Package leaflet: Information for the user

Adabonib, 3.5 mg, powder for solution for injection
Bortezomib
Please read all of this leaflet carefully before using this medicine because it contains
important information for you.

Keep this leaflet. You may need to read it again.
If you have any further questions, ask your doctor or pharmacist.
If you get any side effects, talk to your doctor or pharmacist. This includes any side effects not listed in this leaflet. See section 4.

Contents of the leaflet

What Adabonib is and what it is used for
What you need to know before you use Adabonib
How to use Adabonib
Possible side effects
How to store Adabonib
Contents of the pack and other information

1. What Adabonib is and what it is used for

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

Adabonib is used to treat multiple myeloma (a cancer of the bone marrow) in patients aged at least 18 years:

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

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

2. Important information before using Adabonib

When not to use Adabonib

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
Inform the treating physician if the patient:

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

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

if the patient suspects hepatitis virus infection or has had it in the past. In several cases, patients with prior 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 HBV.

Before starting treatment with Adabonib, carefully read the package leaflets of all medicinal products taken during treatment to obtain information about them. If thalidomide is being used, pregnancy must be ruled out, and effective contraception must be used (see section Pregnancy and breastfeeding).
Children and adolescents
Adabonib should not be used in children and adolescents, as the effect of the medicine in this group is unknown.
Adabonib with other medicines
Inform your doctor or pharmacist about all medicines currently used, recently used, or planned to be used.
In particular, inform the treating physician if the patient is taking medicines containing any of the following active substances:

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

Pregnancy and breastfeeding
Adabonib must not be used during pregnancy unless absolutely necessary.
Both men and women receiving Adabonib must use effective contraception during treatment and for 3 months after treatment ends. If a patient becomes pregnant despite these measures, the doctor must be informed immediately.
Patients must not breastfeed while receiving Adabonib. The timing of safe return to breastfeeding after treatment should be discussed with the doctor.
Thalidomide causes congenital malformations and fetal death. When Adabonib 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
Adabonib may cause fatigue, dizziness, fainting, and blurred vision. If such symptoms occur, the patient must not drive or operate tools or machinery. Even if no symptoms are present, caution should still be exercised.

3. How to use Adabonib

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

Multiple myeloma
If Adabonib is administered as a single agent, the patient will receive 4 doses of Adabonib intravenously or subcutaneously on days 1, 4, 8, and 11, followed by a 10-day treatment break.
This 21-day period (3 weeks) is considered one treatment cycle. The patient may receive up to 8 cycles (24 weeks).
The patient may also receive Adabonib in combination with pegylated liposomal doxorubicin or dexamethasone.

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

When Adabonib is administered together with dexamethasone, the patient will receive Adabonib intravenously or subcutaneously during a 21-day treatment cycle, and dexamethasone will be administered orally at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of the 21-day Adabonib treatment cycle.
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 does not qualify for hematopoietic stem cell transplantation, they will receive Adabonib in combination with other medications: 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, Adabonib is administered twice weekly on days 1, 4, 8, 11, 22, 25, 29, and 32.
During cycles 5–9, Adabonib is administered once weekly on days 1, 8, 22, and 29.

Both melphalan (9 mg/m² BSA) and prednisone (60 mg/m² BSA) 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 qualifies for hematopoietic stem cell transplantation, they will receive Adabonib intravenously or subcutaneously in combination with other medications: dexamethasone or dexamethasone with thalidomide as induction therapy.

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

When Adabonib is administered with dexamethasone and thalidomide, the 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 Adabonib treatment cycle. Thalidomide is administered orally once daily at a dose of 50 mg up to day 14 of the first cycle; if this dose is tolerated, it is increased to 100 mg from days 15 to 28, and may subsequently be increased to 200 mg daily starting from the second cycle.
The patient may receive up to 6 cycles (24 weeks).

Previously untreated mantle cell lymphoma
If the patient has not previously been treated for mantle cell lymphoma, they will receive Adabonib intravenously in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone.
Adabonib is administered intravenously or subcutaneously on days 1, 4, 8, and 11, followed by a "rest period" without administration of drugs. Each treatment cycle lasts 21 days (3 weeks). The patient may receive up to 8 cycles (24 weeks).
The following medications are administered as intravenous infusions on day 1 of each 21-day Adabonib cycle: rituximab at a dose of 375 mg/m² BSA, cyclophosphamide at a dose of 750 mg/m² BSA, and doxorubicin at a dose of 50 mg/m² BSA.
Prednisone is administered orally at a dose of 100 mg/m² BSA on days 1, 2, 3, 4, and 5 of the Adabonib treatment cycle.

How Adabonib is administered
This medicine is administered intravenously or subcutaneously. Adabonib will be administered by trained medical personnel experienced in the use of cytotoxic drugs.
The Adabonib powder must be reconstituted before administration. The reconstitution is performed by trained medical personnel. The prepared solution is then administered either as a rapid intravenous injection over 3 to 5 seconds or subcutaneously. Subcutaneous injection is given in the thigh or abdomen.

Administration of a higher than recommended dose of Adabonib
Since this medicine is administered by a physician or nurse, it is unlikely that the patient will receive an overdose.
However, should this exceptionally occur, the physician will monitor the patient for any adverse reactions.

4. Possible adverse reactions

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

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

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

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

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

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

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

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

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

heart failure, heart attack, chest pain, discomfort in the chest, rapid or slow heart rate;
kidney failure;
phlebitis, blood clots in veins and lungs;
coagulation 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;
arthritis, including arthritis of fingers, toes and jaw;
lung disorders causing breathing difficulties. These include: difficulty breathing, shortness of breath, shortness of breath at rest, shallow breathing or respiratory arrest, wheezing;
hiccups, speech disorders;
increased or decreased urine output (due to kidney damage), painful urination or blood/protein in urine, fluid retention;
altered level of consciousness, confusion, worsening or loss of memory;
hypersensitivity;
hearing loss, deafness, ringing or discomfort in the ears;
hormonal disorders affecting salt and water absorption;
hyperthyroidism;
insufficient insulin production or resistance to normal insulin levels;
eye irritation or inflammation, excessively watery eyes, eye pain, dry eyes, eye infections, chalazion (meibomian gland cyst), redness and swelling of the eyelid, eye discharge, visual disturbances, eye hemorrhage;
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, oral ulcers, esophagus, stomach and intestines, sometimes accompanied by pain and bleeding, impaired intestinal peristalsis (including obstruction), abdominal and esophageal discomfort, difficulty swallowing, vomiting blood;
skin infection;
bacterial and viral infections;
dental infections;
pancreatitis, biliary tract obstruction;
genital organ pain, erectile dysfunction;
weight gain;
thirst;
hepatitis;
injection site reactions or complications related to vascular catheter use;
skin reactions and disorders (which may be severe and life-threatening), skin ulceration;
bruising, falls and injuries;
vascular inflammation or bleeding, manifesting as small red or purple spots (usually on legs) to large, bruise-like subcutaneous patches;
benign cysts;
severe reversible encephalopathy syndrome, including seizures, high blood pressure, headache, fatigue, confusion, blindness or other visual disturbances.

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

heart diseases, including heart attack, angina pectoris;
severe nerve inflammation causing paralysis and breathing difficulties (Guillain-Barré syndrome);
episodes of flushing;
vein discoloration;
spinal cord inflammation;
ear diseases, ear bleeding;
hypothyroidism;
Budd-Chiari syndrome (clinical symptoms caused by obstruction of hepatic veins);
altered or abnormal intestinal function;
intracranial 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 skin hives, swelling of face, lips, tongue and (or) throat, which may cause breathing or swallowing difficulties, collapse;
breast diseases;
vaginal ulceration;
genital edema;
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;
psoriasis-like skin condition;
skin cancer;
skin pallor;
increased platelet or plasma cell (a type of white blood cell) count;
blood clot in small blood vessels (thrombotic microangiopathy);
abnormal reaction to blood transfusion;
partial or complete vision loss;
decreased libido;
drooling;
exophthalmos (protruding eyes);
photophobia (light sensitivity);
increased respiratory rate;
anal pain;
gallstones;
hernia;
cuts;
brittle or weak nails;
abnormal protein deposition in organs;
coma;
intestinal ulceration;
multi-organ failure;
death.

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

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

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

shingles (localized, e.g., around the eyes, or disseminated over 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, hypertension, sweating;
visual disturbances, 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;
abdominal pain, belching;
difficulty swallowing;
infection or inflammation of the stomach or intestines;
abdominal pain;
inflammation of the mouth or lips, sore throat;
altered liver function;
skin itching;
skin redness;
rash;
muscle cramps;
urinary tract infection;
limb pain;
edema affecting eyes and other body parts;
chills;
redness and pain at injection site;
general feeling of illness;
weight loss;
weight gain.

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

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

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

blood clot in small blood vessels (thrombotic microangiopathy);
severe nerve inflammation causing paralysis and breathing difficulties (Guillain-Barré syndrome).

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform the doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Tel.: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Adabonib medicine

Keep the medicine out of the 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.
The diluted solution should be used immediately after preparation. If the diluted solution is not used immediately, the person administering the medicine is responsible for the storage conditions and duration prior to use. However, the prepared solution is stable prior to administration for up to 8 hours when stored at 25°C in the original vial and/or syringe. The total storage time of the solution prior to administration must not exceed 8 hours.
Adabonib medicine is for single use only. Any unused medicine or waste material should be disposed of in accordance with local regulations.

6. Contents of the package and other information

What Adabonib contains

The active substance is bortezomib. Each vial contains 3.5 mg of bortezomib (as a boronic acid ester with mannitol).
The other ingredients (excipients) are: mannitol (E 421).

Solution for intravenous injection:
After reconstitution, 1 ml of intravenous injection solution contains 1 mg of bortezomib.
Solution for subcutaneous injection:
After reconstitution, 1 ml of subcutaneous injection solution contains 2.5 mg of bortezomib.
What Adabonib looks like and contents of the pack
Adabonib powder for solution for injection is a white or off-white lyophilized cake or powder.
Each package of Adabonib 3.5 mg, powder for solution for injection, contains a 20 ml glass vial with a stopper.
Marketing Authorisation Holder
Pentafarma– Sociedade Técnico Medicinal S.A.
Rua da Tapada Grande nº 2, Abrunheira
2710-089 Sintra
Portugal
Tel. (351) 210 41 41 00
Manufacturer
Adamed Pharma S.A.
ul. Marszałka Józefa Piłsudskiego 5
95-200 Pabianice
Oncotec Pharma Produktion GmbH
Am Pharmapark
06861 Dessau-Roßlau
Germany
Tecnimede – Sociedade Técnico-Medicinal S.A.
Quinta da Cerca, Caixaria
2565-187 Dois Portos
Portugal

Information intended exclusively for healthcare professionals:
1. PREPARATION OF THE INJECTION SOLUTION FOR INTRAVENOUS ADMINISTRATION
Warning: Adabonib is a cytotoxic product. Extreme caution must be taken when handling and preparing the medicinal product for use. To protect against skin contact, the use of gloves and other protective clothing is recommended.
SINCE ADABONIB DOES NOT CONTAIN PRESERVATIVES, ASEPTIC TECHNIQUES MUST BE STRICTLY FOLLOWED WHEN HANDLING THE MEDICINAL PRODUCT.
1.1. Preparation of the 3.5 mg vial: carefully add 3.5 ml of sterile 9 mg/ml (0.9%) sodium chloride solution for injection to the vial containing Adabonib powder, using an appropriate syringe, without removing the vial stopper. Dissolution of the lyophilized powder takes less than 2 minutes.
The concentration of the reconstituted solution will be 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. Before administration, visually inspect the solution for particles and discoloration. If particles or discoloration are observed, the solution must be discarded. Ensure that the correct dose is administered by the intravenous route (1 mg/ml).
1.3. The reconstituted product is preservative-free and should be used immediately after preparation. However, the chemical and physical stability of the prepared solution is maintained for up to 8 hours prior to administration when stored 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 medicinal product to the patient is responsible for the time and storage conditions prior to use.
The prepared solution must be protected from light.
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 medicinal product in the syringe (check whether the syringe is labelled for intravenous administration).
Inject the solution as an intravenous bolus over 3 to 5 seconds through a centrally or peripherally placed intravenous catheter.
The intravenous catheter used for administration should be flushed with a small amount of sterile 9 mg/ml (0.9%) sodium chloride solution for injection.

Adabonib powder for solution for injection 3.5 mg is administered
INTRAVENOUSLY OR SUBCUTANEOUSLY. Do not administer by any other route. Intrathecal administration has resulted in death.
3. DISPOSAL OF THE MEDICINAL PRODUCT
The vial is intended for single use only, and any unused solution must be discarded.
Any unused medicinal product or waste material must be disposed of in accordance with local regulations.

The following information is intended exclusively for healthcare professionals:
Only the 3.5 mg vial may be used for subcutaneous administration, as described below.
1. PREPARATION OF THE SOLUTION FOR SUBCUTANEOUS INJECTION
Warning: Adabonib is a cytotoxic product. Extreme caution must be taken when handling and preparing the medicinal product for use. To protect against skin contact, the use of gloves and other protective clothing is recommended.
SINCE ADABONIB DOES NOT CONTAIN PRESERVATIVES, ASEPTIC TECHNIQUES MUST BE STRICTLY FOLLOWED WHEN HANDLING THE MEDICINAL PRODUCT.
1.1. Preparation of the 3.5 mg vial: carefully add 1.4 ml of sterile 9 mg/ml (0.9%) sodium chloride solution for injection to the vial containing Adabonib powder, using an appropriate syringe, without removing the vial stopper. Dissolution of the lyophilized powder takes less than 2 minutes.
The concentration of the reconstituted solution will be 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. Before administration, visually inspect the solution for particles and discoloration. If particles or discoloration are observed, the solution must be discarded. Ensure that the correct dose is administered by the subcutaneous route (2.5 mg/ml).
1.3. The reconstituted product is preservative-free and should be used immediately after preparation. However, the chemical and physical stability of the prepared solution is maintained for up to 8 hours prior to administration when stored 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 medicinal product to the patient is responsible for the time and storage conditions prior to use.
The prepared solution must be protected from light.
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 medicinal product in the syringe (check whether the syringe is labelled for subcutaneous administration).
Inject the solution subcutaneously at a 45–90° angle.
The prepared solution is administered subcutaneously in the thigh (right or left) or abdomen (right or left side).
Injection sites should be rotated with subsequent injections.
In case of local reactions after subcutaneous administration of Adabonib, it is recommended to administer a less concentrated solution of Adabonib subcutaneously (dilution to 1 mg/ml instead of 2.5 mg/ml) or switch to intravenous administration.