BORTEZOMIB HOSPIRA 1 mg POWDER FOR INJECTABLE SOLUTION

Introduction

Package Leaflet: Information for the User

Bortezomib Hospira 1 mg powder for solution for injection EFG

Bortezomib Hospira 2.5 mg powder for solution for injection EFG

Bortezomib Hospira 3 mg powder for solution for injection EFG

Bortezomib Hospira 3.5 mg powder for solution for injection EFG

bortezomib

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

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

Contents of the pack:

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

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

Bortezomib Hospira contains the active substance bortezomib, a "proteasome inhibitor". Proteasomes play a crucial role in controlling cell function and growth. Bortezomib can destroy cancer cells by interfering with their function.

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

• alone or with the medicines doxorubicin liposomal pegylated 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 the medicines melphalan and prednisone, for patients whose disease has not been previously treated and who are not suitable for high-dose chemotherapy before a stem cell transplant.
• in combination with the medicines dexamethasone or dexamethasone and thalidomide, in patients whose disease has not been previously treated and who receive high-dose chemotherapy before a stem cell transplant (induction treatment).

Bortezomib is used to treat mantle cell lymphoma (a type of cancer that affects the lymph nodes) in patients 18 years of age or older in combination with the medicines 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.

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

Do not use Bortezomib Hospira

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

Warnings and precautions

Tell your doctor if you have:

• low red blood cell 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 lightheadedness
• 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
• shingles (localized, including around the eyes, or widespread)
• symptoms of tumor lysis syndrome, such as muscle cramps, muscle weakness, confusion, vision loss, or difficulty breathing
• memory loss, thought disturbances, difficulty walking, or vision loss.

These may be signs of a severe brain infection, and your doctor may advise further tests and monitoring.

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

You must inform your doctor if you have mantle cell lymphoma and are given rituximab with Bortezomib Hospira:

• if you think you currently have or have had hepatitis infection in the past. 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 for signs of active hepatitis B.

Before starting treatment with Bortezomib Hospira, you should read the package leaflets of all the medicines you need to take with Bortezomib Hospira to see the information about these medicines.

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

Children and adolescents

Bortezomib Hospira should not be used in children and adolescents because it is not known how it affects them.

Other medicines and Bortezomib Hospira

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

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

• ketoconazole, to treat fungal infections
• ritonavir, to treat HIV infection
• rifampicin, an antibiotic to treat bacterial infections
• carbamazepine, phenytoin, or phenobarbital, used to treat epilepsy
• St. John's Wort (Hypericum perforatum), used for depression or other conditions
• oral antidiabetics

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.

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

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

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

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

Driving and using machines

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

3. How to use Bortezomib Hospira

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

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

Progressive multiple myeloma

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

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

When bortezomib is given with doxorubicin liposomal pegylated, you will receive bortezomib by intravenous or subcutaneous injection in a 21-day treatment cycle, and doxorubicin liposomal pegylated 30 mg/m2 will be 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 with dexamethasone, you will receive bortezomib by intravenous or subcutaneous injection in a 21-day treatment cycle, and dexamethasone 20 mg will be 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).

Previously untreated multiple myeloma

If you have not been previously treated for multiple myeloma and are not a candidate for a stem cell transplant, you will receive bortezomib by intravenous or subcutaneous injection with two other medicines; melphalan and prednisone.

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

• In cycles 1 to 4, bortezomib is administered twice a week on days 1, 4, 8, 11, 22, 25, 29, and 32.
• In cycles 5 to 9, bortezomib is administered once a week on days 1, 8, 22, and 29.

Melphalan (9 mg/m2) and prednisone (60 mg/m2) are administered orally during the first week of each cycle, on days 1, 2, 3, and 4.

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

When bortezomib is given with dexamethasone, you will receive bortezomib by intravenous or subcutaneous injection in a 21-day treatment cycle, and dexamethasone will be administered orally at a dose 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 with thalidomide and dexamethasone, the duration of one treatment cycle is 28 days (4 weeks).

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

You may receive up to 6 cycles (24 weeks).

Previously untreated mantle cell lymphoma

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

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

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

Rituximab at a dose of 375 mg/m2, cyclophosphamide at a dose of 750 mg/m2, and doxorubicin at a dose of 50 mg/m2. Prednisone is administered orally at a dose of 100 mg/m2 on days 1, 2, 3, 4, and 5 of the bortezomib treatment cycle.

How Bortezomib Hospira is administered

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

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

If you receive more Bortezomib Hospira than you should

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

4. Possible Adverse Effects

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

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

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

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

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

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

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

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

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

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

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

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

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

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

If you are administered bortezomib along with other medicines for the treatment of mantle cell lymphoma, the adverse effects you may experience are included below:

Very Common Adverse 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 hands or feet due to nerve damage
• Nausea or vomiting
• Diarrhea
• Ulcers in the mouth
• Constipation
• Muscle pain, bone pain
• Hair loss and abnormal hair texture
• Exhaustion, feeling of weakness
• Fever

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

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

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

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

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

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

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that does not appear in this prospectus. You can also report them directly to the national reporting system included in Appendix V. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Bortezomib Hospira

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

Do not use this medicine after the expiration date that appears on the vial and on the packaging after CAD. The expiration date is the last day of the month indicated.

This medicine does not require any special storage temperature.

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

The reconstituted solution should be used immediately after preparation. If the reconstituted solution is not used immediately, the storage times after reconstitution and the conditions before use are the responsibility of the user. However, the reconstituted solution is stable for 8 hours at 5°C and 25°C stored in the original vial and/or a syringe; the total storage time of the reconstituted medicine should not exceed 8 hours before administration.

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

6. Container Contents and Additional Information

Composition of Bortezomib Hospira

The active ingredient is bortezomib.

Bortezomib Hospira 1 mg powder for solution for injection EFG

Each vial of powder contains 1 milligram of bortezomib (as boronic acid ester of mannitol).

Bortezomib Hospira 2.5 mg powder for solution for injection EFG

Each vial of powder contains 2.5 milligrams of bortezomib (as boronic acid ester of mannitol).

Bortezomib Hospira 3 mg powder for solution for injection EFG

Each vial of powder contains 3 milligrams of bortezomib (as boronic acid ester of mannitol).

Bortezomib Hospira 3.5 mg powder for solution for injection EFG

Each vial of powder contains 3.5 milligrams of bortezomib (as boronic acid ester of mannitol).

Reconstitution for intravenous administration:

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

Reconstitution for subcutaneous administration:

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

The other components are mannitol (E421).

Appearance of the Product and Container Contents

Bortezomib Hospira powder for solution for injection is a white to off-white paste or powder.

Each container of Bortezomib Hospira 1 mg contains a 5 ml siliconized glass vial with a rubber stopper and an aluminum seal.

Each container of Bortezomib Hospira 2.5 mg, 3 mg, or 3.5 mg contains a 10 ml glass vial with a rubber stopper and an aluminum seal.

Marketing Authorization Holder

Pfizer Europe MA EEIG

Boulevard de la Plaine 17

1050 Bruxelles

Belgium

Manufacturer

Pfizer Service Company BVBA,

Hoge Wei 10,

1930 Zaventem,

Belgium

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Date of Last Revision of this Leaflet:

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

This leaflet can be found in all languages of the European Union/European Economic Area on the European Medicines Agency website.

This information is intended only for healthcare professionals:

1. RECONSTITUTION FOR INTRAVENOUS INJECTION

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

SINCE BORTEZOMIB HOSPIRA DOES NOT CONTAIN PRESERVATIVES, IT IS ADVISED TO STRICTLY FOLLOW ASEPTIC TECHNIQUE DURING ITS HANDLING.

1.1. Preparation of a 1 milligram vial: carefully add 1.0 milliliterof sterile sodium chloride 9 milligrams/milliliter (0.9%) injection solution to the vial containing the Bortezomib Hospira powder using a suitable-sized syringe without removing the vial stopper. The dissolution of the lyophilized powder is complete in less than 2 minutes.

Preparation of a 2.5 milligram vial: carefully add 2.5 millilitersof sterile sodium chloride 9 milligrams/milliliter (0.9%) injection solution to the vial containing the Bortezomib Hospira powder using a suitable-sized syringe without removing the vial stopper. The dissolution of the lyophilized powder is complete in less than 2 minutes.

Preparation of a 3 milligram vial: carefully add 3.0 millilitersof sterile sodium chloride 9 milligrams/milliliter (0.9%) injection solution to the vial containing the Bortezomib Hospira powder using a suitable-sized syringe without removing the vial stopper. The dissolution of the lyophilized powder is complete in less than 2 minutes.

Preparation of a 3.5 milligram vial: carefully add 3.5 millilitersof sterile sodium chloride 9 milligrams/milliliter (0.9%) injection solution to the vial containing the Bortezomib Hospira powder using a suitable-sized syringe without removing the vial stopper. The dissolution of the lyophilized powder is complete in less than 2 minutes.

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

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

1.3. The reconstituted solution does not contain preservatives and should be used immediately after preparation. However, chemical and physical stability during use has been demonstrated for 8 hours at 25°C stored in the original vial and/or syringe. The total storage time of the reconstituted medicinal product should not exceed 8 hours before administration. If the reconstituted solution is not used immediately, the storage times after reconstitution and the conditions before use are the responsibility of the user.

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

1. ADMINISTRATION

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

BORTEZOMIB HOSPIRA SHOULD ONLY BE ADMINISTERED BY INTRAVENOUS OR SUBCUTANEOUS ROUTE. Do not administer by other routes. Intrathecal administration has caused death.

1. ELIMINATION

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

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

The following information is intended only for healthcare professionals:

The 1 mg, 2.5 mg, 3 mg, and 3.5 mg vials can be administered subcutaneously, as described below.

1. RECONSTITUTION FOR SUBCUTANEOUS INJECTION

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

SINCE BORTEZOMIB HOSPIRA DOES NOT CONTAIN PRESERVATIVES, IT IS ADVISED TO STRICTLY FOLLOW ASEPTIC TECHNIQUE DURING ITS HANDLING.

1.1. Preparation of a 1 milligram vial: carefully add 0.4 millilitersof sterile sodium chloride 9 milligrams/milliliter (0.9%) injection solution to the vial containing the Bortezomib Hospira powder using a suitable-sized syringe without removing the vial stopper. The dissolution of the lyophilized powder is complete in less than 2 minutes.

Preparation of a 2.5 milligram vial: carefully add 1.0 millilitersof sterile sodium chloride 9 milligrams/milliliter (0.9%) injection solution to the vial containing the Bortezomib Hospira powder using a suitable-sized syringe without removing the vial stopper. The dissolution of the lyophilized powder is complete in less than 2 minutes.

Preparation of a 3 milligram vial: carefully add 1.2 millilitersof sterile sodium chloride 9 milligrams/milliliter (0.9%) injection solution to the vial containing the Bortezomib Hospira powder using a suitable-sized syringe without removing the vial stopper. The dissolution of the lyophilized powder is complete in less than 2 minutes.

Preparation of a 3.5 milligram vial: carefully add 1.4 millilitersof sterile sodium chloride 9 milligrams/milliliter (0.9%) injection solution to the vial containing the Bortezomib Hospira powder using a suitable-sized syringe without removing the vial stopper. The dissolution of the lyophilized powder is complete in less than 2 minutes.

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

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

1.3. The reconstituted solution does not contain preservatives and should be used immediately after preparation. However, chemical and physical stability during use has been demonstrated for 8 hours at 25°C stored in the original vial and/or syringe. The total storage time of the reconstituted medicinal product should not exceed 8 hours before administration. If the reconstituted solution is not used immediately, the storage times after reconstitution and the conditions before use are the responsibility of the user.

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

1. ADMINISTRATION

• Once dissolved, withdraw the appropriate amount of the reconstituted solution based on the calculated dose based on the patient's Body Surface Area.
• Confirm the dose and concentration contained in the syringe before use (check that the syringe is labeled 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 administration site after subcutaneous injection of Bortezomib Hospira, either a less concentrated solution of Bortezomib Hospira (1 mg/ml instead of 2.5 mg/ml) can be administered subcutaneously or it is recommended to switch to intravenous injection.

BORTEZOMIB HOSPIRA SHOULD ONLY BE ADMINISTERED BY INTRAVENOUS OR SUBCUTANEOUS ROUTE. Do not administer by other routes. Intrathecal administration has caused death.

1. ELIMINATION

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

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