Prospecto: information for the user

Bortezomib STADA 2.5 mg/ml injectable solution

Read this prospectus carefully before starting to use this medicine, as it contains important information for you.

-Keep this prospectus, as you may need to read it again.

-If you have any questions, consult your doctor, pharmacist, or nurse.

-If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this prospectus. See section 4.

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

2.What you need to know before starting to use Bortezomib STADA

3.How to use Bortezomib STADA

4.Possible adverse effects

5.Storage of Bortezomib STADA

6.Contents of the package and additional information

Bortezomib STADA contains the active ingredient bortezomib, a “proteasome inhibitor”.Proteasomes play an important role in controlling cell function and growth. Bortezomib can destroy cancer cells, interfering with their function.

Bortezomib is used in the treatment of multiple myeloma (a bone marrow cancer) in patients 18 years of age or older:

-alone or in combination with pegylated liposomal doxorubicin or dexamethasone, for patients whose disease is worsening (in progression) after receiving at least one previous treatment and for those patients whose stem cell transplant did not work or is not suitable.

-in combination with melphalan and prednisone, for patients whose disease has not been previously treated and is not suitable to receive high doses of chemotherapy prior to a stem cell transplant.

-in combination with dexamethasone or dexamethasone with thalidomide, in patients whose disease has not been previously treated and who receive high doses of chemotherapy prior to a stem cell transplant (induction treatment).

Bortezomib is used in the treatment of mantle cell lymphoma (a type of cancer that affects lymph nodes) in patients 18 years of age or older in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone, in patients whose disease has not been previously treated and for those patients who are not considered suitable for a stem cell transplant.

Do not use Bortezomib STADA

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

-if you have severe lung or heart problems.

Warnings and precautions

Inform your doctor, pharmacist, or nurse before using bortezomib, especially if you have the following:

?low red or white blood cell count

?bleeding problems and/or low platelet count in blood

?diarrhea, constipation, nausea, or vomiting

?history of fainting, dizziness, or drowsiness

?kidney problems

?liver problems of moderate to severe degree

?numbness, tingling, or pain in the hands or feet (neuropathy) in the past

?heart problems or high blood pressure

?difficulty breathing or coughing

?seizures

?shingles (including around the eyes or spread throughout the body)

?symptoms of tumor lysis syndrome, such as muscle cramps, muscle weakness, confusion, loss or changes in vision, and difficulty breathing

?memory loss, thought changes, difficulty walking, or loss of vision.

These may be signs of a severe brain infection, and your doctor may advise further testing and follow-up.

You will need to have regular blood tests before and during treatment with Bortezomib STADA to check your blood cell count regularly.

Inform your doctor if you have mantle cell lymphoma and are being given rituximab in combination with Bortezomib STADA:

?if you think you currently have or have had in the past a hepatitis infection. In a few cases, patients who have had hepatitis B may have repeated attacks of hepatitis, which can be fatal. If you have a history of hepatitis B infection, you will be closely monitored by your doctor to detect signs of active hepatitis B.

Before starting treatment with Bortezomib STADA, read the leaflets of all the medicines you are taking in combination with Bortezomib STADA, to consult the information related to these medicines.

When using thalidomide, special attention should be paid to the performance of pregnancy tests and to preventive measures (see Pregnancy and Breastfeeding in this section).

Children and adolescents

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

Use of Bortezomib STADA with other medicines

Inform your doctor, pharmacist, or nurse if you are taking, have taken recently, or may need to take other medicines.

Particularly, inform your doctor if you are using medicines that contain any of the following active ingredients:

-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 to treat depression or other conditions

-oral antidiabetic drugs

Pregnancy and breastfeeding

You should not use Bortezomib STADA if you are pregnant unless it is clearly necessary.

Both men and women using Bortezomib STADA should use effective contraception during and for up to 3 months after treatment. If, despite these measures, you become pregnant, inform your doctor immediately.

You should not breastfeed while using Bortezomib STADA. Consult your doctor when it is safe to resume breastfeeding after completing your treatment.

Thalidomide causes birth defects and fetal death. When Bortezomib STADA is administered in combination with thalidomide, the thalidomide pregnancy prevention program should be followed (see the thalidomide leaflet).

Driving and operating machines

Bortezomib STADA may cause fatigue, dizziness, fainting, or blurred vision. Do not drive or operate tools or machines if you experience these side effects; even if you do not experience them, you should still be cautious.

Bortezomib STADA contains sodium

This medicine contains less than 23 mg (1mmol) of sodium per vial; it is essentially "sodium-free".

Your doctor will tell you the dose of bortezomib based on your height and weight (body surface area). The usual starting dose of bortezomib is 1.3 mg/m2 of body surface area twice a week. Your doctor may change the dose and the total number of treatment cycles depending on your response to treatment, the appearance of certain side effects, and your underlying condition (e.g., liver problems).

Progressive multiple myeloma

When bortezomib is given alone, you will receive 4 doses of bortezomib by intravenous or subcutaneous injection on days 1, 4, 8, and 11, followed by a 10-day "rest" period without treatment. This 21-day (3-week) period corresponds to a treatment cycle. You may receive up to 8 cycles (24 weeks).

You may also receive bortezomib together with the medications doxorubicin liposomal pegylated or dexamethasone.

When bortezomib is given together with doxorubicin liposomal pegylated, you will receive bortezomib by intravenous or subcutaneous injection in a 21-day treatment cycle, and doxorubicin liposomal pegylated 30 mg/m2 is administered on day 4 of the bortezomib 21-day treatment cycle by intravenous infusion after the injection of bortezomib. You may receive up to 8 cycles (24 weeks).

When bortezomib is given together with dexamethasone, you will receive bortezomib by intravenous or subcutaneous injection in a 21-day treatment cycle, and dexamethasone 20 mg is administered orally on days 1, 2, 4, 5, 8, 9, 11, and 12 of the bortezomib 21-day treatment cycle. You may receive up to 8 cycles (24 weeks).

Untreated multiple myeloma

If you have not been treated before for multiple myeloma and are not a candidate to receive a stem cell transplant, you will receive bortezomib together with two other medications: melphalan and prednisone.

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

You will receive bortezomib twice a week on days 1, 4, 8, 11, 22, 25, 29, and 32 in cycles 1 to 4.

You will receive bortezomib once a week on days 1, 8, 22, and 29 in cycles 5 to 9.

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

If you have not received any treatment before for multiple myeloma and are a candidate to receive a stem cell transplant, you will receive bortezomib by intravenous or subcutaneous injection together with the medications dexamethasone, or dexamethasone and thalidomide, as induction treatment.

When bortezomib is given together with dexamethasone, you will receive bortezomib by intravenous or subcutaneous injection in a 21-day treatment cycle, and dexamethasone is administered orally in doses of 40 mg 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 administered orally on days 1, 2, 3, 4, 8, 9, 10, and 11 of the bortezomib 28-day treatment cycle, and thalidomide is administered orally once a day in doses of 50 mg until day 14 of the first cycle, and if tolerated, the thalidomide dose is increased to 100 mg on days 15-28, and from the second cycle and onwards, it may be increased further to 200 mg daily. You may receive up to 6 cycles (24 weeks).

Untreated mantle cell lymphoma

If you have not been treated before for mantle cell lymphoma, you will receive bortezomib by intravenous or subcutaneous injection together with the medications rituximab, cyclophosphamide, doxorubicin, and prednisone.

Bortezomib is administered by intravenous or subcutaneous injection 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 may receive up to 8 cycles (24 weeks).

The following medications are administered by intravenous infusion on day 1 of the bortezomib 21-day treatment cycle:

Rituximab in doses of 375 mg/m2, cyclophosphamide in doses of 750 mg/m2, and doxorubicin in doses of 50 mg/m2.

Prednisone is administered orally in doses of 100 mg/m2 on days 1, 2, 3, 4, and 5 of the bortezomiv 21-day treatment cycle.

How Bortezomib STADA is administered

This medication is administered by subcutaneous injection and, after dilution, also by intravenous injection. You will receive bortezomib from a healthcare professional expert in the use of cytotoxic medications.

The solution is injected after into a vein or under the skin. The injection into the vein is rapid, lasting between 3 and 5 seconds. The injection under the skin is administered in the thighs or abdomen.

If you receive more Bortezomib STADA than you should

This medication will be administered by your doctor or nurse, so it is unlikely that you will receive an excessive amount. In the unlikely event of an overdose, your doctor will monitor you for any adverse effects.

Like all medicines, this medicine can cause side effects, although not everyone will experience them. Some of these side effects can be serious.

If you are givenBortezomib STADAfor multiple myeloma or mantle cell lymphoma, tell your doctor immediately if you notice any of the following symptoms:

-Muscle cramps, muscle weakness

-Confusion, loss or changes in vision, blindness, seizures, headaches

-Difficulty breathing, swelling of the feet or changes in heart rhythm, high blood pressure, fatigue, fainting

-Coughs and difficulty breathing or chest tightness.

The treatment withBortezomib STADAcan cause a very frequent decrease in the number of red and white blood cells and platelets in the blood. Therefore, regular blood tests will be performed before and during treatment withBortezomib STADA, to regularly check your blood cell count. You may experience a reduction in the number of:

-Platelets, which may make you more prone to bruising (bruises), or bleeding without apparent injury (for example, intestinal, stomach, mouth and gum bleeding or

bleeding in the brain or liver bleeding)

-Red blood cells, which can cause anemia, with symptoms such as fatigue and paleness

-White blood cells, which may make you more prone to infections or symptoms similar to the flu.

If you are givenBortezomib STADAfor multiple myeloma, the side effects you may experience are listed below:

Frequent side effects (can affect more than 1 in 10 patients)

?Sensitivity, numbness, tingling or burning sensation in the skin or pain in the hands or feet due to nerve damage

?Decrease in the number of red and white blood cells (see above)

?Fever

?Feeling unwell (nausea) or vomiting, loss of appetite

?Constipation with or without swelling (may be severe)

?Dyspepsia

?Diarrhea: if it occurs, it is essential to drink more water than usual. Your doctor may give you another medicine to control diarrhea

?Exhaustion (fatigue), feeling weak

?Muscle pain, bone pain

Common side effects (can affect up to 1 in 10 patients)

?Low blood pressure, sudden drop in blood pressure when standing, which could lead to fainting

?High blood pressure

?Renal dysfunction

?Headache

?General feeling of discomfort, pain, dizziness, disorientation, feeling weak or loss of consciousness

?Chills

?Infections, including pneumonia, respiratory infections, bronchitis, flu-like illness

?Herpes (localized, including around the eyes or spread over the body)

?Chest pain or difficulty breathing while exercising

?Different types of rashes

?Itching skin, skin lumps or dry skin

?Facial flushing or capillary rupture

?Redness of the skin

?Dehydration

?Heartburn, swelling, belching, flatulence, stomach pain, intestinal or stomach bleeding

?Liver dysfunction

?Mouth or lip sores, dry mouth, mouth ulcers or throat pain

?Weight loss, loss of taste

?Muscle cramps, muscle spasms, muscle weakness, pain in the limbs

?Blurred vision

?Eye infections, including conjunctivitis

?Nasal bleeding

?Difficulty or problems sleeping, sweating, anxiety, mood changes, depressed mood, restlessness or agitation, changes in mental state, disorientation

?Swelling of the body, including around the eyes and in other parts of the body

Rare side effects (can affect up to 1 in 100 patients)

?Heart failure, heart attack, chest pain, chest discomfort, increase or decrease in heart rate

?Renal failure

?Vein inflammation, blood clots in veins and lungs

?Blood clotting disorders

?Poor circulation

?Pericarditis or fluid around the heart

?Infections, including urinary tract infections, flu, viral herpes infection, ear infections, and cellulitis

?Membranous mucosal bleeding or hemorrhages, for example, in the mouth or vagina

?Cerebrovascular disorders

?Paralysis, seizures, falls, movement disorders, changes or decreases in sensitivity (tactile, hearing, taste, smell), attention disorders, tremors, shakiness

?Arthritis, including inflammation of the joints of the hands and feet and jaw

?Respiratory disorders, preventing the body from receiving a sufficient amount of oxygen. Some of them are difficulty breathing, shortness of breath, shortness of breath without exercise, shallow, difficult or stopping breathing, labored breathing

?Hiccup, speech disorders

?Changes or abnormalities in kidney function

?Changes in the level of consciousness, confusion, memory loss or alteration

?Hypersensitivity

?Loss of hearing, deafness or tinnitus, ear discomfort

?Alterations in hormone levels that may affect the absorption of salt and water

?Hyperthyroidism

?Inability to produce sufficient insulin or resistance to normal insulin levels

?Eye irritation or inflammation, excessive eye moisture, eye pain, eye infections, chalazion, red and swollen eyelids, watery eyes (lacrimation), abnormal vision, eye hemorrhage

?Lymph node swelling

?Joint or muscle stiffness, feeling heavy, pain in the groin

?Loss of hair and abnormal hair texture

?Allergic reactions

?Redness or pain at the injection site

?Mouth pain

?Mouth or lip sores, dry mouth, mouth ulcers or throat pain

?Infections or inflammation of the mouth, ulcers in the mouth, esophagus, stomach, and intestines, sometimes associated with pain or bleeding, slow movement of the intestines (including obstruction), abdominal or esophageal discomfort, difficulty swallowing, vomiting blood

?Skin infections

?Bacterial and viral infections

?Dental infections

?Pancreatitis, bile duct obstruction

?Genital pain, erectile dysfunction

?Weight gain

?Thirst

?Hepatitis

?Device-related or injection-site reactions

• Reactions and skin disorders (which can be severe and life-threatening), skin ulcers

?Bruises, falls, and injuries

?Vein inflammation or hemorrhage that can appear as small red or purple spots (usually on the legs) to large patches similar to hematomas under the skin or tissue.

?Benign cysts

?A severe and reversible brain disorder that includes seizures, high blood pressure, headaches, fatigue, confusion, blindness, or other vision problems.

Rare side effects (can affect up to 1 in 1,000 patients)

• Coagulation of blood in small blood vessels (microangiopathy)
• Severe nerve inflammation, which can cause paralysis and respiratory difficulty (Guillain-Barré syndrome)

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Use: https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the vial and on the packaging after CAD.

Store the unopened vial in the refrigerator (between 2°C and 8°C). Store the vial in the outer packaging to protect it from light.

The diluted solution must be used immediately after preparation. If the diluted solution is not used immediately, the storage times and conditions before use are the responsibility of the user. However, the diluted solution is chemically and physically stable for 28 days stored between 2°C and 8°C protected from light, 7 days stored at 25°C protected from light, or 24 hours stored at 25°C (in normal interior lighting conditions) in the original vial and/or a polipropylene syringe.

Regarding stability in the vial and/or syringe, the same storage times apply to the diluted and undiluted solution.

Bortezomib is exclusively for single use. The disposal of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations.

Composition of Bortezomib STADA

-The active ingredient is bortezomib.

Cada vial contains 1.4 ml of injectable solution containing 3.5 mg of bortezomib (as manitol boric ester).

Cada vial contains 2.8 ml of injectable solution containing 7 mg of bortezomib (as manitol boric ester).

-The other components are manitol, sodium chloride, and water for injectable preparations.

Route of administration: intravenous:

After dilution, 1 ml of the intravenous injection solution contains 1 mg of bortezomib.

Route of administration: subcutaneous:

1 ml of the subcutaneous injection solution contains 2.5 mg of bortezomib.

Aspect of the product and content of the package

Bortezomib STADA injectable solution is a transparent and colorless to light yellow solution.

Vial containing 1.4 ml of injectable solution/3.5 mg of bortezomib

Cada envase de Bortezomib STADA 2.5 mg/ml solución inyectable contiene 1 vial de cristal de 10 ml con flip-off amarillo de polipropileno.

Vial containing 2.8 ml of injectable solution/7 mg of bortezomib

Cada envase de Bortezomib STADA 2.5 mg/ml solución inyectable contiene 1 vial de cristal de 10 ml con flip-off azul oscuro de polipropileno.

[Cada vial está envasado en un recipiente transparente de policarbonato (PC) con tapa con flip-off de polipropileno (PP) a prueba de manipulaciones que puede volver a cerrarse.]

Marketing Authorization Holder

Laboratorio STADA, S.L.

C/Frederic Mompou, 5

08960 Sant Just Desvern (Barcelona)

España

[email protected]

Responsible for manufacturing

STADA Arzneimittel AG

Stadastrasse 2 – 18

61118 Bad Vilbel

Alemania

Last review date of this leaflet:May 2022

The detailed information of this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/

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The following information is only for healthcare professionals:

1.PREPARATION FOR INJECTIONINTRAVENOUS

Pregnant women should not handle this medicine.

Nota: Bortezomib is a cytotoxic agent. Therefore, caution should be exercised during handling and preparation. It is recommended to use gloves and other protective clothing to prevent skin contact.

BECAUSE BORTEZOMIB STADA LACKS PRESERVATIVES, IT IS RECOMMENDED TO FOLLOW STRICT ASPTIC TECHNIQUE DURING HANDLING.

Vial containing 1.4 ml of injectable solution/3.5 mg of bortezomib

1.1.Preparation of a 3.5 mg vial: add 2.1 mlof sterile solution for injection of sodium chloride 9 mg/ml (0.9%) to the vial containing Bortezomib STADA.

The resulting solution concentration will be 1 mg/ml. The solution must be transparent and colorless, with a final pH of 4 to 7. No pH check is required.

Vial containing 2.8 ml of injectable solution/7 mg of bortezomib

1.1.Preparation of a 7 mg vial: add 4.2 mlof sterile solution for injection of sodium chloride 9 mg/ml (0.9%) to the vial containing Bortezomib STADA.

The resulting solution concentration will be 1 mg/ml. The solution must be transparent and colorless to light yellow, with a final pH of 4 to 7. No pH check is required.

1.2.Before administration, visually inspect the solution to discard the presence of particles and discoloration. If any discoloration or particles are observed, the solution must be discarded. Check that the correct dose is being used for intravenous administration (1 mg/ml).

1.3.The diluted solution lacks preservatives and must be used immediately after preparation. If the diluted solution is not used immediately, the storage times and conditions before use are the responsibility of the user. However, the chemical and physical stability during use has been demonstrated for 28 days stored between 2°C and 8°C protected from light, 7 days stored at 25°C protected from light, or 24 hours stored at 25°C (in normal interior lighting conditions) in the original vial and/or polipropylene syringe.

During preparation for administration and during administration, the product does not need to be protected from light.

2.ADMINISTRATION

?Once diluted, remove the appropriate amount of the diluted solution according to the calculated dose based on the patient's Body Surface Area.

?Confirm the dose and concentration contained in the syringe before use (check that the syringe ismarked for intravenous administration).

?Inject the solution through a 3-5 second intravenous bolus, through a peripheral or central intravenous catheter in a vein.

?Wash the peripheral or intravenous catheter with sterile sodium chloride solution, 9 mg/ml (0.9%).

Bortezomib STADA 2.5 mg/ml injectable solution IS FOR USE BY INTRAVENOUS OR SUBCUTANEOUS ROUTE. Do not administer by other routes. Intrathecal administration has caused cases of death.

3.ELIMINATION

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

The elimination of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations for cytotoxic medications.

The following information is only for healthcare professionals:

1.PREPARATION FOR INJECTIONSUBCUTANEOUS

Pregnant women should not handle this medicine.

Nota: Bortezomib is a cytotoxic agent. Therefore, caution should be exercised during handling and preparation. It is recommended to use gloves and other protective clothing to prevent skin contact.

BECAUSE BORTEZOMIB STADA LACKS PRESERVATIVES, IT IS RECOMMENDED TO FOLLOW STRICT ASPTIC TECHNIQUE DURING HANDLING.

1.1Bortezomib STADA is prepared for use.

The resulting solution concentration will be 2.5 mg/ml. The solution is transparent and colorless, with a pH of 4.0 to 6.0. No pH check is required.

1.2Before administration, visually inspect the solution to discard the presence of particles and discoloration. If any discoloration or particles are observed, the solution must be discarded. Check that the correct dose is being used for subcutaneous administration (2.5 mg/ml).

1.3The medicine lacks preservatives and must be used immediately after removing the appropriate amount of solution. If the solution is not used immediately, the storage times and conditions before use are the responsibility of the user. However, the chemical and physical stability during use has been demonstrated for 28 days stored between 2°C and 8°C protected from light, 7 days stored at 25°C protected from light, or 24 hours stored at 25°C (in normal interior lighting conditions) in the original vial and/or polipropylene syringe.

During preparation for administration and during administration, the product does not need to be protected from light.

2.ADMINISTRATION

?Remove the appropriate amount of the solution according to the calculated dose based on the patient's Body Surface Area.

?Confirm the dose and concentration contained in the syringe before use (check that the syringe ismarked for subcutaneous administration)

?Inject the solution subcutaneously, at an angle of 45-90°.

?The solution is administered subcutaneously in the thigh (right or left) or in the abdomen (right or left side).

?The administration sites should be rotated with each injection.

?If local reactions occur at the administration site after subcutaneous injection of Bortezomib STADA, oryou can administer a less concentrated solution of Bortezomib STADA(1 mg/mlinstead of 2.5 mg/ml) or it is recommended to change to an intravenous injection.

Bortezomib STADA 2.5 mg/ml injectable solution IS FOR USE BY INTRAVENOUS OR SUBCUTANEOUS ROUTE. Do not administer by other routes. Intrathecal administration has caused cases of death.

3.ELIMINATION

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

The elimination of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations for cytotoxic medications.