Bortezomib adamed: detailed information

Bortezomib Adamed, 2.5 mg, powder for solution for injection
Bortezomibum
Please read the entire leaflet carefully before using the medicine, as it contains
important information for the patient.

Keep this leaflet, so that you can read it again if necessary.
If you have any doubts, please consult your doctor or pharmacist.
If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents

What is Bortezomib Adamed and what is it used for
Important information before using Bortezomib Adamed
How to use Bortezomib Adamed
Possible side effects
How to store Bortezomib Adamed
Contents of the pack and other information

1. What is Bortezomib Adamed and what is it used for

Bortezomib Adamed contains an active substance called bortezomib, which is a so-called
"proteasome inhibitor". Proteasomes play an essential role in controlling cell functions and their
development process. By interfering with their function, bortezomib may lead to the death of
tumor cells.
Bortezomib Adamed 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 after at least one prior therapy and who have either failed or are not eligible for hematopoietic stem cell transplantation;
in combination with melphalan and prednisone, in patients who have not been previously treated and who are not eligible for high-dose chemotherapy combined with hematopoietic stem cell transplantation;
in combination with dexamethasone or with dexamethasone and thalidomide, in patients who have not been previously treated and who are eligible for high-dose chemotherapy combined with hematopoietic stem cell transplantation (induction treatment).

Bortezomib Adamed 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 those who have not been previously treated and who are not eligible for hematopoietic stem cell transplantation.

2. Important information before using Bortezomib Adamed

When not to use Bortezomib Adamed

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 particularly severe lung or heart diseases.

Warnings and precautions
Before starting treatment with Bortezomib Adamed, discuss with the doctor if the patient has:

too low number of red or white blood cells;
bleeding disorders and/or low platelet count;
diarrhoea, constipation, nausea or vomiting;
fainting, dizziness or vertigo experienced in the past;
kidney disease;
moderate or severe liver function disorders;
numbness, tingling or pain in hands and feet (symptoms of neuropathy) experienced in the past;
heart disease or problems with blood pressure;
shortness of breath or cough;
seizures;
shingles (around the eyes or disseminated 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 loss of vision. These may be symptoms of a serious brain infection and the doctor may recommend further tests and monitoring.

Blood tests will be performed before treatment and regularly during treatment with Bortezomib Adamed to monitor blood cell counts.

If the patient has mantle cell lymphoma and is receiving rituximab-containing therapy together with Bortezomib Adamed, inform the doctor:

if the patient suspects hepatitis virus infection or has had it in the past. In some cases, patients with hepatitis B virus (HBV) infection have experienced reactivation of hepatitis, which could be fatal. If the patient has a history of HBV infection, the doctor will closely monitor for signs of active hepatitis.

Before starting treatment with Bortezomib Adamed, carefully read the package leaflets of all medicinal products that will be used concomitantly with Bortezomib Adamed to obtain information about them. When taking thalidomide, it is particularly important to rule out pregnancy and then use effective contraception (see section Pregnancy and breast-feeding).

Children and adolescents
Bortezomib Adamed must not be used in children and adolescents, as the effect of the medicine in this population has not been established.

Bortezomib Adamed and other medicines
Inform the doctor about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.
In particular, inform the treating 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 breast-feeding
Do not use Bortezomib Adamed during pregnancy unless absolutely necessary.
Both men and women receiving Bortezomib Adamed must use effective contraception during treatment and for 3 months after completion of treatment. If a woman becomes pregnant despite using contraception, inform the doctor immediately.
A woman must not breast-feed during treatment with Bortezomib Adamed. The timing of safe resumption of breast-feeding after treatment should be discussed with the doctor.
Thalidomide causes congenital malformations and fetal death. When Bortezomib Adamed is used in combination with thalidomide, patients must comply with the requirements of the "Thalidomide Pregnancy Prevention Programme" (see the thalidomide package leaflet).

Driving and operating machinery
Bortezomib Adamed may cause fatigue, dizziness, fainting, and blurred vision. If such symptoms occur, the patient must not drive or operate tools or machinery. Even if these symptoms do not occur, caution should still be exercised.

3. How to use Bortezomib Adamed

Your doctor will determine the appropriate dose of Bortezomib Adamed based on the patient's height and body weight (body surface area). The most commonly used starting dose of Bortezomib Adamed is 1.3 mg/m² of 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, adverse reactions, and any additional medical conditions (e.g. liver diseases).

Multiple myeloma
If Bortezomib Adamed is administered as a single agent, the patient will receive 4 doses of Bortezomib Adamed 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 will receive up to 8 cycles (24 weeks).

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

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

When Bortezomib Adamed is administered together with dexamethasone, the patient will receive Bortezomib Adamed intravenously or subcutaneously during each 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 Adamed. The patient may receive up to 8 cycles (24 weeks).

Previously untreated multiple myeloma
If the patient has not previously been treated for multiple myeloma and the patient is not eligible for hematopoietic stem cell transplantation, the patient will receive Bortezomib Adamed in combination with other medicines: melphalan and prednisone.

In this case, each treatment cycle lasts 42 days (6 weeks). The patient will receive 9 cycles (54 weeks).

During cycles 1–4, Bortezomib Adamed is administered twice weekly on days: 1, 4, 8, 11, 22, 25, 29, and 32.
During cycles 5–9, Bortezomib Adamed is administered once weekly on days: 1, 8, 22, and 29.

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

When Bortezomib Adamed is administered with dexamethasone, the patient will receive Bortezomib Adamed 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 Adamed.
The patient will receive up to 4 cycles (12 weeks).

When Bortezomib Adamed is administered with dexamethasone and thalidomide, each treatment cycle lasts 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 Adamed. 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 on days 15–28, 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 previously been treated for mantle cell lymphoma, the patient will receive Bortezomib Adamed intravenously in combination with the medicines: rituximab, cyclophosphamide, doxorubicin, and prednisone.

Bortezomib Adamed is administered intravenously or subcutaneously on days 1, 4, 8, and 11, followed by a "rest period" without administration of any drugs. Each 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 Adamed:
Rituximab at a dose of 375 mg/m², cyclophosphamide at a dose of 750 mg/m², and doxorubicin at a dose of 50 mg/m².

Prednisone is administered orally at a dose of 100 mg/m² on days 1, 2, 3, 4, and 5 of each treatment cycle with Bortezomib Adamed.

How Bortezomib Adamed is administered
This medicine is administered exclusively intravenously or subcutaneously. Bortezomib Adamed will be administered by trained medical personnel experienced in handling cytotoxic agents.

Bortezomib Adamed is supplied as a powder that must be reconstituted before administration. The reconstitution is performed by trained medical personnel. The resulting solution is then administered intravenously or subcutaneously. Intravenous injection is rapid and lasts from 3 to 5 seconds. Subcutaneous injection is administered into the thigh or abdomen.

Use of a higher than recommended dose of Bortezomib Adamed
Since this medicine is administered by a doctor or nurse, it is unlikely that the patient will receive an overdose.
However, if this occurs exceptionally, the doctor will monitor the patient for any adverse reactions.

4. Possible adverse reactions

Like any medicine, 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 Adamed for the treatment of multiple myeloma or mantle cell lymphoma, inform the doctor immediately if any of the following symptoms occur:

muscle cramps, muscle weakness;
confusion, vision loss or disturbances, blindness, seizures, headaches;
shortness of breath, swelling of the feet, or irregular heartbeat, high blood pressure, fatigue, fainting;
cough and difficulty breathing or chest tightness.

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

platelets, which may lead to a tendency to bruise or bleed without injury (e.g., bleeding from the intestines, stomach, mouth, or gums, or hemorrhage in the brain or liver);
red blood cells, which may lead to anemia, accompanied by symptoms such as fatigue and pallor;
white blood cells, which may increase susceptibility to infections or cause flu-like symptoms.

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

hypersensitivity, numbness, tingling, or burning sensation of the skin, pain in hands or feet due to nerve damage;
decreased 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 additional medication to control diarrhea;
fatigue, feeling of weakness;
muscle pain, bone pain.

Common adverse reactions (may occur in 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 of weakness 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 exertion;
various types of rashes;
skin itching, 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;
infection of the outer layer of the eye and inner surface of the eyelid (conjunctivitis);
nosebleeds;
difficulty falling asleep, sweating, anxiety, mood swings, depressive mood, restlessness or agitation, changes in mental state, disorientation;
swelling, including around the eyes and other parts of the body.

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

heart failure, heart attack, chest pain, chest discomfort, rapid or slow heart rate;
kidney failure;
vein inflammation, blood clots in veins and lungs;
blood clotting disorders;
circulatory failure;
pericarditis (inflammation of the outer lining of the heart) or fluid accumulation 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, twitching;
joint inflammation, including inflammation of joints in fingers, toes, and jaw;
lung disorders causing breathing difficulties. These include: breathing difficulties, shortness of breath, shortness of breath at rest, shallow breathing, or respiratory arrest, wheezing;
hiccups, speech disorders;
increased or decreased urine production (due to kidney damage), painful urination, blood or 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 levels;
eye irritation or inflammation, excessively watery eyes, eye pain, dry eyes, eye infections, eyelid nodule (stye), redness and swelling of the eyelid, eye discharge, vision 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, or 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, bile 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;
inflammation or bleeding of blood vessels, 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 occur in up to 1 in 1000 people):

heart diseases, including heart attack, angina pectoris;
flushing attacks;
discoloration of veins;
spinal cord inflammation;
ear disorders, 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/fainting, severe skin itching or raised skin lumps, swelling of face, lips, tongue, and/or throat, which may cause difficulty breathing and swallowing, collapse;
breast diseases;
vaginal ulceration;
genital swelling;
alcohol intolerance;
wasting or weight loss;
increased appetite;
fistula;
joint effusion;
synovial cyst (ganglion cyst);
bone fractures;
rhabdomyolysis (muscle fiber breakdown) leading to further complications;
liver swelling, liver bleeding;
kidney cancer;
skin condition resembling psoriasis;
skin cancer;
skin pallor;
increased platelet or plasma cell count (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;
severe nerve inflammation, which may lead to paralysis and breathing difficulties (Guillain-Barré syndrome).

If the patient is receiving Bortezomib Adamed in combination with other medicines for the treatment of mantle cell lymphoma, the following adverse reactions may occur:
Very common adverse reactions (may occur in 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 occur in 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, productive cough, flu-like symptoms;
fungal infections;
hypersensitivity (allergic reaction);
insufficient insulin production or resistance to normal insulin levels;
fluid retention;
sleep disturbances;
loss of consciousness;
altered level of consciousness, confusion;
dizziness;
rapid heartbeat, high blood pressure, sweating;
abnormal vision, blurred vision;
heart failure, heart attack, chest pain, chest discomfort, 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;
mouth or throat pain;
abdominal pain, belching;
difficulty swallowing;
infection or inflammation of the stomach or intestines;
abdominal pain;
inflammation of the mouth or lips, sore throat, mouth ulcers;
altered liver function;
skin itching;
skin redness;
rash;
muscle cramps;
muscle and bone pain;
urinary tract infections;
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 occur in 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, or throat, which may cause difficulty swallowing, collapse;
movement disorders, paralysis, muscle twitching;
dizziness;
hearing loss, deafness;
lung disorders causing breathing difficulties. These include: breathing difficulties, 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);
eyelid nodule (stye), redness and swelling of the eyelid.

Rare adverse reactions (may occur in less than 1 in 1000 people)

blood clot in small blood vessels (thrombotic microangiopathy).

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform the doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, 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 to provide more information on the safety of the medicine.

5. How to store Bortezomib Adamed

The medicine should be stored out of sight and reach of children.
Do not use this medicine after the expiry date stated on the vial and outer packaging, after EXP.
Store the vial in the outer packaging to protect it from light.
There are no special requirements regarding the storage temperature of the medicine.

Solution after dilution
The solution is chemically and physically stable for 8 hours at 25°C, at 60% relative humidity, when stored in a protected from light place, both in vials and in polypropylene syringes.
From a microbiological standpoint, the product should be used immediately. If not used immediately, the responsibility for storage conditions and duration lies with the user. The prepared solution should not be stored for longer than 24 hours at 2°C to 8°C, unless reconstitution/dilution (etc.) was carried out under controlled aseptic conditions.

Bortezomib Adamed is intended for single use only. Any unused residues of the medicinal product or waste materials should be disposed of in accordance with local regulations.

6. Contents of the pack and other information

What Bortezomib Adamed contains

The active substance is bortezomib. Each vial contains 2.5 mg of bortezomib (in the form of
mannitol ester and boric acid).
Other ingredients: mannitol (E 421).

Intravenous injection solution:
After reconstitution, 1 ml of intravenous injection solution contains 1 mg of bortezomib.
Subcutaneous injection solution:
After reconstitution, 1 ml of subcutaneous injection solution contains 2.5 mg of bortezomib.
What Bortezomib Adamed looks like and contents of the pack
Bortezomib Adamed is a powder for solution for injection, appearing as a white or off-white,
caked powder or powder.
Bortezomib Adamed is available in a 10 ml colourless type I glass vial, with a bromobutyl rubber
stopper and a yellow flip-off cap.
Each pack contains 1 single-use vial.
Marketing Authorisation Holder
Adamed Pharma S.A.
Pieńków, ul. M. Adamkiewicza 6A
05-152 Czosnów
Manufacturer:
Synthon Hispania SL
C/ Castelló no1, Pol. Las Salinas, Sant Boi de Llobregat
08830 Barcelona
Spain
Synthon, s.r.o.
Brněnská 32/čp. 597
678 01 Blansko
Czech Republic
Adamed Pharma S.A.
Pieńków, ul. M. Adamkiewicza 6A
05-152 Czosnów
This medicinal product is authorised in the European Economic Area countries under the
following names:
Poland Bortezomib Adamed
Netherlands Bortezomib Adamed
04.2021
Information intended exclusively for healthcare professionals:
1. PREPARATION OF INTRAVENOUS INJECTION SOLUTION
Warning: Bortezomib Adamed is a cytotoxic product. Exercise caution when handling and preparing
the product for use. To protect against skin contact, the use of gloves and other protective clothing is
recommended.
SINCE Bortezomib Adamed DOES NOT CONTAIN PRESERVATIVES, ASEPTIC TECHNIQUES
MUST BE STRICTLY FOLLOWED WHEN HANDLING THE PRODUCT.
1.1. Reconstitution of the 2.5 mg vial: add 2.5 ml of sterile 9 mg/ml (0.9%) sodium chloride
injection solution to the vial containing Bortezomib Adamed powder. Reconstitution of the
lyophilised powder takes less than 2 minutes.
The resulting solution will have a concentration of 1 mg/ml. After reconstitution, the solution will be
clear and colourless, with a pH between 4 and 7. There is no need to check the pH of the solution.
1.2. Visually inspect the solution for the presence of particulate matter or discoloration before
administration. If any precipitate or discoloration is observed, the solution must be discarded.
Check the concentration on the vial label to ensure the correct dose is administered intravenously
(1 mg/ml).
1.3. The reconstituted product contains no preservatives and should be used immediately after
preparation. Chemical and physical stability has been demonstrated for up to 8 hours when stored
in the dark at 25°C in the original vial and/or syringe. The total storage time of the solution in the
syringe before administration must not exceed 8 hours. If the diluted solution is not administered
immediately after preparation, the person administering the product to the patient is responsible
for the storage time and conditions prior to use.
2. ADMINISTRATION

After reconstitution, withdraw the appropriate volume of the prepared solution according to the dose calculated based on the patient's body surface area.
Before administration, confirm the dose and concentration of the solution in the syringe (check that the syringe is labelled for intravenous administration).
Administer the solution as a rapid intravenous bolus injection lasting 3 to 5 seconds through a centrally or peripherally inserted intravenous catheter.
Flush the intravenous catheter used for administration with a small amount of sterile 9 mg/ml (0.9%) sodium chloride injection solution.

Bortezomib Adamed 2.5 mg, powder for solution for injection, IS ADMINISTERED
SUBCUTANEOUSLY OR INTRAVENOUSLY. INTRATHECAL ADMINISTRATION HAS RESULTED
IN DEATH.
3. DISPOSAL OF THE PRODUCT
The vial is intended for single use only, and any unused solution must be discarded.
All unused product or waste material must be disposed of in accordance with local regulations.
Information intended exclusively for healthcare professionals:
Only the 2.5 mg vial may be used for subcutaneous administration, as described below.
1. PREPARATION OF SUBCUTANEOUS INJECTION SOLUTION
Warning: Bortezomib Adamed is a cytotoxic product. Exercise caution when handling and preparing
the product for use. To protect against skin contact, the use of gloves and other protective clothing is
recommended.
SINCE Bortezomib Adamed DOES NOT CONTAIN PRESERVATIVES, ASEPTIC TECHNIQUES
MUST BE STRICTLY FOLLOWED WHEN HANDLING THE PRODUCT.
1.1. Reconstitution of the 2.5 mg vial: add 1.0 ml of sterile 9 mg/ml (0.9%) sodium chloride
injection solution to the vial containing Bortezomib Adamed powder. Reconstitution of the
lyophilised powder takes less than 2 minutes.
The resulting solution will have a concentration of 2.5 mg/ml. After reconstitution, the solution will
be clear and colourless, with a pH between 4 and 7. There is no need to check the pH of the solution.
1.2. Visually inspect the solution for the presence of particulate matter or discoloration before
administration. If any precipitate or discoloration is observed, the solution must be discarded.
Ensure that the correct dose is administered subcutaneously (2.5 mg/ml).
1.3. The reconstituted product contains no preservatives and should be used immediately after
preparation. Chemical and physical stability has been demonstrated for up to 8 hours when stored
in the dark at 25°C in the original vial and/or syringe. The total storage time of the solution in the
syringe before administration must not exceed 8 hours. If the diluted solution is not administered
immediately after preparation, the person administering the product to the patient is responsible
for the storage time and conditions prior to use.
2. ADMINISTRATION

After reconstitution, withdraw the appropriate volume of the prepared solution according to the dose calculated based on the patient's body surface area.
Before administration, confirm the dose and concentration of the solution in the syringe (check that the syringe is labelled for subcutaneous administration).
Inject the solution subcutaneously at an angle of 45–90°.
The prepared solution is administered subcutaneously in the thigh (right or left) or abdomen (right or left side).
Rotate injection sites for subsequent injections.
In case of local reactions following subcutaneous administration of Bortezomib Adamed, it is recommended to administer a less concentrated subcutaneous solution (diluted to 1 mg/ml instead of 2.5 mg/ml) or switch the route of administration to intravenous.

Bortezomib Adamed 2.5 mg powder for solution for injection IS ADMINISTERED
INTRAVENOUSLY OR SUBCUTANEOUSLY. DO NOT ADMINISTER BY OTHER ROUTES.
INTRATHECAL ADMINISTRATION HAS RESULTED IN DEATH.
3. DISPOSAL OF THE PRODUCT
The vial is intended for single use only, and any unused solution must be discarded.
All unused product or waste material must be disposed of in accordance with local regulations.