Leaflet: information for the user

Bortezomib EVER Pharma 2.5 mg/ml injectable solution

Read this leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

1. What is Bortezomib EVER Pharma and what it is used for

2. What you need to know before using Bortezomib EVER Pharma

3. How to use Bortezomib EVER Pharma

4. Possible side effects

5. Storage of Bortezomib EVER Pharma

6. Contents of the pack and additional information

This medication contains 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.

Bortezomib is used in the treatment of multiple myeloma (a bone marrow cancer) in patients aged 18 years 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 who are 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).

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

Do not use Bortezomib EVER Pharma

• if you are allergic to bortezomib, boron, or any of the other ingredients in 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
• mild 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
• shingles (including around the eyes or spread over the body)
• symptoms of tumor lysis syndrome, such as muscle cramps, muscle weakness, confusion, loss or changes in vision, and difficulty breathing
• memory loss, changes in thought, difficulty walking, or loss of vision. These may be signs of a severe brain infection, and your doctor may recommend 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 multiple myeloma 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 hepatitis attacks, 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 prevention 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.

Use of Bortezomib EVER Pharma with other medications

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

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 for 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.

Bortezomib EVER Pharma contains sodium

This medication contains less than 23 mg (1mmol) of sodium per vial; it is essentially "sodium-free".

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 giventogether with pegylated liposomal doxorubicin, you will receive bortezomib by intravenous or subcutaneous injection in a 21-day treatment cycle, and pegylated liposomal doxorubicin 30 mg/m2is 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 giventogether with dexamethasone, you will receive bortezomib by intravenous or subcutaneous injection in a 21-day treatment cycle, and dexamethasone 20 mg is administered orally on days 1, 2, 4, 5, 8, 9, 11, and 12 of the bortezomiv 21-day treatment cycle. You may receive up to 8 cycles (24 weeks).

Untreated multiple myeloma

If you have not been treated before for multiple myeloma andare nota candidate to receive a blood stem cell transplant, you will receive bortezomibtogether 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, bortezomiv 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 andarea candidate to receive a blood stem cell transplant, you will receive bortezomiv by intravenous or subcutaneous injection together with the medications dexamethasone, or dexamethasone and thalidomide, as induction treatment.

When bortezomiv is giventogether with dexamethasone, you will receive bortezomiv 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 bortezomiv 21-day treatment cycle. You will receive 4 cycles (12 weeks).

When bortezomiv is giventogether 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 bortezomiv 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 may 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 before for mantle cell lymphoma, you will receive bortezomiv by intravenous or subcutaneous injection together with the medications rituximab, cyclophosphamide, doxorubicin, and prednisone.

Bortezomiv 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 bortezomiv 21-day treatment cycle:

• Rituximab in doses of 375 mg/m2, cyclophosphamide in doses of 750 mg/m2, and doxorubicin in doses of 50 mg/m2.
• Prednisone is administered orally in doses of 100 mg/m2on days 1, 2, 3, 4, and 5 of the bortezomiv 21-day treatment cycle.

How Bortezomiv EVER Pharma is administered

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

The 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 Bortezomiv EVER Pharma 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.

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, inform your doctor immediately 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
• Coughs and difficulty breathing or chest tightness.

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 bruising (bruises), or bleeding without visible 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 are listed below:

Very common side effects (can affect more than 1 in 10 patients)

• 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)
• Diarrhea: if it occurs, it is essential to drink more water than usual. Your doctor may give you another medicine to control diarrhea
• Fatigue, feeling weak
• Muscle pain, bone pain

Common side effects (can affect up to 1 in 10 patients)

• 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, fungal infections, coughs with phlegm, flu-like illness
• 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
• Alteration of liver function
• 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
• Conjunctivitis (infection of the outer layer of the eye and the inner surface of the eyelids)

• 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 (can affect up to 1 in 100 patients)

• Heart failure, heart attack, chest pain, chest discomfort, increased or decreased heart rate
• Renal failure
• Vein inflammation, blood clots in veins and lungs
• Blood clotting problems
• Poor circulation
• Pericarditis (inflammation of the heart lining) or fluid around the heart
• Infections, including urinary tract infections, flu, herpes virus infection, ear infections, and cellulitis
• Mucous membrane bleeding or hemorrhages, for example, in the mouth or vagina
• Cerebrovascular disorders
• Paralysis, seizures, falls, movement disorders, changes or decreases in sensitivity (touch, hearing, taste, smell), attention disorders, tremors, spasms
• Arthritis, including inflammation of the joints of the fingers of the hands and feet and jaw
• Lung 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, rapid breathing
• Hypophonia, speech disorders
• Decreased or increased urine production (due to renal damage), pain while urinating or blood/protein in the urine, fluid retention
• Alteration of consciousness, confusion, alteration or loss of memory
• Hypersensitivity
• Loss of hearing, deafness or tinnitus, 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, excessive eye moisture, eye pain, dry eyes, eye infections, chalazion, red and swollen eyelids, watery eyes (lacrimation), abnormal vision, eye hemorrhage
• Swelling of 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
• Mouth or lip sores, mouth dryness, mouth ulcers, esophageal, stomach, or intestinal ulcers, associated with pain or bleeding, slow intestinal movement (including obstruction), abdominal or esophageal discomfort, difficulty swallowing, vomiting blood
• Skin infections
• Bacterial and viral infections
• Dental infections
• Pancreatitis, bile duct obstruction
• Genital pain, erectile dysfunction
• 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 wounds
• Inflammation or hemorrhage of 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 (can affect up to 1 in 1,000 patients)

• Heart problems, including heart attack, angina
• Severe nerve inflammation, which can cause paralysis and difficulty breathing (Guillain-Barré syndrome)
• Flushing
• Vein discoloration
• Spinal nerve inflammation
• Ear problems, ear hemorrhage
• Hypothyroidism
• 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 bumps, facial swelling, lip, tongue, and/or throat swelling, which may cause difficulty swallowing, collapse
• Mastitis
• Vaginal rupture
• Genital inflammation
• Inability to tolerate alcohol consumption
• Emaciation or loss of body mass
• Increased appetite
• Fistula
• Joint effusion
• Benign synovial cysts
• Fracture
• Disintegration of muscle fibers that causes other complications
• Swelling of the liver, liver hemorrhage
• Renal cancer
• Dermatological disease similar to psoriasis
• Skin cancer
• Pale skin
• Increased platelets or plasma cells (a type of white blood cell) in the blood
• Blood clots in small blood vessels (microangiopathy)
• Abnormal reaction to blood transfusions
• Partial or complete loss of vision
• Loss of libido
• Halitosis
• Protruding eyes
• Photophobia
• Accelerated breathing
• Rectal pain
• Biliary calculi
• Hernia
• Wounds
• Weak or brittle nails
• Anomalous protein deposits in vital organs
• Coma
• Intestinal ulcers
• Multi-organ failure
• Death

If you are given bortezomib together with other medicines for the treatment of mantle cell lymphoma, the side effects you may experience are listed below:

Very common side effects (can affect more than 1 in 10 patients)

• 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
• Diarrhea
• Mouth ulcers
• Constipation
• Muscle pain, bone pain
• Loss of hair and abnormal hair texture
• Fatigue, feeling weak
• Fever

Common side effects (can affect up to 1 in 10 patients)

• Herpes zoster (localized including around the eyes or extended over the body)
• Herpes virus infection
• Bacterial and viral infections
• Respiratory infections, bronchitis, coughs with phlegm, flu-like illness
• 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 consciousness, confusion
• 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 while exercising
• Coughs
• Hypophonia
• Tinnitus, ear discomfort
• Intestinal or stomach bleeding
• Heartburn
• Abdominal or esophageal discomfort
• Difficulty swallowing
• Intestinal or stomach inflammation
• Abdominal pain
• Lip or mouth sores, throat pain
• Alteration of liver function
• Itching skin
• Redness of the skin
• Rashes
• 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 (can affect up to 1 in 100 patients)

• 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 bumps, facial swelling, lip, tongue, and/or throat swelling, which may cause difficulty swallowing, collapse
• Movement disorders, paralysis, spasms
• Dizziness
• Loss of hearing, deafness
• Lung 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, rapid breathing
• Blood clots in the lungs
• Yellow discoloration of the eyes and skin (jaundice)
• Chalazion, red and swollen eyelids

Rare side effects (can affect up to 1 in 1,000 patients)

• Blood clots in small blood vessels (microangiopathy)
• Severe nerve inflammation, which can cause paralysis and difficulty breathing (Guillain-Barré syndrome)

Reporting 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:https://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. The expiration date is the last day of the month indicated.

Store in refrigerator (2 °C – 8 °C).

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

The solution must be used immediately after the first opening/dilution. If the solution (diluted) is not used immediately, the storage times and conditions before use are the responsibility of the user. However, when the solution is stored in the original vial and/or in a polipropylene syringe, the diluted solution is stable for 28 days at 2 °C - 8 °C and up to 25 °C protected from light, and for 24 hours up to 25 °C in normal interior lighting conditions.

Regarding stability within the syringe, the same storage time applies to the diluted solution and the undiluted solution.

Bortezomib is exclusively for single use. The disposal of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations.

Composition of Bortezomib EVER Pharma

The active ingredient is bortezomib. 1 milliliter of injectable solution contains 2.5 milligrams of bortezomib (as manitol boric ester). Each vial with 1 milliliter of injectable solution contains 2.5 milligrams of bortezomib (as manitol boric ester). Each vial with 1.4 milliliters of injectable solution contains 3.5 milligrams of bortezomib (as manitol boric ester).

Each vial contains an additional overfill of 0.2 ml.

The other components are manitol (E421), sodium chloride, sodium hydroxide (to adjust the pH), hydrochloric acid (to adjust the pH), and water for injectable preparations.

Vial of 1 ml

Subcutaneous route: The product is ready for use with its concentration of 2.5 mg/ml.

Intravenous route: Add 1.8 ml of sodium chloride solution 0.9% to obtain a final concentration of 1 mg/ml.

Vial of 1.4 ml

Subcutaneous route: The product is ready for use with its concentration of 2.5 mg/ml.

Intravenous route: Add 2.4 ml of sodium chloride solution 0.9% to obtain a final concentration of 1 mg/ml.

Appearance of Bortezomib EVER Pharma and packaging content

Bortezomib EVER Pharma 2.5 mg/ml injectable solution is a transparent, colorless to light yellow solution.

Bortezomib EVER Pharma is presented in a colorless glass vial with a rubber stopper and an aluminum cap with a plastic flip-off closure.

Packaging sizes

1 vial of 1 ml (2.5 mg/1 ml)

5 vials of 1 ml (2.5 mg/1 ml)

1 vial of 1.4 ml (3.5 mg/1.4 ml)

5 vials of 1.4 ml (3.5 mg/1.4 ml)

Only some packaging sizes may be marketed.

Marketing Authorization Holder

EVER Valinject GmbH

Oberburgau 3

4866 Unterach am Attersee

Austria

Manufacturer

EVER Pharma Jena GmbH

Otto Schott Str. 15

07745 Jena

Germany

EVER Pharma Jena GmbH

Brüsseler Str. 18

07747 Jena

Germany

Further information on this medicinal product can be obtained from the local representative of the marketing authorization holder:

EVER Pharma Therapeutics Spain, S.L.

C/Toledo 170

28005 Madrid

Spain

This medicinal product is authorized in the Member States of the EEA with the following denominations:

Last review date of this leaflet: 09/2021

The detailed and updated information on this medicinal product is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) (http:/www.aemps.gob.es)

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This information is intended solely for healthcare professionals:

1.PREPARATION FOR INTRAVENOUS INJECTION

Nota: Bortezomib is a cytotoxic agent. Therefore, caution should be exercised during manipulation and preparation. The use of gloves and other protective clothing is recommended to prevent skin contact. Pregnant women should not handle this medication.

BECAUSE BORTEZOMIB LACKS PRESERVATIVES, IT IS RECOMMENDED TO FOLLOW STRICTLY AN Aseptic TECHNIQUE DURING ITS HANDLING.

Or

Preparation of a 1.4 ml vial: add 2.4 millilitersof sterile injectable solution of sodium chloride 9 mg/ml (0.9%) to the vial containing bortezomib.

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

1.3.The solution lacks preservatives and must be used immediately after preparation. However, chemical and physical stability have been demonstrated in use of the diluted solution for:

• 28 days at 2 °C - 8 °C and protected from light
• 28 days at 25 °C and protected from light
• 24 hours, when stored at 25 °C and in normal interior lighting conditions in the original vial and/or in a polipropylene syringe.

If the diluted solution is not used immediately, the storage times and previous use conditions are the responsibility of the user.

1. ADMINISTRATION

• Once diluted, remove the appropriate amount of the diluted 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 by a 3-5 second intravenous bolus, through a peripheral or central intravenous catheter in a vein.
• Clean the peripheral or intravenous catheter with sodium chloride solution 0.9% sterile.

Bortezomib EVER Pharma 2.5 mg/ml 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

A 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 for cytotoxic agents.

This information is intended solely for healthcare professionals:

1.PREPARATION FOR SUBCUTANEOUS INJECTION

Nota: Bortezomib is a cytotoxic agent. Therefore, caution should be exercised during manipulation and preparation. The use of gloves and other protective clothing is recommended to prevent skin contact. Pregnant women should not handle this medication.

BECAUSE BORTEZOMIB LACKS PRESERVATIVES, IT IS RECOMMENDED TO FOLLOW STRICTLY AN Aseptic TECHNIQUE DURING ITS HANDLING.

1.1Bortezomib is ready for use. The solution concentration will be 2.5 mg/ml. The solution is transparent, colorless to light yellow, with a pH of 4.0 to 5.5. 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 solution lacks preservatives and must be used immediately after extracting the appropriate amount of solution. However, chemical and physical stability have been demonstrated in the solution for:

o 28 days at 2 °C - 8 °C and protected from light

o 28 days at 25 °C and protected from light

o 24 hours, when stored at 25 °C and in normal interior lighting conditions in the original vial and/or in a polipropylene syringe.

If the solution is not used immediately, the storage times and previous use conditions are the responsibility of the user

During preparation for administration and during administration itself, the medication does not need to be protected from light.

2.ADMINISTRATION

• Remove the appropriate amount of 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 by subcutaneous route, at an angle of 45-90°.
• The solution is administered by subcutaneous route 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 administration site after subcutaneous injection of bortezomib, either administer a less concentrated solution (1 mg/ml instead of 2.5 mg/ml) by subcutaneous route or recommend switching to intravenous administration.

Bortezomib EVER Pharma 2.5 mg/ml 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

A 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 for cytotoxic agents.