.

Chemical and physical stability has been demonstrated for 7 days at 25°C.

From a microbiological point of view, the medicine should be used immediately unless the opening/reconstitution/dilution method prevents the risk of microbiological contamination.

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

Bortezomib is for single use. The disposal of any unused product or waste material should be eliminated according to local regulations.

6. Container Contents and Additional Information

Composition of Bortezomib Aurovitas

• The active ingredient is bortezomib. Each vial contains 3.5 mg of bortezomib (as boric acid mannitol ester).
• The other component is: mannitol.

Reconstitution for intravenous administration:

After reconstitution, 1 ml of the solution for intravenous injection contains 1 mg of bortezomib.

Reconstitution for subcutaneous administration:

After reconstitution, 1 ml of the solution for subcutaneous injection contains 2.5 mg of bortezomib.

Appearance of the Product and Container Contents

White or off-white lyophilized paste or powder.

Each container of Bortezomib Aurovitas 3.5 mg powder for injectable solution EFG contains 10 ml Type I transparent glass vials, closed with a gray bromobutyl rubber stopper and sealed with an aluminum cap with a polypropylene disc.

Container sizes: 1, 3, 5, or 10 vials with or without a protective sleeve.

Only some container sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Eugia Pharma (Malta) Limited

Vault 14, Level 2, Valletta Waterfront

Floriana, FRN 1914

Malta

Manufacturer

APL Swift Services (Malta) Limited

HF26, Hal Far Industrial Estate, Hal Far

Birzebbugia, BBG 3000

Malta

Or

Generis Farmacêutica, S.A.

Rua João de Deus, nº 19, Venda Nova

2700-487 Amadora

Portugal

Or

Arrow Génériques

26 Avenue Tony Garnier

69007 Lyon

France

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

Aurovitas Spain, S.A.U.

Avda. de Burgos, 16-D

28036 Madrid

Spain

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

Germany: Bortezomib PUREN 3.5 mg Pulver zur Herstellung einer Injektionslösung

Belgium: Bortezomib Eugia 3.5 mg poeder voor oplossing voor injectie / poudre pour solution injectable / Pulver zur Herstellung einer Injektionslösung

Spain: Bortezomib Aurovitas 3.5 mg polvo para solución inyectable EFG

France: Bortezomib Arrow 3.5 mg poudre pour solution injectable

Italy: Bortezomib Aurobindo

Netherlands: Bortezomib Eugia 3.5 mg, poeder voor oplossing voor injectie

Poland: Bortezomib Eugia

Portugal: Bortezomib Generis

Date of the last revision of this leaflet: July 2025

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/).

This information is intended only for healthcare professionals:

1. RECONSTITUTION FOR INTRAVENOUS INJECTION

Note: Bortezomib Aurovitas is a cytotoxic agent. Therefore, caution should be exercised during handling and preparation. The use of gloves and other protective clothing is recommended to prevent skin contact.

AS BORTEZOMIB DOES NOT CONTAIN PRESERVATIVES, IT IS RECOMMENDED TO STRICTLY FOLLOW ASEPTIC TECHNIQUE DURING ITS HANDLING.

1.1 Preparation of a 3.5 mg vial: carefully add 3.5 mlof sterile sodium chloride 9 mg/ml (0.9%) injectable solution to the vial containing the Bortezomib Aurovitas powder using a suitable-sized syringe without removing the vial stopper. The dissolution of the lyophilized powder is completed in less than 2 minutes.

The concentration of the resulting solution will be 1 mg/ml. The solution should be colorless and transparent, with a final pH of 4 to 7. It is not necessary to check the pH of the solution.

1.2 Before administration, visually inspect the solution to rule out the presence of particles and discoloration. If any discoloration or particles are observed, the solution should be discarded. Check that the correct dose is being used for administration by intravenous route(1 mg/ml).

1.3 The reconstituted solution does not contain preservatives and should be used immediately after preparation. However, chemical and physical stability has been demonstrated for 7 days at 25°C stored in the original vial and/or syringe. The total storage time of the reconstituted medicinal product should not exceed 7 days before administration. If the reconstituted solution is not used immediately, the storage times and conditions before use are the responsibility of the user.

It is not necessary to protect the reconstituted product from light.

1. ADMINISTRATION

• Once dissolved, withdraw the appropriate amount of the reconstituted solution based on the calculated dose based on the patient's Body Surface Area.
• Confirm the dose and concentration contained in the syringe before use (check that the syringe is marked for intravenous administration).
• Inject the solution through a peripheral or central intravenous catheter in a vein as a bolus over 3-5 seconds.
• Flush the peripheral or intravenous catheter with sterile sodium chloride 9 mg/ml (0.9%) solution.

Bortezomib 3.5 mg powder for injectable solution SHOULD ONLY BE ADMINISTERED BY INTRAVENOUS OR SUBCUTANEOUS ROUTE. Do not administer by other routes. Intrathecal administration has caused death.

1. ELIMINATION

A vial is for single use and the remaining solution should be discarded.

The disposal of unused medicinal products and all materials that have come into contact with them will be carried out in accordance with local regulations.

This information is intended only for healthcare professionals:

Only the 3.5 mg vial can be administered subcutaneously, as described below.

1. RECONSTITUTION FOR SUBCUTANEOUS INJECTION

Note: Bortezomib Aurovitas is a cytotoxic agent. Therefore, caution should be exercised during handling and preparation. The use of gloves and other protective clothing is recommended to prevent skin contact.

AS BORTEZOMIB DOES NOT CONTAIN PRESERVATIVES, IT IS RECOMMENDED TO STRICTLY FOLLOW ASEPTIC TECHNIQUE DURING ITS HANDLING.

1.1 Preparation of a 3.5 mg vial: carefully add 1.4 mlof sterile sodium chloride 9 mg/ml (0.9%) injectable solution to the vial containing the Bortezomib Aurovitas powder using a suitable-sized syringe without removing the vial stopper. The dissolution of the lyophilized powder is completed in less than 2 minutes.

The concentration of the resulting solution will be 2.5 mg/ml. The solution should be colorless and transparent, with a final pH of 4 to 7. It is not necessary to check the pH of the solution.

1.2 Before administration, visually inspect the solution to rule out the presence of particles and discoloration. If any discoloration or particles are observed, the solution should be discarded. Check that the correct dose is being used for administration by subcutaneous route(2.5 mg/ml).

1.3 The reconstituted solution does not contain preservatives and should be used immediately after preparation. However, chemical and physical stability has been demonstrated for 7 days at 25°C stored in the original vial and/or syringe. The total storage time of the reconstituted medicinal product should not exceed 7 days before administration. If the reconstituted solution is not used immediately, the storage times and conditions before use are the responsibility of the user.

It is not necessary to protect the reconstituted product from light.

1. ADMINISTRATION

• Once dissolved, withdraw the appropriate amount of the reconstituted solution based on the calculated dose based on the patient's Body Surface Area.
• Confirm the dose and concentration contained in the syringe before use (check that the syringe is marked for subcutaneous administration).
• Inject the solution subcutaneously at an angle of 45-90°.
• The reconstituted solution is administered subcutaneously in the thigh (right or left) or in the abdomen (right or left side).
• The injection sites should be rotated with each injection.
• If local reactions occur at the injection site after subcutaneous injection of bortezomib, a less concentrated solution of bortezomib (1 mg/ml instead of 2.5 mg/ml) may be administered subcutaneously or it is recommended to switch to intravenous injection.

Bortezomib 3.5 mg powder for injectable solution SHOULD ONLY BE ADMINISTERED BY INTRAVENOUS OR SUBCUTANEOUS ROUTE. Do not administer by other routes. Intrathecal administration has caused death.

1. ELIMINATION

A vial is for single use and the remaining solution should be discarded.

The disposal of unused medicinal products and all materials that have come into contact with them will be carried out in accordance with local regulations.