Package Insert: Information for the Patient

Bortezomib Kern Pharma 3.5 mg Powder for Injectable Solution EFG

Read this package insert carefully before starting to take this medication, as it contains important information for you.

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

1. What isBortezomibKern Pharmaand what is it used for

2. What you need to know before starting to takeBortezomibKern Pharma

3. How to takeBortezomibKern Pharma

4. Possible adverse effects

5. Storage ofBortezomibKern Pharma

6. Contents of the package and additional information

BortezomibKern Pharmacontains 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.

BortezomibKern Pharmais 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)

BortezomibKern Pharmais 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 who are not considered suitable for a stem cell transplant.

Do not takeBortezomibKern Pharma:

• if you are allergic to bortezomib, boron, or any of the other components of this medication (listed in section 6).
• if you have severe lung or heart problems.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to take bortezomib if you have 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.
• convulsions.
• 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 advise further testing and follow-up.

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

Inform your doctor if you have multiple myeloma and are being given rituximab together with Bortezomib Kern Pharma:

• 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 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 to detect any signs of active hepatitis B.

Before starting treatment with Bortezomib Kern Pharma, read the leaflets of all the medications you are taking in combination with Bortezomib Kern Pharma 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 Kern Pharma should not be used in children and adolescents because it is not known how the medication will affect them.

Use of Bortezomib Kern Pharma with other medications

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

In particular, 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 Kern Pharma if you are pregnant, unless it is clearly necessary.

Both men and women using Bortezomib Kern Pharma 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 Kern Pharma. Consult your doctor when it is safe to resume breastfeeding after completing your treatment.

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

Driving and operating machinery

Bortezomib Kern Pharma 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 ofBortezomibKern Pharmabased on your height and weight (body surface area). The usual starting dose ofBortezomibKern Pharmais 1.3 mg/m2of body surface area twice a week. Your doctor may adjust 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

WhenBortezomibKern Pharmais administered alone, you will receive 4 doses ofBortezomibKern Pharmaintravenously or subcutaneously 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 receiveBortezomibKern Pharmaalong with the medications doxorubicin liposomal pegylated or dexamethasone.

WhenBortezomibKern Pharmais administered with doxorubicin liposomal pegylated, you will receiveBortezomibKern Pharmaintravenously or subcutaneously in a 21-day treatment cycle, and doxorubicin liposomal pegylated 30 mg/m2is administered on day 4 of theBortezomibKern Pharma21-day treatment cycle via intravenous infusion after the injection ofBortezomibKern Pharma.

You may receive up to 8 cycles (24 weeks).

WhenBortezomibKern Pharmais administered with dexamethasone, you will receiveBortezomibKern Pharmaintravenously or subcutaneously 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 theBortezomibKern Pharma21-day treatment cycle.

You may receive up to 8 cycles (24 weeks).

Untreated multiple myeloma

If you have not been treated for multiple myeloma before andare nota candidate to receive a blood stem cell transplant, you will receiveBortezomibKern Pharmaintravenously or subcutaneouslyalong 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, BortezomibKern Pharmais administered twice a week on days 1, 4, 8, 11, 22, 25, 29, and 32.
• In cycles 5 to 9, BortezomibKern Pharmais administered once a week on days 1, 8, 22, and 29.

Melphalan (9 mg/m2) and prednisone (60 mg/m2) are administered orally on 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 receiveBortezomibKern Pharmaintravenously or subcutaneously along with the medications dexamethasone, or dexamethasone and thalidomide, as induction treatment.

When BortezomibKern Pharmais administered with dexamethasone, you will receive BortezomibKern Pharmaintravenously or subcutaneously 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 theBortezomibKern Pharma21-day treatment cycle. You will receive 4 cycles (12 weeks).

When BortezomibKern Pharmais administered 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

tratamiento de BortezomibKern Pharmade 28 días and thalidomide is administered orally once a day in doses of 50 mg until day 14 of the first cycle, and if tolerated, the dose of thalidomide 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 for mantle cell lymphoma before, you will receiveBortezomibKern Pharmaintravenously or subcutaneously along with the medications rituximab, cyclophosphamide, doxorubicin, and prednisone.

BortezomibKern Pharmais administered intravenously or subcutaneously 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 via intravenous infusion on day 1 of theBortezomibKern Pharma21-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

tratamiento deBortezomibKern Pharma.

How Bortezomib Kern Pharma is administered

This medication is administered intravenously or subcutaneously. You will receive BortezomibKern Pharmafrom a healthcare professional experienced in the use of cytotoxic medications.

The powder of BortezomibKern Pharmamust 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 Kern 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 givenBortezomibKern Pharmafor 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, dizziness
• Cough and difficulty breathing or chest tightness.

The treatment withBortezomibKern Pharmacan cause very frequently a 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 withBortezomibKern Pharma, 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 may 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 givenBortezomibKern Pharmafor the treatment of multiple myeloma, the side effects you may experience are listed below:

Very common side effects(may 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 of discomfort (nausea) or vomiting, loss of appetite
• Constipation with or without swelling (may be severe)
• Dyspepsia: if it occurs, it is essential to drink more water than usual. Your doctor may give you another medicine to control diarrhea
• Fatigue, feeling of weakness
• Muscle pain, bone pain

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

• Low blood pressure, sudden drop in blood pressure when standing, which could lead to dizziness

• High blood pressure
• Decreased kidney function
• Headache
• General feeling of discomfort, pain, dizziness, feeling of weakness or loss

of consciousness

• Chills
• Infections, including pneumonia, respiratory infections, bronchitis, fungal infections, cough with mucus, 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
• 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
• Conjunctivitis (infection of the outermost layer of the eye and the inner surface of the eyelids)
• Nasal hemorrhages
• Difficulty or problems sleeping, sweating, anxiety, mood changes, depressed mood, unease or agitation, changes in mental state, disorientation

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

• Heart failure, heart attack, chest pain, chest discomfort, increased or

decreased heart rate

• Kidney 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 infection, and cellulitis

• Bleeding from mucous membranes, for example, mouth,

vagina

• Cerebrovascular disorders
• Paralysis, seizures, falls, movement disorders, changes or decreases in, or

sensory changes (touch, hearing, taste, smell), attention disorders, tremors, shakiness

• Arthritis, including inflammation of the joints of the fingers of the hands and feet and jaw
• Disorders affecting the lungs, 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
• Increased or decreased urine production (due to kidney damage), pain while urinating or blood/protein in the urine, fluid retention
• Alteration of the level of consciousness, confusion, alteration or loss of memory
• Hypersensitivity
• Loss of hearing, deafness or ringing in the ears, ear discomfort
• Alterations in hormone levels that may affect salt and water absorption
• Hyperactivity of the thyroid gland
• 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 (cyst in the eyelid), red or 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
• Mouth, esophagus, stomach, or intestine ulcers, associated with pain or bleeding, slow movement of the intestine (including obstruction), abdominal or esophageal discomfort, difficulty swallowing, vomiting blood

infections or inflammation of the mouth, esophagus, stomach, or intestine, 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 infections
• Pancreatitis, bile duct obstruction
• Genital pain, erectile dysfunction
• Weight gain
• Thirst
• Hepatitis
• Injection site or device-related problems
• Severe skin reactions (life-threatening), skin ulcers

cutaneous

• Brusing, falls, and injuries
• Small blood vessel inflammation or bleeding, which may appear as small red or purple spots (normal on the legs) to large skin 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 patients)

• Heart problems, including heart attack, angina
• Flushing
• Vein discoloration
• Spinal cord nerve inflammation
• Ear problems, ear hemorrhage
• Thyroid gland hypofunction
• Budd-Chiari syndrome (clinical symptoms caused by hepatic vein obstruction)

hepatic)

• 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, intense itching of the skin or skin bumps, facial swelling, lips, tongue, and/or throat swelling, which may cause difficulty swallowing, collapse
• Breast disorders
• Vaginal rupture
• Genital inflammation
• Inability to tolerate alcohol consumption
• Emaciation or weight loss
• Increased appetite
• Fistula
• Joint effusion
• Benign synovial cysts
• Fracture
• Muscle fiber breakdown that causes other complications
• Swollen 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
• Microangiopathic thrombosis (blood clots in small blood vessels)
• Abnormal reaction to blood transfusions
• Partial or total loss of vision
• Loss of libido
• Edema
• Proptosis
• Photophobia
• Tachypnea
• Rectal pain
• Bile stones
• Hernia
• Wounds
• Weak or brittle nails
• Anomalous protein deposits in vital organs
• Coma
• Intestinal ulcers
• Severe nerve inflammation, which may cause paralysis and respiratory difficulty (Guillain-Barré syndrome)
• Multi-organ failure
• Death

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

Very common side effects(may 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
• Dyspepsia
• Diarrhea
• Mouth ulcers
• Constipation
• Muscle pain, bone pain
• Loss of hair and abnormal hair texture
• Fatigue, feeling of weakness
• Fever

Common side effects(may 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, cough with mucus, 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 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, increased or

decreased heart rate

• High or low blood pressure
• Sudden drop in blood pressure when standing, which could lead to dizziness
• Difficulty breathing with exercise
• Cough
• Hiccup
• Tinnitus, ear discomfort
• Intestinal or stomach bleeding
• Heartburn
• Abdominal or esophageal discomfort
• Difficulty swallowing
• Intestinal or stomach infection or inflammation
• Abdominal or esophageal 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
• Swollen body, including around the eyes and in other parts of the body
• Chills
• Redness and pain at the injection site
• General feeling of discomfort
• Weight loss
• Weight gain

Uncommon side effects(may 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, intense itching of the skin or skin bumps, facial swelling, lips, tongue, and/or throat swelling, which may cause difficulty swallowing, collapse
• Movement disorders, paralysis, shakiness
• Dizziness
• Loss of hearing, deafness
• Disorders affecting the lungs, 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

• Clots in the lungs
• Yellow discoloration of the eyes and skin (jaundice)
• Chalazion (cyst in the eyelid), red or swollen eyelids

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

• Microangiopathic thrombosis (blood clots in small blood vessels)

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, 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 the vial in its original packaging to protect it from light.

This medication does not require any special storage temperature.

Reconstituted solution

The chemical and physical stability of the reconstituted solution has been demonstrated for a period of 8 days at 25°C/60% and 15 days at 2-8°CRH when stored in the dark in the original vial and/or a polipropylene syringe.

From a microbiological point of view, unless the reconstitution/dilution method excludes the risk of microbial contamination, the product should be used immediately. If not used immediately, storage times and conditions during use are the responsibility of the user.

BortezomidKern Pharmais exclusively for single use.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications that you no longer need. In this way, you will help protect the environment.

Composition of Bortezomib Kern Pharma

• The active ingredient is bortezomib. Each vial contains 3.5 mg of bortezomib (as manitol borate ester).

The other component is mannitol (E421).

• The reconstitution intravenous:

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

Reconstitution subcutaneous

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

Appearance of the product and contents of the package

Bortezomib Kern Pharma powder for injectable solution is a white to off-white paste or powder.

Each package of Bortezomib Kern Pharma 3.5 mg powder for injectable solution contains 1 glass vial with a rubber stopper and a blue flip-off cap.

Each package contains 1 single-use vial.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

Kern Pharma, S.L.

Venus, 72 – Pol. Ind. Colón II

08228 Terrassa – Barcelona

Spain

Responsible for manufacturing:

Synthon Hispania, S.L.

C/ Castelló no1, Pol. Las Salinas

08830 Sant Boi de Llobregat (Barcelona)

Spain

or

Synthon s.r.o.

Brnenská 32/cp. 597,

678 01 Blansko

Republic of Czech

This medicinal product is authorized in the member states of the European Economic Area with the following names:

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

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

France:Bortezomib Synthon 3.5 mg powder for injectable solution

Spain:Bortezomib Kern Pharma 3.5 mg powder for injectable solution EFG

United Kingdom:Bortezomib 3.5 mg powder for solution for injection

Last review date of this leaflet: February 2021

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

The following information is only for healthcare professionals:

1. RECONSTITUTION FOR INTRAVENOUS INJECTION

Nota: Bortezomib Kern Pharma 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 BORTEZOMIB KERN PHARMA LACKS 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 injection solution of sodium chloride 9 mg/ml (0.9%) to the vial containing the Bortezomib Kern Pharma 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. It is not necessary to check the pH of the solution.

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, the chemical and physical stability during use has been demonstrated for 8 days at 25°C/60%RH and 15 days at 2-8°C, stored in the dark in the original vial and/or syringe.

From a microbiological point of view, unless the reconstitution/dilution method excludes the risk of microbial contamination, the product must be used immediately. If not used immediately, the storage times and conditions are the responsibility of the user.

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.

Lavage the peripheral or intravenous catheter with sterile sodium chloride solution, 9 mg/ml (0.9%).

BORTEZOMIB KERN PHARMA 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

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.

The following information is only for healthcare professionals:

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

1. RECONSTITUTION FOR SUBCUTANEOUS INJECTION

Nota: Bortezomib Kern Pharma 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 BORTEZOMIB KERN PHARMA LACKS 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 injection solution of sodium chloride 9 mg/ml (0.9%) to the vial containing the Bortezomib Kern Pharma 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. It is not necessary to check the pH of the solution.

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, the chemical and physical stability during use has been demonstrated for 8 days at 25°C/60%RH and 15 days at 2-8°C, stored in the dark in the original vial and/or syringe.

From a microbiological point of view, unless the reconstitution/dilution method excludes the risk of microbial contamination, the product must be used immediately. If not used immediately, the storage times and conditions are the responsibility of the user.

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).
• Rotate the administration sites with each injection.
• If local reactions occur at the administration site after subcutaneous injection of Bortezomib Kern Pharma, or if you can administer a less concentrated solution of Bortezomib Kern Pharma (1 mg/ml instead of 2.5 mg/ml) or recommend switching to intravenous injection.

BORTEZOMIB KERN PHARMA 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

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.