Bortezomib ever pharma

Package leaflet: Information for the user

Bortezomib EVER Pharma, 2.5 mg/mL, solution for injection
bortezomib
Please read all of this leaflet carefully before using this medicine, because it contains
important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor or pharmacist.
• If you experience any side effects, including any not listed in this leaflet, please tell your doctor or pharmacist. See section 4.

Contents of the leaflet

1. What Bortezomib EVER Pharma is 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. Contents of the pack and other information

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

Bortezomib EVER Pharma contains an active substance called bortezomib, which is a so-called "proteasome inhibitor". Proteasomes play an important role in controlling cell functions and their development process. By interfering with their function, bortezomib may lead to the death of cancer cells.

Bortezomib EVER Pharma is used in the treatment of multiple myeloma (a cancer of the bone marrow) in patients aged at least 18 years:

• as monotherapy or in combination with other medicines: pegylated liposomal doxorubicin or dexamethasone, in patients whose disease has progressed (worsened) after at least one prior therapy and for whom stem cell transplantation has failed or is not possible.
• in combination with melphalan and prednisone, in patients who have not received prior treatment and who are not eligible for high-dose chemotherapy followed by stem cell transplantation.
• in combination with dexamethasone or dexamethasone with thalidomide, in patients who have not received prior treatment and who are eligible for high-dose chemotherapy followed by stem cell transplantation (induction treatment).

Bortezomib EVER Pharma is also used in the treatment of mantle cell lymphoma (a type of cancer affecting the lymph nodes) in patients aged at least 18 years, in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone, in patients who have not received prior treatment and who are not eligible for stem cell transplantation.

2. Important information before using Bortezomib EVER Pharma

When not to use Bortezomib EVER Pharma

• if the patient is allergic to bortezomib, boron, or any of the other ingredients
  of this medicine (listed in section 6).

• if the patient has certain severe lung or heart diseases.

Warnings and precautions
You should inform your doctor if any of the following apply to the patient:

• low number of red or white blood cells
• bleeding disorders and/or low platelet count
• diarrhoea, constipation, nausea, or vomiting
• history of fainting, dizziness, or lightheadedness
• kidney diseases
• moderate to severe liver function disorders
• history of numbness, tingling, and pain in hands and feet (symptoms of neuropathy)
• heart diseases or blood pressure disorders
• shortness of breath or cough
• seizures occur
• shingles (around the eyes or widespread throughout the body)
• tumour lysis syndrome symptoms such as muscle cramps, muscle weakness, confusion, vision loss or disturbances, and difficulty breathing
• memory loss, thinking disorders, difficulty walking, or vision loss. These may be symptoms of a serious brain infection, and the doctor may recommend further tests and monitoring.

Regular blood tests must be performed in the patient before and during treatment with
Bortezomib EVER Pharma to regularly monitor blood cell counts.
If the patient has mantle cell lymphoma and is receiving rituximab-containing medication together with Bortezomib EVER Pharma, inform the doctor:

• if the patient suspects a hepatitis virus infection or has had it in the past. In several cases, patients who had hepatitis B virus (HBV) infection experienced reactivation of hepatitis, which could lead to death. If the patient has a history of HBV infection, the doctor will closely monitor for symptoms of active HBV.

Before starting treatment with Bortezomib EVER Pharma, carefully read the package leaflets
of all medicinal products being taken during treatment to obtain information about them. If thalidomide is being used, ensure the patient is not pregnant, and then use effective contraception (see section "Pregnancy and breastfeeding").
Children and adolescents
Bortezomib EVER Pharma should not be used in children and adolescents, as its efficacy and safety in this patient group are unknown.
Bortezomib EVER Pharma and other medicines
Inform the doctor about all medicines currently taken or recently used, as well as any medicines the patient plans to use.
In particular, inform the doctor if the patient is 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 and other conditions
• oral antidiabetic medicines

Pregnancy and breastfeeding
Do not use Bortezomib EVER Pharma during pregnancy unless absolutely necessary.
Both men and women receiving Bortezomib EVER Pharma must use effective contraception during treatment and for 3 months after treatment ends. If a woman becomes pregnant despite using these methods, she must inform her doctor immediately.
Women should not breastfeed during treatment with Bortezomib EVER Pharma. The timing of safe return to breastfeeding after treatment should be discussed with the doctor.
Thalidomide causes birth defects and fetal death. When Bortezomib EVER Pharma is used in combination with thalidomide, patients must comply with the requirements of the "Thalidomide Pregnancy Prevention Programme" (see thalidomide package leaflet).
Driving and operating machinery
Bortezomib EVER Pharma may cause fatigue, dizziness, fainting, and blurred vision. If such symptoms occur, the patient must not drive or operate tools or machinery. Even if symptoms do not occur, caution should still be exercised.
Bortezomib EVER Pharma contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per vial, meaning the medicine is considered "sodium-free".

3. How to use Bortezomib EVER Pharma

Your doctor will determine the appropriate dose of Bortezomib EVER Pharma based on the patient's height and body weight (body surface area). The most commonly used starting dose of Bortezomib EVER Pharma is 1.3 mg/m² body surface area administered twice weekly.
The doctor may adjust the dose and the total number of treatment cycles depending on the patient's response to treatment, occurrence of adverse reactions, and additional medical conditions (e.g. liver disease).

Multiple myeloma
If Bortezomib EVER Pharma is administered as monotherapy, the patient will receive 4 doses of Bortezomib EVER Pharma intravenously or subcutaneously on days 1, 4, 8, and 11, followed by a 10-day treatment break. This 21-day period (3 weeks) is considered one treatment cycle.
The patient may receive up to 8 cycles (24 weeks).

The patient may also receive Bortezomib EVER Pharma in combination with the following medicines: pegylated liposomal doxorubicin or dexamethasone.

When Bortezomib EVER Pharma is administered in combination with pegylated liposomal doxorubicin, the patient will receive Bortezomib EVER Pharma intravenously or subcutaneously during a 21-day treatment cycle, and pegylated liposomal doxorubicin will be administered as an intravenous infusion at a dose of 30 mg/m² after administration of Bortezomib EVER Pharma on day 4 of the 21-day treatment cycle. The patient may receive up to 8 cycles (24 weeks).

When Bortezomib EVER Pharma is administered in combination with dexamethasone, the patient will receive Bortezomib EVER Pharma intravenously or subcutaneously during a 21-day treatment cycle, and dexamethasone will be administered 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. The patient may receive up to 8 cycles (24 weeks).

Previously untreated multiple myeloma
If the patient has not been previously treated for multiple myeloma and the patient is not eligible for hematopoietic stem cell transplantation, the patient will receive Bortezomib EVER Pharma in combination with other medicines: melphalan and prednisone. In this case, the duration of each treatment cycle is 42 days (6 weeks). The patient will receive 9 cycles (54 weeks).

• During cycles 1–4, Bortezomib EVER Pharma is administered twice weekly on days 1, 4, 8, 11, 22, 25, 29, and 32.
• During cycles 5–9, Bortezomib EVER Pharma is administered once weekly on days 1, 8, 22, and 29. Both melphalan (at a dose of 9 mg/m² body surface area) and prednisone (at a dose of 60 mg/m² body surface area) are administered orally on days 1, 2, 3, and 4 of the first week of each cycle.

If the patient has not been previously treated for multiple myeloma and the patient is eligible for hematopoietic stem cell transplantation, the patient will receive Bortezomib EVER Pharma intravenously or subcutaneously in combination with dexamethasone or with dexamethasone and thalidomide as induction therapy.

When Bortezomib EVER Pharma is administered with dexamethasone, the patient will receive Bortezomib EVER Pharma intravenously or subcutaneously in 21-day cycles, and dexamethasone at a dose of 40 mg will be administered orally on days 1, 2, 3, 4, 8, 9, 10, and 11 of each 21-day treatment cycle with Bortezomib EVER Pharma. The patient will receive up to 4 cycles (12 weeks).

When Bortezomib EVER Pharma is administered with thalidomide and dexamethasone, the treatment cycle duration is 28 days (4 weeks).
Dexamethasone at a dose of 40 mg will be administered orally on days 1, 2, 3, 4, 8, 9, 10, and 11 of each 28-day treatment cycle with Bortezomib EVER Pharma. Thalidomide is administered orally once daily at a dose of 50 mg up to day 14 of the first cycle; if tolerated, the dose is increased to 100 mg from days 15 to 28, and may subsequently be increased to 200 mg daily starting from the second cycle. The patient may receive up to 6 cycles (24 weeks).

Previously untreated mantle cell lymphoma
If the patient has not been previously treated for mantle cell lymphoma, the patient will receive Bortezomib EVER Pharma intravenously in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone.
Bortezomib EVER Pharma is administered intravenously on days 1, 4, 8, and 11, followed by a "rest period" without administration of any drugs. One treatment cycle lasts 21 days (3 weeks). The patient will receive up to 8 cycles (24 weeks).

The following medicines are administered as intravenous infusions on day 1 of each 21-day treatment cycle with Bortezomib EVER Pharma:

• Rituximab at a dose of 375 mg/m² body surface area, cyclophosphamide at a dose of 750 mg/m² body surface area, and doxorubicin at a dose of 50 mg/m² body surface area.
• Prednisone is administered orally at a dose of 100 mg/m² body surface area on days 1, 2, 3, 4, and 5 of the Bortezomib EVER Pharma treatment cycle.

How Bortezomib EVER Pharma is administered
This medicine is administered subcutaneously or, after reconstitution, intravenously. Bortezomib EVER Pharma will be administered by trained medical personnel experienced in the use of cytotoxic medicines.
The solution is injected either intravenously or subcutaneously. The intravenous injection is administered very rapidly and lasts between 3 and 5 seconds. The subcutaneous injection is given in the thigh or abdomen.

Administration of a higher than recommended dose of Bortezomib EVER Pharma
This medicine is administered by a doctor or nurse; therefore, it is highly unlikely that the patient would receive an overdose.
However, if an overdose occurs exceptionally, the doctor will monitor the patient for any adverse reactions.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Some of these adverse reactions may be serious.
If the patient is receiving Bortezomib EVER Pharma for the treatment of multiple myeloma or mantle cell lymphoma, inform the doctor immediately if the patient experiences any of the following symptoms:

• muscle cramps, muscle weakness
• confusion, loss or disturbances of vision, blindness, seizures, headaches
• shortness of breath, swelling of the feet or change in heart rhythm, high blood pressure, fatigue, fainting
• cough and difficulty breathing or chest tightness

Treatment with Bortezomib EVER Pharma may very frequently lead to a reduction in the patient's blood levels of red and white blood cells and platelets. Therefore, blood tests must be performed frequently before and during treatment with Bortezomib EVER Pharma to regularly monitor blood cell counts. The patient may experience a decrease in:

• platelets, which may lead to a tendency to bruise or bleeding not caused by injury (e.g., bleeding from the intestines, stomach, mouth and gums, or hemorrhage in the brain or liver)
• red blood cells, which may lead to anemia, associated with symptoms such as fatigue and pallor
• white blood cells, which may lead to increased susceptibility to infections or flu-like symptoms

If the patient is receiving Bortezomib EVER Pharma for the treatment of multiple myeloma, the following adverse reactions may occur:
Very common adverse reactions (may affect more than 1 in 10 people)

• hypersensitivity, numbness, tingling or burning sensation of the skin, pain in hands or feet due to nerve damage
• reduction in the number of red and (or) white blood cells (see above)
• fever
• nausea or vomiting, loss of appetite
• constipation with or without bloating (symptoms may be severe)
• diarrhea: if it occurs, the patient must drink more fluids than usual; the doctor may recommend taking additional medicines to control diarrhea
• fatigue, feeling of weakness
• muscle pain, bone pain

Common adverse reactions (may affect up to 1 in 10 people)

• low blood pressure, sudden drop in blood pressure upon standing, which may lead to fainting
• high blood pressure
• reduced kidney function
• headache
• general feeling of being unwell, pain, dizziness, lightheadedness, feeling weak or loss of consciousness
• chills
• infections, including: pneumonia, respiratory tract infections, bronchitis, fungal infections, cough with sputum, flu-like symptoms
• shingles (localized, e.g., around the eyes, or disseminated throughout the body)
• chest pain, shortness of breath during physical exercise
• various types of skin rashes
• itchy skin, skin nodules or dry skin
• facial flushing or capillary rupture
• skin redness
• dehydration
• heartburn, bloating, belching, flatulence, abdominal pain, bleeding from the intestine or stomach
• liver function disorders
• inflammation of the mouth or lips, dry mouth, mouth ulcers or sore throat
• weight loss, loss of taste
• muscle cramps, muscle weakness, limb pain
• blurred vision
• conjunctivitis
• nosebleeds
• difficulty sleeping, sweating, anxiety, mood swings, depressive mood, restlessness or agitation, mental status changes, disorientation
• edema, including around the eyes and in other parts of the body

Uncommon adverse reactions (may affect up to 1 in 100 people)

• heart failure, heart attack, chest pain, discomfort in the chest, rapid or slow heart rate

• kidney failure

• phlebitis, blood clots in veins and lungs

• blood clotting disorders

• circulatory failure

• pericarditis (inflammation of the outer lining of the heart) or fluid in the pericardium

• infections, including: urinary tract infections, influenza, herpes, ear infection, connective tissue infection

• blood in stool, mucosal bleeding, e.g., from the mouth, vagina

• cerebral vascular disorders

• paralysis, seizures, falls, movement disorders, abnormal, altered or reduced sensation (touch, hearing, taste, smell), attention disorders, tremor, sudden jerking movements

• arthritis, including arthritis of fingers, toes and jaw joints

• lung disorders making breathing difficult. These include: difficulty breathing, shortness of breath, shortness of breath at rest, shallow breathing or respiratory arrest, wheezing

• hiccups, speech disorders

• increased or decreased urine output (due to kidney damage), painful urination or blood/protein in urine, fluid retention

• altered level of consciousness, confusion, worsening or loss of memory

• hypersensitivity

• hearing loss, deafness, ringing or discomfort in the ears

• hormonal disorders affecting salt and water absorption

• hyperthyroidism

• insufficient insulin production or resistance to normal insulin concentration

• eye irritation or inflammation, excessively watery eyes, eye pain, dry eyes, eye infections,
  stye (hordeolum), redness and swelling of the eyelid, eye discharge,
  visual disturbances, eye bleeding

• enlarged lymph nodes

• joint or muscle stiffness, feeling of heaviness, groin pain

• hair loss and abnormal hair structure

• allergic reactions

• redness or pain at the injection site

• mouth pain

• infection or inflammation of the mouth, esophagus, stomach and intestines, sometimes with associated pain and bleeding, weak intestinal peristalsis (including obstruction), abdominal and esophageal discomfort, difficulty swallowing, vomiting blood

• skin infection

• bacterial and viral infections

• dental infections

• pancreatitis, biliary duct obstruction

• genital organ pain, erectile dysfunction

• weight gain

• thirst

• hepatitis

• injection site reactions or complications related to vascular catheter use

• skin reactions and disorders (which may be severe and life-threatening), skin ulceration

• bruising, falls and injuries

• vascular inflammation or bleeding, manifesting as small red or purple spots (usually on legs) to large, bruise-like subcutaneous patches

• benign cysts

• severe reversible encephalopathy syndrome, including seizures, high blood pressure, headache, fatigue, confusion, blindness or other visual disturbances

Rare adverse reactions (may affect up to 1 in 1000 people)

• heart diseases, including heart attack, angina
• severe nerve inflammation, which may cause paralysis and breathing difficulties (Guillain-Barré syndrome)
• flushing attacks
• vein discoloration
• spinal cord inflammation
• ear diseases, ear bleeding
• hypothyroidism
• Budd-Chiari syndrome (clinical symptoms caused by blockage of hepatic veins)
• altered or abnormal intestinal function
• brain hemorrhage
• yellowing of eyes or skin (jaundice)
• severe allergic reaction (anaphylactic shock) with symptoms such as: difficulty breathing, chest pain or tightness and (or) dizziness and (or) fainting, severe skin itching or raised skin lumps, swelling of face, lips, tongue and (or) throat, which may cause breathing and swallowing difficulties, collapse
• breast diseases
• vaginal ulceration
• genital swelling
• alcohol intolerance
• wasting or weight loss
• increased appetite
• fistula
• joint effusion
• synovial cyst (ganglion cyst)
• bone fractures
• muscle fiber breakdown leading to further complications
• liver swelling, liver bleeding
• kidney cancer
• psoriasis-like skin condition
• skin cancer
• skin pallor
• increased number of platelets or plasma cells (a type of white blood cell)
• blood clot in small blood vessels (thrombotic microangiopathy)
• abnormal reaction to blood transfusion
• partial or complete vision loss
• decreased libido
• drooling
• exophthalmos (protruding eyes)
• photophobia (light sensitivity)
• increased respiratory rate
• anal pain
• gallstones
• hernia
• cuts
• brittle or weak nails
• abnormal protein deposition in organs
• coma
• intestinal ulceration
• multi-organ failure
• death

If the patient is receiving Bortezomib EVER Pharma in combination with other medicines for the treatment of mantle cell lymphoma, the following adverse reactions may occur:
Very common adverse reactions (may affect more than 1 in 10 people)

• pneumonia
• loss of appetite
• hypersensitivity, numbness, tingling or burning sensation of the skin, pain in hands or feet due to nerve damage
• nausea or vomiting
• diarrhea
• mouth ulcers
• constipation
• muscle pain, bone pain
• hair loss and abnormal hair structure
• fatigue, feeling of weakness
• fever

Common adverse reactions (may affect up to 1 in 10 people)

• shingles (localized, e.g., around the eyes, or disseminated throughout the body)
• herpes virus infection
• bacterial and viral infections
• respiratory tract infections, bronchitis, wet cough, flu-like symptoms
• fungal infections
• hypersensitivity (allergic reaction)
• insufficient insulin production or resistance to normal insulin concentration
• fluid retention
• sleep disturbances
• loss of consciousness
• altered level of consciousness, confusion
• dizziness
• rapid heartbeat, high blood pressure, sweating
• visual disturbances, blurred vision
• heart failure, heart attack, chest pain, discomfort in the chest, rapid or slow heart rate
• high or low blood pressure
• sudden drop in blood pressure upon changing position, which may lead to fainting
• shortness of breath during exertion
• cough
• hiccups
• ringing in the ears, ear discomfort
• bleeding from the intestine or stomach
• heartburn
• abdominal pain, belching
• difficulty swallowing
• infection or inflammation of the stomach or intestines
• abdominal pain
• inflammation of the mouth or lips, sore throat
• altered liver function
• itchy skin
• skin redness
• rash
• muscle cramps
• urinary tract infection
• limb pain
• swelling affecting eyes and other body parts
• chills
• redness and pain at the injection site
• general feeling of illness
• weight loss
• weight gain

Uncommon adverse reactions (may affect up to 1 in 100 people)

• hepatitis
• severe allergic reaction (anaphylactic reaction), symptoms of which may include: difficulty breathing, chest pain or tightness, dizziness or fainting, severe skin itching or blisters, swelling of face, lips, tongue, throat, which may cause swallowing difficulties, collapse
• movement disorders, paralysis, muscle twitching
• dizziness
• hearing loss, deafness
• lung disorders making breathing difficult. These include: difficulty breathing, shortness of breath, shortness of breath at rest, shallow breathing or respiratory arrest, wheezing
• blood clots in the lungs
• jaundice (yellowing of skin and eyes)
• stye (hordeolum), redness and swelling of the eyelid

Rare adverse reactions (may affect up to 1 in 1000 people)

• blood clot in small blood vessels (thrombotic microangiopathy);
• severe nerve inflammation, which may cause paralysis and breathing difficulties (Guillain-Barré syndrome).

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform a doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181 C, 02-222 Warsaw, Tel.: +48 22 49 21 301,
Fax: +48 22 49 21 309, Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps provide more information on the safety of the 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 stated on the label of the vial and on the outer packaging after "Expiry date (EXP)". The expiry date refers to the last day of the stated month.
Store in a refrigerator (2°C - 8°C).
Keep the vial in the outer packaging to protect from light.
The solution should be used immediately after first opening/dilution. If the diluted solution is not administered immediately after preparation, the user is responsible for the storage conditions and duration prior to use. However, the (diluted) solution remains stable for 28 days when stored in the original vial and/or in a polypropylene syringe, if kept refrigerated (2°C - 8°C) or at temperatures up to 25°C, protected from light, and for 24 hours at temperatures up to 25°C under normal indoor lighting conditions.
With regard to solution stability in a syringe, the same storage conditions apply to both diluted and undiluted solutions.
Bortezomib EVER Pharma is intended for single use only. Any unused medicinal product or waste material should be disposed of in accordance with local regulations.

6. Contents of the pack and other information

What Bortezomib EVER Pharma contains

• The active substance is bortezomib. 1 mL of solution contains 2.5 mg of bortezomib (as mannitol boronic ester). Each vial containing 1 mL of injection solution contains 2.5 mg of bortezomib (as mannitol boronic ester). Each vial containing 1.4 mL of injection solution contains 3.5 mg of bortezomib (as mannitol boronic ester). Each vial contains an additional overfill of 0.2 mL.
• The other components are: mannitol (E 421), sodium chloride, sodium hydroxide (for pH adjustment), hydrochloric acid (for pH adjustment), and water for injections.

1 mL vial:
Subcutaneous injection solution: The product is ready for use at a concentration of 2.5 mg/mL.
Intravenous administration: Add 1.8 mL of 0.9% sodium chloride solution to achieve a final concentration of 1 mg/mL.

1.4 mL vial:
Subcutaneous injection solution: The product is ready for use at a concentration of 2.5 mg/mL.
Intravenous administration: Add 2.4 mL of 0.9% sodium chloride solution to achieve a final concentration of 1 mg/mL.

What Bortezomib EVER Pharma looks like and contents of the pack
Bortezomib EVER Pharma is a clear, colourless to slightly yellow solution.
Bortezomib EVER Pharma is supplied in a vial made of colourless type 1 glass, closed with a rubber stopper and an aluminium seal with a plastic flip-off cap, packed in a cardboard box.

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
EVER Valinject GmbH
Oberburgau 3
4866 Unterach am Attersee
Austria

Manufacturer
EVER Pharma Jena GmbH
Otto-Schott-Strasse 15
07745 Jena
Germany
EVER Pharma Jena GmbH
Brüsseler Str. 18
07747 Jena
Germany

For further information, contact the local representative of the marketing authorisation holder:
EVER Pharma Poland Sp. z o.o.
e-mail: [email protected]

This medicinal product is authorised in the Member States of the European Economic Area under the following names:
Belgium Bortezomib EVER Pharma 2.5 mg/ml oplossing voor injectie/solution injectable/Injektionslösung
Bulgaria Бортезомиб EVER Pharma 2.5 mg/ml инжекционен разтвор
Croatia Bortezomib EVER Pharma 2.5 mg/ml otopina za injekciju
Denmark Bortezomib EVER Pharma 2.5 mg/ml
Finland Bortezomib EVER Pharma 2.5 mg/ml injektioneste, liuos/injektionsvätska, lösning
France BORTEZOMIB EVER PHARMA 2.5 mg/mL, solution injectable
Spain Bortezomib EVER Pharma 2.5 mg/ml solución inyectable
Netherlands Bortezomib EVER Pharma 2.5 mg/ml oplossing voor injectie
Ireland Bortezomib 2.5 mg/ml
Norway Bortezomib EVER Pharma 2.5 mg/ml injeksjonsvæske, oppløsning
Poland Bortezomib EVER Pharma
Portugal Bortezomib EVER Pharma 2.5 mg/ml solução injetável
Czech Republic Bortezomib EVER Pharma
Romania Bortezomib EVER Pharma 2.5 mg/ml soluție injectabilă
Slovakia Bortezomib EVER Pharma 2.5 mg/ml injekčný roztok
Slovenia Bortezomib EVER Pharma 2.5 mg/ml raztopina za injiciranje
Sweden Bortezomib EVER Pharma 2.5 mg/ml injektionsvätska, lösning
Hungary Bortezomib EVER Pharma 2.5 mg/ml oldatos injekció
Italy Bortezomib EVER Pharma 2.5 mg/ml soluzione iniettabile

Information intended exclusively for medical professionals:

1. PREPARATION OF INJECTION SOLUTION FOR INTRAVENOUS ADMINISTRATION

Warning: Bortezomib EVER Pharma is a cytotoxic medicinal product. Therefore, caution must be exercised when handling Bortezomib EVER Pharma and during its preparation for use. To avoid skin contact, the use of gloves and protective clothing is recommended. Pregnant healthcare personnel should not handle this medicinal product.
ASEPTIC TECHNIQUE MUST BE STRICTLY FOLLOWED WHEN HANDLING BORTEZOMIB EVER PHARMA, AS IT DOES NOT CONTAIN ANY PRESERVATIVES.

1.1. For the 1 mL vial: add 1.8 mL of sterile 9 mg/mL (0.9%) sodium chloride injection solution to the vial containing Bortezomib EVER Pharma medicinal product.
OR
For the 1.4 mL vial: add 2.4 mL of sterile 9 mg/mL (0.9%) sodium chloride injection solution to the vial containing Bortezomib EVER Pharma medicinal product.
The resulting solution will have a concentration of 1 mg/mL. After reconstitution, the solution will be clear and colourless to slightly yellow, with a pH between 4 and 7. Checking the pH of the solution is not required.

1.2. Before administration, visually inspect the solution for particulate matter and discoloration. If discoloration or particulate matter is observed, the solution must be discarded. Ensure that the correct dose is administered intravenously (1 mg/mL).

1.3. The solution contains no preservatives and should be used immediately after preparation. However, chemical and physical stability of the reconstituted solution has been demonstrated for:

• 28 days when stored refrigerated (2°C - 8°C)
• 28 days when stored at temperatures up to 25°C and protected from light
• 24 hours when stored at temperatures up to 25°C under normal indoor lighting conditions
  in the original vial and/or in a polypropylene syringe. If the reconstituted solution is not administered immediately after preparation, responsibility for the storage time and conditions prior to use lies with the user.

2. ADMINISTRATION

• After dilution, withdraw the appropriate volume of the diluted solution according to the dose calculated based on the patient's body surface area.
• Before administration, confirm the dose and concentration of the drug in the syringe (check that the syringe is labelled for intravenous use).
• Inject the drug solution as an intravenous bolus over 3 to 5 seconds through an indwelling central or peripheral intravenous catheter.
• The intravenous catheter used for drug administration should be flushed with a small amount of sterile 9 mg/mL (0.9%) sodium chloride injection solution.

BORTEZOMIB EVER PHARMA MUST BE ADMINISTERED ONLY INTRAVENOUSLY OR SUBCUTANEOUSLY. DO NOT ADMINISTER BY OTHER ROUTES. INTRATHECAL ADMINISTRATION HAS RESULTED IN DEATH.

3. DISPOSAL OF THE MEDICINAL PRODUCT

The vial is intended for single use only, and any unused portion of the solution must be discarded.
Any unused medicinal product or waste material must be disposed of in accordance with local regulations for cytotoxic drugs.

Information intended exclusively for medical professionals:

1. PREPARATION OF THE SOLUTION FOR SUBCUTANEOUS INJECTION

Warning: Bortezomib EVER Pharma is a cytotoxic medicinal product. When handling
and preparing the product for use, caution must be exercised. To protect against skin contact
with the drug, the use of gloves and other protective clothing is recommended. Pregnant women
should not handle this medicinal product.
SINCE THE BORTEZOMIB EVER PHARMA MEDICINAL PRODUCT DOES NOT CONTAIN
PRESERVATIVES, ASEPTIC TECHNIQUES MUST BE STRICTLY FOLLOWED
DURING HANDLING OF THE PRODUCT.
1.1. The Bortezomib EVER Pharma medicinal product is ready for administration.
The solution concentration will be 2.5 mg/mL. The solution is clear and colorless to slightly yellow, with a pH of 4 to 7. Testing the pH of the solution is not required.
1.2. Before administration, visually inspect the solution for the presence of particulate matter or discoloration. If discoloration or particulate matter is observed, the solution must be discarded. Ensure that the correct dose is administered subcutaneously (2.5 mg/mL).
1.3. The solution does not contain preservatives and should be used immediately after preparation. However, chemical and physical stability of the solution has been demonstrated for:

• 28 days, when stored refrigerated (2°C – 8°C)
• 28 days, when stored at temperatures up to 25°C and protected from light
• 24 hours, when stored at temperatures up to 25°C under normal indoor lighting conditions.
  In the original vial and (or) polypropylene syringe. If the solution is not administered immediately after preparation, the responsibility for storage time and conditions prior to use lies with the user.
  Protection of the medicinal product from light is not required during preparation for administration or during administration.

2. ADMINISTRATION

• Withdraw the appropriate volume of solution according to the dose calculated based on the patient's body surface area.
• Before administration, confirm the dose and drug concentration in the syringe (check whether the syringe is labeled for subcutaneous administration).
• Inject the solution subcutaneously at an angle of 45–90°.
• The solution is administered subcutaneously into the thigh (right or left) or abdomen (right or left side).
• Rotate injection sites for consecutive injections.
• In case of local reaction after subcutaneous administration of Bortezomib EVER Pharma, it is recommended to administer subcutaneously a more diluted solution of Bortezomib EVER Pharma (dilution to 1 mg/mL instead of 2.5 mg/mL) or switch to intravenous administration.

BORTEZOMIB EVER PHARMA MUST BE ADMINISTERED EXCLUSIVELY BY INTRAVENOUS OR
SUBCUTANEOUS ROUTE. Do not administer by any other route. Intrathecal administration has resulted in death.

3. DISPOSAL OF THE MEDICINE

The vial is intended for single use only, and any remaining solution must be discarded.
Any unused product or waste material must be disposed of in accordance with local regulations regarding cytotoxic medicines.