Onbort 1 mg/0.4 ml/2.5 mg/3.5 mg/1.4 ml Solution

ONBORT belongs to a group of medicines called cytotoxic medicines. These are used to kill cancer cells. ONBORT is used for the treatment of multiple myeloma (a cancer of the bone marrow)

• In combination with the other medicines (melphalan and prednisone), for patients who have not been previously treated for multiple myeloma.
• Alone (monotherapy) for patients whose disease is worsening (progressive) after receiving at least one prior treatment for multiple myeloma.
• 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.

ONBORT should not be administered to you

• If you are hypersensitive (allergic) to bortezomib, or any of the other ingredients of ONBORT
• If you have severe lung or heart problems.
• If you have severe liver problems.

Warnings and precautions

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

• Diabetes (a blood sugar condition).
• Liver disease.
• Kidney disease or if you are on dialysis.
• Diarrhoea, constipation, nausea or vomiting, as this may become worse during ONBORT treatment.
• A bleeding or blood clotting disorder.
• A low level of platelet or white or red blood cells, as these conditions may become worse during treatment with ONBORT.
• A history of fainting, dizziness or light-headedness.
• Shortness of breath or cough.
• Seizures.
• Symptoms of tumour 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.
• Herpes or a history of shingles.
• High or low blood pressure.
• Nerve problems such as numbness, burning pain or tingling feeling. This effect may become worse during ONBORT treatment.
• If you have been diagnosed with a condition called amyloidosis (that results from the abnormal deposit of a particular protein (called amyloid), in various tissues of the body).
• If you are pregnant or breastfeeding.

Take special care with ONBORT:

If you have mantle cell lymphoma ((a blood cancer in the lymph glands) and are given the medicine rituximab with ONBORT you should tell your doctor:

• If you think you have a 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.
• When thalidomide is used, particular attention to pregnancy testing and prevention requirements is needed (see Pregnancy, breastfeeding and fertility).

Children and adolescents

ONBORT has not been studied in children or adolescents and therefore should not be used in this patient population.

Elderly

There is no evidence to suggest that dose adjustments are necessary in the elderly.

Other medicines and ONBORT

Always tell your health care provider if you are taking any other medicine. (This includes all complementary or traditional medicines). In particular, tell your doctor if you are using medicines containing any of the following active substances:

Do not share medicines prescribed for you with any other person. ONBORT IS FOR INTRAVENOUS USE. ONBORT will be administered by a healthcare professional experienced in the use of cytotoxic medicines. ONBORT reconstitution solution before administration. This will be done by a healthcare professional. Injection into a vein is rapid (bolus), taking 3 to 5 seconds.

Your doctor will work out your dose of ONBORT according to your height and weight (body surface area). The usual starting dose of ONBORT is 1,3 mg/m2 body surface area twice weekly for two weeks (days 1, 4, 8 and 11) followed by a 10-day rest period (days 12-21). This 3 week period is considered a treatment cycle. At least 72 hours should be between consecutive doses of ONBORT. 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 ONBORT is given alone, you will receive 4 doses of ONBORT 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. 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 ONBORT 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, ONBORT is administered twice weekly on days 1, 4, 8, 11, 22, 25, 29 and 32.
• In cycles 5 to 9, ONBORT 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. You will not be expected to give yourself ONBORT. It will be given to you by a person who is qualified to do so.

If you are given more ONBORT than you should

Since a health care provider will administer ONBORT, he/she will control the dosage. However, in the event of dosage your doctor will manage the overdosage.

If you forget to take ONBORT

Since a health care provider will administer ONBORT, it is unlikely that the dose will be missed. Call your doctor for instructions if you will miss an appointment for your bortezomib injection.

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

If any of the following happens, stop taking ONBORT and tell your doctor immediately or 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 ONBORT. You may need urgent medical attention or hospitalisation.

Tell your doctor immediately or go to the casualty department at your nearest hospital if you notice any of the following:

Frequent:

• Treatment with ONBORT 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 ONBORT, 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.
• Low blood pressure, which may lead to fainting, high blood pressure.
• Reduced functioning of your kidneys, failing of your kidneys.

Infections, including:

• pneumonia, respiratory infections, bronchitis, fungal infections, coughing with phlegm, urinary tract infections, herpes virus infections, ear infection and cellucitis.

Less frequent:

• Heart failure, heart attack, angina, inflammation of the lining around your heart or fluid around your heart.
• Inflammation of a vein, blood clots in your veins and lungs, problems with blood clotting.
• Insufficient circulation.
• Cerebrovascular disorders (limited or no blood flow to affected areas of the brain).
• Paralysis, seizures, falling, movement disorders.
• 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, breathing that becomes shallow, difficult or stops, wheezing.

• Store all medicines out of reach of children.

• Store at 2°C - 8°C, in a dry place, well closed in the original container, protected from light and moisture.

• Keep the vial in the outer carton until required for use.

• There are no special storage instructions for ONBORT.

• Do not store in a bathroom.

• Do not use after the expiry date stated on the label / carton / bottle.

• Return all unused medicine to your pharmacist.

• Do not dispose of unused medicines in drains or sewerage system.