1 mg/ml, concentrate for solution for injection, solution
arsenic trioxide
What TRISENOX is and what it is used for
TRISENOX is used in adult patients with newly diagnosed acute promyelocytic leukemia (APL) with low to intermediate risk, as well as in adult patients when the disease has not improved after other treatments. APL is a unique form of myeloid leukemia, a disease in which abnormal white blood cells are produced and abnormal bleeding and bruising occur.
What you need to know before you are given TRISENOX
You should not receive TRISENOX
If you are allergic to arsenic trioxide or any of the other ingredients of this medicine (listed in section 6).
TRISENOX must be given under the supervision of a doctor experienced in treating acute leukemia.
Warnings and precautions
You must talk to your doctor or nurse before you are given TRISENOX
- you have reduced kidney function
- you have liver problems
Your doctor will take the following precautions:
- Tests are performed to check the amount of potassium, magnesium, calcium, and creatinine in your blood before your first dose of TRISENOX.
- The electrical activity of the heart ( electrocardiogram, EKG ) should be measured before you receive the first dose.
- Blood tests ( potassium, calcium, magnesium, and liver function) are then repeated during your treatment with TRISENOX.
- In addition, an EKG is taken on you twice a week.
- If you are at risk of a certain type of abnormal heart rhythm (eg torsade de pointes or QTc prolongation), your heart will be continuously monitored.
- The doctor can monitor your health during and after treatment, because arsenic trioxide, the active substance in TRISENOX, can cause other types of cancer. You must report any new and unusual symptoms and circumstances each time you see the doctor.
- Follow-up of your cognitive functions and your mobility if you are at risk of vitamin B1 deficiency.
Children and young people
TRISENOX is not recommended for children under 18 years of age.
Other medicines and TRISENOX
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those without a prescription
In particular, tell the doctor if you are taking any of the different types of medicine that could cause a change in the heart rhythm. These include:
- certain types of antiarrhythmics (medicines used to correct irregular heart rhythms eg quinidine, amiodarone, sotalol, and dofetilide)
- medicines for the treatment of psychosis (loss of perception of reality, eg thioridazine)
- medicines for depression (eg amitriptyline)
- certain types of medicines to treat bacterial infections (eg erythromycin and sparfloxacin)
- certain medicines for the treatment of allergies such as hay fever, so-called antihistamines (e.g. terfenadine and astemizole)
- any medicine that causes a decrease in the amount of magnesium or potassium in the blood (eg amphotericin B)
- cisapride a medicine used to relieve some stomach problems).
The effect of these medicines on your heart rhythm may be worsened by TRISENOX. Therefore, you must inform the doctor about all the medicines you are taking.
- if you are taking or have recently taken any medication that may affect your liver. Show the bottle or packaging to the doctor if you are unsure.
TRISENOX with food, drink, and alcohol
- There are no restrictions on food and drink while you are receiving TRISENOX.
Pregnancy, breastfeeding, and fertility
Pregnancy
Ask your doctor or pharmacist for advice before taking any medicine.
TRISENOX can harm the fetus when used by pregnant women.
If you can become pregnant, you must use effective contraception during treatment with TRISENOX and for 6 months after stopping treatment.
If you are pregnant or if you become pregnant during treatment with TRISENOX, you must consult your doctor.
Men receiving TRISENOX must use effective contraception and should be advised not to make a woman pregnant while receiving TRISENOX and for 3 months after stopping treatment.
Breast-feeding
Ask your doctor or pharmacist for advice before taking any medicine.
The arsenic in TRISENOX passes into breast milk.
Because TRISENOX can harm breastfed babies, you must not breastfeed while you are being treated with TRISENOX and within two weeks after the last dose.
Driving ability and use of machinery
TRISENOX is expected to have no or negligible effect on the ability to drive and use machines.
If you experience discomfort or if you feel unwell after a TRISENOX injection, you should wait until the symptoms disappear before driving or operating machinery.
TRISENOX contains sodium
TRISENOX contains less than 1 mmol sodium (23 mg) per dose . This means that the medicine is almost “sodium-free”.
3. How TRISENOX is given
Treatment time and treatment frequency
Patients with newly diagnosed acute promyelocytic leukemia
Your doctor will give you TRISENOX once a day as an infusion. In your first round of treatment, you may receive treatment every day for up to a maximum of 60 days or until your doctor judges that your disease has improved. If your disease is improved by TRISENOX, you will receive 4 more cycles. Each cycle consists of 20 doses given 5 days a week (followed by 2 days off) for 4 weeks, followed by 4 weeks off. Your doctor will decide exactly how long you should continue to be treated with TRISENOX.
Patients with acute promyelocytic leukemia who have not responded to other treatments
Your doctor will give you TRISENOX once a day as an infusion. In your first treatment cycle, you may receive treatment every day for up to a maximum of 50 days or until your doctor judges that your disease has improved. If your disease improves with TRISENOX, you will have another treatment cycle of 25 doses given 5 days a week (followed by 2 days off) for 5 weeks. Your doctor will decide exactly how long you should continue to be treated with TRISENOX.
Method of administration and route of administration
TRISENOX must be diluted with a solution containing glucose or a solution containing sodium chloride.
TRISENOX is normally given by a doctor or nurse. It is given as a drip (an infusion ) into a vein over 1–2 hours, but it may take longer if side effects such as skin redness and dizziness occur.
TRISENOX should not be mixed with or passed through the same tube together with, other medicines.
If your doctor or nurse gives you more TRISENOX than he/she should
You may experience convulsions, muscle weakness, and confusion. If this happens, stop treatment with TRISENOX immediately and your doctor will treat the arsenic overdose.
If you have further questions about this medicine, contact your doctor, pharmacist, or nurse.
Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Tell your doctor or nurse straight away if you notice the following side effects, as they may be signs of a serious condition called ‘differentiation syndrome’ which can be fatal:
Tell your doctor or nurse immediately if you notice one or more of the following side effects, as these may be signs of an allergic reaction:
- hard to breathe
- fever
- sudden weight gain
- water accumulation
- fainting
- palpitations (strong heartbeats that you can feel in your chest)
While you are being treated with TRISENOX, you may experience some of the following reactions:
Very common (may affect more than 1 in 10 people):
- dullness (fatigue), pain, fever, and headache.
- nausea, vomiting, diarrhea
- dizziness, muscle pain, numbness, or tingling
- rash or itching
- high blood sugar, edema (swelling due to excess fluid)
- shortness of breath, palpitations, abnormal ECG measurement
- decreased potassium or magnesium in the blood, abnormal liver function tests including excess bilirubin or gamma glutamyltransferase in the blood.
Common (may affect up to 1 in 10 people):
- decreased number of blood cells ( platelets, red and/or white blood cells ), increased number of white blood cells
- chills, weight gain
- fever due to infection and low white blood cell count, herpes zoster infection
- chest pain, bleeding in the lungs, hypoxia (lack of oxygen), fluid accumulation around the heart or lungs, low blood pressure, abnormal heart rhythm
- cramps, joint or leg pain, inflammation of the blood vessels
- increased sodium or magnesium, ketones in blood and urine ( ketoacidosis ), abnormal kidney function tests, kidney failure
- stomach pain (abdominal pain)
- redness, swollen face, and blurred vision.
Frequency not known (frequency cannot be estimated from available data):
- infection in the lungs, infection in the blood
- pneumonia-causing chest pain and shortness of breath, heart failure
- dehydration, confusion
- brain disease ( encephalopathy, Wernicke’s encephalopathy ) with various manifestations including difficulty using arms and legs, speech disorders, and confusion.
How to store TRISENOX
Keep this medicine out of the sight and reach of children.
Use before the expiry date stated on the ampoule label and carton.
No special storage instructions.
If the solution is not used immediately after dilution, your doctor, pharmacist, or nurse is responsible for storage times and conditions before use. Normally, this time should not be longer than 24 hours at 2 to 8 ºC, unless dilution has taken place in a sterile environment.
The medicine must not be used if you see that the solution contains foreign particles or if the solution is discolored.
Medicines must not be thrown into the drain or among the household waste. Ask the pharmacist how to dispose of medicines that are no longer used. These measures will help to protect the environment.
Contents of the packaging and other information
Contents declaration
- The active substance is arsenic trioxide. Each ml of concentrate contains 1 mg of arsenic trioxide. Each ampoule of 10 ml contains 10 mg of arsenic trioxide.
- Other ingredients are sodium hydroxide, hydrochloric acid, and water for injections. See section 2 “TRISENOX contains sodium”.
Appearance and package sizes of the medicine
- TRISENOX is a concentrate for infusion liquid, solution (sterile concentrate). TRISENOX is supplied in glass ampoules in the form of a concentrated, clear, colorless aqueous solution. Each carton contains 10 glass ampoules for single use.
Marketing Authorisation Holder
TEVA BV Swensweg 5, 2031 GA Haarlem, The Netherlands
Manufacturer:
Almac Pharma Services Limited, Almac House, 20 Seagoe Industrial Estate, Craigavon, BT63 5QD, United Kingdom
Almac Pharma Services (Ireland) Limited; Finnabair Industrial Estate, Dundalk, Co. Louth, A91 P9KD, Ireland
Teva Pharmaceuticals Europe BV, Swensweg 5, 2031 GA Haarlem, The Netherlands