Bortezomib Ever

Italy
Brand name Bortezomib Ever
Form solution for injection
Active substance / Dosage
BORTEZOMIB
Prescription type Restricted prescription – hospital or equivalent facility use only
ATC code
L01XG01
Registration number 049717
Manufacturer EVER VALINJECT GMBH
Bortezomib Ever solution for injection

Table of Contents

Package leaflet: Information for the user

Bortezomib EVER Pharma 2.5 mg/ml injection solution

bortezomib
Read this leaflet carefully before using this medicine because it contains important information for you.

  • Keep this leaflet. You may need to read it again.
  • If you have any questions, ask your doctor or pharmacist.
  • If you experience any side effects, including those not listed in this leaflet, please inform 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 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 the active substance bortezomib, a so-called "proteasome inhibitor". Proteasomes play an important role in controlling cell functions and cell growth. By interfering with their function, bortezomib can kill tumour cells.
Bortezomib EVER Pharma is used to treat multiple myeloma (a type of malignant neoplasm of the bone marrow) in patients aged over 18 years:

  • alone or in combination with pegylated liposomal doxorubicin or dexamethasone, for patients with progressive disease after having received at least one prior therapy or in whom blood stem cell transplantation has failed or is not feasible
  • in combination with melphalan and prednisone, for previously untreated patients who are not eligible for high-dose chemotherapy with blood stem cell transplantation
  • in combination with dexamethasone or dexamethasone plus thalidomide, for previously untreated patients prior to receiving high-dose chemotherapy with blood stem cell transplantation (induction treatment)

Bortezomib EVER Pharma is used to treat mantle cell lymphoma (a type of malignant neoplasm affecting the lymph nodes) in patients aged 18 years or older. In this case, Bortezomib EVER Pharma is used in combination with the medicines rituximab, cyclophosphamide, doxorubicin and prednisone, for previously untreated patients 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
Contact your doctor if you have:

  • low number of red or white blood cells
  • bleeding problems and/or low number of platelets in the blood
  • diarrhoea, constipation, nausea or vomiting
  • previous episodes of fainting, dizziness or lightheadedness
  • kidney problems
  • moderate to severe liver problems
  • previous history of numbness, tingling or pain in the hands or feet (neuropathy)
  • heart disorder or blood pressure problems
  • shortness of breath or cough
  • seizures
  • shingles (including localized around the eyes or spreading to other parts of the body)
  • symptoms of tumour lysis syndrome such as 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 monitoring. You will need regular blood tests before and during treatment with Bortezomib EVER Pharma to monitor your blood cell counts consistently.

If you have mantle cell lymphoma and are receiving rituximab together with Bortezomib EVER Pharma,
you must inform your doctor:

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

Please read the package leaflets of all the 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 administered together with the medicine thalidomide, pay
particular attention to the instructions regarding pregnancy testing and the pregnancy prevention programme (see “Pregnancy and breastfeeding” in this section).

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

Other medicines and Bortezomib EVER Pharma
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
In particular, inform your doctor if you are taking medicines containing any of the following active substances:

  • ketoconazole, used to treat fungal infections
  • ritonavir, used to treat HIV infection
  • rifampicin, an antibiotic used to treat bacterial infections
  • carbamazepine, phenytoin or phenobarbital, used to treat epilepsy
  • St John’s wort (Hypericum perforatum), used to treat depression or other conditions
  • oral antidiabetic medicines.

Pregnancy and breastfeeding
You must not use Bortezomib EVER Pharma during pregnancy unless absolutely necessary.
Men and women undergoing treatment with Bortezomib EVER Pharma must use effective contraceptive methods during treatment and for up to 3 months after treatment ends. If pregnancy occurs despite these precautions, inform your doctor immediately.
You must not breast-feed during treatment with Bortezomib EVER Pharma. Discuss with your doctor the most appropriate time to resume breast-feeding after treatment ends.
The medicine thalidomide causes birth defects and fetal death. When Bortezomib EVER Pharma is
administered together with thalidomide, you must follow thalidomide’s pregnancy prevention programme (see the package leaflet of thalidomide).

Driving and using machines
Bortezomib EVER Pharma may cause fatigue, dizziness, fainting or blurred vision. Do not drive or operate machinery if you experience any of these symptoms. Exercise particular caution 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

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

Relapsed multiple myeloma
When Bortezomib 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) constitutes one treatment cycle. You may receive up to 8 cycles (24 weeks).
You may also receive Bortezomib EVER Pharma in combination with pegylated liposomal doxorubicin or dexamethasone.

When Bortezomib EVER Pharma is administered in combination with pegylated liposomal doxorubicin, you will receive a 21-day treatment cycle with Bortezomib EVER Pharma administered intravenously or subcutaneously, and 30 mg/m² of pegylated liposomal 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 in combination with dexamethasone, you will receive a 21-day treatment cycle with Bortezomib EVER Pharma administered intravenously or subcutaneously, and oral dexamethasone at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of the 21-day 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 not eligible for stem cell transplantation, you will receive Bortezomib EVER Pharma in combination with two other medicines: melphalan and prednisone. In this case, the duration of one treatment cycle is 42 days (6 weeks). You will receive 9 cycles (54 weeks).

  • In cycles 1 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 administered orally on days 1, 2, 3, and 4 of the first week of each cycle.

If you have never been treated before for multiple myeloma and you are eligible for stem cell transplantation, you will receive Bortezomib EVER Pharma intravenously or subcutaneously in combination with dexamethasone, or with dexamethasone and thalidomide, as induction treatment.

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

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

Previously untreated mantle cell lymphoma
If you have never previously received specific treatment for mantle cell lymphoma, you will receive Bortezomib EVER Pharma intravenously or subcutaneously in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone.
Bortezomib EVER Pharma is administered intravenously or subcutaneously on days 1, 4, 8, and 11, followed by a "rest period" without treatment. The treatment cycle duration is 21 days (3 weeks). You may receive up to 8 treatment cycles (24 weeks).
The following medicines are administered on day 1 of each 21-day treatment cycle of Bortezomib EVER Pharma as intravenous infusions:

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

How Bortezomib EVER Pharma is administered
This medicine 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 medicines.
The solution is injected into a vein or under the skin. Intravenous injection is rapid, administered over a period of 3 to 5 seconds. Subcutaneous injection can be administered either in the thigh or the abdomen.

If you receive more Bortezomib EVER Pharma than you should
Since this medicine is administered by a doctor or nurse, it is unlikely that you will receive more than the intended dose. In the unlikely event of overdose, your doctor will monitor you for any adverse effects.

4. Possible side effects

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

  • Muscle cramps, muscle weakness
  • Confusion, vision disturbances or loss of vision, blindness, seizures, headache
  • Shortness of breath, swelling of the feet or changes in heartbeat, high blood pressure, fatigue, fainting
  • Cough and difficulty breathing or chest tightness

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

  • Platelets, which could make you more prone to bruising or bleeding without apparent injury (e.g. intestinal, stomach, mouth and gum bleeding, or brain or liver haemorrhage)
  • Red blood cells, which can cause anaemia, with symptoms such as fatigue and paleness
  • White blood cells, which may increase your susceptibility to infections or flu-like symptoms

If you are being administered 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)

  • Numbness, tingling, burning sensation or pain in the skin, or pain in the hands or feet due to nerve damage
  • Decrease in the number of red and/or white blood cells (see above)
  • Fever
  • Nausea or vomiting, loss of appetite
  • Constipation with or without excess intestinal gas (can be severe)
  • Diarrhoea: if this occurs, it is important that you drink much more water than usual. Your doctor may prescribe medication to control diarrhoea
  • Tiredness (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, which may lead to fainting
  • Increased blood pressure
  • Reduced kidney function
  • Headache
  • General feeling of discomfort, pain, dizziness, feeling of emptiness in the head, weakness or loss of consciousness
  • Chills
  • Infections, including pneumonia, respiratory infections, bronchitis, fungal infection, cough with phlegm, flu-like illness
  • Herpes zoster infection (localized, including around the eyes, or disseminated throughout the body)
  • Chest pain or difficulty breathing during physical activity
  • Various types of skin rash
  • Itching of the skin, skin nodules or dry skin
  • Facial flushing or small capillary ruptures
  • Skin redness
  • Dehydration
  • Heartburn, bloating, belching, gas, stomach pain, intestinal or stomach bleeding
  • Altered 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 outer layer of the eye and inner surface of the eyelids (conjunctivitis)
  • Nosebleeds
  • Sleep disturbances or problems, sweating, anxiety, mood changes, depressed mood, restlessness or agitation, changes in mental state, disorientation
  • Swelling of the body, including around the eyes and other body parts

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

  • Heart failure, heart attack, chest pain, chest discomfort, increased or decreased heart rate
  • Kidney failure
  • Vein inflammation, blood clots in veins and lungs
  • Blood clotting problems
  • Circulatory failure
  • Inflammation of the membrane surrounding the heart or fluid accumulation around the heart
  • Infections including urinary tract infections, influenza, herpes virus infections, ear infection and cellulitis
  • Blood in stools, or mucosal bleeding (e.g. mouth, vagina)
  • Cerebrovascular disorders
  • Paralysis, seizures, falls, movement disorders, abnormal or reduced sensation (touch, hearing, taste, smell), attention disorders, tremor, spasms
  • Arthritis, including inflammation of the joints of the fingers, toes and jaw
  • Disorders affecting the lungs, preventing the body from receiving sufficient oxygen. Some of these include difficulty breathing, shortness of breath, laboured breathing even without physical activity, shallow or difficult breathing or need to pause breathing, wheezing
  • Hiccups, speech disorders
  • Increased or decreased urine production (kidney damage), painful urination or presence of blood/protein in urine, fluid retention
  • Altered levels of consciousness, confusion, memory impairment or loss
  • Hypersensitivity
  • Hearing loss, deafness or ringing in the ears, ear discomfort
  • Hormonal changes that may affect the reabsorption of salts and water
  • Overactivity of the thyroid gland
  • Inability to produce enough insulin or resistance to normal insulin levels
  • Irritated or inflamed eyes, excessively watery eyes, eye pain, dry eyes, eye infections, eyelid swelling (chalazion), red and swollen eyelids, eye discharge, vision disturbances, eye bleeding
  • Enlarged lymph nodes
  • Joint or muscle stiffness, feeling of heaviness, groin pain
  • Hair loss or abnormal hair texture
  • Allergic reactions
  • Redness or pain at the injection site
  • Mouth pain
  • Infection or inflammation of the mouth, mouth ulcers, oesophagus, stomach and intestine, sometimes associated with pain or bleeding, reduced intestinal motility (including intestinal blockage), abdominal or oesophageal discomfort, difficulty swallowing, vomiting with blood
  • Skin infections
  • Bacterial and viral infections
  • Dental infections
  • Pancreatitis, obstruction of bile ducts
  • Genital pain, erectile dysfunction
  • Weight gain
  • Feeling of thirst
  • Hepatitis
  • Injection site or injection device site reactions
  • Skin reactions or disorders (which may be severe and life-threatening), skin ulcerations
  • Bruising, falls and injuries
  • Inflammation or bleeding of blood vessels, which may appear as small red or purple spots (usually on the legs) that may develop into large bruises on the skin or tissues
  • Benign cysts
  • A serious, reversible brain condition including seizures, high blood pressure, headache, fatigue, confusion, blindness or other vision problems

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

  • Heart problems including heart attack, angina
  • Severe nerve inflammation, which may cause paralysis and breathing difficulties (Guillain-Barré syndrome)
  • Hot flushes
  • Change in vein colour
  • Spinal nerve inflammation
  • Ear problems, ear bleeding
  • Reduced activity of the thyroid gland
  • Budd-Chiari syndrome (clinical signs caused by blockage of liver veins)
  • Altered or abnormal bowel function
  • Cerebral haemorrhage
  • Yellowing of the eyes and skin (jaundice)
  • Severe allergic reaction (anaphylactic shock): signs include difficulty breathing, chest pain or tightness, and/or dizziness/weakness, severe skin itching or skin swellings, facial, lip, tongue and/or throat swelling causing difficulty swallowing, collapse
  • Breast disorders
  • Vaginal discharge
  • Swelling of the genitals
  • Inability to tolerate alcohol consumption
  • Wasting or loss of body mass
  • Increased appetite
  • Fistulas
  • Joint effusion
  • Cysts in the membrane covering the joints (synovial cysts)
  • Fractures
  • Muscle fibre rupture leading to further complications
  • Enlarged liver, liver haemorrhage
  • Kidney tumour
  • Skin condition similar to psoriasis
  • Skin tumour
  • Pale skin
  • Increased platelets or plasma cells (a type of white blood cell) in the blood
  • Blood clotting in small blood vessels (thrombotic microangiopathy)
  • Abnormal reaction to blood transfusion
  • Partial or total loss of vision
  • Decreased libido
  • Loss of saliva
  • Eye protrusion
  • Light sensitivity
  • Rapid breathing
  • Rectal pain
  • Gallstones
  • Hernia
  • Injuries
  • Brittle or weak nails
  • Abnormal protein deposition in vital organs
  • Coma
  • Intestinal ulcers
  • Damage to multiple organs
  • Death

If you are being administered Bortezomib EVER Pharma in combination 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
  • Numbness, tingling, burning sensation or pain in the skin, or pain in the hands or feet due to nerve damage
  • Nausea and vomiting
  • Diarrhoea
  • Mouth ulcers
  • Intestinal constipation
  • Muscle pain, bone pain
  • Hair loss or abnormal hair texture
  • Tiredness, feeling 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 phlegm, flu-like illness
  • Fungal infections
  • Hypersensitivity (allergic reaction)
  • Inability to produce enough insulin or resistance to normal insulin levels
  • Fluid retention
  • Difficulty or problems sleeping
  • Loss of consciousness
  • Altered levels of consciousness, confusion
  • Dizziness
  • Increased heart rate, high blood pressure, sweating
  • Vision disturbances, blurred vision
  • Heart failure, heart attack, chest pain, chest discomfort, increased or decreased heart rate
  • High or low blood pressure
  • Sudden drop in blood pressure when standing, which may lead to fainting
  • Shortness of breath during physical activity
  • Cough
  • Hiccups
  • Ringing in the ears, ear discomfort
  • Intestinal or stomach bleeding
  • Heartburn
  • Stomach pain, bloating
  • Difficulty swallowing
  • Infection or inflammation of the stomach and intestine
  • Stomach pain
  • Irritation of the mouth or lips, sore throat
  • Altered liver function
  • Skin itching
  • Skin redness
  • Rash
  • Muscle spasms
  • Urinary tract infection
  • Limb pain
  • Body swelling, including around the eyes and other body parts
  • Chills
  • Redness and pain at the injection site
  • General feeling of discomfort
  • Loss of body weight
  • Increased body weight

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

  • Hepatitis
  • Severe allergic reaction (anaphylactic reaction), signs of which may include difficulty breathing, chest pain or tightness, and/or dizziness/weakness, severe skin itching or skin swellings, facial, lip, tongue and/or throat swelling causing difficulty swallowing, collapse
  • Movement disorders, paralysis, contractions
  • Dizziness
  • Hearing loss, deafness
  • Disorders affecting the lungs, preventing the body from receiving sufficient oxygen. Some of these include difficulty breathing, shortness of breath, laboured breathing even without physical activity, breathing becoming shallow, difficult or interrupted, wheezing
  • Blood clots in the lungs
  • Yellowing of the eyes and skin (jaundice)
  • Eyelid swelling (chalazion), red and swollen eyelids

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

  • Blood clotting in small blood vessels (thrombotic microangiopathy)
  • Severe nerve inflammation, which may cause paralysis and breathing difficulties (Guillain-Barré syndrome)

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
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 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 should be used immediately after first opening/dilution. If the solution (diluted) is not used immediately, the conditions and duration of use 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 under normal indoor lighting conditions.
Regarding stability in the syringe, the same storage period applies to both diluted and undiluted solution.
Bortezomib EVER Pharma is for single use only. Unused product and waste material must 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 injectable solution contains 2.5 mg of bortezomib (as
mannitol boronic ester). Each 1 ml vial of injectable solution contains 2.5 mg of bortezomib (as
mannitol boronic ester). Each 1.4 ml vial of injectable 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 (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 clear, colourless to pale yellow solution.
Bortezomib EVER Pharma is available in a colourless glass vial (Type I), with a rubber stopper and an aluminium cap, and a plastic flip-off 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
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 European Economic Area member states 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

The following information is intended exclusively for physicians or healthcare professionals:

1. INTRAVENOUS INJECTION PREPARATION

Note: Bortezomib EVER Pharma is a cytotoxic agent. Therefore, particular care must be taken during handling and preparation. It is recommended to wear gloves and other protective clothing to prevent skin contact. Pregnant personnel must not handle this medicinal product.
DUE TO THE ABSENCE OF ANY TYPE OF PRESERVATIVE, ASEPTIC TECHNIQUE MUST BE OBSERVED DURING THE HANDLING OF BORTEZOMIB EVER PHARMA.
1.1 Preparation of the 1 ml vial: add 1.8 ml of sterile sodium chloride 9 mg/ml (0.9%) injection solution 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%) injection solution to the vial containing Bortezomib EVER Pharma.
The concentration of the resulting solution is 1 mg/ml. The solution will be clear and colourless to pale yellow with a final pH between 4 and 7. There is no need to check the pH of the solution.
1.2 The solution must be inspected visually before administration to check for the presence of particulate matter or discoloration. If particulate matter or discoloration is observed, the solution must be discarded. Ensure that the correct dose is administered by intravenous route (1 mg/ml).
1.3 The solution is preservative-free and should be used immediately after preparation. However, the in-use chemical and physical stability of the diluted solution has been demonstrated:

  • for 28 days at 2 °C–8 °C and protected from light
  • for 28 days at 25 °C and protected from light
  • for 24 hours when stored at 25 °C under 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 duration of use are the responsibility of 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.
  • Confirm the dose and concentration in the syringe before use (check that the syringe is labeled for intravenous administration).
  • Inject the solution as an intravenous bolus over 3–5 seconds through a peripheral or central venous catheter.
  • Flush the venous or peripheral catheter with sterile sodium chloride solution 9 mg/ml (0.9%).

BORTEZOMIB EVER PHARMA IS FOR SUBCUTANEOUS OR INTRAVENOUS USE. Do not
administer by other routes. Intrathecal administration has resulted in deaths.

3. DISPOSAL

The vial is for single use only, and any remaining solution must be discarded.
Unused medicine and waste materials resulting from the use of this medicine must be disposed of in accordance with local regulations for cytotoxic agents.
The following information is intended exclusively for physicians or healthcare professionals:
1 PREPARATION FOR SUBCUTANEOUS INJECTION
Note: Bortezomib EVER Pharma is a cytotoxic agent. Therefore, particular care must be taken during handling and preparation. It is recommended to wear gloves and other protective clothing to prevent skin contact. Pregnant personnel should not handle this medicine.
DUE TO THE ABSENCE OF ANY TYPE OF PRESERVATIVE, ASEPTIC TECHNIQUES MUST BE OBSERVED DURING THE HANDLING OF BORTEZOMIB EVER PHARMA.
1.1 Bortezomib EVER Pharma is ready for use.
The concentration of the solution is 2.5 mg/ml. The solution is clear and colourless to pale yellow, with a final pH between 4.0 and 5.5. There is no need to check the pH of the solution.
1.2 The solution should be inspected visually before administration to check for the presence of particulate matter or discoloration. If particulate matter or discoloration is observed, the solution must be discarded. Ensure that the correct dose is administered by subcutaneous route (2.5 mg/ml).
1.3 The solution is preservative-free and should be used immediately after withdrawing the appropriate amount. 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
  • for 28 days, at 25 °C and protected from light
  • for 24 hours, when stored at 25 °C under normal indoor lighting conditions
    in the original vial and/or in a polypropylene syringe. If the solution is not used immediately, the conditions and duration 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 volume of solution according to the dose calculated based on the patient's body surface area.
  • Confirm the dose and concentration in the syringe before use (check that the syringe is labeled for subcutaneous administration).
  • Inject the solution subcutaneously at an angle of 45–90°.
  • The solution is administered subcutaneously in the thighs (right or left) or in the abdomen (right or left).
  • For subsequent administrations, the injection site must be rotated.
  • If local reactions occur at the injection site after subcutaneous administration 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 by other routes. Intrathecal administration has resulted in fatalities.

3. DISPOSAL

The vial is for single use only, and any remaining solution must be discarded.
Unused medicine and waste materials resulting from this medicine must be disposed of in accordance with
local regulations governing cytotoxic agents.