Bortezomib Krka

Leaflet accompanying the packaging: information for the user

Bortezomib Krka, 3.5 mg, powder for solution for injection

Bortezomib

You should carefully read the contents of the leaflet before using the medicine, as it contains important information for the patient.

• You should keep this leaflet, so that you can read it again if you need to.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• If you experience any side effects, including those not listed in this leaflet, you should tell your doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet:

• 1. What is Bortezomib Krka and what is it used for
• 2. Important information before using Bortezomib Krka
• 3. How to use Bortezomib Krka
• 4. Possible side effects
• 5. How to store Bortezomib Krka
• 6. Contents of the packaging and other information

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

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

Bortezomib Krka is used to treat multiple myeloma (a type of bone marrow cancer) in patients over 18 years of age:

• as a single drug or in combination with other drugs: pegylated liposomal doxorubicin or dexamethasone in patients whose disease has progressed after at least one previous treatment and for whom hematopoietic stem cell transplantation was not successful or not possible;
• in combination with the drugs: 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 the drugs: 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). Bortezomib Krka is used to treat mantle cell lymphoma (a type of lymph node cancer) in patients over 18 years of age in combination with the drugs: rituximab, cyclophosphamide, doxorubicin, and prednisone, in patients who have not been previously treated and do not qualify for hematopoietic stem cell transplantation.

2. Important information before using Bortezomib Krka

When not to use Bortezomib Krka

• if you are allergic to bortezomib, boron, or any of the other ingredients of this medicine (listed in section 6);
• if you have certain severe lung or heart diseases.

Warnings and precautions

You should inform your doctor if you:

• have a low number of red or white blood cells;
• have bleeding disorders and (or) a low platelet count;
• experience diarrhea, constipation, nausea, or vomiting;
• have a history of fainting, dizziness, and blurred vision;
• have kidney disease;
• have moderate to severe liver function disorders;
• have a history of numbness, tingling, and pain in the hands or 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, and shortness of breath;
• experience memory loss, thinking disorders, difficulty walking, or loss of vision. These may be symptoms of a severe brain infection. Your doctor may recommend further tests and observation. You will need to have regular blood tests before and during treatment with Bortezomib Krka to regularly check your blood cell count. If you have mantle cell lymphoma and are receiving rituximab at the same time as Bortezomib Krka, you should tell your doctor:
• if you suspect you have a hepatitis virus infection or have had it in the past. In a few cases, patients who have had viral hepatitis B may have a recurrence of hepatitis, with a possible fatal outcome. In patients with a history of hepatitis B virus infection, the doctor will closely monitor for signs of active hepatitis B. Before starting treatment with Bortezomib Krka, you should carefully read the leaflets of all medicines you are taking at the same time to obtain information about them. If you are taking thalidomide, you must rule out pregnancy and use effective contraception (see below "Pregnancy and breastfeeding").

Children and adolescents

Bortezomib Krka should not be used in children and adolescents, as it is not known how the medicine works in this group of people.

Bortezomib Krka and other medicines

You should tell your doctor about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take.

In particular, you should inform your doctor if you are taking medicines containing 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 for the treatment of epilepsy;
• St. John's Wort (Hypericum perforatum) for the treatment of depression and other conditions;
• oral antidiabetic drugs.

Pregnancy and breastfeeding

Bortezomib Krka should not be used during pregnancy, unless it is absolutely necessary.

Both men and women receiving Bortezomib Krka must use effective contraception during treatment and for 3 months after its completion. If, despite the use of contraception, you become pregnant, you should immediately tell your doctor.

You should not breastfeed during treatment with Bortezomib Krka. You should discuss with your doctor the safe time to return to breastfeeding after completing treatment.

Thalidomide causes birth defects and fetal death. When Bortezomib Krka is used in combination with thalidomide, patients must follow the "Thalidomide Pregnancy Prevention Program" (see thalidomide leaflet).

Driving and using machines

Bortezomib Krka may cause fatigue, dizziness, fainting, and blurred vision. If you experience these symptoms, you should not drive or operate tools or equipment; even if the symptoms do not occur, you should still be cautious.

3. How to use Bortezomib Krka

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

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

Progressive multiple myeloma

If Bortezomib Krka is administered as a single drug, the patient will receive 4 doses of Bortezomib Krka intravenously on days: 1, 4, 8, and 11, followed by a 10-day break in treatment. The described 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 Krka in combination with the drugs: pegylated liposomal doxorubicin or dexamethasone.

When Bortezomib Krka is administered in combination with pegylated liposomal doxorubicin, the patient will receive Bortezomib Krka intravenously during a 21-day treatment cycle, and pegylated liposomal doxorubicin will be administered at a dose of 30 mg/m2 in an intravenous infusion after the injection of Bortezomib Krka on day 4 of the 21-day cycle.

The patient may receive up to 8 cycles (24 weeks).

When Bortezomib Krka is administered in combination with dexamethasone, the patient will receive Bortezomib Krka intravenously 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 treatment cycle with Bortezomib Krka.

The patient may receive up to 8 cycles (24 weeks).

Previously untreated multiple myeloma

If the patient has not been previously treated for multiple myeloma and the patient does notqualify for hematopoietic stem cell transplantation, they will receive Bortezomib Krka in combination with other drugs: melphalan and prednisone.

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

• During cycles 1-4, Bortezomib Krka is administered twice a week, on days: 1, 4, 8, 11, 22, 25, 29, and 32.
• 25, 29, and 32.
• During cycles 5-9, Bortezomib Krka is administered once a week, 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 been previously treated for multiple myeloma and the patientqualifies for hematopoietic stem cell transplantation, they will receive Bortezomib Krka intravenously in combination with other drugs: dexamethasone or dexamethasone with thalidomide in induction treatment.

When Bortezomib Krka is administered with dexamethasone, the patient will receive Bortezomib Krka intravenously during a 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 treatment cycle with Bortezomib Krka.

The patient will receive up to 4 cycles (12 weeks).

When Bortezomib Krka is administered with dexamethasone and thalidomide, the duration of the treatment cycle is 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 treatment cycle with Bortezomib Krka, and thalidomide will be administered orally once a day at a dose of 50 mg until day 14 of the first cycle, and if the dose is tolerated, it will be increased to 100 mg on days 15-28 and may be further increased to 200 mg per day from the second cycle.

The patient may receive up to 6 cycles (24 weeks).

Previously untreated mantle cell lymphoma

If the patient has not been previously treated for mantle cell lymphoma, they will receive Bortezomib Krka intravenously in combination with the drugs: rituximab, cyclophosphamide, doxorubicin, and prednisone.

Bortezomib Krka is administered intravenously on days 1, 4, 8, and 11, followed by a "rest period" without administration of the drug. One treatment cycle lasts 21 days (3 weeks). The patient will receive up to 8 cycles (24 weeks).

The following drugs are administered as intravenous infusions on day 1 of each 21-day treatment cycle with Bortezomib Krka: 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 the treatment cycle with Bortezomib Krka.

How Bortezomib Krka is administered

This medicine is administered intravenously or subcutaneously. Bortezomib Krka will be administered by a qualified medical professional with experience in the use of cytotoxic drugs.

The powder of Bortezomib Krka must be dissolved before administration. The preparation of the medicine is carried out by a qualified medical professional.

Then, the prepared solution is injected quickly intravenously, over 3 to 5 seconds, or subcutaneously. The subcutaneous injection is given in the thigh or abdomen.

Use of a higher than recommended dose of Bortezomib Krka

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

If, exceptionally, this happens, the doctor will monitor the patient for any side effects.

4. Possible side effects

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

Some of these side effects may be serious.

If you are receiving Bortezomib Krka for the treatment of 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, or blurred 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 Bortezomib Krka may very often cause a decrease in the number of red and white blood cells and platelets in the patient's blood. Therefore, the patient will need to have frequent blood tests before and during treatment with Bortezomib Krka to regularly check the blood cell count.

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 occurring with or without bloating (symptoms may be severe);
• diarrhea: if it occurs, the patient should drink more water than usual. The doctor may recommend taking additional medicines to control diarrhea;
• fatigue, feeling of weakness;
• muscle pain, bone pain.

Common side effects (may affect less than 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, drowsiness, feeling of weakness or loss of consciousness;
• chills;
• infections, including: pneumonia, respiratory tract infections, bronchitis, fungal infections, cough with expectoration, flu-like symptoms;
• shingles (localized around the eyes or widespread on the body);
• chest pain, shortness of breath during exercise;
• various types of rash;
• itching of the skin, skin nodules or dryness of the skin;
• flushing of the face or bursting of blood vessels;
• redness of the skin;
• dehydration;
• heartburn, bloating, belching, gas, abdominal pain, gastrointestinal bleeding;
• liver function disorders;
• mouth pain or lip pain, dry mouth, mouth ulcers or throat pain;
• weight loss, loss of taste;
• muscle spasms, muscle weakness, muscle pain;
• blurred vision;
• infection of the outer layer of the eye and the mucous membrane lining the eyelids (conjunctivitis);
• nosebleeds;
• difficulty sleeping, increased 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 side effects (may affect less than 1 in 100 people):

• heart failure, heart attack, chest pain, feeling of discomfort in the chest, accelerated or slowed 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, viral herpes infections, ear infections, and connective tissue infections;
• blood in the stool, bleeding from mucous membranes, e.g., from the mouth, vagina;
• cerebrovascular disorders;
• paralysis, seizures, falls, movement disorders, abnormal or changed sensation (touch, hearing, taste, smell), attention disorders, tremors, muscle tremors;
• joint inflammation, including joint inflammation of the fingers, toes, and jaw;
• lung disorders, making breathing difficult. Some of these include: difficulty breathing, shortness of breath, shortness of breath at rest, shallow breathing, or cessation of breathing, wheezing;
• hiccups, speech disorders;
• increased or decreased urine production (due to kidney damage), pain when urinating or blood (or) protein in the urine, fluid retention;
• consciousness disorders, 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 resistance to normal insulin levels;
• eye irritation or inflammation, excessive tearing, eye pain, dry eyes, eye infections, eyelid cyst (hordeolum), redness and swelling of the eyelids, eye discharge, vision disorders, bleeding in the eyes;
• lymph node enlargement;
• joint stiffness or muscle stiffness, feeling of heaviness, pain in the groin;
• hair loss and abnormal hair structure;
• allergic reactions;
• redness or pain at the injection site;
• mouth pain;
• infections or inflammation of the mouth, esophagus, stomach, and intestines, sometimes with accompanying pain or bleeding, poor intestinal motility (including obstruction), feeling of discomfort in the abdominal or esophageal area, difficulty swallowing, vomiting blood;
• skin infections;
• bacterial and viral infections;
• tooth infection;
• pancreatitis, bile duct obstruction;
• genital pain, erectile dysfunction disorders;
• weight gain;
• thirst;
• hepatitis;
• disorders at the injection site or related to the use of a venous catheter;
• skin reactions and disorders (which can be severe and life-threatening), skin ulcers;
• bruises, falls, and injuries;
• inflammation or bleeding from blood vessels in the form of small red or purple spots (usually on the legs) to large, bruise-like spots under the skin;
• mild cysts;
• severe reversible brain disorders, including seizures, high blood pressure, headaches, fatigue, confusion, blindness, or other vision disorders.

Rare side effects (may affect less than 1 in 1000 people):

• heart disease, including heart attack, angina pectoris;
• severe nerve inflammation, which can cause paralysis and difficulty breathing (Guillain-Barré syndrome);
• flushing attacks;
• vein discoloration;
• spinal cord inflammation;
• ear diseases, ear bleeding;
• hypothyroidism;
• Budd-Chiari syndrome (clinical symptoms caused by blockage of liver veins);
• changed or abnormal intestinal motility;
• brain bleeding;
• yellowing of the eyes and skin (jaundice);
• severe allergic reaction (anaphylactic shock) with symptoms such as: difficulty breathing, pain or pressure in the chest and (or) feeling of dizziness or fainting, severe itching of the skin or hives on the skin, swelling of the face, lips, tongue, and (or) throat, which can cause difficulty breathing and swallowing, collapse;
• breast diseases;
• vaginal ulcers;
• genital swelling;
• alcohol intolerance;
• weight loss or gain;
• increased appetite;
• fistula;
• joint effusion;
• ganglion cyst;
• bone fractures;
• muscle fiber breakdown leading to further complications;
• liver swelling, liver bleeding;
• kidney cancer;
• skin changes similar to psoriasis;
• skin cancer;
• skin pallor;
• increased blood platelet count or plasma cells (a type of white blood cell);
• blood clotting in small blood vessels (microangiopathic thrombosis);
• abnormal reaction to blood transfusion;
• partial or complete loss of vision;
• decreased libido;
• salivation;
• exophthalmos;
• photosensitivity;
• accelerated breathing;
• rectal pain;
• gallstones;
• hernia;
• injuries;
• brittleness or weakness of nails;
• abnormal protein deposition in organs;
• coma;
• intestinal ulcers;
• multi-organ failure;
• death.

If you are receiving Bortezomib Krka in combination with other medicines for the treatment of 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 less than 1 in 10 people):

• shingles (localized around the eyes or widespread on the body);
• herpes virus infection;
• bacterial and viral infections;
• respiratory tract infections, bronchitis, cough with expectoration, flu-like symptoms;
• fungal infections;
• hypersensitivity (allergic reaction);
• insulin deficiency or resistance to normal insulin levels;
• fluid retention;
• sleep disorders;
• loss of consciousness;
• consciousness disorders, confusion;
• dizziness;
• accelerated heart rate, high blood pressure, sweating;
• abnormal vision, blurred vision;
• heart failure, heart attack, chest pain, feeling of discomfort in the chest, accelerated or slowed heart rate;
• high or low blood pressure;
• sudden drop in blood pressure when changing body position, which can lead to fainting;
• shortness of breath during exercise;
• cough;
• hiccups;
• ringing or discomfort in the ears;
• gastrointestinal bleeding;
• heartburn;
• abdominal pain, bloating;
• difficulty swallowing;
• infection or inflammation of the stomach or intestines;
• abdominal pain;
• mouth pain or lip pain, throat pain;
• liver function changes;
• itching of the skin;
• redness of the skin;
• 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 malaise;
• weight loss;
• weight gain.

Uncommon side effects (may affect less than 1 in 100 people):

• hepatitis;
• severe allergic reaction (anaphylactic reaction), whose symptoms may include: difficulty breathing, pain or pressure in the chest, feeling of dizziness or fainting, severe itching of the skin or hives on the skin, swelling of the face, lips, tongue, and (or) throat, which can cause difficulty swallowing, collapse;
• movement disorders, paralysis, muscle tremors;
• dizziness;
• hearing loss, deafness;
• lung disorders, making breathing difficult. Some of these include: difficulty breathing, shortness of breath, shortness of breath at rest, shallow breathing, or cessation of breathing, wheezing;

If you experience any side effects, including those not listed in this leaflet, you should tell your doctor, pharmacist, or nurse.

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, you should tell your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocidal Products of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products:

Jerozolimskie Avenue 181C, 02-222 Warsaw

tel.: +48 22 49 21 301

fax: +48 22 49 21 309

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 Bortezomib Krka

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 packaging after EXP. The expiry date refers to the last day of that month.

Do not store above 30°C.

Store the vial in the outer packaging to protect from light.

It has been demonstrated that the reconstituted solution is chemically and physically stable for up to 8 hours at 25°C in the original vial.

From a microbiological point of view, unless the method of opening/constitution precludes the risk of microbial contamination, the diluted solution should be used immediately. If not used immediately, the in-use storage times and conditions before administration are the responsibility of the user.

The total storage time of the diluted medicinal product before administration should not exceed 8 hours.

Do not use this medicine if you notice any damage to the vial.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the packaging and other information

What Bortezomib Krka contains

• The active substance of Bortezomib Krka is bortezomib. Each vial contains 3.5 mg of bortezomib (as boronic acid ester and mannitol).
• The other ingredients are mannitol and nitrogen.

What Bortezomib Krka looks like and contents of the pack

Bortezomib Krka powder for solution for injection is a white or off-white lyophilized powder or powder.

The vial is a 10 ml glass vial, type I, with a gray rubber stopper and a blue flip-off cap, containing 3.5 mg of bortezomib.

Bortezomib Krka is available in packs containing 1 vial.

Marketing authorization holder and manufacturer

Krka, d.d., Novo mesto

Šmarješka cesta 6

8501 Novo mesto

Slovenia

For further information on the medicinal product, please contact the local representative of the marketing authorization holder:

Krka-Polska Sp. z o.o.

Równoległa 5

02-235 Warsaw

tel. 22 57 37 500

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

DE:

Bortezomib Krka 1 mg Pulver zur Herstellung einer Injektionslösung

Bortezomib Krka 3.5 mg Pulver zur Herstellung einer Injektionslösung

SK:

CZ:

Bortezomib Krka

PL:

Bortezomib Krka

HU:

Bortezomib Krka 1 mg por oldatos injekcióhoz

Bortezomib Krka 3.5 mg por oldatos injekcióhoz

BG:

Бортезомиб Крка 1 mg прах за инжекционен разтвор

Бортезомиб Крка 3.5 mg прах за инжекционен разтвор

RO:

Bortezomib Krka 1 mg pulbere pentru soluţie injectabilă

Bortezomib Krka 3.5 mg pulbere pentru soluţie injectabilă

LT:

Bortezomib Krka 1 mg milteliai injekciniam tirpalui

Bortezomib Krka 3.5 mg milteliai injekciniam tirpalui

LV:

Bortezomib Krka 1 mg pulveris injekciju šķīduma pagatavošanai

Bortezomib Krka 3.5 mg pulveris injekciju šķīduma pagatavošanai

EE:

Bortezomib Krka

SI:

Bortezomib Krka 1 mg prašek za raztopino za injiciranje

Bortezomib Krka 3.5 mg prašek za raztopino za injiciranje

HR:

Bortezomib Krka 1 mg prašak za otopinu za injekciju

Bortezomib Krka 3.5 mg prašak za otopinu za injekciju

AT:

Bortezomib HCS 1 mg Pulver zur Herstellung einer Injektionslösung

Bortezomib HCS 3.5 mg Pulver zur Herstellung einer Injektionslösung

BE:

Bortezomib Krka 1 mg poeder voor oplossing voor injectie

Bortezomib Krka 3.5 mg poeder voor oplossing voor injectie

DK:

Bortezomib Krka

Date of last revision of the leaflet:29.04.2021

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Information intended for healthcare professionals only:

Bortezomib Krka, 3.5 mg, powder for solution for injection

1. Preparation of the solution for intravenous injection

Caution: Bortezomib Krka is a cytotoxic drug. When handling the drug and preparing it for use, caution should be exercised. To protect the skin from contact with the drug, it is recommended to wear gloves and other protective clothing.

AS BORTEZOMIB KRKA DOES NOT CONTAIN PRESERVATIVES, ASEPTIC TECHNIQUES MUST BE STRICTLY FOLLOWED WHEN HANDLING THE DRUG.

• 1.1 Preparation of the vial: carefully add 3.5 mlof sterile, 9 mg/ml (0.9%) sodium chloride solution for injection to the vial containing the Bortezomib Krka powder, using a 1 ml syringe, without removing the vial cap. The dissolution of the lyophilized powder takes less than 2 minutes. The concentration of the resulting solution will be 1 mg/ml. After dissolution, 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, the solution should be visually inspected for particulate matter and discoloration. If any discoloration or precipitate is observed, the solution should be discarded. The concentration on the vial should be checked to ensure that the correct dose is administered intravenously(1 mg/ml).
• 1.3 The prepared solution does not contain preservatives and should be used immediately after preparation. However, the chemical and physical stability of the prepared solution is maintained for up to 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 diluted solution is not administered immediately, the person administering the drug to the patient is responsible for the storage time and conditions before use. There is no need to protect the prepared solution from light.

2. Administration

• After dissolution, the appropriate amount of the prepared solution should be drawn up according to the dose calculated based on the patient's body surface area.
• Before administration, the dose and concentration of the drug in the syringe should be confirmed (check if the syringe is labeled for intravenous administration).
• The solution is injected intravenously over 3 to 5 seconds (bolus) through a peripheral or central venous catheter.
• The intravenous catheter through which the drug was administered should be flushed with a small amount of sterile 9 mg/ml (0.9%) sodium chloride solution.

Bortezomib Krka 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 drug

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

Any unused product or waste material should be disposed of in accordance with local regulations.

The following information is intended for healthcare professionals only:

Only the 3.5 mg vial can be used for subcutaneous administration, as described below.

1. Preparation of the solution for subcutaneous injection

Caution: Bortezomib Krka is a cytotoxic drug. When handling the drug and preparing it for use, caution should be exercised. To protect the skin from contact with the drug, it is recommended to wear gloves and other protective clothing.

AS BORTEZOMIB KRKA DOES NOT CONTAIN PRESERVATIVES, ASEPTIC TECHNIQUES MUST BE STRICTLY FOLLOWED WHEN HANDLING THE DRUG.

• 1.4 Preparation of the vial: carefully add 1.4 mlof sterile, 9 mg/ml (0.9%) sodium chloride solution for injection to the vial containing the Bortezomib Krka powder, using an appropriate syringe, without removing the vial cap. The dissolution of the lyophilized powder takes less than 2 minutes. The concentration of the resulting solution will be 2.5 mg/ml. After dissolution, 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.
• 1.5 Before administration, the solution should be visually inspected for particulate matter and discoloration. If any discoloration or precipitate is observed, the solution should be discarded. The concentration on the vial should be checked to ensure that the correct dose is administered subcutaneously(2.5 mg/ml).
• 1.6 The prepared solution does not contain preservatives and should be used immediately after preparation. However, the chemical and physical stability of the prepared solution is maintained for up to 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 diluted solution is not administered immediately, the person administering the drug to the patient is responsible for the storage time and conditions before use. There is no need to protect the prepared solution from light.

2. Administration

• After dissolution, the appropriate amount of the prepared solution should be drawn up according to the dose calculated based on the patient's body surface area.
• Before administration, the dose and concentration of the drug in the syringe should be confirmed (check if the syringe is labeled for subcutaneous administration).
• The solution is injected subcutaneously at an angle of 45-90°.
• The prepared solution is administered subcutaneously in the thigh (right or left) or abdomen (right or left).
• The injection site should be changed for each subsequent injection.
• If a local reaction occurs after subcutaneous injection of Bortezomib Krka, it is recommended to administer the solution subcutaneously with a lower concentration (dilution to 1 mg/ml instead of 2.5 mg/ml) or to change to intravenous administration.

3. DISPOSAL OF THE MEDICINE

The vial is intended for single use only and any remaining solution should be
discarded.
Any unused product or waste material should be disposed of in accordance with local
regulations.