Bortezomib Equity 3,5 mg Solution

Bortezomib Equity 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 Equity is used for the treatment of:

• Multiple Myeloma (a cancer of the bone marrow) in adult patients:
• alone (monotherapy) or together with the medicines pegylated liposomal doxorubicin or dexamethasone for patients whose disease is worsening (progressive) after receiving at least one prior treatment for Multiple Myeloma and for whom blood stem cell transplantation was not successful or is unsuitable.
• in combination with the medicine dexamethasone or dexamethasone together with thalidomide, for patients whose disease has not been previously treated and before receiving high-dose chemotherapy with blood cell transplantation (induction treatment).
• in combination with other medicines (melphalan and prednisone), for patients who have not been previously treated for Multiple Myeloma and are unsuitable for high-dose chemotherapy with blood stem cell transplantation.
• Mantle Cell Lymphoma (a blood cancer in the lymph glands) in adults:
• whose disease is worsening (progressive) after receiving at least one prior treatment, one of which should have included the medicine anthracycline (or mitoxantrone) and/or rituximab as part of their chemotherapy treatment.
• in combination with the medicine rituximab, cyclophosphamide, doxorubicin and prednisone, for patients whose disease has not been previously treated and for whom blood cell transplantation is unsuitable.

Bortezomib Equity should not be administered to you if:

• if you are hypersensitive (allergic) to bortezomib, boron or to any other ingredients of Bortezomib Equity (listed in section 6)
• if you have certain severe lung or heart problems

Warnings and precautions

Tell your doctor or healthcare provider before being given the injection: Special care should be taken with Bortezomib Equity:

• if you are suffering from diarrhoea, constipation, nausea or vomiting as this may become worse during Bortezomib Equity treatment
• if you have low numbers of red, or white blood cells
• if you have bleeding problems and/or low number of platelets in your blood
• if you have had any problems with numbness, tingling, or pain in the hands or feet (neuropathy) in the past. This effect may become worse during Bortezomib Equity treatment
• if you are suffering of have been suffering from shingles (localised including around the eyes or spread across the body)
• if you have any heart or blood pressure problems
• if you have memory loss, trouble thinking, difficulty with walking or loss of vision. These may be signs of a serious brain condition and your doctor may suggest further testing and follow-up
• if you have kidney problems
• if you have moderate to severe liver problems
• if you suffer from seizures
• if you have experienced or have new or increased shortness of breath or cough
• if you have experienced or have new or increased symptoms of tumour lysis syndrome such as vomiting muscle cramping, muscle weakness, confusion, fits, excess fluid build-up, heart failure, irregular heart rhythm, fainting, visual loss or disturbances and shortness of breath
• if you have a history of fainting, dizziness or light-headedness
• if you have been diagnosed with a condition called amyloidosis (that results from abnormal deposit of a particular protein (called amyloid), in various tissues of the body)

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

If you have mantle cell lymphoma and are given the medicine rituximab with Bortezomib Equity 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.

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

Always tell your healthcare provider if you are taking any other medicine. (This includes all complementary or traditional medicines.) Tell your doctor if you are taking any of the following medicines:

• 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
• pain medicines
• blood pressure or medicines used for your heart e.g., angiotensin inhibitors, beta-blockers, antihypertensives, calcium channel blockers, angiotensin receptor blockers and diuretics
• amiodarone, used for heart rhythm problems
• anti-viral medicines
• isoniazid, an antibiotic used in the treatment of tuberculosis (TB)
• nitrofurantoin, an antibiotic used in the treatment of bladder infections

You will not be expected to give yourself Bortezomib Equity. It will be given to you by a person who is qualified to do so.

This medicine is for intravenous (administered into a vein) or subcutaneous (under the skin) use. The dose will be calculated from your height and weight (body surface area).

Monotherapy

Relapsed multiple myeloma and relapsed mantle cell lymphoma: When Bortezomib Equity is given alone, one cycle of treatment with Bortezomib Equity consists of a total of 4 doses. Doses are given on days 1, 4, 8 and 11, followed by a 10-day ‘rest period’ without treatment. Therefore, the duration of a treatment cycle is 21 days (3 weeks). You may receive up to 8 cycles (24 weeks) of treatment.

Combination therapy

Previously untreated multiple myeloma not suitable for blood stem cell transplantation: If you have not been treated before for multiple myeloma and you are not suitable for blood stem cell transplantation, you will receive Bortezomib Equity together with two other medicines containing melphalan and prednisone. In this case, the duration of a cycle is 6 weeks. The treatment consists of a total of 9 cycles (54 weeks). In cycles 1 to 4, Bortezomib Equity is administered twice weekly on days 1, 4, 8, 11, 22, 25, 29 and 32. In cycles 5 to 9, Bortezomib Equity is administered once weekly on days 1, 8, 22 and 29. Melphalan and prednisone are both given orally on days 1, 2, 3 and 4 of the first week of each cycle.

Previously untreated multiple myeloma suitable for blood stem cell transplantation: If you have not been treated before for multiple myeloma, and you are suitable for blood stem cell transplantation, you will receive Bortezomib Equity subcutaneously together with the medicines dexamethasone, or dexamethasone and thalidomide, as induction treatment. Bortezomib Equity is given twice weekly on Days 1, 4, 8, and 11, followed by a rest period of 10-18 days. This is considered as a treatment cycle. You will be given 3-6 cycles of treatment.

Relapsed multiple myeloma: If you have been treated before for multiple myeloma and you are unsuitable for blood stem cell transplantation or if you have already received a blood stem cell transplantation, you will receive Bortezomib Equity together with a medicine called pegylated liposomal doxorubicin or a medicine called dexamethasone. When Bortezomib Equity is given together with pegylated liposomal doxorubicin, you will receive Bortezomib Equity subcutaneously as a 21-day treatment cycle and pegylated liposomal doxorubicin 30 mg/m2 is given on day 4 of the Bortezomib Equity 21-day treatment cycle as an intravenous infusion after the Bortezomib Equity injection. You might receive up to 8 cycles (24 weeks).

When Bortezomib Equity is given together with dexamethasone, you will receive Bortezomib Equity subcutaneously as a 21-day treatment cycle and dexamethasone 20 mg is given orally on the day of and the day after the Bortezomib Equity injection.

Previously untreated mantle cell lymphoma: If you have not been treated before for mantle cell lymphoma you will receive Bortezomib Equity subcutaneously together with the following medicines: rituximab, cyclophosphamide, doxorubicin and prednisone. Bortezomib Equity is given 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 medicines are given on day 1 of each Bortezomib Equity 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 Equity treatment cycle.

Your doctor will tell you how long your treatment with Bortezomib Equity will last. If you have the impression that the effect of Bortezomib Equity is too strong or too weak, tell your doctor or pharmacist.

Method of administration

Bortezomib Equity 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 use more Bortezomib Equity than you should Since a healthcare provider will administer Bortezomib Equity, he / she will control the dosage. However, in the event of overdosage your doctor will manage the overdosage.

If you forget to use Bortezomib Equity Since a healthcare provider will administer Bortezomib Equity, it is unlikely that the dose will be missed.

Bortezomib Equity can have side effects. Not all side effects reported for Bortezomib Equity are included in this leaflet. Should your general health worsen or if you experience any untoward effects while receiving Bortezomib Equity, please consult your healthcare provider for advice.

If any of the following happens, stop receiving Bortezomib Equity and tell your doctor immediately and go to the casualty department at your nearest hospital:

• swelling of the hands, feet, ankles, face, lips, mouth or throat, which may cause difficulty in swallowing or breathing,
• rash or itching,
• fainting.

These are all very serious side effects. If you have them, you may have had a serious reaction to Bortezomib Equity. You may need urgent medical attention or hospitalisation.

If you are given Bortezomib Equity for multiple myeloma or mantle cell lymphoma, tell your doctor immediately or go to the casualty department at your nearest hospital if you notice any of the following:

• muscle cramping, muscle weakness
• confusion, visual loss or disturbances, blindness, seizures, headaches
• shortness of breath, swelling of your feet or changes in your heartbeat, high blood pressure, tiredness, fainting
• coughing and breathing difficulties or tightness in the chest.

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.

These are all serious side effects. You may need urgent medical attention.

Tell your doctor if you notice any of the following: If you are given Bortezomib Equity for the treatment of multiple myeloma the side effects you may get are listed below:

Frequent side effects:

• infections, including lung infection, respiratory infections, bronchitis, fungal infections, coughing with phlegm, flu like illness
• shingles (localised including around the eyes or spread across the body)
• loss of appetite, dehydration, reduced potassium, reduced sodium, reduced calcium levels in your blood
• anxiety, mood swings and disorders, sleep disorders
• sensitivity, numbness, weakness, tingling or burning sensation of the skin, or pain in the hands or feet, due to nerve damage
• loss of consciousness, progressive, asymmetric muscle weakness and atrophy (wasting), abnormal sense of touch, bad taste, headache, lack of energy
• eye swelling, abnormal vision and inflammation/infection of the conjunctiva
• spinning sensation
• low blood pressure, sudden fall of blood pressure on standing which may lead to fainting, high blood pressure
• difficulty breathing, nose bleeding, respiratory infection, cough
• feeling sick (nausea) or vomiting, diarrhoea, constipation, indigestion, stomach pain, wind, any problem that affects your mouth can make it hard to eat, drink, or even smile, inflammation of the mucous membrane of the mouth, bloating or swelling of the belly, bleeding from your bowels or stomach

Less frequent side effects:

• bacterial and viral infections
• infections including urinary tract infections, the flu, herpes virus infections, ear infection and cellulitis
• a red, painful lump near the edge of the eyelid that may look like a boil or pimple, tooth infection, injection site or injection device related disorders
• a severe reversible brain condition which includes seizures, high blood pressure, headaches, tiredness, confusion, blindness or other vision problems.
• sexually transmitted infection marked by genital pain and sores, infection of the tonsils, an infection that affects the mastoid bone, located behind the ear
• a disease characterised by profound fatigue, sleep abnormalities, pain and other symptoms that are made worse by exertion
• cancer of the kidney, a large body of matter with no definite shape, mass of slow growing localized tumour, skin cancer
• low numbers of white blood cells, problems with blood clotting, swelling of your lymph glands, 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
• thrombosis in capillaries and arterioles, blood disorders include anaemia, bleeding disorders such as haemophilia, blood clots, and blood cancers such as leukaemia, lymphoma, and myeloma
• abnormal protein deposits in your vital organs

Store all medicines out of reach of children. Store at or below 25 °C and protect from light. Do not freeze. Do not use this medicine after the expiry date which is stated on the syringe or pen label and on the outer carton after EXP. The expiry date refers to the last day of that month. Return all unused medicine to your pharmacist. Do not dispose of unused medicine in drains or sewerage systems (e.g., toilets).