TRISENOX 1 mg/ml, concentrate for solution for infusion

TRISENOX is used in patients with acute promyelocytic leukaemia (APL) whose disease has not responded to other therapies. APL is a unique type of myeloid leukaemia, a disease in which abnormal white blood cells and abnormal bleeding and bruising occur.

TRISENOX must be injected under the supervision of a physician experienced in the treatment of acute leukaemias.

Do not use TRISENOX

• if you are hypersensitive (allergic) to arsenic trioxide or any of the other ingredients of TRISENOX.

Take special care with TRISENOX
Please tell your doctor immediately if you have any of the following symptoms: shortness of breath, fever, sudden weight gain, fainting, water retention or palpitations (strong heartbeat you can feel in your chest). .
Your doctor must check your blood to be sure that you do not have low amounts of potassium or magnesium before your first dose of TRISENOX. You should also have a 12-lead electrocardiogram performed before your first dose. Blood tests should be repeated twice weekly while you are receiving TRISENOX. In addition, you will receive electrocardiograms twice weekly. If you are at risk for a certain type of abnormal heart rhythm (e.g. torsade de pointes or QTc prolongation) your heart will be monitored continuously.
You must tell your doctor if you have impaired kidney or liver function.

Using other medicines
Please tell your doctor if you are taking any of various types of medicines which could cause a change in the rhythm of your heartbeat. These include:

• some types of antiarrhythmics (drugs used to correct irregular heart beats, e.g. quinidine, amiodarone, sotalol, dofetilide)
• antipsychotics (e.g. thioridazine)
• antidepressants (e.g. amitriptyline)
• some types of antibiotics (e.g. erythromycin and sparfloxacin)
• some antihistamines (e.g. terfenadine and astemizole)
• any medicines that cause a decrease in magnesium or potassium in your blood (e.g. amphotericin B)
• cisapride (a medicine used to relieve certain stomach problems). The effect of these medicines on your heartbeat can be made worse by TRISENOX. You must be sure to tell your doctor about all medicines you are taking.

Please inform your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without prescription.

Using TRISENOX with food and drink

• no restrictions on your food or drink are needed while you are receiving TRISENOX.

Pregnancy

Ask your doctor or pharmacist for advice before taking any medicine. TRISENOX may cause harm to the foetus when used by pregnant women. If you are able to become pregnant, you must use effective birth control during treatment with TRISENOX. If you are pregnant or you become pregnant during the treatment with TRISENOX, you must ask your doctor for advice.

Men should also use effective contraception during treatment with TRISENOX.

Breast-feeding

Ask your doctor or pharmacist for advice before taking any medicine. Arsenic will be present in the milk of TRISENOX patients who are breast-feeding. Because of the potential for serious side-effects in nursing infants from TRISENOX, do not breast-feed while on TRISENOX.

Driving and using machines

The effect of TRISENOX on your ability to drive is not known. If you experience discomfort or if you feel unwell after a TRISENOX injection, you should wait until the symptoms go away before driving or using machines.

Important information about some of the ingredients of TRISENOX

Trisenox contains less than 1 mmol sodium (23 mg) per dose i.e. essentially ?sodium-free?.

Your doctor will dilute TRISENOX with 100 to 250 ml of glucose 50 mg/ml (5%) injection, or sodium chloride 9 mg/ml (0.9%) injection.

Your doctor will infuse TRISENOX through a tube into a blood vessel over 1-2 hours, but the infusion may last longer if side-effects like flushing and dizziness occur.

Your doctor will give you TRISENOX once every day as a single infusion each day. In your first treatment cycle, you may be treated every day up to 50 days at most, or until your doctor determines that your disease is better. If your disease responds to TRISENOX, you will be given a second treatment cycle of 25 doses, one infusion every weekday for 5 weeks. Your doctor will decide exactly how long you must continue on therapy with TRISENOX.

Each TRISENOX ampoule must be used only once and does not contain any preservatives. Unused portions of each ampoule must be discarded properly.

Do not save any unused portions for later use.

TRISENOX must not be mixed with, or infused through the same tube with other medicinal products.

If your doctor gives you more TRISENOX than he/she should

You may experience convulsions, muscle weakness and confusion. If this happens, treatment with TRISENOX must be stopped immediately and your doctor will treat the arsenic overdose.

Like all medicines, TRISENOX can have side effects.

While on treatment with TRISENOX, you may experience some of the following reactions: common side effects (greater than or equal to 1 in 100 but less than 1 in 10): fatigue (weariness), increased blood sugar, shortness of breath, cough, headache.
uncommon side effects (greater than or equal to 1 in 1000 but less than 1 in 100): increased white blood cell count, Herpes zoster, pneumonia, sepsis, anaemia, dehydration, confusion, blurry vision, cardiac failure, hypotension, pneumonitis, chills, renal failure, increased weight, nausea, vomiting, diarrhoea, stomach ache, oedema (water retention), rash or itching, change in your heart rhythm or dizziness.
Frequency unknown: decreased blood cell counts, a syndrome including fever, together with difficulty in breathing, coughing and chest pain. If you experience these symptoms, you should inform your doctor immediately.

Other side effects not mentioned above may also occur in some patients.

Tell your doctor immediately if you experience shortness of breath, fever, sudden weight gain, water retention, fainting or palpitations (strong heartbeat you can feel in your chest).

If you notice any side effects not mentioned in this leaflet, please inform your doctor or pharmacist.

Keep out of the reach and sight of children

Do not use after the expiry date stated on the ampoule label.
Do not freeze

After dilution, if not used immediately, in-use storage times and conditions before use are the responsibility of your doctor and would normally not be longer than 24 hours at 2ºC ? 8ºC, unless dilution has taken place in a sterile environment.

Do not use TRISENOX if you notice foreign particulate matter or if discolouration is present.

What TRISENOX contains

• The active substance is arsenic trioxide 1 mg/ml
• The other ingredients are sodium hydroxide, hydrochloric acid and water for injections

What TRISENOX looks like and contents of the pack

• TRISENOX is a concentrate for solution for infusion. TRISENOX is supplied in glass ampoules as a concentrated, sterile, clear, colourless, aqueous solution that is prepared and diluted at the hospital

and given as an infusion into a blood vessel. Each carton contains 10 single-use glass ampoules. Each ampoule contains 10 mg of arsenic trioxide.

Marketing Authorisation Holder and Manufacturer

• Marketing Authorisation Holder: Cephalon Europe, 5 Rue Charles Martigny, 94700 Maisons Alfort, FRANCE
• Manufacturer: Almac Pharma Services Limited, Almac House, 20 Seagoe Industrial Estate, Craigavon, BT63 5QD, United Kingdom

This leaflet was last approved in {MM/YYYY}

Detailed information on this medicine is available on the EMEA web site:http://www.emea.europa.eu There are also links to other websites about rare diseases and treatments.

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The following information is intended for medical or healthcare professionals only:

Preparation of TRISENOX

ASEPTIC TECHNIQUE MUST BE STRICTLY OBSERVED THROUGHOUT HANDLING OF TRISENOX SINCE NO PRESERVATIVE IS PRESENT.

TRISENOX must be diluted with 100 to 250 ml of glucose 50 mg/ml (5%) injection or sodium chloride 9 mg/ml (0.9%) injection immediately after withdrawal from the ampoule. For single use only. Unused portions of each ampoule must be discarded properly. Do not save any unused portions for later administration.

TRISENOX must not be mixed with or concomitantly administered in the same intravenous line with other medicinal products.

TRISENOX must be administered intravenously over 1-2 hours. The infusion duration may be extended up to 4 hours if vasomotor reactions are observed. A central venous catheter is not required.

The diluted solution must be clear and colourless. All parenteral solutions must be inspected visually for particulate matter and discoloration prior to administration. Do not use the preparation if foreign particulate matter is present.

After dilution in intravenous solutions, TRISENOX is chemically and physically stable for 24 hours at 15-30°C and 48 hours at refrigerated (2-8°C) temperatures. From a microbiological point of view, the product must be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2-8°C, unless dilution has taken place in controlled and validated aseptic conditions.

Procedure for proper disposal

Any unused product, any items that come into contact with the product, and waste material must be disposed of in accordance with local requirements.