Prospect: information for the user

Bortezomib Aurovitas 3.5 mg powder for injectable solution EFG

Read this prospect carefully before starting to use this medication, as it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.

• This medication has been prescribed only to you, and you should not give it to other people even if they have the same symptoms as you, as it may harm them.

• If you experience adverse effects, consult your doctor or pharmacist, even if they are not listed in this prospect. See section 4.

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

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

3.How to use Bortezomib Aurovitas

4.Possible adverse effects

5.Storage of Bortezomib Aurovitas

6.Contents of the package and additional information

Bortezomib Aurovitascontains the active ingredient bortezomib, a “proteasome inhibitor”. Proteasomes play an important role in controlling the functioning and growth of cells. Bortezomib can destroy cancer cells, interfering with their functioning.

Bortezomibis used in the treatment of multiple myeloma (a bone marrow cancer) in patients 18 years of age or older:

-Alone or in combination with pegylated liposomal doxorubicin or dexamethasone, for patients whose disease is worsening (in progression) after receiving at least one previous treatment and for those patients whose stem cell transplant did not work or is not suitable.

-In combination with melphalan and prednisone, for patients whose disease has not been previously treated and is not suitable to receive high doses of chemotherapy prior to a stem cell transplant.

-In combination with dexamethasone or dexamethasone with thalidomide, in patients whose disease has not been previously treated and who receive high doses of chemotherapy prior to a stem cell transplant (induction treatment).

Bortezomibis used in the treatment of mantle cell lymphoma (a type of cancer that affects lymph nodes) in patients 18 years of age or older in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone, in patients whose disease has not been previously treated and for those patients for whom a stem cell transplant is not considered suitable.

No use Bortezomib Aurovitas

•If you are allergic to bortezomib, boron, or any of the other components of this medication (listed in section 6).

•If you have certain severe lung or heart problems.

Warnings and Precautions

Inform your doctor if you experience the following:

•Low red or white blood cell count.

•Bleeding problems and/or low platelet count in the blood.

•Diarrhea, constipation, nausea, or vomiting.

•History of fainting, dizziness, or drowsiness.

•Kidney problems.

•Moderate to severe liver problems.

•Numbness, tingling, or pain in the hands or feet (neuropathy) in the past.

•Heart problems or high blood pressure.

•Difficulty breathing or coughing.

•Seizures.

•Herpes zoster (localized, including around the eyes, or widespread over the body).

•Symptoms of tumor lysis syndrome, such as muscle cramps, muscle weakness, confusion, vision loss or changes, and difficulty breathing.

•Memory loss, thought changes, difficulty walking, or vision loss. These may be signs of a severe brain infection, and your doctor may advise further testing and follow-up.

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

Inform your doctor if you have mantle cell lymphoma and are receiving rituximab in combination with bortezomib:

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

Before starting treatment with bortezomib, read the prospectuses of all medications you are taking in combination with bortezomib to consult the information related to these medications.

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

Children and Adolescents

Bortezomib should not be used in children and adolescents because its effects on them are unknown.

Other Medications and Bortezomib Aurovitas

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication.

Particularly, inform your doctor if you are using medications that contain any of the following active ingredients:

•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 to treat depression or other conditions.

•Oral antidiabetic medications.

Pregnancy and Breastfeeding

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

Both men and women using bortezomib should use effective contraception during and for up to 3 months after treatment. If, despite these measures, you become pregnant, inform your doctor immediately.

You should not breastfeed while using bortezomib. Consult your doctor when it is safe to resume breastfeeding after completing your treatment.

Talidomide causes birth defects and fetal death. When bortezomib is administered in combination with thalidomide, follow the thalidomide pregnancy prevention program (see the thalidomide prospectus).

Driving and Operating Machinery

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

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/m2of body surface area twice a week.

Your doctor may change the dose and the total number of treatment cycles based on your response to treatment, the appearance 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 (3-week) period corresponds to a treatment cycle. You may receive up to 8 cycles (24 weeks).

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

When bortezomib is given along with pegylated liposomal doxorubicin, you will receive bortezomib by intravenous or subcutaneous injection in a 21-day treatment cycle and 30 mg/m2of pegylated liposomal doxorubicin administered on day 4 of the bortezomib 21-day treatment cycle by intravenous infusion after the bortezomib injection. You may receive up to 8 cycles (24 weeks).

When bortezomib is given along 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 bortezomib 21-day treatment cycle. You may receive up to 8 cycles (24 weeks).

Untreated multiple myeloma

If you have not been treated for multiple myeloma and are not a candidate for a blood stem cell transplant, you will receive bortezomib along with two other medications; melphalan and prednisone.

In this case, the duration of a 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 along with the medications dexamethasone, or dexamethasone and thalidomide, as induction treatment.

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

When bortezomib is given along with thalidomide and dexamethasone, the duration of a 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 bortezomib 28-day treatment cycle and thalidomide is administered orally once a day in doses of 50 mg until 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 and onwards it can be increased further to 200 mg daily. You may receive up to 6 cycles (24 weeks).

Untreated mantle cell lymphoma

If you have not been treated for mantle cell lymphoma, you will receive bortezomib by intravenous or subcutaneous injection along with the medications 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 a treatment cycle is 21 days (3 weeks). You may receive up to 8 cycles (24 weeks).

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

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

Prednisone is administered orally at doses of 100 mg/m2on days 1, 2, 3, 4, and 5 of the bortezomib 21-day treatment cycle.

How bortezomib is administered

This medication is administered by intravenous or subcutaneous injection. You will receive bortezomib from a healthcare professional experienced in the use of cytotoxic medications.

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

If you receive more Bortezomib Aurovitas than you should

This medication will be administered by your doctor or nurse, so it is unlikely that you will receive an excessive amount. In the unlikely event of an overdose, your doctor will monitor you for any adverse effects.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone 91 562 04 20, indicating the medication and the amount administered.

Like all medicines, this medicine can cause side effects, although not everyone will experience them. Some of these side effects can be serious.

If you are given bortezomib for multiple myeloma or mantle cell lymphoma, tell your doctor right away if you notice any of the following symptoms:

•Muscle cramps, muscle weakness.

•Confusion, loss or changes in vision, blindness, seizures, headaches.

•Difficulty breathing, swelling of the feet or changes in heart rhythm, high blood pressure, fatigue, fainting.

•Cough and difficulty breathing or chest tightness.

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

•Platelets, which may make you more prone to the appearance of bruises (bruises), or of bleeding without evident injury (for example, 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 may make you more prone to infections or symptoms similar to the flu.

If you are given bortezomib for the treatment of multiple myeloma, the side effects you may experience include the following:

Very common side effects (may affect more than 1 in 10 people)

•Sensitivity, numbness, tingling or burning sensation in the skin or pain in the hands or feet due to nerve damage.

•Decrease in the number of red and white blood cells (see above).

•Fever.

•Feeling unwell (nausea) or vomiting, loss of appetite.

•Constipation with or without swelling (may be severe).

•Dyspepsia: if it appears, it is essential to drink more water than usual. Your doctor may give you another medicine to control diarrhea.

•Fatigue (tiredness), feeling weak.

•Muscle pain, bone pain.

Common side 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.

•General feeling of being unwell, pain, dizziness, feeling weak or loss of consciousness.

•Chills.

•Infections, including pneumonia, respiratory infections, bronchitis, flu-like symptoms.

•Herpes zoster (localized including around the eyes or extended over the body).

•Chest pain or difficulty breathing while exercising.

•Different types of rashes.

•Itching skin, skin lumps or dry skin.

•Facial flushing or small blood vessel rupture.

•Redness of the skin.

•Dehydration.

•Heartburn, swelling, belching, flatulence, stomach pain, intestinal or stomach bleeding.

•Liver function alteration.

•Mouth or lip sores, dry mouth, mouth ulcers or throat pain.

•Weight loss, loss of taste.

•Muscle cramps, muscle spasms, muscle weakness, pain in the limbs.

•Blurred vision.

•Eye infection and internal surface of the eyelids (conjunctivitis).

•Nasal bleeding.

•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.

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

•Heart failure, heart attack, chest pain, chest discomfort, increase or decrease in heart rate.

•Kidney failure.

•Vein inflammation, blood clots in veins and lungs.

•Blood clotting problems.

•Poor circulation.

•Pericarditis, fluid around the heart.

•Infections, including urinary tract infections, flu, viral herpes infection, ear infection and cellulitis.

•Bleeding from mucous membranes, for example, from the mouth or vagina.

•Cerebrovascular disorders.

•Paralysis, seizures, falls, movement disorders, changes or decrease in sensitivity (touch, hearing, taste, smell), attention disorders, tremors, shakiness.

•Arthritis, including inflammation of the joints of the fingers of the hands and feet and jaw.

•Respiratory disorders, preventing the body from receiving a sufficient amount of oxygen. Some of them are difficulty breathing, shortness of breath, shortness of breath without exercise, shallow, difficult or stopping breathing, labored breathing.

•Hiccup, speech disorders.

•Changes or decrease in urine production (due to kidney damage), pain while urinating or blood/protein in the urine, fluid retention.

•Alteration of the level of consciousness, confusion, memory loss.

•Hypersensitivity.

•Loss of hearing, deafness or ringing in the ears, ear discomfort.

•Alterations in hormone levels that may affect salt and water absorption.

•Hyperthyroidism.

•Inability to produce sufficient insulin or resistance to normal insulin levels.

•Irritation or inflammation of the eyes, too moist eyes, eye pain, dry eyes, eye infections, chalazion, red and swollen eyelids, watery eyes (lacrimation), abnormal vision, eye hemorrhage.

•Swollen lymph nodes.

•Joint or muscle stiffness, feeling of heaviness, pain in the groin.

•Loss of hair and abnormal hair texture.

•Allergic reactions.

•Redness or pain at the injection site.

•Mouth pain.

•Infections or inflammation of the mouth, ulcers in the mouth, esophagus, stomach and intestine, sometimes associated with pain or bleeding, slow movement of the intestine (including obstruction), abdominal or esophageal discomfort, difficulty swallowing, vomiting blood.

•Skin infections.

•Bacterial and viral infections.

•Dental infection.

•Pancreatitis, bile duct obstruction.

•Pain in the genitals, difficulty achieving an erection.

•Weight gain.

•Thirst.

•Hepatitis.

•Problems at the injection site or related to the injection device.

•Severe skin reactions (life-threatening), skin ulcers.

•Bruises, falls and injuries.

•Inflammation or bleeding of small blood vessels that may appear as small red or purple spots (usually on the legs) to large patches similar to hematomas under the skin or tissue.

•Benign cysts.

•A severe and reversible brain disorder that includes seizures, high blood pressure, headaches, fatigue, confusion, blindness or other vision problems.

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

•Heart problems, including heart attack, angina.

•Severe nerve inflammation, which can cause paralysis and difficulty breathing (Guillain-Barré syndrome).

•Flushing.

•Vein discoloration.

•Nerve root inflammation.

•Ear problems, ear hemorrhage.

•Hyperthyroidism.

•Budd-Chiari syndrome (clinical symptoms caused by obstruction of the hepatic veins).

•Changes or abnormalities in intestinal function.

•Brain hemorrhage.

•Yellow discoloration of the eyes and skin (jaundice).

•Severe allergic reaction (anaphylactic shock), whose signs may be difficulty breathing, chest pain or tightness and/or dizziness/fainting, intense itching skin or skin lumps, facial swelling, lips, tongue and/or throat swelling, which may cause difficulty swallowing, collapse.

•Breast disorders.

•Vaginal tear.

•Genital inflammation.

•Inability to tolerate alcohol consumption.

•Demacración or loss of body mass.

•Increased appetite.

•Fistula.

•Joint effusion.

•Joint cysts (synovial cysts).

•Fracture.

•Muscle fiber breakdown that causes other complications.

•Swelling of the liver, liver hemorrhage.

•Renal cancer.

•Skin disease similar to psoriasis.

•Skin cancer.

•Pale skin.

•Increased platelets or plasma cells (a type of white blood cell) in the blood.

•Blood clot in small blood vessels (microangiopathy).

•Abnormal reaction to blood transfusions.

•Partial or total loss of vision.

•Loss of libido.

•Exophthalmos.

•Photophobia.

•Accelerated breathing.

•Rectal pain.

•Bile stones.

•Hernia.

•Wounds.

•Weak or brittle nails.

•Abnormal protein deposits in vital organs.

•Coma.

•Intestinal ulcers.

•Multi-organ failure.

•Death.

The following are the side effects you may experience if you are given bortezomib along with other medicines for the treatment of mantle cell lymphoma:

Very common side 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 the hands or feet due to nerve damage.

•Nausea or vomiting.

•Dyspepsia.

•Ulcers in the mouth.

•Constipation.

•Muscle pain, bone pain.

•Loss of hair and abnormal hair texture.

•Agitation, feeling weak.

•Fever.

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

•Herpes zoster (localized including around the eyes or extended over the body).

•Herpes virus infection.

•Bacterial and viral infections.

•Respiratory infections, bronchitis, cough with mucus, flu-like symptoms.

•Fungal infections.

•Hypersensitivity (allergic reaction).

•Inability to produce sufficient insulin or resistance to normal insulin levels.

•Fluid retention.

•Difficulty or problems sleeping.

•Loss of consciousness.

•Alteration of the level of consciousness, confusion.

•Dizziness.

•Increased heart rate, high blood pressure, sweating.

•Abnormal vision, blurred vision.

•Heart failure, heart attack, chest pain, chest discomfort, increase or decrease in heart rate.

•High or low blood pressure.

•Sudden drop in blood pressure when standing, which could lead to fainting.

•Difficulty breathing with exercise.

•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.

•Mouth or lip sores, throat pain.

•Liver function alteration.

•Itching 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.

•General feeling of being unwell.

•Weight loss.

•Weight gain.

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

•Hepatitis.

•Severe allergic reaction (anaphylactic reaction), whose signs may be difficulty breathing, chest pain or tightness and/or dizziness/fainting, intense itching skin or skin lumps, facial swelling, lips, tongue and/or throat swelling, which may cause difficulty swallowing, collapse.

•Movement disorders, paralysis, shakiness.

•Dizziness.

•Loss of hearing, deafness.

•Respiratory disorders, preventing the body from receiving a sufficient amount of oxygen. Some of them are difficulty breathing, shortness of breath, shortness of breath without exercise, shallow, difficult or stopping breathing, labored breathing.

•Blood clots in the lungs.

•Yellow discoloration of the eyes and skin (jaundice).

•Chalazion, red and swollen eyelids.

Reporting of side effects

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

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

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

Store 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 use over 7 days at 25°C.

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

If not used immediately, 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 use over 7 days at 25°C.

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

If not used immediately, 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 must be in accordance with local regulations.

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 intravenous injection solution contains 1 mg of bortezomib.

Reconstitution for subcutaneous administration:

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

Appearance of the product and contents of the package

White or off-white lyophilized paste or powder.

Each package of Bortezomib Aurovitas 3.5 mg powder for injectable solution EFG contains10 ml glass vials, Type I transparent, closed with a grey bromobutyl rubber stopper and sealed with an aluminum cap with a polypropylene disc.

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

Only some package sizes may be commercially available.

Marketing authorization holder and responsible manufacturer

Marketing authorization holder

Eugia Pharma (Malta) Limited

Vault 14, Level 2, Valletta Waterfront

Floriana, FRN 1914

Malta

Responsible manufacturer

APL Swift Services (Malta) Limited

HF26, Hal Far Industrial Estate, Hal Far

Birzebbugia, BBG 3000

Malta

O

Generis Farmacêutica, S.A.

Rua João de Deus, nº 19, Venda Nova

2700-487 Amadora

Portugal

O

Arrow Génériques

26 Avenue Tony Garnier

69007 Lyon

France

For more information about this medication, please contact the local representative of the marketing authorization holder:

Aurovitas Spain, S.A.U.

Avda. de Burgos, 16-D

28036 Madrid

Spain

This medication is authorized in the European Economic Area member states with the following names:

Germany:Bortezomib PUREN 3.5 mg Powder for the preparation of an injection solution

Belgium:Bortezomib Eugia 3.5 mg powder for solution for injection /poudre pour solution injectable/ Powder for the preparation of an injection solution

Spain:Bortezomib Aurovitas 3.5 mg powder for injectable solution EFG

France:Bortezomib Arrow 3.5 mg powder for solution injectable

Italy:Bortezomib Aurobindo

Netherlands:Bortezomib Eugia 3.5 mg, powder for solution for injection

Poland:Bortezomib Eugia

Portugal:Bortezomib Generis

Last review date of this leaflet: August 2024

For detailed and updated information about this medication, please visit the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) (http://www.aemps.gob.es/).

This information is intended solely for healthcare professionals:

1.RECONSTITUTION FOR INTRAVENOUS ADMINISTRATION

Nota: Bortezomib Aurovitas is a cytotoxic agent. Therefore, caution should be exercised during manipulation and preparation. It is recommended to use gloves and other protective clothing to prevent skin contact.

AS BORTEZOMIBLACKS PRESERVATIVES, IT IS RECOMMENDED TO FOLLOW STRICTLY AN Aseptic TECHNIQUE DURING ITS HANDLING.

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

The resulting solution concentration will be 1 mg/ml. The solution must be colorless and transparent, with a final pH of 4 to 7. The pH of the solution does not need to be checked.

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

1.3The reconstituted solution lacks preservatives and must be used immediately after preparation. However, chemical and physical stability in use has been demonstrated for 7 days at 25°C, stored in the original vial and/or syringe. The total time of conservation of the reconstituted medication 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.

No protection of the reconstituted product from light is required.

2.ADMINISTRATION

•Once dissolved, remove the appropriate amount of the reconstituted solution according to 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 3-5 second intravenous bolus, through a peripheral or central intravenous catheter in a vein.

•Wash the peripheral or intravenous catheter with sterile 0.9% sodium chloride injection solution.

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

3.ELIMINATION

One vial is for single use and the remaining solution must be discarded.

The elimination of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations.

This information is intended solely for healthcare professionals:

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

1.RECONSTITUTION FOR SUBCUTANEOUS ADMINISTRATION

Nota: Bortezomib Aurovitas is a cytotoxic agent. Therefore, caution should be exercised during manipulation and preparation. It is recommended to use gloves and other protective clothing to prevent skin contact.

AS BORTEZOMIBLACKS PRESERVATIVES, IT IS RECOMMENDED TO FOLLOW STRICTLY AN Aseptic TECHNIQUE DURING ITS HANDLING.

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

The resulting solution concentration will be 2.5 mg/ml. The solution must be colorless and transparent, with a final pH of 4 to 7. The pH of the solution does not need to be checked.

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

1.3The reconstituted solution lacks preservatives and must be used immediately after preparation. However, chemical and physical stability in use has been demonstrated for 7 days at 25°C, stored in the original vial and/or syringe. The total time of conservation of the reconstituted medication 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.

No protection of the reconstituted product from light is required.

2.ADMINISTRATION

•Once dissolved, remove the appropriate amount of the reconstituted solution according to 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 administration sites should be rotated with each injection.

•If local reactions occur at the injection site after subcutaneous administration of bortezomib, a less concentrated bortezomib solution (1 mg/ml instead of 2.5 mg/ml) may be administered subcutaneously or it is recommended to change to an intravenous injection.

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

3.ELIMINATION

One vial is for single use and the remaining solution must be discarded.

The elimination of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations.