Bortezomib Mylan

Package leaflet: Information for the user

Bortezomib Mylan 3.5 mg powder for solution for injection

bortezomib
Generic medicine
Please read all of this leaflet carefully before you use this medicine because 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 experience any side effects, including any not listed in this leaflet, inform 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 Bortezomib Mylan is and what it is used for

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

• alone or in combination with pegylated liposomal doxorubicin or dexamethasone, for patients with disease that has worsened (progressed) after having received at least one previous treatment and for whom blood stem cell transplantation has not been successful or is not suitable
• in combination with the medicines melphalan and prednisone, for patients with previously untreated disease who cannot receive high-dose chemotherapy with blood stem cell transplantation
• in combination with dexamethasone or dexamethasone together with thalidomide, for patients with previously untreated disease and prior to receiving high-dose chemotherapy with blood stem cell transplantation (induction treatment).

Bortezomib Mylan is used to treat mantle cell lymphoma (a type of cancer affecting the
lymph nodes) in patients aged 18 years or older, in combination with the medicines rituximab, cyclophosphamide,
doxorubicin and prednisone, for patients with previously untreated disease 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 have any of the following conditions:

• low red or white blood cell count
• bleeding problems and/or low platelet count in the blood
• diarrhoea, constipation, nausea, or vomiting
• previous episodes of fainting, dizziness, or lightheadedness
• kidney problems
• moderate to severe liver problems
• previous nerve problems such as numbness, tingling, or pain in the hands or feet (neuropathy)
• heart or blood pressure problems
• shortness of breath or cough
• seizures
• herpes zoster (including around the eyes or spreading to other parts of the body)
• symptoms of tumour lysis syndrome such as muscle cramps, muscle weakness, confusion, visual disturbances, or 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 examinations.

You will need to have regular blood tests before and during treatment with Bortezomib Mylan to continuously monitor your blood cell counts.
If you have mantle cell lymphoma and are being given rituximab together with Bortezomib Mylan, 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 experience a reactivation of the infection, which can be fatal. If you have previously had a hepatitis B infection, your doctor will need to closely monitor you for signs and symptoms of active hepatitis B.

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

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

Other medicines and Bortezomib Mylan
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those without a prescription.
In particular, inform 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 antidiabetic medicines.

Pregnancy and breastfeeding
You must not use Bortezomib Mylan during pregnancy unless absolutely necessary.
Women of childbearing potential must use effective contraceptive methods during treatment and for up to 8 months after completion of treatment. Inform your doctor if you wish to freeze your eggs before starting treatment.
Male patients must not father a child during treatment with Bortezomib Mylan and must use effective contraception during treatment and for 5 months after completion of treatment.
You must not breastfeed during treatment with 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 administered together with thalidomide, you must follow the thalidomide pregnancy prevention programme (see the thalidomide package leaflet).

Driving and using machines
Bortezomib Mylan may cause fatigue, dizziness, fainting, or blurred vision. Do not drive or operate tools or machinery if you experience any of these symptoms. Exercise particular caution even if these effects do not occur.

3. How to use Bortezomib Mylan

Your doctor will calculate the dose of Bortezomib Mylan based on your height and weight (body surface area). The standard starting dose of Bortezomib Mylan is 1.3 mg/m² of body surface area, administered twice weekly. Your doctor may adjust the dose and the total number of treatment cycles depending on your response to treatment, the occurrence of certain side effects, and your overall health condition (e.g. liver problems).

Relapsed multiple myeloma
When Bortezomib Mylan is given alone, you will receive 4 doses of Bortezomib Mylan intravenously or subcutaneously on days 1, 4, 8, and 11, followed by a 10-day "rest" period without treatment. This 21-day period (3 weeks) constitutes one treatment cycle. You may receive up to 8 cycles (24 weeks).

You may also receive Bortezomib Mylan in combination with 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 administered intravenously or subcutaneously, and 30 mg/m² of pegylated liposomal doxorubicin will be administered on day 4 of the 21-day Bortezomib Mylan treatment cycle 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 administered intravenously or subcutaneously, and oral dexamethasone at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of the 21-day Bortezomib Mylan treatment cycle.
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 not eligible for blood stem cell transplantation, you will receive Bortezomib Mylan in combination 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 1–4, Bortezomib Mylan is administered twice weekly on days 1, 4, 8, 11, 22, 25, 29, and 32.
• In cycles 5–9, Bortezomib Mylan is administered once weekly 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 never been treated before for multiple myeloma and you are eligible for blood stem cell transplantation, you will receive Bortezomib Mylan intravenously or subcutaneously in combination with dexamethasone, or with 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 administered intravenously or subcutaneously, and oral dexamethasone 40 mg on days 1, 2, 3, 4, 8, 9, 10, and 11 of the 21-day Bortezomib Mylan treatment cycle.
You will receive 4 cycles (12 weeks).

When Bortezomib Mylan is administered together with thalidomide and dexamethasone, the treatment cycle duration 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 Bortezomib Mylan treatment cycle, and thalidomide is administered daily by mouth at a dose of 50 mg up to day 14 of the first cycle; if tolerated, the thalidomide dose is increased to 100 mg on days 15–28, and may subsequently be increased up to 200 mg per day starting from the second cycle onward. You may receive up to 6 cycles (24 weeks).

Previously untreated mantle cell lymphoma
If you have never previously received treatment for mantle cell lymphoma, you will receive Bortezomib Mylan intravenously or subcutaneously in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone.
Bortezomib Mylan is administered intravenously or subcutaneously on days 1, 4, 8, and 11, followed by a "rest" period without treatment. The treatment cycle duration 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 Bortezomib Mylan treatment cycle as intravenous infusions: rituximab at 375 mg/m², cyclophosphamide at 750 mg/m², and doxorubicin at 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 Mylan treatment cycle.

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 reconstituted 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 intravenous injection is rapid, taking between 3 and 5 seconds. The subcutaneous injection can be administered either in the thigh or the abdomen.

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

4. Possible side effects

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

• muscle cramps, muscle weakness
• confusion, vision disturbances or loss of vision, 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 may very commonly cause a decrease in the number of red and white blood cells and platelets in the blood. Therefore, you will need regular blood tests before and during treatment with Bortezomib Mylan to monitor your blood cell counts regularly. You may experience a reduction in the number of:

• platelets, which could make you more prone to bruising or bleeding without apparent injury (for example, bleeding from the intestine, stomach, mouth and gums, or brain or liver haemorrhage)
• red blood cells, which can cause anaemia, 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 being treated with Bortezomib Mylan for multiple myeloma, the possible side effects are listed below.
Very common side effects (may affect more than 1 in 10 people)

• Sensitivity, numbness, tingling or burning sensation of the skin, or pain in the hands or feet due to nerve damage.
• Decrease in the number of red and/or white blood cells (see above).
• Fever.
• Feeling unwell (nausea) or vomiting, loss of appetite.
• Constipation with or without swelling (may be severe).
• Diarrhoea: if this occurs, it is important that you drink much more water than usual. Your doctor may prescribe medicines to control diarrhoea.
• Tiredness (fatigue), feeling weak.
• Muscle pain, bone pain.

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

• Low blood pressure, sudden drop in blood pressure when standing, which may lead to fainting.
• Increased blood pressure.
• Reduced kidney function.
• Headache.
• General feeling of discomfort, pain, dizziness, feeling of emptiness in the head, weakness or loss of consciousness.
• Chills.
• Infections, including pneumonia, respiratory infections, bronchitis, fungal infection, cough with phlegm, flu-like illness.
• Infection with Herpes zoster (localized, including around the eyes, or disseminated throughout the body).
• Chest pain or difficulty breathing during physical activity.
• Various types of skin rash.
• Itchy skin, skin nodules or dry skin.
• Facial flushing or small capillary ruptures.
• Skin redness.
• Dehydration.
• Heartburn, bloating, belching, gas, stomach pain, intestinal or stomach bleeding.
• Changes in liver function.
• Irritation of 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 outer layer of the eye and inner surface of the eyelids (conjunctivitis).
• Nosebleeds.
• Sleep disturbances or problems, sweating, anxiety, mood changes, depressed mood, restlessness or agitation, changes in mental state, disorientation.
• Body swelling, including swelling around the eyes and 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.

• Vein inflammation, blood clots in veins and lungs.

• Blood clotting problems.

• Circulatory failure.

• Inflammation of the membrane surrounding the heart or fluid accumulation around the heart.

• Infections including urinary tract infections, influenza, herpes virus infections, ear infection and cellulitis.

• Blood in stools, or bleeding from mucous membranes, for example mouth, vagina.

• Cerebrovascular disorders.

• Paralysis, seizures, fall, movement disorders, abnormal, altered or reduced sensation (feeling, hearing, taste, smell), attention disorders, tremor, spasms.

• Arthritis, including inflammation of joints in fingers, toes and jaw.

• Lung disorders preventing your body from receiving sufficient oxygen. Some of these include difficulty breathing, shortness of breath, laboured breathing even without physical activity, shallow or difficult breathing or need to stop, wheezing.

• Hiccups, speech disorders.

• Increased or decreased urine production (kidney damage), painful urination or presence of blood/protein in urine, fluid retention.

• Altered levels of consciousness, confusion, memory failure or loss.

• Hypersensitivity.

• Hearing loss, deafness or ringing in the ears, ear discomfort.

• Hormonal changes that may affect reabsorption of salts and water.

• Overactivity of the thyroid gland.

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

• 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 disturbances, eye bleeding.

• Enlarged 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, mouth ulcers, oesophagus, stomach and intestine, sometimes associated with pain or bleeding, reduced intestinal motility (including intestinal blockage), abdominal or oesophageal discomfort, difficulty swallowing, vomiting with blood.

• Skin infections.

• Bacterial and viral infections.

• Dental infections.

• Pancreatitis, obstruction of bile ducts.

• Genital pain, erectile problems.

• Weight gain.

• Feeling thirsty.

• Hepatitis.

• Injection site or infusion device site reactions.

• Skin reactions or disorders (which may be severe and life-threatening), skin ulcerations.

• Bruising, falls and injuries.

• Inflammation or bleeding of blood vessels, which may appear as small red or purple spots (usually on the legs) that may develop into large bruises under the skin or tissues.

• Benign cysts.

• A serious but reversible brain condition including 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 flushes.
• Change in vein colour.
• Inflammation of the spinal nerve.
• Ear problems, ear bleeding.
• Reduced activity of the thyroid gland.
• Budd-Chiari syndrome (clinical symptoms caused by blockage of the liver veins).
• Changes or abnormal intestinal function.
• Cerebral haemorrhage (bleeding in the brain).
• Yellowing of the eyes and skin (jaundice).
• Severe allergic reaction (anaphylactic shock), signs include difficulty breathing, chest pain or tightness, and/or dizziness/weakness, severe skin itching or skin swellings, swelling of the face, lips, tongue and/or throat which may cause difficulty 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.
• Muscle fibre rupture leading to further complications.
• Enlarged liver, liver haemorrhage.
• Kidney cancer.
• Skin condition similar to psoriasis.
• Skin cancer.
• Pale skin.
• Increased 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 complete loss of vision.
• Decreased libido.
• Loss of saliva.
• Severe nerve inflammation, which may cause paralysis and breathing difficulties (Guillain-Barré syndrome).
• Eye protrusion.
• Photophobia (excessive sensitivity of the eye to light).
• Rapid breathing.
• Rectal pain.
• Gallstones.
• Hernia.
• Injuries.
• Brittle or weak nails.
• Abnormal protein deposits in vital organs.
• Coma.
• Intestinal ulcers.
• Damage to multiple organs.
• Death.

If you are administered Bortezomib Mylan in combination with other medicines for the treatment of mantle cell lymphoma, the possible side effects are listed below.
Very common side effects (may affect more than 1 in 10 people)

• Pneumonia.
• Loss of appetite.
• Sensitivity, numbness, tingling or burning sensation of the skin, or pain in the hands or feet due to nerve damage.
• Nausea and vomiting.
• Diarrhoea.
• Mouth ulcers.
• Intestinal constipation.
• Muscle pain, bone pain.
• Hair loss or abnormal hair texture.
• Tiredness, feeling weak.
• Fever.

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

• Infection with Herpes zoster (localized, including around the eyes, or disseminated throughout the body).
• Infection with herpes virus.
• Bacterial and viral infections.
• Respiratory infections, bronchitis, cough with phlegm, flu-like illness.
• Fungal infections.
• Hypersensitivity (allergic reaction).
• Inability to produce enough insulin or resistance to normal insulin levels.
• Fluid retention.
• Difficulty or problems sleeping.
• Loss of consciousness.
• Altered levels of consciousness, confusion.
• Dizziness.
• Increased heart rate, high blood pressure, sweating.
• Vision disturbances, 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 may 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.
• Infection or inflammation of the stomach and intestine.
• Stomach pain.
• Irritation of mouth or lips, sore throat.
• Changes in liver function.
• Itchy skin.
• Skin redness.
• Skin rash.
• Muscle spasms.
• Urinary tract infection.
• Limb pain.
• Body swelling, including swelling around the eyes and other parts of the body.
• Chills.
• Redness and pain at the injection site.
• General feeling of discomfort.
• Loss of body weight.
• Increase in body weight.

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

• Hepatitis.
• Severe allergic reaction (anaphylactic reaction), signs of which may include difficulty breathing, chest pain or tightness, and/or dizziness/weakness, severe skin itching or skin swellings, swelling of the face, lips, tongue and/or throat which may cause difficulty swallowing, collapse.
• Movement disorders, paralysis, contractions.
• Dizziness.
• Hearing loss, deafness.
• Lung disorders preventing your body from receiving sufficient oxygen. Some of these include difficulty breathing, shortness of breath, laboured breathing even without physical activity, breathing becoming shallow, difficult or interrupted, 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).
• Severe nerve inflammation, which may cause paralysis and breathing difficulties (Guillain-Barré syndrome).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
Reporting side effects 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 stated on the vial and outer carton following EXP.
Store the vial in the outer packaging to protect the medicine from light.
This medicine does not require any specific storage temperature.

Reconstituted solution
Chemical and physical in-use stability has been demonstrated for 8 days at 25°C and for 15 days at 5 ± 3°C in the dark, both in the vial and in a polypropylene syringe.
From a microbiological standpoint, unless the method of reconstitution/dilution excludes the risk of microbial contamination, the product should be used immediately. If not used immediately, the duration of in-use storage and the conditions prior to use are the responsibility of the user.
Bortezomib Mylan is for single use only. Any unused medicine and waste material arising from this medicine must be disposed of in accordance with local regulations.

6. Package contents and other information

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

Description of the appearance of Bortezomib Mylan and contents of the pack
Bortezomib Mylan powder for injectable solution is a mass or white to off-white powder.
Bortezomib Mylan is supplied in a glass vial with a rubber stopper and a blue tear-off seal.
Each pack contains 1 single-use vial.

Marketing Authorization Holder
Mylan S.p.A., Via Vittor Pisani 20, 20124 Milano

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 for healthcare professionals only.

1. RECONSTITUTION FOR INTRAVENOUS INJECTION

Note: Bortezomib Mylan is a cytotoxic agent. Therefore, particular care must be taken 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 TECHNIQUES MUST BE FOLLOWED DURING THE HANDLING OF BORTEZOMIB MYLAN.
1.1 Preparation of the 3.5 mg vial: add 3.5 ml of sterile sodium chloride 9 mg/ml (0.9%) solution for injection to the vial containing Bortezomib Mylan powder, using an appropriately sized syringe without removing the vial stopper. The lyophilized powder dissolves completely within less than 2 minutes.
The concentration of the resulting solution is 1 mg/ml. The solution will be clear and colourless with a final pH between 4 and 7. There is no need to check the pH of the solution.
1.2 The solution should be inspected visually before administration to check for the presence of particulate matter or discoloration. If particulate matter or discoloration is observed, the solution must not be used and should be discarded. Confirm the concentration on the vial to ensure that the correct dose is administered by intravenous route (1 mg/ml).
1.3 The reconstituted solution is preservative-free and must be used immediately after preparation. However, chemical and physical in-use stability has been demonstrated for 8 days at 25°C and for 15 days at 5 ± 3°C, protected from light, when stored in the original vial and/or in a syringe. From a microbiological standpoint, unless the reconstitution/dilution process excludes the risk of microbiological contamination, the product should be used immediately. If not used immediately, it is the responsibility of the user to ensure appropriate storage conditions and duration.

2. ADMINISTRATION

• After reconstitution, withdraw the appropriate volume of the reconstituted solution according to 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 labeled for intravenous administration).
• Administer the solution by intravenous bolus injection over 3 to 5 seconds through a peripheral or central intravenous catheter.
• Flush the intravenous catheter with sterile sodium chloride 9 mg/ml (0.9%) solution for injection.

Bortezomib Mylan 3.5 mg powder for injectable solution IS FOR SUBCUTANEOUS OR
INTRAVENOUS USE. Do not administer by other routes. Intrathecal administration has
resulted in deaths.

3. DISPOSAL

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

1. RECONSTITUTION FOR SUBCUTANEOUS INJECTION

Note: Bortezomib Mylan is a cytotoxic agent. Therefore, particular care must be taken during handling and preparation. It is recommended to wear gloves and other protective clothing to prevent skin contact.
DUE TO THE ABSENCE OF ANY KIND OF PRESERVATIVE, ASEPTIC TECHNIQUE MUST BE OBSERVED DURING THE HANDLING OF BORTEZOMIB MYLAN.
1.1 Preparation of the 3.5 mg vial: add 1.4 ml of sterile sodium chloride 9 mg/ml (0.9%) injection solution to the vial containing Bortezomib Mylan lyophilized powder using an appropriate size 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 colourless with a final pH between 4 and 7. There is no need to check the pH of the solution.
1.2 The solution should be visually inspected before administration to check for the presence of particulate matter or discoloration. If particulate matter or discoloration is observed, the solution must not be used and should be discarded. Confirm the concentration on the vial label to ensure that the correct dose is administered by subcutaneous route (2.5 mg/ml).
1.3 The reconstituted solution is preservative-free and must be used immediately after preparation. However, the chemical and physical in-use stability of the reconstituted solution has been demonstrated for 8 days at 25°C and for 15 days at 5 ± 3°C in the dark, when stored in the original vial and/or in a syringe. From a microbiological standpoint, unless the reconstitution/dilution process excludes the risk of microbiological contamination, the product should be used immediately. If not used immediately, it is the responsibility of the user to ensure appropriate storage conditions and duration.

2. ADMINISTRATION

• After reconstitution, withdraw the appropriate volume of the reconstituted solution according to 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 labeled 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 abdomen (right or left).
• For subsequent administrations, rotate the injection site.
• If local reactions at the injection site occur after subcutaneous administration 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 by other routes. Intrathecal administration has
resulted in deaths.

3. DISPOSAL

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