Bortezomib EVER Pharma 2.5 mg/ml – patient leaflet, side effects, dosage

1. What Bortezomib EVER Pharma is 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 function and growth. By interfering with their function, bortezomib can kill cancer cells.

Bortezomib EVER Pharma is used for the treatment of multiple myeloma (a cancer of the bone marrow) in patients older than 18 years:

• alone or together with the medicines pegylated liposomal

  doxorubicin or dexamethasone, for patients whose disease is worsening (progressive) after receiving at least one prior treatment and for whom blood stem cell transplantation was not successful or is unsuitable

• in combination with the medicines melphalan and prednisone,

  for patients whose disease has not been previously treated and are unsuitable for high-dose chemotherapy with blood stem cell transplantation

• in combination with the medicines dexamethasone or

  dexamethasone together with thalidomide, for patients whose disease has not been previously treated and before receiving high-dose chemotherapy with blood stem cell transplantation (induction treatment)

Bortezomib EVER Pharma is used for the treatment of mantle cell lymphoma (a type of cancer affecting the lymph nodes) in patients 18 years or older in combination with the medicines rituximab, cyclophosphamide, doxorubicin and prednisone, for patients whose disease has not been previously treated and for whom blood stem cell transplantation is unsuitable.

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

DO NOT use Bortezomib EVER Pharma

• if you are allergic to bortezomib, boron or to any of the other

  ingredients of this medicine (listed in section 6)

• if you have certain severe lung or heart problems Warnings and precautions

Talk to your doctor if you have any of the following:

• low numbers of red or white blood cells
• bleeding problems and/or low number of platelets in your blood
• diarrhoea, constipation, nausea or vomiting
• fainting, dizziness or light-headedness in the past
• kidney problems
• moderate to severe liver problems

• numbness, tingling, or pain in the hands or feet (neuropathy) in the

  past

• heart or blood pressure problems
• shortness of breath or cough
• seizures

• shingles (localised, including around the eyes or spread across the

  body)

• symptoms of tumour lysis syndrome such as muscle cramping,

  muscle weakness, confusion, visual loss or disturbances and shortness of breath

• memory loss, trouble thinking, difficulty with walking or loss of

  vision. These may be signs of a serious brain infection and your doctor may suggest further testing and follow-up

You will have to take regular blood tests before and during your treatment with Bortezomib EVER Pharma, to check your blood cell counts regularly.

If you have mantle cell lymphoma and are given the medicine rituximab with Bortezomib EVER Pharma you should tell your doctor:

• if you think you have hepatitis infection now or have had it in the

You must read the package leaflets of all medicines to be taken in combination with Bortezomib EVER Pharma for information related to these medicines before starting treatment with Bortezomib EVER Pharma. When thalidomide is used, particular attention to pregnancy testing and prevention requirements is needed (see Pregnancy and breast-feeding 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 will affect them. Other medicines and Bortezomib EVER Pharma

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

In particular, tell your doctor if you are using medicines 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 for depression or

  other conditions

• oral antidiabetics

Pregnancy and breast-feeding

You should not use Bortezomib EVER Pharma if you are pregnant, unless clearly necessary.

Both men and women receiving Bortezomib EVER Pharma must use effective contraception during and for up to 3 months after treatment. If, despite these measures, pregnancy occurs, tell your doctor immediately.

You should not breast-feed while using Bortezomib EVER Pharma. Discuss with your doctor when it is safe to restart breast-feeding after finishing your treatment.

Thalidomide causes birth defects and foetal death. When Bortezomib EVER Pharma is given in combination with thalidomide you must follow the pregnancy prevention programme for thalidomide (see package leaflet for thalidomide).

Driving and using machines

Bortezomib EVER Pharma might cause tiredness, dizziness, fainting, or blurred vision. Do not drive or operate tools or machines if you experience such side effects; even if you do not, you should still be cautious.

Bortezomib EVER Pharma contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially “sodium free”.

3. How to use Bortezomib EVER Pharma

Your doctor will work out your dose of Bortezomib EVER Pharma according to your height and weight (body surface area). The usual starting dose of Bortezomib EVER Pharma is 1.3 mg/m² body surface area twice a week. Your doctor may change the dose and total number of treatment cycles, depending on your response to the treatment, the occurrence of certain side effects, and your underlying conditions (e.g. liver problems).

Progressive multiple myeloma

When Bortezomib EVER Pharma is given alone, you will receive 4 doses of Bortezomib EVER Pharma 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) corresponds to one treatment cycle. You might receive up to 8 cycles (24 weeks).

You may also be given Bortezomib EVER Pharma together with the medicines pegylated liposomal doxorubicin or dexamethasone. When Bortezomib EVER Pharma is given together with pegylated liposomal doxorubicin, you will receive Bortezomib EVER Pharma intravenously or subcutaneously as a 21-day treatment cycle and pegylated liposomal doxorubicin 30 mg/m² is given on day 4 of the Bortezomib EVER Pharma 21-day treatment cycle as an intravenous infusion after the Bortezomib EVER Pharma injection. You might receive up to 8 cycles (24 weeks).

When Bortezomib EVER Pharma is given together with dexamethasone, you will receive Bortezomib EVER Pharma intravenously or subcutaneously as a 21-day treatment cycle and dexamethasone 20 mg is given orally on days 1, 2, 4, 5, 8, 9, 11, and 12, of the Bortezomib EVER Pharma 21-day treatment cycle. You might receive up to 8 cycles (24 weeks).

Previously untreated multiple myeloma

If you have not been treated before for multiple myeloma, and you are not suitable for blood stem cell transplantation you will receive Bortezomib EVER Pharma together with two other medicines: melphalan and prednisone.

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

• In cycles 1 to 4, Bortezomib EVER Pharma is administered twice

  weekly on days 1, 4, 8, 11, 22, 25, 29 and 32

• In cycles 5 to 9, Bortezomib EVER Pharma is administered once

  weekly on days 1, 8, 22 and 29

Melphalan (9 mg/m²) and prednisone (60 mg/m²) are both given orally on days 1, 2, 3 and 4 of the first week of each cycle. If you have not been treated before for multiple myeloma, and you are suitable for blood stem cell transplantation you will receive Bortezomib EVER Pharma intravenously or subcutaneously together with the medicines dexamethasone, or dexamethasone and thalidomide, as induction treatment.

When Bortezomib EVER Pharma is given together with dexamethasone, you will receive Bortezomib EVER Pharma intravenously or subcutaneously as a 21-day treatment cycle and dexamethasone 40 mg is given orally on days 1, 2, 3, 4, 8, 9, 10 and 11 of the Bortezomib EVER Pharma 21-day treatment cycle. You will receive 4 cycles (12 weeks).

When Bortezomib EVER Pharma is given together with thalidomide and dexamethasone, the duration of a treatment cycle is 28 days (4 weeks).

Dexamethasone 40 mg is given orally on days 1, 2, 3, 4, 8, 9, 10 and 11 of the Bortezomib EVER Pharma 28- day treatment cycle and thalidomide is given orally daily at 50 mg up to day 14 of the first cycle, and if tolerated the thalidomide dose is increased to 100 mg on days 15-28 and may be further increased to 200 mg daily from the second cycle onwards. You might receive up to 6 cycles (24 weeks). Previously untreated mantle cell lymphoma

If you have not been treated before for mantle cell lymphoma you will receive Bortezomib EVER Pharma intravenously or subcutaneously together with the medicines rituximab, cyclophosphamide, doxorubicin and prednisone.

Bortezomib EVER Pharma is given intravenously or subcutaneously on days 1, 4, 8 and 11, followed by a ‘rest period’ without treatment. The duration of a treatment cycle is 21 days (3 weeks). You might receive up to 8 cycles (24 weeks).

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

• Rituximab at 375 mg/m², cyclophosphamide at 750 mg/m² and

  doxorubicin at 50 mg/m².

• Prednisone is given orally at 100 mg/m² on days 1, 2, 3, 4 and 5 of

  the Bortezomib EVER Pharma treatment cycle.

How Bortezomib EVER Pharma is given

This medicine is for subcutaneous or - after dilution - intravenous use. Bortezomib EVER Pharma will be administered by a health care professional experienced in the use of cytotoxic medicines. The solution is either injected into a vein or under the skin. Injection into a vein is rapid, taking 3 to 5 seconds. Injection under the skin is in either the thighs or the abdomen.

If you are given too much Bortezomib EVER Pharma

As this medicine is being given by your doctor or nurse, it is unlikely that you will be given too much. In the unlikely event of an overdose, your doctor will monitor you for side effects.

4. Possible side effects

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

• muscle cramping, muscle weakness
• confusion, visual loss or disturbances, blindness, seizures, headaches
• shortness of breath, swelling of your feet or changes in your heart beat, high blood pressure, tiredness, fainting
• coughing and breathing difficulties or tightness in the chest

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

• platelets, which may make you more prone to bruising, or to bleeding without obvious injury (e.g. bleeding from your bowels, stomach, mouth and gums or bleeding in the brain or bleeding from the liver)
• red blood cells, which can cause anaemia, with symptoms such as tiredness and paleness
• white blood cells may make you more prone to infections or flu-like symptoms

If you are given Bortezomib EVER Pharma for the treatment of multiple myeloma the side effects you may get 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

• reduction in the number of red blood cells and or white blood cells

  (see above)

• fever
• feeling sick (nausea) or vomiting, loss of appetite
• constipation with or without bloating (can be severe)
• diarrhoea: if this happens, it is important that you drink more water than usual. Your doctor may give you another medicine 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 fall of blood pressure on standing which may lead to fainting
• high blood pressure
• reduced kidney function
• headache
• general ill feeling, pain, vertigo, light-headedness, a feeling of weakness or loss of consciousness
• shivering
• infections, including pneumonia, respiratory infections, bronchitis, fungal infections, coughing with phlegm, flu-like illness
• shingles (localised, including around the eyes or spread across the body)
• chest pains or shortness of breath with exercise
• different types of rash
• itching of the skin, lumps on the skin or dry skin
• facial blushing or tiny broken capillaries
• redness of the skin
• dehydration
• heartburn, bloating, belching, wind, stomach pain, bleeding from your bowels or stomach
• alteration of liver functioning
• sore mouth or lips, dry mouth, mouth ulcers or throat pain
• weight loss, loss of taste
• muscle cramps, muscle spasms, muscle weakness, pain in your limbs
• blurred vision
• infection of the outermost layer of the eye and the inner surface of the eyelids (conjunctivitis)
• nose bleeds
• difficulty or problems in sleeping, sweating, anxiety, mood swings, depressed mood, restlessness or agitation, changes in your mental status, disorientation
• swelling of body, including 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 reduced heart rate
• kidney failure
• inflammation of a vein, blood clots in your veins and lungs
• problems with blood clotting
• insufficient circulation
• inflammation of the lining around your heart or fluid around your heart
• infections, including urinary tract infections, the flu, herpes virus infections, ear infection and cellulitis
• bloody stools, or bleeding from mucosal membranes, e.g. mouth, vagina
• cerebrovascular disorders
• paralysis, seizures, falling, movement disorders, abnormal, change in, or reduced sensation (feeling, hearing, tasting, smelling), attention disturbance, trembling, twitching
• arthritis, including inflammation of the joints in the fingers, toes, and the jaw
• disorders that affect your lungs, preventing your body from getting enough oxygen. Some of these include difficulty breathing, shortness of breath, shortness of breath without exercise, breathing that becomes shallow, difficult or stops, wheezing
• hiccups, speech disorders
• increased or decreased urine production (due to kidney damage), painful passing of urine or blood/proteins 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
• hormone abnormality which may affect salt and water absorption
• overactive thyroid gland
• inability to produce enough insulin or resistance to normal levels of insulin

The following information is intended for healthcare professionals only:

1. 1. PREPARATION FOR INTRAVENOUS INJECTION

Note: Bortezomib EVER Pharma is a cytotoxic agent. Therefore, caution should be used during handling and preparation. Use of gloves and other protective clothing to prevent skin contact is recommended. Pregnant personnel should not handle this medicine.

ASEPTIC TECHNIQUE MUST BE STRICTLY OBSERVED THROUGHOUT HANDLING OF Bortezomib EVER Pharma SINCE NO PRESERVATIVE IS PRESENT.

1.1 Preparation of the 1 ml vial: add 1.8 ml of sterile sodium

chloride 9 mg/ml (0.9 %) solution for injection to the vial containing Bortezomib EVER Pharma.

OR

Preparation of the 1.4 ml vial: add 2.4 ml of sterile sodium

chloride 9 mg/ml (0.9 %) solution for injection to the vial containing Bortezomib EVER Pharma.

The concentration of the resulting solution will be 1 mg/ml. The

solution will be clear and colourless to light yellow, with a final pH of 4 to 7. You do not need to check the pH of the solution.

1.2 Before administration, visually inspect the solution for particulate

matter and discolouration. If any discolouration or particulate matter is observed, the solution should be discarded. Be sure that the correct dose is being given for the intravenous route of administration (1 mg/ml).

1.3 The solution is preservative free and should be used immediately

after preparation. However, the chemical and physical in-use stability of the diluted solution has been demonstrated for:

• 28 days at 2 °C – 8 °C and protected from light
• 28 days at 25 °C and protected from light

• 24 hours, when stored at 25 °C and normal indoor lighting

  conditions in the original vial and/or a polypropylene syringe. If the diluted solution is not used immediately, in-use storage times and conditions prior to use are the responsibility of the user.

• ADMINISTRATION

• Once diluted, withdraw the appropriate amount of the diluted

  solution according to calculated dose based upon the patient´s Body Surface Area.

• Confirm the dose and concentration in the syringe prior to use

  (check that the syringe is marked as intravenous administration).

• Inject the solution as a 3-5 second bolus intravenous injection

  through a peripheral or central intravenous catheter into a vein.

  • Flush the peripheral or intravenous catheter with sterile, 9 mg/ml

    (0.9 %) sodium chloride solution.

Bortezomib EVER Pharma 2.5 mg/ml Solution for Injection IS FOR SUBCUTANEOUS OR INTRAVENOUS USE. Do not give by other rou-tes. Intrathecal administration has resulted in death.

1. 3. DISPOSAL

A vial is for single use only and the remaining solution must be discarded. Any unused medicinal product or waste material should be disposed of in accordance with local requirements for cytotoxic agents.

• irritated or inflamed eyes, excessively wet eyes, painful eyes, dry

  eyes, eye infections, lump in the eyelid (chalazion), red and swollen eyelids, discharge from the eyes, abnormal vision, bleeding of the eye

• swelling of your lymph glands
• joint or muscle stiffness, sense of heaviness, pain in your groin
• hair loss and abnormal hair texture
• allergic reactions
• redness or pain at the injection site
• mouth pain

• infections or inflammation of the mouth, mouth ulcers, oesophagus,

  stomach and intestines, sometimes associated with pain or bleeding, poor movement of the intestines (including blockage), abdominal or oesophageal discomfort, difficulty swallowing, vomiting of blood

• skin infections
• bacterial and viral infections
• tooth infection
• inflammation of the pancreas, obstruction of the bile duct
• genital pain, problem having an erection
• weight increase
• thirst
• hepatitis
• injection site or injection device related disorders

• skin reactions and disorders (which may be severe and life

  threatening), skin ulcers

• bruises, falls and injuries

• inflammation or haemorrhage of the blood vessels that can appear

  as small red or purple dots (usually on the legs) to large bruise-like patches under the skin or tissue

• benign cysts

• a severe reversible brain condition which includes seizures, high

  blood pressure, headaches, tiredness, confusion, blindness or other vision problems

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

• heart problems including heart attack, angina

• serious nerve inflammation, which may cause paralysis and

  difficulty breathing (Guillain-Barré syndrome)

• flushing
• discolouration of the veins
• inflammation of the spinal nerve
• problems with your ears, bleeding from your ears
• underactivity of your thyroid gland

• Budd-Chiari syndrome (the clinical symptoms caused by blockage

  of the hepatic veins)

• changes in or abnormal bowel function
• bleeding in the brain
• yellow discolouration of eyes and skin (jaundice)

• serious allergic reaction (anaphylactic shock) signs of which may

  include difficulty breathing, chest pain or chest tightness, and/or feeling dizzy/faint, severe itching of the skin or raised lumps on the skin, swelling of the face, lips, tongue and /or throat, which may cause difficulty in swallowing, collapse

• breast disorders
• vaginal tears
• genital swelling
• inability to tolerate alcohol consumption
• wasting, or loss of body mass
• increased appetite
• fistula
• joint effusion
• cysts in the lining of joints (synovial cysts)
• fracture
• breakdown of muscle fibres leading to other complications
• swelling of the liver, bleeding from the liver
• kidney cancer
• psoriasis like skin condition
• skin cancer
• paleness of the skin

• increase of platelets or plasma cells (a type of white cell) in the

  blood

• blood clot in small blood vessels (thrombotic microangiopathy)
• abnormal reaction to blood transfusions
• partial or total loss of vision
• decreased sex drive
• drooling
• bulging eyes
• sensitivity to light
• rapid breathing
• rectal pain
• gallstones
• hernia
• injuries
• brittle or weak nails
• abnormal protein deposits in your vital organs
• coma
• intestinal ulcers
• multi-organ failure
• death

If you are given Bortezomib EVER Pharma together with other medicines for the treatment of mantle cell lymphoma the side effects you may get 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
• constipation
• muscle pain, bone pain
• hair loss and abnormal hair texture
• tiredness, feeling weak
• fever

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

• shingles (localised, including around the eyes or spread across the body)
• herpes virus infections
• bacterial and viral infections

• respiratory infections, bronchitis, coughing with phlegm, 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 in sleeping
  • loss of consciousness
  • altered level of consciousness, confusion
  • feeling dizzy
  • increased heartbeat, high blood pressure, sweating
  • abnormal vision, blurred vision
  • heart failure, heart attack, chest pain, chest discomfort, increased or reduced heart rate
  • high or low blood pressure
  • sudden fall of blood pressure upon standing which may lead to fainting
  • shortness of breath with exercise
  • cough
  • hiccups
  • ringing in the ears, ear discomfort
  • bleeding from your bowels or stomach
  • heartburn
  • stomach pain, bloating
  • difficulty swallowing
  • infection or inflammation of the stomach and intestines
  • stomach pain
  • sore mouth or lips, throat pain
  • alteration of liver function
  • itching of skin
  • skin redness
  • rash
  • muscle spasms
  • urinary tract infection
  • pain in limbs
  • swelling of body, including the eyes and other parts of the body
  • shivering
  • redness and pain at injection site
  • general ill feeling
  • weight loss
  • weight increase

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 chest tightness, and/or feeling dizzy/faint, severe itching of the skin or raised lumps on the skin, swelling of the face, lips, tongue and /or throat, which may cause difficulty in swallowing, collapse
• movement disorders, paralysis, twitching
• vertigo
• hearing loss, deafness
• disorders that affect your lungs, preventing your body from getting enough oxygen. Some of these include difficulty breathing, shortness of breath, shortness of breath without exercise, breathing that becomes shallow, difficult or stops, wheezing
• blood clots in your lungs
• yellow discoloration of the eyes and skin (jaundice)
• lump in 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)
• serious nerve inflammation, which may cause paralysis and difficulty breathing (Guillain-Barré syndrome)

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme (Website: www.mhra.gov.uk/yellowcard).

By reporting side effects you 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 stated on the vial and the carton 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 carton in order to protect from light.

The solution should be used immediately after first opening/dilution. If the (diluted) solution is not used immediately, in-use storage times and conditions prior to use are the responsibility of the user. However, when stored in the original vial and/or a polypropylene syringe the (diluted) solution is stable for 28 days at 2 °C – 8 °C and at up to 25 °C protected from light, and for 24 hours at up to 25 °C under normal indoor lighting conditions.

With regard to stability within the syringe, the same storage time applies to the diluted solution and the undiluted solution. Bortezomib EVER Pharma is for single use only. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

6. Contents of the pack and other information

What Bortezomib EVER Pharma contains

The active substance is bortezomib.

1 ml solution for injection contains 2.5 mg bortezomib (as a mannitol boronic ester).

Each vial with 1 ml solution for injection contains 2.5 mg bortezomib (as a mannitol boronic ester).

Each vial with 1.4 ml solution for injection contains 3.5 mg bortezomib (as a mannitol boronic ester).

Each vial contains an additional overfill 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 to use with its concentration of 2.5 mg/ml.

Intravenous use: Add 1.8 ml 0.9 % sodium chloride solution to make 1 mg/ml final concentration.

1.4 ml vial:

Subcutaneous use: the product is ready to use with its concentration of 2.5 mg/ml.

Intravenous use: Add 2.4 ml 0.9 % sodium chloride solution to make 1 mg/ml final concentration.

What Bortezomib EVER Pharma looks like and contents of the pack

Bortezomib EVER Pharma solution for injection is a clear and colourless to light yellow solution.

Bortezomib EVER Pharma is provided in a colourless glass vial with rubber stopper and an aluminium cap with plastic flip-off. 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

Brüsseler Str 18

07747 Jena

Germany

This leaflet was last revised in December 2025.

The following information is intended for healthcare professionals only:

1. 1. PREPARATION FOR SUBCUTANEOUS INJECTION

Note: Bortezomib EVER Pharma is a cytotoxic agent. Therefore, caution should be used during handling and preparation. Use of gloves and other protective clothing to prevent skin contact is recommended. Pregnant personnel should not handle this medicinal product. ASEPTIC TECHNIQUE MUST BE STRICTLY OBSERVED THROUGHOUT HANDLING OF Bortezomib EVER Pharma SINCE NO PRESERVATIVE IS PRESENT.

1.1 Bortezomib EVER Pharma is ready to use.

The concentration of the solution is 2.5 mg/ml.

The solution is clear and colourless to light yellow, with a pH of 4.0

to 5.5. You do not need to check the pH of the solution. 1.2 Before administration, visually inspect the solution for particulate

matter and discolouration. If any discolouration or particulate matter is observed, the solution should be discarded. Be sure that the correct dose is being given for the subcutaneous route of administration (2.5 mg/ml).

1.3 The solution is preservative free and should be used immediately after

withdrawal of the appropriate amount of solution. However, the chemical

and physical in-use stability of the solution has been demonstrated for:

• 28 days at 2 °C – 8 °C and protected from light
• 28 days at 25 °C and protected from light
• 24 hours, when stored at 25 °C and normal indoor lighting conditions in the original vial and/or a polypropylene syringe. If the solution is not used immediately, in-use storage times and conditions prior to use are the responsibility of the user. During preparation for administration and during administration itself it is not necessary to protect the medicinal product from light.
• ADMINISTRATION
• Withdraw the appropriate amount of the solution according to calculated dose based upon the patient´s Body Surface Area.

• Confirm the dose and concentration in the syringe prior to use

  (check that the syringe is marked as subcutaneous administration).

• Inject the solution subcutaneously, under a 45-90° angle.

• The solution is administered subcutaneously through the thighs

  (right or left) or abdomen (right or left).

• Injection sites should be rotated for successive injections.

• If local injection site reactions occur following Bortezomib EVER

  Pharma injection subcutaneously, either a less concentrated Bortezomib EVER Pharma solution (1 mg/ml instead of 2.5 mg/ml)

  may be administered subcutaneously or a switch to intravenous injection is recommended.

  Bortezomib EVER Pharma 2.5 mg/ml Solution for Injection IS FOR SUBCUTANEOUS OR INTRAVENOUS USE. Do not give by other routes. Intrathecal administration has resulted in death.

  1. 3. DISPOSAL

A vial is for single use only and the remaining solution must be discarded. Any unused medicinal product or waste material should be disposed of in accordance with local requirements for cytotoxic agents.