BORTEZOMIB 3.5 MG Порошок для инъекционного раствора

Содержание инструкции

1. Bortezomib Mylan 1 mg powder for injectable solution, 3.5 mg powder for injectable solution
   1. What is Bortezomib Mylan and what it is used for
   2. What you need to know before using Bortezomib Mylan
   3. How to use Bortezomib Mylan
   4. Possible side effects
   5. How to store Bortezomib Mylan
   6. Contents of the pack and other information
   7. RECONSTITUTION FOR INTRAVENOUS INJECTION
   8. ADMINISTRATION
   9. DISPOSAL
   10. RECONSTITUTION FOR SUBCUTANEOUS INJECTION
   11. ADMINISTRATION
2. Bortezomib Mylan 3.5 mg powder for injectable solution IS FOR SUBCUTANEOUS
   1. DISPOSAL

Bortezomib Mylan 1 mg powder for injectable solution, 3.5 mg powder for injectable solution

Bortezomib

Equivalent Medicinal Product
Read this leaflet carefully before you start to use this medicine as it contains important
information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

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

Bortezomib Mylan contains the active substance bortezomib, a so-called “proteasome inhibitor”. Proteasomes play an important role in controlling cell functions and growth. By interfering with their function, bortezomib can kill cancer cells.
Bortezomib Mylan is used in the treatment of multiple myeloma (a cancer of the bone marrow) in patients over the age of 18:

• alone or together with the medicines liposomal pegylated doxorubicin or dexamethasone, for patients with worsening (progressive) disease after receiving at least one prior treatment and for whom blood stem cell transplantation has not been successful or is not indicated
• in association with the medicines melphalan and prednisone for patients with previously untreated disease who cannot receive high doses of chemotherapy with blood stem cell transplantation
• in association with dexamethasone or dexamethasone together with thalidomide, for patients with previously untreated disease and before receiving high doses of chemotherapy with blood stem cell transplantation (induction treatment).

Bortezomib Mylan is used for the treatment of mantle cell lymphoma (a type of cancer that affects the lymph nodes) in patients aged 18 years or older in association with the medicines rituximab, cyclophosphamide, doxorubicin and prednisone, for patients with previously untreated disease and for whom blood stem cell transplantation is not indicated.

2. What you need to know before using Bortezomib Mylan

Do not use Bortezomib Mylan

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

Warnings and precautions
Talk to your doctor or pharmacist before using Bortezomib Mylan if you suffer from any of the following
conditions:

• low number of red blood cells or white blood cells
• bleeding problems and/or low number of platelets in the blood
• diarrhoea, constipation, nausea or vomiting
• previous experiences of fainting, dizziness or feeling lightheaded
• kidney problems
• moderate to severe liver problems
• previous disorders such as numbness, tingling or pain in the hands or feet (neuropathy)
• heart or blood pressure problems
• shortness of breath or cough
• convulsions
• herpes zoster(even if localized around the eyes or spreading to the rest of the body)
• symptoms of tumor lysis syndrome such as, for example, muscle cramps, muscle weakness, confusion, vision disturbances or loss of vision and shortness of breath
• memory loss, difficulty thinking, difficulty walking or loss of vision. These may be signs of a serious brain infection and your doctor may prescribe further tests and checks.

You will need to have regular blood tests before and during therapy with Bortezomib Mylan, to
constantly monitor blood cell values.
If you have mantle cell lymphoma and are given rituximab together with Bortezomib Mylan, you must inform
your doctor:

• if you think you have hepatitis or have had it in the past. In some cases, patients who have had hepatitis B may have a new attack of hepatitis, which can be fatal. If you have had a hepatitis B infection in the past, your doctor will need to monitor you carefully for signs and symptoms of active hepatitis B.

Read the package leaflets of all medicines you are taking in combination with Bortezomib Mylan for
information about these medicines before starting treatment with Bortezomib Mylan.
When Bortezomib Mylan is given together with the medicine thalidomide, pay particular attention
to the instructions on pregnancy testing and the pregnancy prevention program (see “Pregnancy
and breastfeeding” in this section).

Children and adolescents
Bortezomib Mylan should not be used in children and adolescents because it is not known how the
medicine works in these subjects.

Other medicines and Bortezomib Mylan
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other
medicines, including those available without a prescription.
In particular, tell your doctor if you are taking medicines containing any of the following active substances:

• ketoconazole, used to treat fungal infections
• ritonavir, used to treat HIV infection
• rifampicin, an antibiotic used 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 antidiabetics.

Pregnancy and breastfeeding
You should not use Bortezomib Mylan if you are pregnant, unless strictly necessary.
Men and women undergoing therapy with Bortezomib Mylan must use effective contraceptive methods during and
for up to 3 months after treatment. If, despite these precautions, pregnancy occurs, inform
your doctor immediately.
You should not breastfeed while taking Bortezomib Mylan. Discuss with your doctor the most
appropriate time to resume breastfeeding after the end of therapy.
Thalidomide causes birth defects and fetal death. When Bortezomib Mylan is given together with
thalidomide, you must follow the thalidomide pregnancy prevention program (see thalidomide package
leaflet).

Driving and operating machinery
Bortezomib Mylan can cause fatigue, dizziness, fainting or blurred vision. Do not drive
vehicles, or operate tools or machinery if you experience any of these symptoms. Also take
particular care even if these effects do not occur.

3. How to use Bortezomib Mylan

The doctor will calculate the dose of Bortezomib Mylan according to your height and weight (body surface area). The standard initial dose of Bortezomib Mylan is 1.3 mg/m of body surface area twice a week. The doctor may change the dose and the total number of treatment cycles based on your response to treatment, the occurrence of certain side effects, and your overall health conditions (e.g. liver problems).

Multiple myeloma in progression
When Bortezomib Mylan is administered alone, you will receive 4 doses of Bortezomib Mylan via intravenous or subcutaneous route on days 1, 4, 8 and 11 followed by a “pause” period of 10 days without treatment. This period of 21 days (3 weeks) corresponds to a treatment cycle. You may receive up to 8 cycles (24 weeks).
You may also receive Bortezomib Mylan together with the medicines pegylated liposomal doxorubicin or dexamethasone.
When Bortezomib Mylan is administered together with pegylated liposomal doxorubicin, you will receive a 21-day treatment cycle with Bortezomib Mylan via intravenous or subcutaneous route and 30 mg/m of pegylated liposomal doxorubicin will be administered on day 4 of the 21-day treatment cycle of Bortezomib Mylan as an intravenous infusion after the injection of Bortezomib Mylan.
You may receive up to 8 cycles (24 weeks).
When Bortezomib Mylan is administered together with dexamethasone you will receive a 21-day treatment cycle with Bortezomib Mylan via intravenous or subcutaneous route and dexamethasone orally at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11 and 12, of the 21-day treatment cycle with Bortezomib Mylan.
You may receive up to 8 cycles (24 weeks).

Previously untreated multiple myeloma
If you have never been treated before for multiple myeloma and you are noteligible for stem cell transplantation, you will receive Bortezomib Mylan via intravenous route together with two other medicines: 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 1-4, Bortezomib Mylan is administered twice a week on days 1, 4, 8, 11, 22, 25, 29 and 32.
• In cycles 5-9, Bortezomib Mylan is administered once a week on days 1, 8, 22 and 29.

Melphalan (9 mg/m ) and prednisone (60 mg/m ) are administered orally on days 1, 2, 3 and 4 of the first week of each cycle.
If you have never been treated before for multiple myeloma and you areeligible for stem cell transplantation, you will receive Bortezomib Mylan via intravenous or subcutaneous route together with the medicines: dexamethasone, or dexamethasone and thalidomide, as induction treatment.
When Bortezomib Mylan is administered together with dexamethasone, you will receive a 21-day treatment cycle with Bortezomib Mylan via intravenous or subcutaneous route and dexamethasone 40 mg orally on days 1, 2, 3, 4, 8, 9, 10 and 11 of the 21-day treatment cycle of Bortezomib Mylan.
You will receive 4 cycles (12 weeks).
When Bortezomib Mylan is administered together with thalidomide and dexamethasone, the duration of the treatment cycle is 28 days (4 weeks).
Dexamethasone 40 mg is administered orally on days 1, 2, 3, 4, 8, 9, 10 and 11 of the 28-day treatment cycle with Bortezomib Mylan and thalidomide is administered daily orally at a dose 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 may be subsequently increased up to 200 mg per day from the second cycle onwards. You may receive up to 6 cycles (24 weeks).

Previously untreated mantle cell lymphoma
If you have never received treatment for mantle cell lymphoma in the past, you will receive Bortezomib Mylan via intravenous or subcutaneous route together with the medicines rituximab, cyclophosphamide, doxorubicin and prednisone.
Bortezomib Mylan is administered via intravenous route on days 1, 4, 8 and 11, followed by a “pause” period without treatment. The duration of the treatment cycle is 21 days (3 weeks). You may receive up to 8 treatment cycles (24 weeks).
The following medicines are administered on day 1 of each 21-day treatment cycle of Bortezomib Mylan as an intravenous infusion: rituximab at 375 mg/m , cyclophosphamide at 750 mg/m and doxorubicin at 50 mg/m .
Prednisone is administered orally at a dose of 100 mg/m on days 1, 2, 3, 4 and 5 of the treatment cycle with Bortezomid Mylan.

How Bortezomib Mylan is administered
This medicine is for intravenous or subcutaneous use. Bortezomib Mylan will be administered by a healthcare professional experienced in the use of cytotoxic medicines.
The Bortezomib Mylan powder must be dissolved before administration. This will be done by a healthcare professional. The resulting solution is then injected rapidly into a vein or under the skin.
The injection into the vein is rapid, in a period of time from 3 to 5 seconds. The subcutaneous injection can be performed either in the thigh or in the abdomen.

If you take more Bortezomib Mylan than you should
Since this medicine is administered by the doctor or nurse it is unlikely that you will take more than you should. In the unlikely event of an overdose, the doctor will monitor for side effects.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Some of these effects may be serious.
If you are given Bortezomib Mylan for multiple myeloma or mantle cell lymphoma, tell your doctor immediately if you notice any of the following symptoms:

• muscle cramps, muscle weakness
• confusion, vision disturbances or vision loss, blindness, seizures, headache
• shortness of breath, swelling of the feet or changes in heartbeat, high blood pressure, fatigue, fainting
• cough and difficulty breathing or a feeling of tightness in the chest.

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

• platelets, which may make you more prone to bruising or bleeding without obvious injury (for example, bleeding from the intestines, stomach, mouth and gums, or brain hemorrhage or liver hemorrhage)
• red blood cells, which can cause anemia, with symptoms such as fatigue and paleness
• white blood cells, which may make you more susceptible to infections or flu-like symptoms.

If you are given Bortezomib Mylan for the treatment of multiple myeloma, the side effects
that may occur are listed below.

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

• Sensitization, numbness, tingling or burning sensation of the skin, or pain in the hands or feet, due to nerve damage.
• Reduction in the number of red blood cells and/or white blood cells (see above).
• Fever.
• Feeling unwell (nausea) or vomiting, loss of appetite.
• Constipation with or without bloating (may be severe).
• Diarrhea: if it occurs, it is important to drink more water than usual. Your doctor may prescribe medicines to control the diarrhea.
• Fatigue, feeling of weakness.
• Muscle pain, bone pain.

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

• Low blood pressure, sudden drop in blood pressure when standing up which can lead to fainting.
• Increased blood pressure.
• Reduced kidney function.
• Headache.
• Feeling generally unwell, pain, dizziness, feeling lightheaded, feeling weak or loss of consciousness.
• Chills.
• Infections, including pneumonia, respiratory infections, bronchitis, fungal infection, cough with mucus, flu-like illness.
• Herpes zosterinfection (localized, including around the eyes, or widespread on the body).
• Chest pain or difficulty breathing during physical activity.
• Different types of skin rash.
• Itching of the skin, skin nodules or dry skin.
• Redness of the face or small broken blood vessels.
• Skin redness.
• Dehydration.
• Heartburn, bloating, belching, presence of gas, stomach pain, intestinal or stomach bleeding.
• Impaired liver function.
• Irritation of the mouth or lips, dry mouth, mouth ulcers or sore throat.
• Weight loss, loss of taste.
• Muscle cramps, muscle spasms, muscle weakness, pain in arms and legs.
• Blurred vision.
• Infection of the outermost layer of the eyes and the inner surface of the eyelids (conjunctivitis).
• Nosebleeds.
• Changes or problems with sleep, sweating, anxiety, mood changes, depressed mood, restlessness or agitation, changes in mental state, disorientation.
• Swelling of the body, including swelling around the eyes and in other parts of the body.

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

• Heart failure, heart attack, chest pain, chest discomfort, increased or decreased heart rate.
• Kidney failure.
• Inflammation of a vein, blood clots in the veins and lungs.
• Problems with blood clotting.
• Circulatory failure.
• Inflammation of the membrane around the heart or presence of fluid around the heart.
• Infections including urinary tract infections, influenza, herpes virus infections, ear infection and cellulitis.
• Blood in the stool, or bleeding from mucous membranes for example mouth, vagina.
• Cerebrovascular disorders.
• Paralysis, seizures, falls, movement disorders, abnormal sensitivity, modified or reduced (feeling, hearing, tasting, smelling), attention disorder, tremor, spasms.
• Arthritis, including inflammation of the joints of the fingers of the hands, toes and jaw.
• Disorders affecting the lungs, preventing your body from getting enough oxygen. Some of these include difficulty breathing, shortness of breath, labored breathing even without physical activity, shallow or difficult breathing, or wheezing.
• Hiccups, speech disorders.
• Increased or decreased urine production (kidney damage), painful urination or presence of blood/protein in the urine, fluid retention.
• Altered levels of consciousness, confusion, memory impairment or loss.
• Hypersensitivity.
• Hearing loss, deafness or ringing in the ears, ear discomfort.
• Hormonal changes that can affect the reabsorption of salts and water.
• Hyperactivity of the thyroid gland.
• Inability to produce enough insulin or resistance to normal levels of insulin.
• Irritated or inflamed eyes, excessively watery eyes, eye pain, dry eyes, eye infections, cysts on the eyelid (chalazion), red and swollen eyelids, eye discharge, vision disorders, bleeding of the eyes.
• Swollen lymph nodes.
• Joint or muscle stiffness, feeling of heaviness, groin pain.
• Hair loss or abnormal hair texture.
• Allergic reactions.
• Redness or pain at the injection site.
• Mouth pain.
• Infection or inflammation of the mouth, ulcers of the mouth, esophagus, stomach and intestines sometimes associated with pain or bleeding, reduced intestinal motility (including bowel obstruction), abdominal or esophageal discomfort, difficulty swallowing, vomiting with blood.
• Skin infections.
• Bacterial and viral infections.
• Dental infection.
• Inflammation of the pancreas, obstruction of the bile ducts.
• Pain in the genitals, problems with erection.
• Weight gain.
• Feeling of thirst.
• Hepatitis.
• Disorders at the injection site or at the injection device site.
• Skin reactions or disorders (which can be severe and life-threatening), skin ulcerations.
• Bruises, falls and injuries.
• Inflammation or bleeding of blood vessels that can manifest with small red or purple dots (usually on the legs) that can become like large bruises under the skin or on the tissues.
• Benign cysts.
• A serious and reversible condition of the brain that includes seizures, high blood pressure, headache, fatigue, confusion, blindness or other vision problems.

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

• Heart problems including heart attack, angina.
• Hot flashes.
• Alteration of the color of the veins.
• Inflammation of the spinal nerve.
• Ear problems, bleeding from the ear.
• Reduced activity of the thyroid gland.
• Budd-Chiari syndrome (clinical symptoms are caused by blockage of the liver veins).
• Change or abnormal bowel function.
• Brain hemorrhage.
• Yellowing of the eyes and skin (jaundice).
• Severe allergic reaction (anaphylactic shock) the signs include difficulty breathing, chest pain or tightness, and/or feeling dizzy/weak, severe itching of the skin or appearance of swellings on the skin, swelling of the face, lips, tongue and/or throat that can cause difficulty in swallowing, collapse.
• Breast disorders.
• Vaginal discharge.
• Swelling of the genitals.
• Inability to tolerate alcohol consumption.
• Wasting or loss of body mass.
• Increased appetite.
• Fistulas.
• Joint effusion.
• Cysts in the membrane covering the joints (synovial cysts).
• Fractures.
• Rupture of muscle fibers leading to other complications.
• Enlarged liver, liver hemorrhage.
• Kidney cancer.
• Skin condition similar to psoriasis.
• Skin cancer.
• Paleness of the skin.
• Increase of platelets or plasma cells (a type of white blood cells) in the blood.
• Blood clot in small blood vessels (thrombotic microangiopathy)
• Abnormal reaction to blood transfusion.
• Partial or total loss of vision.
• Decreased libido.
• Loss of saliva.
• Protrusion of the eyeballs.
• Photophobia (excessive sensitivity of the eye to light).
• Rapid breathing.
• Rectal pain.
• Gallstones.
• Hernia.
• Injuries.
• Brittle or weak nails.
• Abnormal deposition of proteins in vital organs.
• Coma.
• Intestinal ulcers.
• Damage to multiple organs.
• Death.

If you are given Bortezomib Mylan together with other medicines for the treatment of mantle cell lymphoma, the side effects that may occur are listed below.

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

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

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

• Herpes zosterinfection (localized, including around the eyes or widespread on the body).
• Herpes virusinfection.
• Bacterial and viral infections.
• Respiratory infections, bronchitis, cough with mucus, flu-like illness.
• Fungal infections.
• Hypersensitivity (allergic reaction).
• Inability to produce enough insulin or resistance to normal levels of insulin.
• Fluid retention.
• Difficulty or problems sleeping.
• Loss of consciousness.
• Altered levels of consciousness, confused state.
• Dizziness.
• Increased heartbeat, high blood pressure, sweating.
• Vision disorders, 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 up which can lead to fainting.
• Shortness of breath during physical activity.
• Cough.
• Hiccups.
• Ringing in the ears, ear discomfort.
• Intestinal or stomach bleeding.
• Heartburn.
• Stomach pain, bloating.
• Difficulty swallowing.
• Inflammation of the stomach and intestines.
• Stomach pain.
• Irritation of the mouth or lips, sore throat.
• Impaired liver function.
• Itching of the skin.
• Skin redness.
• Skin rash.
• Muscle spasms.
• Urinary tract infection.
• Pain in the limbs.
• Swelling of the body, including swelling around the eyes and in other parts of the body.
• Chills.
• Redness and pain at the injection site.
• Feeling generally unwell.
• Weight loss.
• Weight gain.

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

• Hepatitis.
• Severe allergic reaction (anaphylactic reaction) whose signs may include difficulty breathing, chest pain or tightness, and/or feeling dizzy/weak, severe itching of the skin or appearance of swellings on the skin, swelling of the face, lips, tongue and/or throat that can cause difficulty in swallowing, collapse.
• Movement disorders, paralysis, contractions.
• Vertigo.
• Hearing loss, deafness.
• Disorders affecting the lungs, preventing your body from getting enough oxygen. Some of these include difficulty breathing, shortness of breath, labored breathing even without physical activity, breathing that becomes shallow, difficult or stops, wheezing.
• Blood clots in the lungs.
• Yellowing of the eyes and skin (jaundice).
• Cysts on the eyelid (chalazion), red and swollen eyelids

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

• Blood clot in small blood vessels (thrombotic microangiopathy)

Reporting of adverse reactions
If you experience any adverse reaction, including those not listed in this leaflet, please contact your
doctor or pharmacist. You can also report adverse reactions directly through the national reporting system at
https://www.aifa.gov.it/web/guest/content/segnalazioni-reazioni-avverse. By reporting adverse reactions you can help
provide more information on the safety of this medicine.

5. How to store Bortezomib Mylan

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the vial and the packaging box after
EXP.
Store the vial in the outer packaging to protect the medicine from light.
This medicine does not require any particular storage temperature.
Reconstituted solution
The chemical and physical stability in use has been demonstrated for 8 hours at 25°C in the dark both in the vial and in a
polypropylene syringe.
From a microbiological point of view, unless the reconstitution/dilution method precludes the risk of
microbial contamination, the product must be used immediately. If not used immediately,
the in-use storage time and conditions are the responsibility of the user.
Bortezomib Mylan is for single use. Any unused medicine and waste materials resulting from this medicine must
be disposed of in accordance with current local regulations.

6. Contents of the pack and other information

What Bortezomib Mylan contains
Each vial contains 1 mg of bortezomib (as the boronic ester of mannitol).
Each vial contains 3.5 mg of bortezomib (as the boronic ester of mannitol).
The excipient is mannitol (E421).
Only for 1 mg. After reconstitution, 1 ml of injectable solution contains 1 mg of bortezomib.
Only for 3.5 mg
Reconstitution for intravenous use:
After reconstitution, 1 ml of solution for intravenous injection contains 1 mg of bortezomib.
Reconstitution for subcutaneous use:
After reconstitution, 1 ml of solution for subcutaneous injection contains 2.5 mg of bortezomib.

Description of the appearance of Bortezomib Mylan and contents of the pack
Bortezomib Mylan powder for solution for injection is a mass or powder from white to off-white in color.
1 mg
Bortezomib Mylan is packaged in a glass vial with a rubber stopper and a green tear-off seal.
3.5 mg
Bortezomib Mylan is packaged in a glass vial with a rubber stopper and a blue tear-off seal.
Each pack contains 1 single-use vial.

Marketing Authorisation Holder
Mylan S.p.A., Via Vittor Pisani 20, 20124 Milan

Manufacturers
Synthon Hispania S.L. Castelló 1 Polígono Las Salinas 08830 Sant Boi de Llobregat Spain
Synthon s.r.o. Blansko Brnenska 32/c.p.597 678 01 Blansko Czech Republic
The following information is intended exclusively for healthcare professionals

1. RECONSTITUTION FOR INTRAVENOUS INJECTION

Note: Bortezomib Mylan is a cytotoxic agent. Consequently, particular attention must be paid during handling and preparation. It is recommended to wear gloves and other protective clothing to prevent skin contact.
DUE TO THE ABSENCE OF ANY TYPE OF PRESERVATIVE, ASEPTIC TECHNIQUE RULES MUST BE FOLLOWED DURING THE HANDLING OF BORTEZOMIB MYLAN.

• 1.1 Preparation of the 1 mg [or 3.5 mg] vial: add 1.0 ml [or 3.5 ml]of sterile sodium chloride injection solution 9 mg/ml (0.9%) to the vial containing Bortezomib Mylan powder using an appropriately sized 1 ml syringe without removing the vial stopper. The lyophilized powder dissolves completely in less than 2 minutes.

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

• 1.2 The solution must be visually inspected before administration to check for the presence of particulate matter or color change. If particulate matter or color change is present, the solution must not be used and must be discarded. Confirm the concentration on the vial to ensure that the correct dose is administered intravenously(1 mg/ml).
• 1.3 The reconstituted solution is preservative-free and must be used immediately after preparation. In any case, chemical-physical stability in use has been demonstrated for 8 hours at 25°C in the dark, stored in the original vial and/or in a syringe. From a microbiological point of view, unless the reconstitution/dilution method excludes the risk of microbiological contamination, the product must be used immediately. If it is not used immediately, it is the user's responsibility to comply with the storage conditions and times.

2. ADMINISTRATION

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

Bortezomib Mylan 1 or 3.5 mg powder for injectable solution IS FOR
SUBCUTANEOUS OR INTRAVENOUS USE ONLY. Do not administer via other routes. Intrathecal administration has resulted in death.

3. DISPOSAL

The vial is for single use and any remaining solution must be discarded.
Unused medicine and waste from this medicine must be disposed of in
accordance with local regulations.
The following information is intended for healthcare professionals only:
Only the 3.5 mg vial can be administered subcutaneously, as described below.

1. RECONSTITUTION FOR SUBCUTANEOUS INJECTION

Note: Bortezomib Mylan is a cytotoxic agent. Consequently, particular care must be taken
during handling and preparation. It is recommended to wear gloves and
other protective clothing to prevent skin contact.
GIVEN THE ABSENCE OF ANY TYPE OF PRESERVATIVE, DURING THE
HANDLING OF BORTEZOMIB MYLAN, ASEPTIC TECHNIQUE RULES MUST BE
RESPECTED.

• 1.1 Preparation of the 3.5 mg vial: add 1.4 mlof sterile sodium chloride 9 mg/ml (0.9%) injection solution to the vial containing Bortezomib Mylan powder using an appropriately sized syringe without removing the vial stopper. The lyophilized powder dissolves completely in less than 2 minutes.

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

• 1.2 The solution must be visually inspected before administration to check for the presence of particulate matter or color change. If particulate matter or color change is present, the solution must not be used and must be discarded. Confirm the concentration on the vial to ensure that the correct dose is administered subcutaneously(2.5 mg/ml).
• 1.3 The reconstituted solution is preservative-free and must be used immediately after preparation. In any case, the chemical-physical stability during use of the reconstituted solution has been demonstrated for 8 hours at 25°C in the dark, stored in the original vial and/or in a syringe. From a microbiological point of view, unless the reconstitution/dilution method excludes the risk of microbiological contamination, the product must be used immediately. If not used immediately, it is the user's responsibility to comply with the storage conditions and times.

2. ADMINISTRATION

• Once dissolved, withdraw the appropriate amount of the reconstituted solution in accordance with the dose calculated based on the patient's body surface area.
• Confirm the dose and concentration 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 thighs (right or left) or in the abdomen (right or left)
• In subsequent administrations, it is necessary to rotate the injection site.
• If local reactions occur at the injection site after subcutaneous injection of

Bortezomib Mylan, a lower concentration of Bortezomib Mylan solution (1 mg/ml instead of 2.5 mg/ml) may be administered or switching to intravenous injection is recommended.

Bortezomib Mylan 3.5 mg powder for injectable solution IS FOR SUBCUTANEOUS

OR INTRAVENOUS USE. Do not administer through other routes. Intrathecal administration
has caused deaths.

3. DISPOSAL

The vial is for single use and any remaining solution must be discarded.
Unused medicine and waste from this medicine must be disposed of in
accordance with current local regulations.