Botigen Solution

BOTIGEN 3,5 contains bortezomib as the active ingredient and belongs to a group of medicines called cytostatic medicines. These are used to kill cancer cells.

BOTIGEN 3,5 is used for the treatment of:

Multiple Myeloma (a cancer of the bone marrow) in adults:

• In combination with other medicines (melphalan and prednisone), for patients who have not been previously treated and are unsuitable for high-dose chemotherapy with blood stem cell transplantation
• 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 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).

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 medicines rituximab, cyclophosphamide, doxorubicin and prednisone, for patients whose disease has not been previously treated and for whom blood stem cell transplantation is unsuitable.

You should not be administered BOTIGEN 3,5:

• If you are hypersensitive (allergic) to bortezomib or any of the other ingredients of BOTIGEN 3,5.
• If you are hypersensitive (allergic) to mannitol or boron.
• If you have certain severe lung or heart problems.

Warning and Precautions

Tell your doctor or healthcare provider before being given the injection if you have:

• severe lung, liver or heart problems.
• low numbers of red blood cells, platelets or white blood cells, as these might worsen during treatment.
• bleeding problems and/or low number of platelets in your blood.
• diarrhoea, constipation, nausea or vomiting, as this might worsen during treatment.
• a history of fainting, dizziness or light-headedness in the past.
• kidney problems.
• liver problems.
• numbness, tingling, or pain in the hands or feet (neuropathy) in the past, as it might worsen during treatment.
• heart or blood pressure problems.
• amyloidosis (as a result of abnormal deposit of amyloid (a protein) in various tissues in the body).
• 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.

• mantle cell lymphoma and are given the medicine rituximab with BOTIGEN 3,5 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

BOTIGEN 3,5 has not been studied in children or adolescents and therefore should not be used in this patient population.

Other medicines and BOTIGEN 3,5

Always tell your healthcare provider if you are taking any other medicine. (This includes complementary or traditional medicines).

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.
• Ritonavir used to treat HIV infection.

You will not be expected to give yourself BOTIGEN 3,5. It will be given to you by a person who is qualified to do so.

The usual starting dose of BOTIGEN 3,5 is 1,3 mg/m2 body surface area twice a week. Your doctor will work out your dose of BOTIGEN 3,5 according to your height and weight (body surface area).

You will receive BOTIGEN 3,5 in a specialised medical unit, under the supervision of a doctor experienced in the use of cytotoxic medicines.

You will be given BOTIGEN 3,5 intravenously (in a vein) or subcutaneously (under the skin). BOTIGEN 3,5 powder has to be dissolved before administration. This will be done by a healthcare provider. The resulting solution is then either injected into a vein or under the skin. Injection into the vein is rapid, taking 3 to 5 seconds. Injection under the skin is in either the thigh or the abdomen.

Your doctor will tell you how long your treatment with BOTIGEN 3,5 will last. 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 BOTIGEN 3,5 is given alone, you will receive 4 doses of BOTIGEN 3,5 intravenously 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. At least 72 hours should elapse between consecutive doses of BOTIGEN 3,5. You might receive up to 8 cycles (24 weeks).

You may also be given BOTIGEN 3,5 together with the medicines pegylated liposomal doxorubicin or dexamethasone.

When BOTIGEN 3,5 is given together with pegylated liposomal doxorubicin

You will receive BOTIGEN 3,5 intravenously as a 21-day treatment cycle and pegylated liposomal doxorubicin 30 mg/m2 is given on day 4 of the BOTIGEN 3,5, 21-day treatment cycle as an intravenous infusion after the BOTIGEN 3,5 intravenous injection. You might receive up to 8 cycles (24 weeks).

Previously untreated multiple myeloma

Patients with previously untreated multiple myeloma may also be given BOTIGEN 3,5 together with the 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, BOTIGEN 3,5 is administered twice weekly on days 1, 4, 8, 11, 22, 25, 29 and 32.
• In cycles 5 to 9, BOTIGEN 3,5 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 BOTIGEN 3,5 intravenously together with the medicines dexamethasone, or dexamethasone and thalidomide, as induction treatment.

BOTIGEN 3,5 can have side effects. Not all side effects reported for BOTIGEN 3,5 are included in this leaflet. Should your general health worsen or if you experience any untoward effects while given BOTIGEN 3,5, please consult your health care provider for advice.

If any of the following happens stop using BOTIGEN 3,5 and tell your doctor immediately or go to the casualty department at your nearest hospital:

• Swelling of the hands, feet ankles, face, lips and mouth or throat, which may cause difficulty in swallowing or breathing.
• Peeling and blistering of the skin, mouth, eyes and genitals.
• Rash or itching affecting your whole body.
• Fainting.

These are all very serious side effects. If you have them, you may have had a serious allergic reaction to BOTIGEN 3,5. You may need urgent medical attention or hospitalisation.

If you are given BOTIGEN 3,5, tell your doctor immediately or go to the casualty department of your nearest hospital if you notice any of the following:

• muscle cramping.
• muscle weakness.
• tingling, burning, pain, and loss of feeling in your hands and feet, any of which can be severe.
• confusion.
• visual loss or disturbances.
• blindness.
• seizures.
• headaches.
• shortness of breath.
• swelling of your feet or changes in your heartbeat.
• high or low blood pressure.
• tiredness.
• fainting.
• dizziness.
• wheezing, coughing and breathing difficulties or tightness in the chest.
• chest pressure or pain.
• yellow discoloration of the eyes and skin (jaundice) and changes in liver enzymes measured in blood tests.

These are all serious side-effects. You may need medical attention. Treatment with BOTIGEN 3,5 can frequently 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 BOTIGEN 3,5, 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.

The following side-effects have been reported, tell your doctor if you notice any of the following:

Frequent:

• Herpes zoster infection (including disseminated).
• Pneumonia, bronchitis, infection of the sinus passages.
• Reduction in the number of red blood cells and or white blood cells (see above).
• Dehydration and loss of appetite.
• Changes in potassium in your blood, too much sugar in your blood.
• Depression which may be severe, confusion.
• Difficulty in sleeping, sweating, anxiety.
• Sensitivity, numbness, tingling or burning sensation of the skin, or pain in the hands or feet, due to nerve damage.
• Fever, shivering fits.
• Blurred vision, eye pain.
• General ill feeling, dizziness, light-headedness, or a feeling of weakness.
• Sudden fall of blood pressure on standing which may lead to fainting, high blood pressure, infection or swelling of a vein or tissue.
• Chest pains or coughing with phlegm, shortness of breath with exercise.
• Difficulty in breathing, nose bleeds, cough, runny nose.
• Heartburn, bloating, belching, wind or stomach pain, hiccups.
• A sore mouth or lip, dry mouth, mouth ulcers or throat pain.
• Constipation with or without bloating (can be severe), abdominal pain.
• Feeling sick (nausea) or vomiting, loss of appetite.
• Diarrhoea: if this happens, it is important that you drink more water than usual. Your doctor may give you another medicine to control diarrhoea.
• Rash.

BOTIGEN 3,5 will be stored in the pharmacy. Store all medicines out of reach of children. Do not use this medicine after the expiry date stated on the vial and the carton after EXP: Before reconstitution: Store at or below 25 °C. Keep the vial in the outer carton in order to protect from light.

Reconstituted solutions: The reconstituted solution should be used immediately after preparation. If the reconstituted solution is not used immediately, in-use storage times and conditions prior to use are the responsibility of the user. However, the reconstituted solution is stable for 8 hours at 25 °C stored in the original vial and/or a syringe, with a total storage time for the reconstituted medicine not exceeding 8 hours prior to administration. BOTIGEN 3,5 is for single use only. Discard any unused portion as per current requirements.