BORTEZOMIB 2.5 MG POWDER FOR SOLUTION FOR INJECTION - patient leaflet, side effects, dosage

Patient leaflet - BORTEZOMIB 2.5 MG POWDER FOR SOLUTION FOR INJECTION

Bortezomib 2.5 mg

powder for solution for injection

Bortezomib

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

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

What is in this leaflet

1. What Bortezomib is and what it is used for
2. What you need to know before you use Bortezomib
3. How to use Bortezomib
4. Possible side effects
5. How to store Bortezomib
6. Contents of the pack and other information

1. what bortezomib is and what it is used for

Bortezomib contains the active substance bortezomib, a so-called ‘proteasome inhibitor’. Proteasomes play an important role in controlling cell function and growth. By interfering with their function, bortezomib can kill cancer cells.

Bortezomib is used for the treatment of multiple myeloma (a cancer of the bone marrow) in patients older than 18 years: alone or together with the medicines pegylated liposomal doxorubicin or dexamethasone, for patients whose disease is worsening (progressive) after receiving at least one prior treatment and for whom blood stem cell transplantation was not successful or is unsuitable.
in combination with the medicines melphalan and prednisone, for patients whose disease has not been previously treated and are unsuitable for high-dose chemotherapy with blood stem cell transplantation.
in combination with the medicines dexamethasone or dexamethasone together with thalidomide, for patients whose disease has not been previously treated and before receiving high-dose chemotherapy with blood stem cell transplantation (induction treatment).

Bortezomib is used for the treatment of mantle cell lymphoma (a type of cancer affecting the lymph nodes) in patients 18 years or older in combination with the medicines rituximab, cyclophosphamide, doxorubicin and prednisone, for patients whose disease has not been previously treated and for whom blood stem cell transplantation is unsuitable.

2. what you need to know before you use bortezomib

Do not use Bortezomib

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

Warnings and precautions

Talk to your doctor or pharmacist before using Bortezomib, if you have any of the following:

low numbers of red or white blood cells
bleeding problems and/or low number of platelets in your blood
diarrhoea, constipation, nausea or vomiting
fainting, dizziness or light-headedness in the past
kidney problems
moderate to severe liver problems
numbness, tingling, or pain in the hands or feet (neuropathy) in the past
heart or blood pressure problems
shortness of breath or cough
seizures
shingles (localised including around the eyes or spread across the body)
symptoms of tumor lysis syndrome such as muscle cramping, muscle weakness, confusion, visual loss or disturbances and shortness of breath
memory loss, trouble thinking, difficulty with walking or loss of vision. These may be signs of a serious brain infection and your doctor may suggest further testing and follow-up.

You will have to take regular blood tests before and during your treatment with Bortezomib, to check your blood cell counts regularly.

If you have mantle cell lymphoma and are given the medicine rituximab with Bortezomib you should tell your doctor:

if you think you have hepatitis infection now or have had it in the past. In a few cases, patients who have had hepatitis B might have a repeated attack of hepatitis, which can be fatal.

If you have a history of hepatitis B infection you will be carefully checked by your doctor for signs of active hepatitis B.

You must read the package leaflets of all medicinal products to be taken in combination with Bortezomib for information related to these medicines before starting treatment with Bortezomib. When thalidomide is used, particular attention to pregnancy testing and prevention requirements is needed (see Pregnancy and breast-feeding in this section).

Children and adolescents

Bortezomib should not be used in children and adolescents because it is not known how the medicine will affect them.

Other medicines and Bortezomib

Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines.

In particular, tell your doctor if you are using medicines containing any of the following active substances:

ketoconazole, used to treat fungal infections
ritonavir, used to treat HIV infection
rifampicin, an antibiotic used to treat bacterial infections
carbamazepine, phenytoin or phenobarbital used to treat epilepsy
St. John’s Wort (Hypericum perforatum), used for depression or other conditions
oral antidiabetics

Pregnancy and breast-feeding

You should not use Bortezomib if you are pregnant, unless clearly necessary.

Both men and women receiving Bortezomib must use effective contraception during and for up to 3 months after treatment. If, despite these measures, pregnancy occurs, tell your doctor immediately.

You should not breast-feed while using Bortezomib. Discuss with your doctor when it is safe to restart breast-feeding after finishing your treatment.

Thalidomide causes birth defects and foetal death. When Bortezomib is given in combination with thalidomide you must follow the pregnancy prevention programme for thalidomide (see package leaflet for thalidomide).

Driving and using machines

Bortezomib might cause tiredness, dizziness, fainting, or blurred vision. Do not drive or operate tools or machines if you experience such side effects; even if you do not, you should still be cautious.

3. how to use bortezomib

Your doctor will work out your dose of Bortezomib according to your height and weight (body surface area). The usual starting dose of Bortezomib is 1.3 mg/m2 body surface area twice a week. Your doctor may change the dose and total number of treatment cycles, depending on your response to the treatment on the occurrence of certain side effects and on your underlying conditions (e.g. liver problems).

Progressive multiple myeloma

When Bortezomib is given alone, you will receive 4 doses of Bortezomib intravenously or subcutaneously on days 1, 4, 8 and 11, followed by a 10-day ‘rest period’ without treatment. This 21-day period (3 weeks) corresponds to one treatment cycle. You might receive up to 8 cycles (24 weeks).

You may also be given Bortezomib together with the medicines pegylated liposomal doxorubicin or dexamethasone.

When Bortezomib is given together with pegylated liposomal doxorubicin, you will receive Bortezomib intravenously or subcutaneously as a 21-day treatment cycle and pegylated liposomal doxorubicin 30 mg/m2 is given on day 4 of the Bortezomib 21-day treatment cycle as an intravenous infusion after the Bortezomib injection.

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

When Bortezomib is given together with dexamethasone, you will receive Bortezomib intravenously or subcutaneously as a 21-day treatment cycle and dexamethasone 20 mg is given orally on days 1, 2, 4, 5, 8, 9, 11, and 12, of the Bortezomib, 21-day treatment cycle.

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

Previously untreated multiple myeloma

If you have not been treated before for multiple myeloma, and you are not suitable for blood stem cell transplantation you will receive Bortezomib intravenously together with two other medicines, melphalan and prednisone.

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

In cycles 1 to 4, Bortezomib is administered twice weekly on days 1, 4, 8, 11, 22, 25, 29 and 32.
In cycles 5 to 9, Bortezomib is administered once weekly on days 1, 8, 22 and 29.

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

If you have not been treated before for multiple myeloma, and you are suitable for blood stem cell transplantation you will receive Bortezomib intravenously or subcutaneously together with the medicines dexamethasone, or dexamethasone and thalidomide, as induction treatment.

When Bortezomib is given together with dexamethasone, you will receive Bortezomib intravenously or subcutaneously as a 21-day treatment cycle and dexamethasone 40 mg is given orally on days 1, 2, 3, 4, 8, 9, 10 and 11 of the Bortezomib 21-day treatment cycle.

You will receive 4 cycles (12 weeks).

When Bortezomib is given together with thalidomide and dexamethasone, the duration of a treatment cycle is 28 days (4 weeks).

Dexamethasone 40 mg is given orally on days 1, 2, 3, 4, 8, 9, 10 and 11 of the Bortezomib 28-day treatment cycle and thalidomide is given orally daily at 50 mg up to day 14 of the first cycle, and if tolerated the thalidomide dose is increased to 100 mg on days 15 – 28 and may be further increased to 200 mg daily from the second cycle onwards. You might receive up to 6 cycles (24 weeks).

Previously untreated mantle cell lymphoma

If you have not been treated before for mantle cell lymphoma you will receive Bortezomib intravenously or subcutaneously together with the medicines rituximab, cyclophosphamide, doxorubicin and prednisone.

Bortezomib is given intravenously or subcutaneously on days 1, 4, 8 and 11, followed by a ‘rest period’ without treatment. The duration of a treatment cycle is 21 days (3 weeks). You might receive up to 8 cycles (24 weeks). The following medicinal products are given on day 1 of each Bortezomib 21-day treatment cycle as intravenous infusions: Rituximab at 375 mg/m2, cyclophosphamide at 750 mg/m2 and doxorubicin at 50 mg/m2.

Prednisone is given orally at 100 mg/m2 on days 1, 2, 3, 4 and 5 of the Bortezomib treatment cycle.

How Bortezomib is given

This medicine is for intravenous or subcutaneous use only. Bortezomib will be administered by a healthcare professional experienced in the use of cytotoxic medicines. Bortezomib powder has to be dissolved before administration. This will be done by a healthcare professional. The resulting solution is then either injected into a vein or under the skin. Injection into a vein is rapid, taking 3 to 5 seconds. Injection under the skin is in either the thighs or the abdomen.

If you are given too much Bortezomib

As this medicine is being given by your doctor or nurse, it is unlikely that you will be given too much. In the unlikely event of an overdose, your doctor will monitor you for side effects.

4. possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. Some of these effects may be serious.

If you are given Bortezomib for multiple myeloma or mantle cell lymphoma, tell your doctor straight away if you notice any of the following symptoms:

muscle cramping, muscle weakness
confusion, visual loss or disturbances, blindness, seizures, headaches
shortness of breath, swelling of your feet or changes in your heart beat, high blood pressure, tiredness, fainting
coughing and breathing difficulties or tightness in the chest.
Treatment with Bortezomib can very commonly cause a decrease in the numbers of red and white blood cells and platelets in your blood. Therefore, you will have to take regular blood tests before and during your treatment with Bortezomib, to check your blood cell counts regularly. You may experience a reduction in the number of platelets, which may make you be more prone to bruising, or to bleeding without obvious injury (e.g., bleeding from your bowels, stomach, mouth and gum or bleeding in the brain or bleeding from the liver)
red blood cells, which can cause anaemia, with symptoms such as tiredness and paleness
white blood cells may make you more prone to infections or flu-like symptoms

If you are given Bortezomib for the treatment of multiple myeloma the side effects you may get are listed below:

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

Sensitivity, numbness, tingling or burning sensation of the skin, or pain in the hands or feet, due to nerve damage
Reduction in the number of red blood cells and or white blood cells (see above)
Fever
Feeling sick (nausea) or vomiting, loss of appetite
Constipation with or without bloating (can be severe)
Diarrhoea: if this happens, it is important that you drink more water than usual. Your doctor may give you another medicine to control diarrhoea
Tiredness (fatigue), feeling weak
Muscle pain, bone pain

Common side effects (may affect up to 1 in 10 people)

Low blood pressure, sudden fall of blood pressure on standing which may lead to fainting
High blood pressure
Reduced functioning of your kidneys
Headache
General ill feeling, pain, vertigo, light-headedness, a feeling of weakness or loss of consciousness
Shivering
Infections, including pneumonia, respiratory infections, bronchitis, fungal infections, coughing with phlegm, flu like illness
Shingles (localised including around the eyes or spread across the body)
Chest pains or shortness of breath with exercise
Different types of rash
Itching of the skin, lumps on the skin or dry skin
Facial blushing or tiny broken capillaries
Redness of the skin
Dehydration
Heartburn, bloating, belching, wind, stomach pain, bleeding from your bowels or stomach
Alteration of liver functioning
A sore mouth or lip, dry mouth, mouth ulcers or throat pain
Weight loss, loss of taste
Muscle cramps, muscle spasms, muscle weakness, pain in your limbs
Blurred vision
Infection of the outermost layer of the eye and the inner surface of the eyelids (conjunctivitis)
Nose bleeds
Difficulty or problems in sleeping, sweating, anxiety, mood swings, depressed mood, restlessness or agitation, changes in your mental status, disorientation
Swelling of body, to include around eyes and other parts of the body

Uncommon side effects (may affect up to 1 in 100 people)

Heart failure, heart attack, chest pain, chest discomfort, increased or reduced heart rate
Failing of your kidneys
Inflammation of a vein, blood clots in your veins and lungs
Problems with blood clotting
Insufficient circulation
Inflammation of the lining around your heart or fluid around your heart
Infections including urinary tract infections, the flu, herpes virus infections, ear infection and cellulitis
Bloody stools, or bleeding from mucosal membranes, e.g., mouth, vagina
Cerebrovascular disorders
Paralysis, seizures, falling, movement disorders, abnormal or change in, or reduced sensation (feeling, hearing, tasting, smelling), attention disturbance, trembling, twitching
Arthritis, including inflammation of the joints in the fingers, toes, and the jaw
Disorders that affect your lungs, preventing your body from getting enough oxygen. Some of these include difficulty breathing, shortness of breath, shortness of breath without exercise, breathing that becomes shallow, difficult or stops, wheezing
Hiccups, speech disorders
Increased or decreased urine production (due to kidney damage), painful passing of urine or blood/proteins in the urine, fluid retention
Altered levels of consciousness, confusion, memory impairment or loss
Hypersensitivity
Hearing loss, deafness or ringing in the ears, ear discomfort
Hormone abnormality which may affect salt and water absorption
Overactive thyroid gland
Inability to produce enough insulin or resistance to normal levels of insulin
Irritated or inflamed eyes, excessively wet eyes, painful eyes, dry eyes, eye infections, lump in the eyelid (chalazion), red and swollen eyelids, discharge from the eyes, abnormal vision, bleeding of the eye
Swelling of your lymph glands
Joint or muscle stiffness, sense of heaviness, pain in your groin
Hair loss and abnormal hair texture
Allergic reactions
Redness or pain at the injection site
Mouth pain
Infections or inflammation of the mouth, mouth ulcers, oesophagus, stomach and intestines, sometimes associated with pain or bleeding, poor movement of the intestines (including blockage), abdominal or oesophageal discomfort, difficulty swallowing, vomiting of blood
Skin infections
Bacterial and viral infections
Tooth infection
Inflammation of the pancreas, obstruction of the bile duct
Genital pain, problem having an erection
Weight increase
Thirst
Hepatitis
Injection site or injection device related disorders
Skin reactions and disorders (which may be severe and life threatening), skin ulcers
Bruises, falls and injuries
Inflammation or haemorrhage of the blood vessels that can appear as small red or purple dots (usually on the legs) to large bruise-like patches under the skin or tissue
Benign cysts
A severe reversible brain condition which includes seizures, high blood pressure, headaches, tiredness, confusion, blindness or other vision problems.

Rare side effects (may affect up to 1 in 1,000 people)

Heart problems to include heart attack, angina
Flushing
Discoloration of the veins
Inflammation of the spinal nerve
Problems with your ear, bleeding from your ear
Underactivity of your thyroid gland
Budd-Chiari syndrome (the clinical symptoms caused by blockage of the hepatic veins)
Changes in or abnormal bowel function
Bleeding in the brain
Yellow discolouration of eyes and skin (jaundice)
Serious allergic reaction (anaphylactic shock) signs of which may include difficulty breathing, chest pain or chest tightness, and/or feeling dizzy/faint, severe itching of the skin or raised lumps on the skin, swelling of the face, lips, tongue and /or throat, which may cause difficulty in swallowing, collapse
Breast disorders
Vaginal tears
Genital swelling
Inability to tolerate alcohol consumption
Wasting, or loss of body mass

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Increased appetite
Fistula
Joint effusion
Cysts in the lining of joints (synovial cysts)
Fracture
Breakdown of muscle fibres leading to other complications
Swelling of the liver, bleeding from the liver
Cancer of the kidney
Psoriasis like skin condition
Cancer of the skin
Paleness of the skin
Increase of platelets or plasma cells (a type of white cell) in the blood
Blood clot in small blood vessels (thrombotic microangiopathy)
Abnormal reaction to blood transfusions
Partial or total loss of vision
Decreased sex drive
Drooling
Bulging eyes
Sensitivity to light
Rapid breathing
Rectal pain
Gallstones
Hernia
Injuries
Brittle or weak nails
Abnormal protein deposits in your vital organs
Coma
Intestinal ulcers
Multi-organ failure
Death
Serious nerve inflammation, which may cause paralysis and difficulty breathing (Guillain-Barre syndrome)

If you are given Bortezomib together with other medicines for the treatment of mantle cell lymphoma the side effects you may get are listed below:

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

Pneumonia
Loss of appetite
Sensitivity, numbness, tingling or burning sensation of the skin, or pain in the hands or feet, due to nerve damage
Nausea and vomiting
Diarrhoea
Mouth ulcers
Constipation
Muscle pain, bone pain
Hair loss and abnormal hair texture
Tiredness, feeling weak
Fever

Common side effects (may affect up to 1 in 10 people)

Shingles (localized including around the eyes or spread across the body)
Herpes virus infections
Bacterial and viral infections
Respiratory infections, bronchitis, coughing with phlegm, flu like illness
Fungal infections
Hypersensitivity (allergic reaction)
Inability to produce enough insulin or resistance to normal levels of insulin
Fluid retention
Difficulty or problems in sleeping
Loss of consciousness
Altered level of consciousness, confusion
Feeling dizzy
Increased heartbeat, high blood pressure, sweating
Abnormal vision, blurred vision
Heart failure, heart attack, chest pain, chest discomfort, increased or reduced heart rate
High or low blood pressure
Sudden fall of blood pressure upon standing which may lead to fainting
Shortness of breath with exercise
Cough
Hiccups
Ringing in the ears, ear discomfort
Bleeding from your bowels or stomach
Heartburn
Stomach pain, bloating
Difficulty swallowing
Infection or inflammation of the stomach and intestines
Stomach pain
Sore mouth or lip, throat pain
Alteration of liver function
Itching of skin
Redness of skin
Rash
Muscle spasms
Infection of the urinary tract
Pain in limbs
Swelling of body, to include eyes and other parts of the body
Shivering
Redness and pain at injection site
General ill feeling
Weight loss
Weight increase

Uncommon side effects (may affect up to 1 in 100 people)

Hepatitis
Severe allergic reaction (anaphylactic reaction) signs of which may include difficulty breathing, chest pain or chest tightness, and/or feeling dizzy/faint, severe itching of the skin or raised lumps on the skin, swelling of the face, lips, tongue and /or throat, which may cause difficulty in swallowing, collapse
Movement disorders, paralysis, twitching
Vertigo
Hearing loss, deafness
Disorders that affect your lungs, preventing your body from getting enough oxygen. Some of these include difficulty breathing, shortness of breath, shortness of breath without exercise, breathing that becomes shallow, difficult or stops, wheezing
Blood clots in your lungs
Yellow discoloration of the eyes and skin (jaundice)
Lump in the eyelid (chalazion), red and swollen eyelids

Rare side effects (may affect up to 1 in 1,000 people)

Blood clot in small blood vessels (thrombotic microangiopathy)

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at: or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.

5. how to store bortezomib

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

Do not use this medicine after the expiry date stated on the vial and the carton after EXP.

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

This medicine does not require any special temperature storage conditions.

Reconstituted solution

Chemical and physical stability has been demonstrated for 8 days at 25°C/60%RH or 15 days at 5+/- 3°C in the dark both in a vial and in a polypropylene syringe.

From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2° to 8°C, unless reconstitution/dilution (etc) has taken place in controlled and validated aseptic conditions.

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

6. contents of the pack and other information

What Bortezomib contains

The active substance is bortezomib. Each vial contains 2.5 mg of bortezomib (as a mannitol boronic ester).
The other ingredient is mannitol (E421).

Intravenous reconstitution:

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

Subcutaneous reconstitution:

After reconstitution, 1 ml of solution for subcutaneous injection contains 2.5 mg bortezomib.

What Bortezomib looks like and contents of the pack Bortezomib powder for solution for injection is a white to off-white cake or powder.

Bortezomib is packed in a glass vial with rubber stopper and a yellow flip-off cap.

Each pack contains 1 single-use vial.

Marketing Authorisation Holder

medac Gesellschaft fur klinische Spezialpraparate mbH Theaterstr. 6

22880 Wedel

Germany

Tel.: +49 4103 8006–0

Fax: +49 4103 8006–100

Manufacturer

Synthon s.r.o. Blansko

Brnenska 32/c.p.597

678 01 Blansko

Czech Republic

This medicinal product is authorised in the Member States of the EEA under the following names:

France: Bortezomib medac, 2.5 mg,

poudre pour solution injectable

Germany: Bortezomib medac 2,5 mg

Pulver zur Herstellung einer Injektionslosung

Italy: Bortezomib medac 2,5 mg

polvere per soluzione iniettabile

Netherlands: Bortezomib medac 2,5 mg,

poeder voor oplossing voor injectie

United Kingdom: Bortezomib 2.5 mg powder for solution for injection

This leaflet was last revised in 07/2021.

The following information is intended for healthcare professionals only:

1. RECONSTITUTION FOR INTRAVENOUS INJECTION

Note: Bortezomib is a cytotoxic agent. Therefore, caution should be used during handling and preparation. Use of gloves and other protective clothing to prevent skin contact is recommended.

ASEPTIC TECHNIQUE MUST BE STRICTLY OBSERVED THROUGHOUT HANDLING OF BORTEZOMIB SINCE NO PRESERVATIVE IS PRESENT.

1.1 Preparation of the 2.5 mg vial: carefully add 2.5 ml of sterile, 9 mg/ml (0.9 %) sodium chloride solution for injection to the vial containing the Bortezomib powder by using a 1 ml syringe of the appropriate size without removing the vial stopper. Dissolution of the lyophilised powder is completed in less than 2 minutes.

The concentration of the resulting solution will be 1 mg/ml. The solution will be clear and colourless, with a final pH of 4 to 7. You do not need to check the pH of the solution.

1.2 Before administration, visually inspect the solution for particulate matter and discolouration. If any discolouration or particulate matter is observed, the solution should be discarded. Confirm concentration on vial to ensure that the correct dose is being given for the intravenous route of administration (1 mg/ml).
1.3 The reconstituted solution is preservative free and should be used immediately after preparation. However, the chemical and physical in-use stability has been demonstrated for 8 days at 25°C/60%RH or 15 days at 5+/- 3°C in the dark stored in the original vial and/ or a syringe. The total storage time for the reconstituted medicinal product should not exceed 24 hours at 2° to 8°C prior to administration. If the reconstituted solution is not used immediately, in-use storage times and conditions prior to use are the responsibility of the user.

2. ADMINISTRATION

Once dissolved, withdraw the appropriate amount of the reconstituted solution according to calculated dose based upon the patient’s Body Surface Area.
Confirm the dose and concentration in the syringe prior to use (check that the syringe is marked as intravenous administration).
Inject the solution as a 3–5 second bolus intravenous injection through a peripheral or central intravenous catheter into a vein.
Flush the peripheral or intravenous catheter with sterile, 9 mg/ml (0.9 %) sodium chloride solution.

Bortezomib 2.5 mg powder for solution for injection IS FOR SUBCUTANEOUS OR INTRAVENOUS USE.

Do not give by other routes. Intrathecal administration has resulted in death.

3. DISPOSAL

A vial is for single use only and the remaining solution must be discarded.

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