Vortemiel

Leaflet accompanying the packaging: information for the user

Vortemyel, 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.
• In case of any doubts, you should consult a doctor, pharmacist, or nurse.
• This medicine has been prescribed specifically for you. 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 side effects not listed in this leaflet, they should tell their doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet

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

1. What is Vortemyel and what is it used for

Vortemyel 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.
Vortemyel is used to treat multiple myeloma (a bone marrow cancer) in patients over 18 years of age:
as a single medicine or in combination with other medicines: pegylated liposomal doxorubicin or dexamethasone in patients:

• whose disease has worsened (progressed) after previous treatment with at least one other type of treatment or whose hematopoietic stem cell transplantation was unsuccessful or not possible;
• in combination with medicines: 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 medicines: 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).

Vortemyel is used to treat mantle cell lymphoma (a type of cancer that affects the lymph nodes) in patients over 18 years of age in combination with medicines: 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 Vortemyel

When not to use Vortemyel

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

Warnings and precautions

The patient should inform their doctor if they:

• have a low number of red or white blood cells;
• have bleeding disorders and (or) a low number of platelets;
• 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 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);
• experience 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 serious brain infection, and the doctor may recommend further tests and observation.

The patient must have regular blood tests before and during treatment with Vortemyel to regularly check the number of blood cells.
If the patient is taking Vortemyel in combination with rituximab, they should tell their doctor:

Before starting treatment with Vortemyel, the patient should carefully read the leaflets of all medicinal products taken during treatment to obtain information about them. When taking thalidomide, pregnancy must be excluded, and effective contraception must be used (see section Pregnancy and breastfeeding).

Children and adolescents

Vortemyel should not be used in children and adolescents, as it is not known how the medicine works in this age group.

Vortemyel 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, including those available without a prescription.
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 conditions;
• oral antidiabetic medicines.

Pregnancy and breastfeeding

Vortemyel should not be used during pregnancy unless it is absolutely necessary.
Both men and women receiving Vortemyel must use effective contraception during and for 3 months after the end of treatment. If, despite the use of these methods, the patient becomes pregnant, they should immediately inform their doctor.
Patients should not breastfeed during treatment with Vortemyel. It is necessary to discuss with the doctor the issue of a safe return to breastfeeding after the end of treatment in the patient.
Thalidomide causes birth defects and fetal death. When Vortemyel is used in combination with thalidomide, patients must follow the "Thalidomide Pregnancy Prevention Program" (see thalidomide leaflet).

Driving and using machines

Vortemyel may cause fatigue, dizziness, fainting, and blurred vision. If these symptoms occur, the patient should not drive or operate tools or machines. If the symptoms do not occur, the patient should be cautious.

3. How to use Vortemyel

The doctor will adjust the appropriate dose of Vortemyel for the patient based on their height and weight (body surface area). The most commonly used initial dose of Vortemyel 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, the occurrence of side effects, and additional diseases (e.g., liver problems).
Progressive multiple myeloma
If Vortemyel is administered as a single medicine, the patient will receive 4 doses of Vortemyel intravenously or subcutaneously on days 1, 4, 8, and 11, followed by a 10-day break in treatment. One treatment cycle lasts 21 days (3 weeks). The patient may receive up to 8 cycles (24 weeks).
The patient may also receive Vortemyel in combination with other medicines: pegylated liposomal doxorubicin or dexamethasone.
When Vortemyel is administered in combination with pegylated liposomal doxorubicin, the patient will receive Vortemyel intravenously or subcutaneously during a 21-day treatment cycle, and pegylated liposomal doxorubicin will be administered in a dose of 30 mg/m2 in an intravenous infusion after Vortemyel injection on day 4 of the 21-day cycle. The patient may receive up to 8 cycles (24 weeks).
When Vortemyel is administered in combination with dexamethasone, the patient will receive Vortemyel intravenously or subcutaneously during a 21-day treatment cycle, and dexamethasone will be administered orally in a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of the 21-day Vortemyel treatment cycle. 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 not qualify
for hematopoietic stem cell transplantation, they will receive Vortemyel intravenously in combination with other medicines: melphalan and prednisone.
In this case, the treatment cycle lasts 42 days (6 weeks). The patient will receive 9 cycles (54 weeks).

• During cycles 1-4, Vortemyel is administered twice a week, on days 1, 4, 8, 11, 22, 25,
• 29, and 32.
• During cycles 5-9, Vortemyel 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 patient qualifiesfor hematopoietic stem cell transplantation, they will receive Vortemyel intravenously or subcutaneously in combination with other medicines: dexamethasone or dexamethasone with thalidomide in induction treatment.
When Vortemyel is administered with dexamethasone, the patient will receive Vortemyel intravenously or subcutaneously in a 21-day cycle, and dexamethasone will be administered orally in a dose of 40 mg on days 1, 2, 3, 4, 8, 9, 10, and 11 of the 21-day Vortemyel treatment cycle. The patient may receive up to 4 cycles (12 weeks).
When Vortemyel is administered with dexamethasone and thalidomide, the treatment cycle lasts 28 days (4 weeks). Dexamethasone will be administered orally in a dose of 40 mg on days 1, 2, 3, 4, 8, 9, 10, and 11 of the 28-day Vortemyel treatment cycle, and thalidomide will be administered orally once a day in 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 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 Vortemyel intravenously or subcutaneously in combination with medicines: rituximab, cyclophosphamide, doxorubicin, and prednisone.
Vortemyel is 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 (24 weeks).
The following medicines are administered as intravenous infusions on day 1 of each 21-day Vortemyel cycle: rituximab in a dose of 375 mg/m2, cyclophosphamide in a dose of 750 mg/m2, and doxorubicin in a dose of 50 mg/m2.
Prednisone is administered orally in a dose of 100 mg/m2 on days 1, 2, 3, 4, and 5 of the Vortemyel cycle.

Method of administration of Vortemyel

This medicine is administered intravenously or subcutaneously. Vortemyel will be administered by a qualified medical professional with experience in the use of cytotoxic medicines.
The Vortemyel powder must be dissolved before administration. The preparation of the medicine is carried out by a qualified medical professional. The prepared solution is injected intravenously or subcutaneously. Intravenous injection is rapid, lasting 3 to 5 seconds.
Subcutaneous injection is administered into the thigh or abdomen.

Use of a higher than recommended dose of Vortemyel

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

4. Possible side effects

Like all medicines, Vortemyel can cause side effects, although not everybody gets them.
Some of the side effects may be serious.
If the patient is receiving Vortemyel for the treatment of multiple myeloma or mantle cell lymphoma, they should immediately tell their doctor if they 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 bortezomib 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 must have frequent blood tests before and during treatment with Vortemyel to regularly check the number of blood cells. The patient may experience a decrease in:

• platelets, which may cause a tendency to bruise or bleed without injury (e.g., gastrointestinal bleeding, bleeding from the mouth, gums, or nose);
• red blood cells, which may lead to anemia, which is accompanied by symptoms such as fatigue and pallor;
• white blood cells, which may lead to increased susceptibility to infections or the occurrence of flu-like symptoms.

If the patient is receiving Vortemyel for the treatment of multiple myeloma, they may experience the following side effects:

Very common side effects(occurring in more than 1 in 10 people):

• allergic reactions, numbness, tingling, or burning sensation of the skin, 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 (symptoms may be severe)
• diarrhea: in case of diarrhea, the patient should drink more water than usual, and the doctor may recommend taking additional medicines to treat diarrhea
• fatigue, feeling of weakness
• muscle pain, bone pain.

Common side effects(occurring in less than 1 in 10 people):

• decreased blood pressure, sudden decrease in blood pressure when standing up, which may lead to fainting
• increased blood pressure
• decreased kidney function
• headache
• general malaise, pain, dizziness, drowsiness, 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
• rash of various types
• itching, skin rash, or dry skin
• flushing of the face or bursting of blood vessels
• redness of the skin
• dehydration
• heartburn, bloating, belching, gas, stomach pain, gastrointestinal bleeding
• liver function disorders
• mouth or lip inflammation, dry mouth, mouth ulcers
• weight loss, loss of taste
• muscle spasms, muscle weakness, limb pain
• blurred vision
• eye infection or inflammation, 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(occurring in less than 1 in 100 people):

• heart failure, heart attack, chest pain, 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 or fluid in the sac
• infections, including urinary tract infections, flu, herpes, ear and soft tissue infections
• blood in the stool, bleeding from mucous membranes, e.g., from the mouth, vagina
• disorders of blood vessels in the brain
• paralysis, seizures, falls, movement disorders, abnormal or changed sensation (touch, hearing, taste, smell), attention disorders, tremors, shaking
• joint inflammation, including inflammation of the fingers, toes, and jaw joints.
• 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, wheezing
• 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
• allergic reactions
• 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, eye bleeding
• lymph node enlargement
• joint stiffness, muscle cramps, or tremors, groin pain
• 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 and bleeding, slowed intestinal movement (including intestinal 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
• weight gain
• thirst
• hepatitis
• disorders related to the injection site or use of a vascular 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 spots similar to bruises under the skin
• mild cysts
• severe reversible disorders of brain function, which include seizures, increased blood pressure, headache, fatigue, confusion, blindness, or other vision disorders.

Rare side effects(occurring in less than 1 in 1,000 people)

• heart disease, including heart attack, angina pectoris
• skin redness
• vein discoloration
• microangiopathic thrombosis (blood clots in small blood vessels)
• inflammation of the spinal cord
• 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)
• severe allergic reaction (anaphylactic shock) with symptoms such as: difficulty breathing, pain or pressure in the chest, and (or) feeling of dizziness/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 disorders
• vaginal ulceration
• genital swelling
• alcohol intolerance
• weight loss or gain
• increased appetite
• fistula
• joint effusion
• ganglion cyst
• bone fractures
• rhabdomyolysis leading to further complications
• liver swelling, liver bleeding
• kidney cancer
• skin condition similar to psoriasis
• skin cancer
• skin pallor
• increased platelet count or plasma cells (a type of white blood cell)
• abnormal reaction to blood transfusion
• partial or complete loss of vision
• decreased libido
• excessive salivation
• exophthalmos
• photosensitivity
• increased respiratory rate
• rectal pain
• gallstones
• hernia
• injuries
• brittle or weak nails
• abnormal protein deposition in organs
• coma
• intestinal ulcers
• multi-organ failure
• death
• severe nerve inflammation, which can cause paralysis and difficulty breathing (Guillain-Barré syndrome).

If the patient is receiving Vortemyel in combination with other medicines for the treatment of mantle cell lymphoma, they may experience the following side effects:

Very common side effects (occurring in more than 1 in 10 people):

• pneumonia;
• loss of appetite;
• allergic reactions, numbness, tingling, or burning sensation of the skin, pain in the hands or feet caused by 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 (occurring in less than 1 in 10 people):

• shingles (localized, e.g., around the eyes or widespread on the body);
• herpes virus infection;
• bacterial and viral infections;
• respiratory tract infections, bronchitis, wet cough, flu-like symptoms;
• fungal infections;
• allergic reactions;
• insulin deficiency or insulin resistance;
• fluid retention;
• difficulty sleeping and sleep disorders;
• loss of consciousness;
• altered level of consciousness, confusion;
• dizziness;
• accelerated heart rate, high blood pressure, sweating;
• abnormal vision, blurred vision;
• heart failure, heart attack, chest pain, discomfort in the chest, accelerated or slowed heart rate;
• high or low blood pressure;
• sudden drop in blood pressure when changing body position, which may lead to fainting;
• shortness of breath during exercise;
• cough;
• hiccups;
• ringing or discomfort in the ears;
• gastrointestinal bleeding;
• heartburn;
• abdominal pain, belching;
• difficulty swallowing;
• infection or inflammation of the stomach or intestines;
• abdominal pain;
• mouth or lip inflammation, sore throat;
• liver function disorders;
• itching;
• skin redness;
• rash;
• muscle cramps;
• 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 (occurring in less than 1 in 100 people)

• hepatitis;
• severe allergic reaction (anaphylactic reaction), which may include symptoms such as: difficulty breathing, pain or pressure in the chest, and (or) feeling of dizziness/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 that make breathing difficult. Some of these include: difficulty breathing, shortness of breath, shortness of breath at rest, shallow breathing, or cessation of breathing, wheezing;
• blood clots in the lungs; jaundice (yellowing of the skin and eyes) stye (hordeolum), eyelid redness and swelling

Rare side effects (occurring in less than 1 in 1,000 people)

• blood clots in small blood vessels (microangiopathic thrombosis).

Reporting side effects

If side effects occur, including any side effects not listed in the leaflet, the patient should tell their 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
Al. Jerozolimskie 181C, 02-222 Warsaw
Phone: +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, more information can be collected on the safety of the medicine.

5. How to store Vortemyel

Store the medicine out of sight and reach of children.
Do not use the medicine after the expiry date stated on the carton after "EXP".
Store the vial in the outer packaging to protect it from light.
There are no special storage temperature requirements.
Reconstituted solution
The physical and chemical stability of the prepared solution has been demonstrated for 8 hours at 25°C/60% RH in the dark, both in vials and polypropylene syringes.
From a microbiological point of view, the product should be used immediately. If the diluted solution is not used immediately, the responsibility for the storage time and conditions before administration lies with the healthcare professional administering the product. This time should not normally exceed 24 hours at 2-8°C if the reconstitution/dilution was performed under aseptic conditions. The total storage time of the solution after reconstitution before administration should not exceed 8 hours.