Adabonib

Package Leaflet: Information for the User

Adabonib, 3.5 mg, Powder for Solution for Injection

Bortezomib

Read All of This Leaflet Carefully Before You Start Taking This Medicine.

• You should 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 possible side effects not listed in this leaflet.

Contents of the Pack

• 1. What Adabonib is and what it is used for
• 2. Before you take Adabonib
• 3. How to take Adabonib
• 4. Possible side effects
• 5. How to store Adabonib
• 6. Contents of the pack and other information

1. What Adabonib is and what it is used for

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

Adabonib is used to treat multiple myeloma (a type of bone marrow cancer) in patients aged 18 years and older:

• as a single medicine or in combination with other medicines: pegylated liposomal doxorubicin or dexamethasone in patients whose disease has progressed after receiving at least one prior treatment and for whom hematopoietic stem cell transplantation was not successful or not feasible;
• in combination with melphalan and prednisone in patients who have not been previously treated and do not qualify for high-dose chemotherapy with hematopoietic stem cell transplantation;
• in combination with dexamethasone or dexamethasone with thalidomide in patients who have not been previously treated and qualify for high-dose chemotherapy with hematopoietic stem cell transplantation (induction treatment).

Adabonib is used to treat mantle cell lymphoma (a type of cancer that affects the lymph nodes) in patients aged 18 years and older in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone, who have not been previously treated and do not qualify for hematopoietic stem cell transplantation.

2. Before you take Adabonib

When Not to Take Adabonib

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

or

• if you have severe lung or heart disease.

Warnings and Precautions

Tell your doctor if you:

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

Regular blood tests must be performed before and during treatment with Adabonib to regularly check the number of blood cells.

If you are taking Adabonib in combination with rituximab for mantle cell lymphoma, tell your doctor:

• if you suspect you have a hepatitis B virus infection or have had it in the past. In a few cases, patients who had hepatitis B infection may have had recurring episodes of hepatitis, which could be fatal. If you have a history of hepatitis B, your doctor will closely monitor you for symptoms of active hepatitis B.

Before starting treatment with Adabonib, read the package leaflets of all medicinal products you are taking during treatment to obtain information about them. If you are taking thalidomide, you must exclude pregnancy and then use effective contraception (see section "Pregnancy and Breastfeeding").

Children and Adolescents

Adabonib should not be used in children and adolescents because it is not known how the medicine works in this age group.

Adabonib and Other Medicines

Tell your doctor or pharmacist about all medicines you are taking, have recently taken, or might take.

In particular, tell your doctor if you are taking medicines that contain any of the following active substances:

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

Pregnancy and Breastfeeding

Do not take Adabonib during pregnancy unless it is absolutely necessary.

Both men and women taking Adabonib must use effective contraceptive methods during and for 3 months after treatment. If, despite these measures, you become pregnant, tell your doctor immediately.

Women should not breastfeed during treatment with Adabonib. It is necessary to discuss with your doctor the safe timing of returning to breastfeeding after treatment.

Thalidomide causes birth defects and fetal death. When taking Adabonib in combination with thalidomide, patients must follow the "Thalidomide Pregnancy Prevention Program" (see thalidomide package leaflet).

Driving and Using Machines

Adabonib may cause fatigue, dizziness, fainting, and blurred vision. If you experience these symptoms, do not drive or operate tools or machinery; even if symptoms do not occur, you should still exercise caution.

3. How to Take Adabonib

Your doctor will adjust the appropriate dose of Adabonib based on your height and weight (body surface area). The most commonly used initial dose of Adabonib is 1.3 mg/m² (body surface area) administered twice a week.

Your doctor may change the dose and total number of treatment cycles based on your response to treatment, the occurrence of side effects, and additional diseases (e.g., liver disease).

Relapsed Multiple Myeloma

If Adabonib is administered as a single medicine, you will receive 4 doses of Adabonib intravenously or subcutaneously on days 1, 4, 8, and 11, followed by a 10-day rest period.

The described 21-day period (3 weeks) is considered one treatment cycle. You will receive up to 8 cycles (24 weeks).

You may also receive Adabonib in combination with pegylated liposomal doxorubicin or dexamethasone.

When Adabonib is administered in combination with pegylated liposomal doxorubicin, you will receive Adabonib intravenously or subcutaneously during the 21-day treatment cycle, and pegylated liposomal doxorubicin will be administered at a dose of 30 mg/m² (body surface area) as an intravenous infusion after Adabonib injection on day 4 of the 21-day Adabonib treatment cycle.

You may receive up to 8 cycles (24 weeks).

When Adabonib is administered in combination with dexamethasone, you will receive Adabonib intravenously or subcutaneously during the 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.

You may receive up to 8 cycles (24 weeks).

Previously Untreated Multiple Myeloma

If you have not been previously treated for multiple myeloma and you do notqualify for hematopoietic stem cell transplantation, you will receive Adabonib in combination with melphalan and prednisone.

In this case, the treatment cycle lasts 42 days (6 weeks). You will receive 9 cycles (54 weeks).

• During cycles 1-4, Adabonib will be administered twice a week on days 1, 4, 8, 11, 22, 25, 29, and 32.
• 29 and 32.
• During cycles 5-9, Adabonib will be administered once a week on days 1, 8, 22, and 29.

Melphalan (9 mg/m²) and prednisone (60 mg/m²) will be administered orally on days 1, 2, 3, and 4 of the first week of each cycle.

If you have not been previously treated for multiple myeloma and youqualify for hematopoietic stem cell transplantation, you will receive Adabonib intravenously or subcutaneously in combination with dexamethasone or dexamethasone with thalidomide as induction treatment.

When Adabonib is administered with dexamethasone, you will receive Adabonib intravenously or subcutaneously during the 21-day cycle, and dexamethasone will be administered orally at a dose of 40 mg on days 1, 2, 3, 4, 8, 9, 10, and 11 of the 21-day Adabonib treatment cycle.

You 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 will be administered orally at a dose of 40 mg on days 1, 2, 3, 4, 8, 9, 10, and 11 of the 28-day Adabonib treatment cycle, and thalidomide will be administered orally once daily at a dose of 50 mg up to day 14 of the first cycle, and if the dose is tolerated, it will be increased to 100 mg from days 15-28 and may be further increased to 200 mg daily from the second cycle.

You may receive up to 6 cycles (24 weeks).

Previously Untreated Mantle Cell Lymphoma

If you have not been previously treated for mantle cell lymphoma, you will receive Adabonib intravenously in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone.

Adabonib will be administered intravenously or subcutaneously on days 1, 4, 8, and 11, followed by a "rest period" without medication administration. One treatment cycle lasts 21 days (3 weeks). You will receive up to 8 cycles (24 weeks).

The following medicines will be administered as intravenous infusions on day 1 of each 21-day Adabonib treatment cycle: 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 will be administered orally at a dose of 100 mg/m² 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 a healthcare professional with experience in the use of cytotoxic medicines.

The powder of Adabonib must be dissolved before administration. The preparation of the medicine is performed by a healthcare professional.

The resulting solution is then injected either rapidly intravenously over 3 to 5 seconds or subcutaneously.

The subcutaneous injection is administered into the thigh or abdomen.

Overdose

Since this medicine is administered by a doctor or nurse, it is unlikely that you will receive too much of the medicine.

If this happens, your doctor will monitor you for side effects.

4. Possible Side Effects

Like all medicines, Adabonib can cause side effects, although not everybody gets them.

Some of these side effects may be serious.

If you are taking Adabonib for multiple myeloma or mantle cell lymphoma, you should immediately tell your doctor if you experience any of the following symptoms:

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

Treatment with Adabonib can very often cause a decrease in the number of red and white blood cells and platelets in the blood. Therefore, regular blood tests must be performed before and during treatment with Adabonib to regularly check the number of blood cells.

You may experience a decrease in:

• platelets, which can lead to bruising or bleeding that is not caused by injury (e.g., bleeding from the gut, stomach, mouth, or gums, or bleeding in the brain or liver);
• red blood cells, which can lead to anemia, characterized by symptoms such as fatigue and paleness;
• white blood cells, which can lead to increased susceptibility to infections or flu-like symptoms.

If you are taking Adabonib for multiple myeloma, you may experience the following side effects:

Very Common Side Effects (May Affect More Than 1 in 10 People):

• hypersensitivity, numbness, tingling, or burning sensation of the skin, 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, which may occur with or without bloating (the severity of symptoms may be significant);
• diarrhea: if this occurs, you should drink more water than usual, and your doctor may recommend taking additional medicines to control diarrhea;
• 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 up, which can lead to fainting;
• high blood pressure;
• decreased 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 widespread on the body);
• chest pain, shortness of breath during exercise;
• various types of rash;
• itching, skin lumps, or dry skin;
• flushing of the face or broken blood vessels;
• redness of the skin;
• dehydration;
• heartburn, bloating, belching, gas, abdominal pain, gastrointestinal bleeding;
• liver function disorders;
• mouth or lip ulcers, sore throat;
• weight loss, loss of taste;
• muscle spasms, muscle weakness, bone pain;
• blurred vision;
• conjunctivitis;
• nosebleeds;
• difficulty sleeping, sweating, anxiety, mood swings, depression, restlessness, or agitation, changes in mental state, disorientation;
• swelling, including around the eyes and other parts of the body.

Uncommon Side Effects (May Affect Up to 1 in 100 People):

• heart failure, heart attack, chest pain, discomfort in the chest, rapid or slow heart rate;
• kidney failure;
• vein inflammation, blood clots in veins and lungs;
• blood clotting disorders;
• circulatory failure;
• inflammation of the sac surrounding the heart (pericarditis) or fluid in the pericardium;
• infections, including urinary tract infections, flu, herpes, ear and soft tissue infections;
• bleeding from the gut or stomach;
• blood clotting disorders;
• nerve damage, paralysis, seizures, falls, movement disorders, abnormal or changed sensation (touch, hearing, taste, smell), attention disorders, tremors;
• joint inflammation, including joint pain in the fingers, toes, and jaw;
• lung disorders that make breathing difficult. Some of these include difficulty breathing, shortness of breath, shortness of breath at rest, shallow breathing, or cessation of breathing;
• hiccups, speech disorders;
• increased or decreased urine production (due to kidney damage), painful urination, or blood/protein in the 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 that can affect salt and water absorption;
• hyperthyroidism;
• insulin deficiency or insulin resistance;
• eye irritation or inflammation, excessive tearing, eye pain, dry eyes, eye infections, stye (hordeolum), eyelid redness and swelling, eye discharge, vision disorders;
• lymph node enlargement;
• joint stiffness or muscle stiffness, feeling of heaviness;
• hair loss and abnormal hair structure;
• allergic reactions;
• redness or pain at the injection site;
• mouth pain;
• mouth or throat infections, mouth or esophageal ulcers, stomach or intestinal ulcers, sometimes with accompanying pain and bleeding;
• skin infections;
• bacterial or viral infections;
• tooth infections;
• pancreatitis, bile duct obstruction;
• genital pain, erectile dysfunction;
• weight gain;
• thirst;
• hepatitis;
• complications at the injection site or related to the use of a venous catheter;
• skin reactions (which can be severe and life-threatening), skin ulcers;
• bruises, falls, and injuries;
• inflammation or bleeding of blood vessels, manifested by small red or purple spots (usually on the legs) to large, bruise-like spots under the skin;
• mild cysts;
• a severe, reversible condition of brain disorders, which includes seizures, high blood pressure, headache, fatigue, confusion, blindness, or other vision disorders.

Rare Side Effects (May Affect Up to 1 in 1000 People):

• heart disease, including heart attack, angina pectoris;
• severe nerve inflammation, which can cause paralysis and breathing difficulties (Guillain-Barré syndrome);
• flushing;
• vein discoloration;
• spinal cord inflammation;
• ear disorders, ear bleeding;
• hypothyroidism;
• Budd-Chiari syndrome (clinical symptoms caused by blockage of liver veins);
• abnormal or changed bowel function;
• brain bleeding;
• jaundice (yellowing of the skin and eyes);
• stye (hordeolum), eyelid redness and swelling.

If you are taking Adabonib in combination with other medicines for mantle cell lymphoma, you may experience the following side effects:

Very Common Side Effects (May Affect More Than 1 in 10 People):

• pneumonia;
• loss of appetite;
• hypersensitivity, numbness, tingling, or burning sensation of the skin, pain in the 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 Side Effects (May Affect Up to 1 in 10 People):

• shingles (localized, e.g., around the eyes, or widespread on the body);
• herpes virus infection;
• bacterial or viral infections;
• respiratory tract infections, bronchitis, wet cough, flu-like symptoms;
• fungal infections;
• hypersensitivity (allergic reaction);
• insulin deficiency or insulin resistance;
• fluid retention;
• sleep disorders;
• loss of consciousness;
• altered level of consciousness, confusion;
• dizziness;
• rapid heartbeat, high blood pressure, sweating;
• abnormal or changed vision;
• heart failure, heart attack, chest pain, discomfort in the chest, rapid or slow heart rate;
• high or low blood pressure;
• sudden drop in blood pressure when standing up, which can lead to fainting;
• shortness of breath during exercise;
• cough;
• hiccups;
• ringing or discomfort in the ears;
• gastrointestinal bleeding;
• heartburn;
• abdominal pain;
• difficulty swallowing;
• infections or inflammation of the stomach or intestines;
• abdominal pain;
• mouth or lip ulcers, sore throat;
• liver function disorders;
• itching;
• skin redness;
• rash;
• muscle spasms;
• urinary tract infections;
• limb pain;
• swelling, including around the eyes and other parts of the body;
• chills;
• redness and pain at the injection site;
• general feeling of illness;
• weight loss;
• weight gain.

Uncommon Side Effects (May Affect Up to 1 in 100 People):

• hepatitis;
• severe allergic reaction (anaphylactic reaction), which can cause symptoms such as difficulty breathing, chest pain or tightness, and dizziness or fainting, severe itching of the skin or hives, swelling of the face, lips, tongue, or throat, which can cause difficulty swallowing, and collapse;
• movement disorders, paralysis, muscle tremors;
• dizziness;
• hearing loss, deafness;
• lung disorders that make breathing difficult. Some of these include difficulty breathing, shortness of breath, shortness of breath at rest, shallow breathing, or cessation of breathing;
• blood clots in the lungs;
• jaundice (yellowing of the skin and eyes);
• stye (hordeolum), eyelid redness and swelling.

Rare Side Effects (May Affect Up to 1 in 1000 People):

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

Reporting of Side Effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.

Side effects can be reported to the national reporting system via the website https://smz.ezdrowie.gov.pl.

Side effects can also be reported to the marketing authorization holder.

By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to Store Adabonib

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the label and carton after EXP.

Store the vial in the outer carton in order to protect from light.

The reconstituted solution should be used immediately after preparation. However, the chemical and physical stability of the reconstituted solution is maintained for 8 hours before 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 should not exceed 8 hours.

Adabonib is for single use only. Any unused solution or waste material should be disposed of in accordance with local requirements.

6. Contents of the Pack 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 are mannitol (E 421).

Reconstituted solution for injection:

After reconstitution, 1 ml of solution for injection contains 1 mg of bortezomib.

Reconstituted solution for subcutaneous injection:

After reconstitution, 1 ml of solution for injection 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 powder or powder.

Each pack of Adabonib 3.5 mg, powder for solution for injection, contains a 20 ml glass vial with a stopper.

Marketing Authorization 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

Date of Last Revision of the Leaflet

Information intended for healthcare professionals only:

1. Preparation of Solution for Intravenous Injection

Caution: Adabonib is a cytotoxic product. When handling the product and preparing it for use, caution should be exercised. To protect against skin contact, the use of gloves and other protective clothing is recommended.

AS Adabonib DOES NOT CONTAIN PRESERVATIVES, ASEPTIC TECHNIQUES MUST BE STRICTLY FOLLOWED WHEN HANDLING THE PRODUCT.

• 1.1. Preparation of the 3.5 mg vial: carefully add 3.5 mlof sterile, 9 mg/ml (0.9%) sodium chloride injection to the vial containing the Adabonib powder, using an appropriate syringe, without removing the vial stopper. Reconstitution of the lyophilized 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 colorless, 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 particulate matter and discoloration. If particulate matter or discoloration is observed, the solution should be discarded. Ensure that the correct dose is administered intravenously(1 mg/ml).
• 1.3. The reconstituted solution is preservative-free and should be used immediately after preparation. However, the chemical and physical stability of the reconstituted solution is maintained for 8 hours before 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 should not exceed 8 hours. If the reconstituted solution is not administered immediately, the responsibility for the storage conditions and time before administration lies with the healthcare professional.

Protect the reconstituted solution from light.

2. Administration

• After reconstitution, withdraw the appropriate dose of Adabonib 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 labeled for intravenous administration).
• Administer the solution as an intravenous bolus injection over 3 to 5 seconds through a central or peripheral intravenous catheter.
• Flush the intravenous catheter with a small amount of sterile, 9 mg/ml (0.9%) sodium chloride injection after administering Adabonib.

Adabonib Powder for Solution for Injection 3.5 mg SHOULD BE ADMINISTERED INTRAVENOUSLY OR SUBCUTANEOUSLY. DO NOT ADMINISTER BY ANY OTHER ROUTE. INTRATHECAL ADMINISTRATION HAS RESULTED IN DEATH.

3. Disposal

The vial is for single use only, and any unused solution should be discarded.

Dispose of any unused product or waste material in accordance with local requirements.