Trisenox 2 mg/ml concentrate for infusion solution

Patient Information Leaflet

Introduction

Package leaflet: Information for the patient

TRISENOX 2mg/ml concentrate for solution for infusion

arsenic trioxide

Read all of this leaflet carefully before you are given this medicine, because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if it is a side effect not listed in this leaflet. See section 4.

Contents of this leaflet

1. What TRISENOX is and what it is used for
2. What you need to know before you are given TRISENOX
3. How TRISENOX is administered
4. Possible side effects
5. How to store TRISENOX
6. Contents of the pack and other information

1. What TRISENOX is and what it is used for

TRISENOX is used in adult patients with low- to intermediate-risk newly diagnosed acute promyelocytic leukemia (APL), and in adult patients whose disease has not responded to other treatments. APL is a unique type of myeloid leukemia, a disease that causes abnormal production of white blood cells, bleeding, and bruising.

2. What you need to know before TRISENOX is administered to you

TRISENOX must be administered under the supervision of a physician experienced in the treatment of acute leukemias.

Do not receive TRISENOX

If you are allergic to arsenic trioxide or to any of the other components of this medicine (listed in section 6).

Warnings and precautions

You should consult your doctor or nurse before receiving TRISENOX if:

• you have renal failure.
• you have any liver problems.

Your doctor will take the following precautions:

• Blood tests will be performed to measure levels of potassium, magnesium, calcium, and creatinine before the first dose of TRISENOX.
• An electrocardiogram (ECG) must be performed before the first dose.
• Blood tests (potassium, calcium, liver function) will be repeated throughout your treatment with TRISENOX.
• Additionally, an electrocardiogram will be performed twice weekly.
• If you are at risk of a certain type of cardiac arrhythmia (e.g., ventricular tachycardia “torsades de pointes” or QT interval prolongation), your heart will be continuously monitored.
• Your doctor may monitor your health during and after treatment, as arsenic trioxide, the active substance in TRISENOX, may cause other cancers. You must report any new or unusual symptoms or conditions whenever you visit your doctor.
• Monitoring of cognitive and motor functions if you are at risk of vitamin B1 deficiency.

Children and adolescents

TRISENOX is not recommended for children and adolescents under 18 years of age.

Other medicines and TRISENOX

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines, including those obtained without a prescription.

In particular, inform your doctor:

• if you are taking any medicine that may cause changes in heart rhythm, including:

• certain types of antiarrhythmics (medicines used to correct irregular heartbeats, e.g., quinidine, amiodarone, sotalol, dofetilide)

• medicines used to treat psychosis (loss of contact with reality; e.g., thioridazine)

• medicines used to treat depression (e.g., amitriptiline)

• certain types of medicines used to treat bacterial infections (e.g., erythromycin and sparfloxacin)

• certain antihistamines used to treat allergies such as hay fever (e.g., terfenadine and astemizole)

• any medicine that causes a decrease in blood magnesium or potassium levels (e.g., amphotericin B)

• cisapride (a medicine used to relieve certain stomach problems).

The effects of these medicines on heart rhythm may be worsened by TRISENOX. You must ensure that you inform your doctor about all medicines you are taking.

• If you are taking or have recently taken any medicine that may affect the liver. If in doubt, show the container to your doctor.

Use of TRISENOX with food and drink

There are no restrictions regarding food or drink while receiving TRISENOX.

Pregnancy

Consult your doctor or pharmacist before using any medicine.

TRISENOX may harm the fetus if administered to pregnant women.

If you are capable of becoming pregnant, you must use an effective method of contraception during treatment with TRISENOX and for 6 months after completion of treatment.

If you are pregnant or become pregnant during treatment with TRISENOX, consult your doctor.

Men must use effective contraception and should be advised not to father a child during treatment with TRISENOX and for 3 months after completion of treatment.

Breast-feeding

Consult your doctor or pharmacist before using any medicine.

Arsenic from TRISENOX passes into breast milk.

As TRISENOX may harm breastfed infants, avoid breast-feeding during treatment with TRISENOX and for at least two weeks after the last dose of TRISENOX.

Driving and use of machines

The influence of TRISENOX on your ability to drive and operate machinery is expected to be none or negligible.

If you experience discomfort or do not feel well after an injection of TRISENOX, you should wait until symptoms have resolved before driving or operating machinery.

TRISENOX contains sodium

TRISENOX contains less than 1 mmol of sodium (23 mg) per dose. This means the medicine is essentially “sodium-free”.

3. How TRISENOX is administered

Duration and frequency of treatment

Patients with newly diagnosed acute promyelocytic leukemia

Your doctor will administer TRISENOX once daily by infusion. In the first treatment cycle, you may receive treatment every day for up to 60 days, or until your doctor considers that your disease has improved. If your disease responds to TRISENOX, you will be given 4 additional treatment cycles. Each cycle consists of 20 doses, administered 5 days per week (followed by 2 days off) for 4 weeks (followed by a 4-week break). Your doctor will decide exactly how long you should continue TRISENOX treatment.

Patients with acute promyelocytic leukemia whose disease has not responded to other treatments

Your doctor will administer TRISENOX once daily by infusion. In your first treatment cycle, you may receive treatment every day for up to 50 days, or until your doctor considers that your disease has improved. If your disease responds to TRISENOX, you will be given a second treatment cycle of 25 doses, administered 5 days per week (followed by 2 days off) for 5 weeks. Your doctor will decide exactly how long you should continue TRISENOX treatment.

Method and route of administration

TRISENOX must be diluted with a glucose-containing solution or a sodium chloride-containing solution.

TRISENOX is normally administered by a doctor or nurse. It is given through an intravenous infusion (drip) into a vein over 1–2 hours, although the infusion may last longer if adverse effects such as flushing and dizziness occur.

TRISENOX must not be mixed or administered through the same tubing with other medicines.

If you are given more TRISENOX than you should by your doctor or nurse

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

If you have any further questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

Tell your doctor or nurse immediately if you notice any of the following adverse effects, as they could be signs of a serious condition called “differentiation syndrome”, which could be life-threatening:

• difficulty breathing
• cough
• chest pain
• fever

Tell your doctor or nurse immediately if you notice one or more of the following adverse effects, as they could be signs of an allergic reaction:

• difficulty breathing
• fever
• sudden weight gain
• fluid retention
• fainting
• palpitations (strong heartbeat felt in the chest)

While you are being treated with TRISENOX, you may experience some of the following reactions:

Very common adverse effects (may affect more than 1 in 10 people):

• fatigue (tiredness), pain, fever, headache
• nausea, vomiting, diarrhoea
• dizziness, muscle pain, numbness or tingling
• skin rash or itching, increased blood sugar, oedema (swelling due to excess fluid)
• shortness of breath, palpitations, abnormalities in electrocardiogram
• decreased potassium or magnesium levels in blood, abnormalities in liver or kidney function tests, including elevated levels of bilirubin or gamma-glutamyl transferase in blood

Common adverse effects (may affect up to 1 in 10 people):

• decreased blood cell counts (platelets, red blood cells and/or white blood cells), increased white blood cell count
• chills, weight gain
• fever due to infection and low white blood cell levels, herpes zoster infection
• chest pain, pulmonary haemorrhage, hypoxia (reduced oxygen levels), fluid accumulation in the pericardium or lungs, hypotension, heart rhythm disturbances
• seizures, bone or joint pain, inflammation of blood vessels
• increased sodium or magnesium, presence of ketones in blood and urine (ketoacidosis), abnormalities in kidney function tests, kidney failure
• stomach (abdominal) pain
• skin redness, facial swelling, blurred vision

Frequency not known (cannot be estimated from available data):

• lung infection, blood infection
• lung inflammation with chest pain and breathing difficulty, heart failure
• dehydration, confusion
• brain disease (encephalopathy, Wernicke’s encephalopathy) with various manifestations, including difficulty using arms and legs, speech disorders and confusion

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through the national reporting system listed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of TRISENOX

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the label of the vial and the carton.

No special storage conditions are required.

After dilution, if not used immediately, the conditions and storage times prior to use are the responsibility of the physician, pharmacist, or nurse, and normally will not exceed 24 hours at 2 to 8°C, unless the dilution has been carried out under sterile conditions.

Do not use this medicine if you notice any foreign particles or if the solution is discolored.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to properly dispose of unused medicines and their packaging. This will help protect the environment.

6. Contents of the pack and other information

Composition of TRISENOX

• The active substance is arsenic trioxide. Each millilitre of concentrate contains 2 mg of arsenic trioxide. Each 6 ml vial contains 12 mg of arsenic trioxide.
• The other components are sodium hydroxide, hydrochloric acid and water for injection. See section 2 “TRISENOX contains sodium”.

Nature of the product and contents of the container

TRISENOX is a concentrate for solution for infusion (sterile concentrate). TRISENOX is supplied in glass vials as a concentrated, clear, colourless, aqueous solution. Each carton contains 10 single-use glass vials.

Marketing Authorisation Holder

Teva B.V., Swensweg 5, 2031 GA Haarlem, The Netherlands

Manufacturer

Teva Pharmaceuticals Europe B.V., Swensweg 5, 2031 GA Haarlem, The Netherlands

Merckle GmbH, Graf-Arco-Str-3, 89079 Ulm, Germany

S.C. Sindan-Pharma S.R.L., B-dul Ion Mihalache nr 11, sector 1, Cod 011171, Bucharest, Romania

Date of the most recent revision of this leaflet: {MM/YYYY}

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu

There are also links to other websites on rare diseases and orphan medicinal products.

This information is intended for healthcare professionals only:

AN ASEPTIC TECHNIQUE MUST BE STRICTLY FOLLOWED WHEN HANDLING TRISENOX AS IT DOES NOT CONTAIN PRESERVATIVES.

Dilution of TRISENOX

TRISENOX must be diluted before administration.

Personnel must be adequately trained in handling and diluting arsenic trioxide and must wear appropriate protective equipment.

Dilution: Carefully insert the needle of a syringe into the vial and withdraw the entire contents.

TRISENOX must be diluted immediately with 100 to 250 ml of glucose 50 mg/ml (5%) injection solution or sodium chloride 9 mg/ml (0.9%) injection solution.

Any unused portion from each vial must be discarded appropriately. Do not store any unused portion for later administration.

Use of TRISENOX

TRISENOX is for single use only. It must not be mixed or co-administered concomitantly through the same intravenous line with other medicinal products.

TRISENOX is administered by intravenous infusion over 1–2 hours; however, the infusion duration may be extended up to 4 hours if vasomotor reactions occur. A central venous catheter is not required.

The diluted solution must be clear and colourless. Prior to administration, all parenteral solutions should be inspected visually for particulate matter and discoloration. Do not use the preparation if particulate matter is observed.

After dilution in intravenous solutions, TRISENOX is chemically and physically stable for 24 hours at 15–30°C and for 72 hours when refrigerated (2–8°C). From a microbiological standpoint, the product should be used immediately. If not used immediately, the conditions and duration of storage prior to use are the responsibility of the user and normally should not exceed 24 hours at 2–8°C, unless the dilution has been carried out under validated and controlled aseptic conditions.

Procedure for proper disposal

Disposal of unused medicinal product and all materials that have come into contact with it must be carried out in accordance with local regulations.