Bortezomib Glenmark

Leaflet accompanying the packaging: information for the user

Bortezomib Glenmark, 3.5 mg, powder for solution for injection

Read the leaflet carefully before using the medicine, as it contains

important information for the patient.

• Keep this leaflet, you may need to read it again.
• In case of any doubts, consult a doctor or pharmacist.
• This medicine has been prescribed specifically for this person. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any not listed in this leaflet, they should tell their doctor or pharmacist. See section 4.

Table of contents of the leaflet

• 1. What is Bortezomib Glenmark and what is it used for
• 2. Important information before using Bortezomib Glenmark
• 3. How to use Bortezomib Glenmark
• 4. Possible side effects
• 5. How to store Bortezomib Glenmark
• 6. Package contents and other information

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

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

• as a single medicine or in combination with other medicines containing pegylated liposomal doxorubicin or dexamethasone in patients whose disease has worsened (progressed) after at least one previous treatment and in whom hematopoietic stem cell transplantation has failed or is not possible;
• in combination with medicines containing melphalan and prednisone in patients who have not received prior treatment and do not qualify for high-dose chemotherapy with hematopoietic stem cell transplantation.
• in combination with medicines containing 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 Glenmark is used to treat mantle cell lymphoma (a type of lymph node cancer) in patients over 18 years of age in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone, who have not been previously treated and do not qualify for hematopoietic stem cell transplantation.

2. Important information before using Bortezomib Glenmark

When not to use Bortezomib Glenmark:

• if the patient is allergic to bortezomib or any of the other ingredients of this medicine (listed in section 6).
• if the patient has certain severe lung or heart diseases.

Warnings and precautions

Before starting treatment with Bortezomib Glenmark, the patient should discuss with their doctor or pharmacist if they:

• 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 the 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, disorientation, vision loss, or shortness of breath
• have memory loss, thinking disorders, difficulty walking, or vision loss. These may be symptoms of a serious brain infection, and the doctor may recommend further tests and monitoring.

The doctor will recommend that the patient have regular blood tests before and during treatment with Bortezomib Glenmark to regularly check the number of blood cells.
If the patient has mantle cell lymphoma and is also receiving rituximab with Bortezomib Glenmark, they should tell their doctor:

• if they suspect or have had hepatitis B virus infection in the past. In some patients who have had hepatitis B virus infection, recurring hepatitis may occur, which can be fatal. If the patient has ever had hepatitis B virus infection, they will be closely monitored by their doctor for signs of active hepatitis.

Before starting treatment with Bortezomib Glenmark, the patient should carefully read the leaflets of all medicinal products taken at the same time as Bortezomib Glenmark to obtain additional information. If the patient is taking thalidomide, they should check if they are not pregnant and should use effective contraception (see section Pregnancy and breastfeeding).

Children and adolescents

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

Bortezomib Glenmark and other medicines

The patient should tell their doctor or pharmacist about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take.
In particular, the patient should inform their doctor if they 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 diseases
• oral antidiabetic drugs

Pregnancy and breastfeeding

Bortezomib Glenmark should not be used during pregnancy, unless it is absolutely necessary.
Women of childbearing age must use effective contraception during treatment and for 8 months after its completion. The patient should discuss with their doctor if they want to freeze eggs before starting treatment.
Men should not father a child while using Bortezomib Glenmark and should use effective contraception during treatment and for up to 5 months after its completion. Before starting treatment, the patient should discuss with their doctor if they want to store sperm.
Patient should not breastfeed while using Bortezomib Glenmark. The patient should discuss with their doctor a safe time to resume breastfeeding after completing treatment.
Thalidomide causes birth defects and fetal death. If Bortezomib Glenmark is used in combination with thalidomide, patients must follow the "Thalidomide Pregnancy Prevention Program" (see thalidomide leaflet).

Driving and using machines

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

3. How to use Bortezomib Glenmark

The doctor will adjust the appropriate dose of Bortezomib Glenmark for the patient based on their height and weight (body surface area). The most commonly used initial dose of Bortezomib Glenmark is 1.3 mg/m2 body surface area administered twice a week.
The doctor may change the dose and total number of treatment cycles depending on the patient's response to treatment or the occurrence of side effects and the patient's condition (e.g., if the patient has liver disease).
Progressive multiple myeloma
If Bortezomib Glenmark is used as a single medicine, the patient will receive 4 doses of Bortezomib Glenmark intravenously or subcutaneously on days: 1, 4, 8, and 11, followed by a 10-day break in treatment.
The described 21-day treatment (3 weeks) is defined as one treatment cycle. The patient may receive up to 8 cycles of treatment (24 weeks).
The patient may also receive Bortezomib Glenmark at the same time as medicines containing pegylated liposomal doxorubicin or dexamethasone.
If Bortezomib Glenmark is used in combination with pegylated liposomal doxorubicin, the patient will receive Bortezomib Glenmark intravenously or subcutaneously during a 21-day treatment cycle. Pegylated liposomal doxorubicin will be administered at a dose of 30 mg/m2 body surface area as an intravenous infusion after Bortezomib Glenmark injection on day 4 of the 21-day Bortezomib Glenmark treatment cycle. The patient may receive up to 8 cycles of treatment (24 weeks).
If Bortezomib Glenmark is used in combination with dexamethasone, the patient will receive Bortezomib Glenmark intravenously or subcutaneously during a 21-day treatment cycle. 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 Bortezomib Glenmark treatment cycle. The patient may receive up to 8 cycles of treatment (24 weeks).
Previously untreated multiple myeloma
If the patient has not been previously treated for multiple myeloma and does not qualifyfor hematopoietic stem cell transplantation, they will receive Bortezomib Glenmark at the same time as two other medicines containing melphalan and prednisone.
In this case, the treatment cycle lasts 42 days (6 weeks). The patient will receive 9 cycles of treatment (54 weeks).

• During cycles 1 to 4, Bortezomib Glenmark will be administered twice a week, on days: 1, 4, 8, 11, 22, 25, 29, and 32.
• 8, 11, 22, and 32.
• During cycles 5 to 9, Bortezomib Glenmark will be administered once a week, on days: 1, 8, 22, and 29. Both melphalan (at a dose of 9 mg/m2 body surface area) and prednisone (at a dose of 60 mg/m2 body surface area) will be administered orally on days 1, 2, 3, and 4 of the first week of each cycle.
• 29. Both melphalan (at a dose of 9 mg/m2 body surface area) and prednisone (at a dose of 60 mg/m2 body surface area) will be 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 qualifiesfor hematopoietic stem cell transplantation, they will receive Bortezomib Glenmark intravenously or subcutaneously at the same time as medicines containing dexamethasone or dexamethasone with thalidomide as initial treatment (induction treatment).
If Bortezomib Glenmark is used in combination with dexamethasone, the patient will receive Bortezomib Glenmark intravenously or subcutaneously during a 21-day treatment cycle. 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 Bortezomib Glenmark treatment cycle. The patient may receive up to 4 cycles of treatment (12 weeks).
If Bortezomib Glenmark is used in combination with thalidomide and dexamethasone, 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 Bortezomib Glenmark treatment cycle, and thalidomide will be administered orally once a day 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 to 28 and then may be increased to 200 mg per day from the second cycle onwards. The patient may receive up to 6 cycles of treatment (24 weeks).
Previously untreated mantle cell lymphoma
If the patient has not been previously treated for mantle cell lymphoma, they will receive Bortezomib Glenmark intravenously or subcutaneously at the same time as medicines containing rituximab, cyclophosphamide, doxorubicin, and prednisone. Bortezomib Glenmark 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). The patient may receive up to 8 cycles of treatment (24 weeks).
The following medicines will be administered as intravenous infusions on day 1 of each 21-day Bortezomib Glenmark treatment cycle:

• Rituximab at a dose of 375 mg/m2 body surface area, cyclophosphamide at a dose of 750 mg/m2 body surface area, and doxorubicin at a dose of 50 mg/m2 body surface area.

Prednisone will be administered orally at a dose of 100 mg/m2 body surface area on days 1, 2, 3, 4, and 5 of the Bortezomib Glenmark treatment cycle.

How to use Bortezomib Glenmark

This medicine is administered intravenously or subcutaneously. Bortezomib Glenmark will be administered by medical personnel experienced in the use of cytotoxic medicines.
The powder of Bortezomib Glenmark must be dissolved before administration. The preparation of the medicine for administration is carried out by medical personnel. The prepared solution is then either injected intravenously or subcutaneously. The injection is administered quickly over 3 to 5 seconds. Subcutaneous injection is performed either in the thigh or in the abdomen.

Use of a higher than recommended dose of Bortezomib Glenmark

Since this medicine is administered by a doctor or nurse, it is unlikely that the patient will receive too much medicine. If this happens, the doctor will monitor the patient for side effects.

4. Possible side effects

Like all medicines, Bortezomib Glenmark can cause side effects, although not everybody gets them.
Some of these side effects may be serious.
If the patient is receiving Bortezomib Glenmark for multiple myeloma or mantle cell lymphoma, they should immediately tell their doctor if they experience any of the following symptoms:

• muscle cramps, muscle weakness
• disorientation, vision loss or disturbances, 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 Glenmark may very often cause a decrease in the number of red and white blood cells and platelets in the patient's blood. Therefore, the doctor will order frequent blood tests before and during treatment with Bortezomib Glenmark to regularly monitor the number of blood cells.
The patient may experience a decrease in the number of:

• platelets, which may cause a tendency to bruise or bleed without being caused by injury (e.g., bleeding from the intestines, stomach, mouth, and gums, or bleeding in the brain or liver)
• red blood cells, which may lead to anemia, which is characterized by symptoms such as fatigue and paleness
• white blood cells, which may lead to increased susceptibility to infections or symptoms similar to the flu

If the patient is receiving Bortezomib Glenmark for multiple myeloma, the following side effects may occur:

Very common side effects (may affect more than 1 in 10 people)

• hypersensitivity, numbness, tingling, or burning sensation of the skin, or pain in the hands or feet caused by 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 (the severity of symptoms may be significant)
• diarrhea: if it occurs, it is important for the patient to drink more water than usual. The doctor may recommend taking other medicines for 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 may lead to fainting
• high blood pressure
• impaired kidney function
• headache
• general malaise, pain, dizziness, lightheadedness, feeling of weakness or loss of consciousness
• chills
• infections, including pneumonia, respiratory tract infections, bronchitis, fungal infections, wet cough, 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 of the skin, skin nodules or dry skin
• flushing of the face or bursting of blood vessels
• redness of the skin
• dehydration
• heartburn, bloating, belching, gas, abdominal pain, bleeding from the intestines or stomach
• liver function disorders
• mouth or lip pain, mouth or throat ulcers
• weight loss, loss of taste
• muscle cramps, muscle weakness, limb pain
• blurred vision
• inflammation of the outer layer of the eye or conjunctivitis
• nosebleeds
• difficulty sleeping, sweating, anxiety, mood swings, depression, restlessness, agitation, or 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 pulmonary veins
• 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 infections, and connective tissue inflammation
• blood in the stool, bleeding from mucous membranes, e.g., from the mouth, vagina
• brain blood vessel disorders
• paralysis, seizures, falls, movement disorders, abnormal or changed senses (touch, hearing, taste, smell), attention disorders, tremors, jerky movements
• joint inflammation, including inflammation of the joints of the fingers, toes, and jaw
• lung disorders that cause the body to not be properly supplied with oxygen. 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 (caused by kidney damage), painful urination, or blood/protein in the urine, fluid retention
• changed level of consciousness, disorientation
• hypersensitivity
• hearing loss, deafness, ringing, or discomfort in the ears
• hormonal disorders that can affect salt and water absorption
• hyperthyroidism
• insulin deficiency or lack of tissue sensitivity to normal insulin levels
• eye irritation or inflammation, excessive tearing, eye pain, dry eyes, eye infections, glaucoma, and redness and swelling of the eyelids, eye discharge, vision disturbances, eye bleeding
• lymph node enlargement
• joint stiffness or muscle stiffness, feeling of heaviness, groin pain
• hair loss and abnormal hair structure
• allergic reactions
• redness or pain at the injection site
• mouth ulcers
• infections or inflammation of the mouth, esophagus, stomach, and intestines, sometimes with accompanying pain and bleeding, impaired intestinal motility (including obstruction), abdominal discomfort, and esophageal discomfort, difficulty swallowing, vomiting blood
• skin infection
• bacterial and viral infections
• tooth infection
• pancreatitis, bile duct obstruction
• genital pain, erectile dysfunction disorders
• weight gain
• thirst
• liver inflammation
• changes at the injection site or related to the use of a vascular catheter
• skin reactions and changes (which can be severe and life-threatening), skin ulcers
• bruises, falls, and injuries
• inflammation or bleeding from blood vessels, manifested by small red or purple spots (usually on the legs) to large spots similar to bruises under the skin or in deeper layers
• mild cysts
• severe, reversible brain disorder that includes seizures, high blood pressure, headache, fatigue, disorientation, blindness, or other vision disturbances

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

• heart diseases, including heart attack, angina pectoris
• flushing attacks
• vein discoloration
• spinal cord inflammation
• ear diseases, ear bleeding
• hypothyroidism
• Budd-Chiari syndrome (clinical symptoms caused by obstruction of the hepatic veins)
• changed or abnormal intestinal function
• brain bleeding
• yellowing of the eyes and skin (jaundice)
• glaucoma and redness and swelling of the eyelids

Very rare side effects (may affect less than 1 in 10,000 people)

• blood clots in small blood vessels (microangiopathic thrombosis)

Reporting side effects

If side effects occur, including any not listed in this leaflet, the patient should tell their doctor or pharmacist. Side effects can be reported directly to the Department of Adverse Reaction Monitoring 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
Side effects can also be reported to the marketing authorization holder.
Reporting side effects will help gather more information on the safety of the medicine.

5. How to store Bortezomib Glenmark

The medicine should be stored out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton after EXP. or on the vial label after EXP.
The vial should be stored in the carton to protect it from light.
There are no special storage temperature requirements for the medicine.
It has been shown that the medicine is chemically and physically stable for 8 hours when stored at 25°C and 60% RH, if stored in the dark, both in the vial and in the polypropylene syringe.
From a microbiological point of view, the prepared solution must be used immediately. If the prepared solution is not used immediately, the time and conditions of its storage before administration are the responsibility of the person administering the medicine. Usually, the medicine should not be stored for more than 24 hours at a temperature between 2°C and 8°C, unless the solution was prepared in controlled and validated aseptic conditions.
Bortezomib Glenmark is for single use only and any unused solution should be discarded.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

6. Package contents and other information

What Bortezomib Glenmark contains

• The active substance is bortezomib. Each vial contains 3.5 mg of bortezomib (as a mannitol and boric acid ester).
• The other ingredient is mannitol.

Intravenous injection solution:
After dissolution, 1 ml of intravenous injection solution contains 1 mg of bortezomib.
Subcutaneous injection solution:
After dissolution, 1 ml of subcutaneous injection solution contains 2.5 mg of bortezomib.

What Bortezomib Glenmark looks like and contents of the pack

Bortezomib Glenmark powder for solution for injection is a white or almost white lyophilized powder or powder.
Bortezomib Glenmark powder for solution for injection is available in a pack containing a vial with a rubber stopper and a plastic flip-off cap.
Each pack contains 1 vial for single use.

Marketing authorization holder

Glenmark Pharmaceuticals s.r.o.
Hvězdova 1716/2b
140 78 Prague 4
Czech Republic

Manufacturer

Synthon Hispania SL
C/ Castelló 1101, Pol. Las Salinas
Sant Boi de Llobregat
08830, Barcelona
Spain
Synthon s.r.o.
Brněská 32/c.p.597
678 01 Blansko
Czech Republic