BORTEZOMIB 2.5 MG/ML Injectable solution

Зміст інструкції

1. Bortezomib EVER Pharma 2.5 mg/ml injectable solution
   1. What is Bortezomib EVER Pharma and what it is used for
   2. What you need to know before using Bortezomib EVER Pharma
   3. How to use Bortezomib EVER Pharma
   4. Possible side effects
   5. How to store Bortezomib EVER Pharma
   6. Package Contents and Other Information
   7. PREPARATION FOR INTRAVENOUS INJECTION
   8. ADMINISTRATION
   9. DISPOSAL
   10. ADMINISTRATION
   11. DISPOSAL

Bortezomib EVER Pharma 2.5 mg/ml injectable solution

bortezomib

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

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

Bortezomib EVER Pharma 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 EVER Pharma is used in the treatment of multiple myeloma (a type of malignant neoplasm of the bone marrow) in patients over 18 years of age:

• alone or together with the medicines liposomal pegylated doxorubicin or dexamethasone, for patients with worsening (progressive) disease after receiving at least one prior treatment or where blood stem cell transplantation has not been successful or is not feasible
• 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 EVER Pharma is used for the treatment of mantle cell lymphoma (a type of malignant neoplasm affecting the lymph nodes) in patients 18 years of age or older. In this case, Bortezomib
EVER Pharma is used 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 feasible.

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

Do not use Bortezomib EVER Pharma

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

Warnings and precautions
Talk to your doctor if you experience:

• 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
• problems with your kidneys
• moderate to severe problems with your liver
• previous conditions such as numbness, tingling or pain in your hands or feet (neuropathy)
• heart or blood pressure problems
• shortness of breath or cough
• convulsions
• herpes zoster (even if localised around the eyes or spreading to the rest of the body)
• symptoms of tumour 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 recommend further tests and checks. You will need to have regular blood tests before and during treatment with Bortezomib EVER Pharma, to constantly monitor your blood cell counts.

If you have mantle cell lymphoma and are given rituximab together with Bortezomib EVER Pharma
you should tell 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 closely for signs and symptoms of active hepatitis B.

Read the package leaflets of all medicines you are taking in combination with Bortezomib EVER Pharma
for information about these medicines before starting treatment with Bortezomib EVER
Pharma. When Bortezomib EVER Pharma 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 EVER Pharma should not be used in children and adolescents because it is not known
how the medicine works in these subjects.

Other medicines and Bortezomib EVER Pharma
Tell your doctor or pharmacist if you are taking, have recently taken or might take
any other medicine.
In particular, tell your doctor if you are using 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 EVER Pharma if you are pregnant, unless strictly necessary.
Men and women undergoing treatment with Bortezomib EVER Pharma must use effective
contraceptive methods during and for up to 3 months after treatment. If, despite these precautions, a
pregnancy occurs, inform your doctor immediately.
You should not breastfeed during the intake of Bortezomib EVER Pharma. Discuss with your doctor
the most appropriate time to restart breastfeeding after the end of therapy.
The medicine thalidomide causes birth defects and fetal death. When Bortezomib EVER Pharma is
given together with thalidomide, you must follow the pregnancy prevention program of

Driving and using machines
Bortezomib EVER Pharma can cause fatigue, dizziness, fainting or blurred vision. Do not
drive cars or use machines if you experience any of these symptoms. Also be particularly careful
even if these effects do not occur.

Bortezomib EVER Pharma contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per vial, i.e. essentially
‘sodium-free’.

3. How to use Bortezomib EVER Pharma

The doctor will calculate the dose of Bortezomib EVER Pharma in proportion to your height and weight
(body surface area). The standard initial dose of Bortezomib EVER Pharma is 1.3 mg/m of
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 general health
condition (e.g., liver problems).
Progressive multiple myeloma
When Bortezomib EVER Pharma is administered alone, you will receive 4 doses of Bortezomib EVER
Pharma intravenously or subcutaneously on days 1, 4, 8 and 11, followed by a “rest 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 EVER Pharma together with the medications liposomal pegylated
doxorubicin or dexamethasone.
When Bortezomib EVER Pharma is administered together with liposomal pegylated doxorubicin,
you will receive a 21-day treatment cycle with Bortezomib EVER Pharma intravenously or
subcutaneously and 30 mg/m of liposomal pegylated doxorubicin will be administered on day 4 of
the 21-day treatment cycle of Bortezomib EVER Pharma as an intravenous infusion after
the injection of Bortezomib EVER Pharma. You may receive up to 8 cycles (24 weeks of
treatment).
When Bortezomib EVER Pharma is administered together with dexamethasoneyou will receive a cycle of
21 days with Bortezomib EVER Pharma intravenously or subcutaneously 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 EVER Pharma. You may receive up to 8 cycles (24 weeks of
treatment).
Previously untreated multiple myeloma
If you have never been treated before for multiple myeloma and you are noteligible for blood stem cell
transplant, you will receive Bortezomib EVER Pharma together with two other medications:
melphalan and prednisone. In this case, the duration of a treatment cycle is 42 days (6 weeks).
You will receive 9 cycles (54 weeks).

• In cycles 1 to 4, Bortezomib EVER Pharma is administered twice a week on days 1, 4, 8, 11, 22, 25, 29 and 32.
• In cycles 5 to 9, Bortezomib EVER Pharma 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 blood stem cell
transplant, you will receive Bortezomib EVER Pharma intravenously or subcutaneously together
with the medications: dexamethasone, or dexamethasone and thalidomide, as induction treatment.
When Bortezomib EVER Pharma is administered together with dexamethasone, you will receive a cycle of
21 days with Bortezomib EVER Pharma intravenously or subcutaneously and
dexamethasone 40 mg orally on days 1, 2, 3, 4, 8, 9, 10 and 11 of the 21-day treatment
cycle of Bortezomib EVER Pharma. You will receive 4 cycles (12 weeks of treatment).
When Bortezomib EVER Pharma 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 cycle of
28 days with Bortezomib EVER Pharma and thalidomide, and talidomide is administered daily for
oral use 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 subsequently be increased to 200 mg per
day from the second cycle onwards. You may receive up to 6 cycles (24 weeks of treatment).
Previously untreated mantle cell lymphoma
If you have never received specific treatment for mantle cell lymphoma in the past, you will receive
Bortezomib EVER Pharma intravenously or subcutaneously together with the medications rituximab,
cyclophosphamide, doxorubicin and prednisone.
Bortezomib EVER Pharma is administered intravenously or subcutaneously on days 1, 4, 8 and 11,
followed by a period of “rest” 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 medications are administered on day 1 of each 21-day treatment cycle of
Bortezomib EVER Pharma 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 Bortezomib EVER Pharma.

How Bortezomib EVER Pharma is administered
This medication is for subcutaneous use and – after dilution – for intravenous use. Bortezomib
EVER Pharma will be administered by a healthcare professional experienced in the use of cytotoxic
medications.
The solution is injected into a vein or subcutaneously. The injection into the vein is rapid, over a period of
time of 3 to 5 seconds. The subcutaneous injection can be performed either in the thigh or in the abdomen.

If you take more Bortezomib EVER Pharma than you should
Since this medication 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 will experience them.
Some of these effects may be serious.
If you are given Bortezomib EVER Pharma for multiple myeloma or mantle cell lymphoma,
immediately inform your doctor if you notice any of the following symptoms:

• muscle cramps, muscle weakness
• confusion, vision disturbances or vision loss, blindness, convulsions, 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 EVER Pharma 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 regularly undergo
blood tests before and during treatment with Bortezomib EVER Pharma, to regularly check
blood cell counts. 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 in the intestine, stomach, mouth and gums, or cerebral or hepatic hemorrhage)
• red blood cells, which can cause anemia, with symptoms such as fatigue and pallor
• white blood cells, which may make you more susceptible to infections or flu-like symptoms. If you are given Bortezomib EVER Pharma 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 of nausea or vomiting, loss of appetite.
• Constipation with or without excessive intestinal gas (may be severe).
• Diarrhea: if this happens it is important to drink more water than usual. Your doctor may prescribe you 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 unwell, pain, dizziness, feeling empty-headed, feeling weak or loss of consciousness.
• Chills.
• Infections, including pneumonia, respiratory infections, bronchitis, fungal infection, cough with mucus, flu-like illness.
• Herpes zoster infection (localized, including around the eyes, or disseminated throughout the body).
• Chest pain or difficulty breathing during physical activity.
• Different types of skin rash.
• Itching of the skin, nodules on the skin or dry skin.
• Redness of the face or small breaks in the capillaries.
• Redness of the skin.
• 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.
• Sleep disturbances or problems, sweating, anxiety, mood changes, depressed mood, restlessness or agitation, changes in mental status, 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.
• Blood clotting problems.
• Circulatory failure.
• Inflammation of the membrane surrounding 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 the mucous membranes for example mouth, vagina.
• Cerebrovascular disorders.
• Paralysis, convulsions, falls, movement disorders, abnormal or reduced sensitivity (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 the need to stop, 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, swelling of the eyelid (chalazion), red and swollen eyelids, eye discharge, visual disturbances, eye bleeding.
• 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 intestine sometimes associated with pain or bleeding, reduced intestinal motility (including intestinal obstruction), discomfort in the abdomen or esophagus, 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 spots (usually on the legs) that can become like large bruises on the skin or tissues.
• Benign cysts.
• A serious and reversible condition of the brain that includes convulsions, 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.
• Severe inflammation of the nerves, which can cause paralysis and difficulty breathing (Guillain-Barré syndrome).
• 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 signs are caused by blockage of the liver veins).
• Change or abnormal intestinal function.
• Brain hemorrhage.
• Yellowing of the eyes and skin (jaundice).
• Swelling of the eyelid (chalazion), red and swollen eyelids.

If you are given Bortezomib EVER Pharma 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.
• Intestinal 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 zoster infection (localized, including around the eyes or disseminated throughout the body).
• Herpes virus infection.
• Bacterial and viral infections.
• Respiratory infections, bronchitis, cough with mucus, flu-like illness.
• Fungal infections.
• Hypersensitivity (allergic reaction).
• Inability to produce enough insulin or resistance to normal levels of insulin.
• Fluid retention.
• Difficulty or problems sleeping.
• Loss of consciousness.
• Altered levels of consciousness, confused state.
• Feeling dizzy.
• Increased heartbeat, 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 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.
• Infection or inflammation of the stomach and intestine.
• Stomach pain.
• Irritation of the mouth or lips, sore throat.
• Impaired liver function.
• Itching of the skin.
• Redness of the skin.
• 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 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 swelling on the skin, swelling of the face, lips, tongue and/or throat that can cause difficulty swallowing, collapse.
• Movement disorders, paralysis, contractions.
• Dizziness.
• 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).
• Swelling of the eyelid (chalazion), red and swollen eyelids.

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

• Blood clotting in small blood vessels (thrombotic microangiopathy).
• Severe inflammation of the nerves, which can cause paralysis and breathing difficulties (Guillain-Barré syndrome).

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

5. How to store Bortezomib EVER Pharma

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 on the label after
EXP. The expiry date refers to the last day of that month.
Store in a refrigerator (2°C-8°C).
Keep the vial in the outer packaging to protect the medicine from light.
The solution must be used immediately after first opening/dilution. If the solution
(diluted) is not used immediately, storage conditions and times are the responsibility
of the user. However, when stored in the original vial and/or in a polypropylene syringe, the solution (diluted) is stable for 28 days at 2°C-8°C and up to 25°C protected from light,
and for 24 hours in normal indoor lighting conditions.
Regarding stability in the syringe, the same storage time applies to both
diluted and undiluted solution.
Bortezomib EVER Pharma is for single use. Unused product and waste must be disposed of in
accordance with current local regulations.

6. Package Contents and Other Information

What Bortezomib EVER Pharma contains
The active ingredient is bortezomib. 1 ml of solution for injection contains 2.5 mg of bortezomib (as
mannitol boronic ester). Each vial of 1 ml injectable solution contains 2.5 mg of
bortezomib (as mannitol boronic ester). Each vial of 1.4 ml injectable solution contains 3.5 mg of
bortezomib (as mannitol boronic ester).
Each vial contains an additional excess of 0.2 ml.
The other ingredients are mannitol (E421), sodium chloride, sodium hydroxide (for pH adjustment),
hydrochloric acid (for pH adjustment) and water for injections.
1 ml Vial
Subcutaneous use: the product is ready for use with a concentration of 2.5 mg/ml.
Intravenous use: add 1.8 ml of 0.9% sodium chloride injectable solution to obtain a
final concentration of 1 mg/ml.
1.4 ml Vial
Subcutaneous use: the product is ready for use with a concentration of 2.5 mg/ml.
Intravenous use: add 2.4 ml of 0.9% sodium chloride injectable solution to obtain a
final concentration of 1 mg/ml.

Description of the appearance of Bortezomib EVER Pharma and contents of the pack
Bortezomib EVER Pharma injectable solution is a transparent solution, from colorless to pale
yellow.
Bortezomib EVER Pharma is available in a colorless glass vial (Type I), with a rubber stopper and
aluminum cap, with a snap-on plastic cap.
Pack sizes
1 x 1 ml vial (2.5 mg/1 ml)
5 x 1 ml vial (2.5 mg/1 ml)
1 x 1.4 ml vial (3.5 mg/1.4 ml)
5 x 1.4 ml vial (3.5 mg/1.4 ml)
Not all pack sizes may be marketed.

Marketing Authorisation Holder and
EVER Valinject GmbH
Oberburgau 3
4866 Unterach am Attersee
Austria

Manufacturer
EVER Pharma Jena GmbH
Otto-Schott-Str. 15
07745 Jena
Germany

This medicinal product is authorised in the Member States of the European Economic Area under the
following names:
Belgium Bortezomib EVER Pharma
Denmark Bortezomib EVER Pharma
Finland Bortezomib EVER Pharma
France Bortezomib EVER Pharma
Ireland Bortezomib
Italy Bortezomib EVER Pharma
Netherlands Bortezomib EVER Pharma
Norway Bortezomib EVER Pharma
Portugal Bortezomib EVER Pharma
Spain Bortezomib EVER Pharma
Sweden Bortezomib EVER Pharma
Hungary Bortezomib EVER Pharma
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The following information is intended exclusively for doctors or healthcare professionals:

1. PREPARATION FOR INTRAVENOUS INJECTION

Note: Bortezomib EVER Pharma 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. Pregnant personnel should not handle this medicine.
GIVEN THE ABSENCE OF ANY TYPE OF PRESERVATIVE, ASEPTIC TECHNIQUE RULES MUST BE FOLLOWED DURING THE HANDLING OF BORTEZOMIB EVER PHARMA.

• 1.1 Preparation of the 1 ml vial: add 1.8 mlof sterile sodium chloride injection solution 9 mg/ml (0.9%) to the vial containing Bortezomib EVER Pharma.

OR

Preparation of the 1.4 ml vial: add 2.4 mlof sterile sodium chloride injection solution
9 mg/ml (0.9%) to the vial containing Bortezomib EVER Pharma.
The concentration of the resulting solution is 1 mg/ml. The solution will be transparent and from colorless to pale yellow 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 a change in color. If particulate matter or a change in color is present, the solution must be discarded. Ensure that the correct dose is administered intravenously(1 mg/ml)
• 1.3 The solution is preservative-free and must be used immediately after preparation. However, the physicochemical stability during use of the diluted solution has been demonstrated: either for 28 days, at 2 °C-8 °C and protected from light or for 28 days, at 25 °C and protected from light or for 24 hours, if stored at 25 °C in normal indoor lighting conditions in the original vial and/or in a polypropylene syringe. If the diluted solution is not used immediately, the conditions and timing of use are the responsibility of the user.

2. ADMINISTRATION

• Once diluted, withdraw the appropriate amount of the diluted 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 labeled for intravenous administration).
• Inject the solution intravenously as a bolus over 3-5 seconds, via a peripheral or central intravenous catheter.
• Flush the intravenous or peripheral catheter with sterile sodium chloride 9 mg/ml (0.9%) solution.

BORTEZOMIB EVER PHARMA IS FOR SUBCUTANEOUS OR INTRAVENOUS USE ONLY. Do
not administer through 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 derived from this medicine must be disposed of in accordance
with local regulations in force for cytotoxic agents.

The following information is intended exclusively for doctors or healthcare professionals:
1PREPARATION FOR SUBCUTANEOUS INJECTION
Note: Bortezomib EVER Pharma 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 contact with the skin. Pregnant personnel should not
handle this medicine.
GIVEN THE ABSENCE OF ANY TYPE OF PRESERVATIVE, DURING THE
HANDLING OF BORTEZOMIB EVER PHARMA, ASEPTIC TECHNIQUE RULES MUST BE
RESPECTED.

• 1.1 Bortezomib EVER Pharma is ready for use. The concentration of the solution is 2.5 mg/ml. The solution is transparent and from colorless to light yellow with a final pH between 4.0 and 5.5. 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 be discarded. Ensure that the correct dose is administered by subcutaneousroute (2.5 mg/ml).
• 1.3 The solution is preservative-free and must be used immediately after taking the appropriate amount of solution. However, the chemical-physical stability during use of the solution has been demonstrated: either for 28 days, at 2 °C-8 °C and protected from light or for 28 days, at 25 °C and protected from light or for 24 hours, if stored at 25 °C in normal indoor lighting conditions in the original vial and/or in a polypropylene syringe. If the solution is not used immediately, the conditions and times of use are the responsibility of the user.

During preparation for administration and during administration itself, it is not
necessary to protect the medicine from light.

2. ADMINISTRATION

• Withdraw the appropriate amount of 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 solution is administered subcutaneously in the thighs (right or left) or in the abdomen (right or left)
• With subsequent administrations, it is necessary to rotate the injection site.
• If local reactions occur at the injection site after subcutaneous injection of Bortezomib EVER Pharma, a lower concentration of Bortezomib EVER Pharma solution (1 mg/ml instead of 2.5 mg/ml) may be administered, or switching to intravenous injection is recommended.

BORTEZOMIB EVER PHARMA IS FOR SUBCUTANEOUS OR INTRAVENOUS USE ONLY. Do not
administer through other routes. Intrathecal administration has caused deaths.

3. DISPOSAL

The vial is for single use and the remaining solution must be discarded.
Unused medicine and waste derived from such medicine must be disposed of in accordance
with current local regulations for cytotoxic agents.