Arsenic trioxide Accord 1 mg/ml concentrate for solution for infusion EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Trióxido de Arsénico Accord 1 mg/ml concentrate for solution for infusion EFG

arsenic trioxide

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

• Keep this leaflet, as 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 the leaflet

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

1. What Trióxido de Arsénico Accord is and what it is used for

Trióxido de Arsénico Accord 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 Trióxido de Arsénico Accord is administered to you

Trióxido de Arsénico Accord must be administered under the supervision of a physician experienced in the treatment of acute leukemias.

Do not receive Trióxido de Arsénico Accord

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

Warnings and precautions

You should consult your doctor or nurse before receiving Trióxido de Arsénico Accord if:

• you have kidney 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 Trióxido de Arsénico Accord.

• An electrocardiogram (ECG) must be performed before the first dose.

• Blood tests (potassium, calcium, magnesium, and liver function) will be repeated throughout your treatment with Trióxido de Arsénico Accord.

• Additionally, an electrocardiogram will be performed twice a week.

• If you are at risk of a certain type of heart rhythm disorder (e.g., ventricular tachycardia "torsades de pointes" or QT interval prolongation), continuous heart monitoring will be required.

• Your doctor may monitor your health during and after treatment, as arsenic trioxide, the active substance in Trióxido de Arsénico Accord, may cause other cancers. You must report any new or unusual symptoms or conditions during visits to your doctor.

• Monitoring of cognitive and motor functions if you are at risk of vitamin B1 deficiency.

Children and adolescents

Trióxido de Arsénico Accord is not recommended for children and adolescents under 18 years of age.

Other medicines and Trióxido de Arsénico Accord

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 antiarrhythmics (medicines used to correct irregular heartbeats, e.g., quinidine, amiodarone, sotalol, dofetilide)
  • medicines for treating psychosis (loss of contact with reality; e.g., thioridazine)
  • medicines for treating depression (e.g., amitriptyline)
  • certain antibiotics (e.g., erythromycin and sparfloxacin)
  • certain antihistamines used for allergies such as hay fever (e.g., terfenadine and astemizole)
  • any medicine that may reduce blood magnesium or potassium levels (e.g., amphotericin B)
  • cisapride (a medicine used to relieve certain stomach problems).

The effect of these medicines on heart rhythm may be worsened by Trióxido de Arsénico Accord. 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 or packaging to your doctor.

Use of Trióxido de Arsénico Accord with food and drink

There are no restrictions regarding food or drink while receiving Trióxido de Arsénico Accord.

Pregnancy

Consult your doctor or pharmacist before using any medicine.

Trióxido de Arsénico Accord may cause harm to the fetus if administered to pregnant women.

If you are able to become pregnant, you must use an effective method of contraception during treatment with Trióxido de Arsénico Accord and for 6 months after the end of treatment.

If you are pregnant or become pregnant during treatment with Trióxido de Arsénico Accord, consult your doctor.

Men must use effective contraception and should be advised not to father a child during treatment with Trióxido de Arsénico Accord and for 3 months after the end of treatment.

Breast-feeding

Consult your doctor or pharmacist before using any medicine.

Arsenic from Trióxido de Arsénico Accord passes into breast milk.

As Trióxido de Arsénico Accord may harm breastfed infants, avoid breast-feeding during treatment with Trióxido de Arsénico Accord and for up to two weeks after the last dose.

Driving and using machines

The influence of Trióxido de Arsénico Accord on your ability to drive and use machines is expected to be none or negligible.

If you experience discomfort or do not feel well after an injection of Trióxido de Arsénico Accord, you should wait until symptoms have resolved before driving or using machines.

Trióxido de Arsénico Accord contains sodium

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

3. How Trióxido de Arsénico Accord is administered

Duration and frequency of treatment

Patients with newly diagnosed acute promyelocytic leukemia

Your doctor will administer Trióxido de Arsénico Accord 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 Trióxido de Arsénico Accord, you will receive 4 additional treatment cycles. Each cycle consists of 20 doses, administered 5 days a week (followed by 2 days off) for 4 weeks (followed by 4 weeks off). Your doctor will decide exactly how long your treatment with Trióxido de Arsénico Accord should continue.

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

Your doctor will administer Trióxido de Arsénico Accord 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 Trióxido de Arsénico Accord, you will receive a second treatment cycle consisting of 25 doses, administered 5 days a week (followed by 2 days off) for 5 weeks. Your doctor will decide exactly how long your treatment with Trióxido de Arsénico Accord should continue.

Method and route of administration

Trióxido de Arsénico Accord must be diluted with a glucose-containing solution or a sodium chloride-containing solution.

Trióxido de Arsénico Accord is normally administered by a doctor or nurse. It is given by intravenous infusion (drip) into a vein over 1–2 hours, although the infusion may last longer if adverse effects such as hot flushes or dizziness occur.

Trióxido de Arsénico Accord must not be mixed or injected through the same tube with other medicines.

If you are given more Trióxido de Arsénico Accord than you should by your doctor or nurse

You may experience seizures, muscle weakness, and confusion. If this occurs, treatment with Trióxido de Arsénico Accord 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.

Immediately tell your doctor or nurse 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

Immediately tell your doctor or nurse 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 being treated with Trióxido de Arsénico Accord, 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):

• pulmonary 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 they are possible adverse effects not listed in this leaflet. You may also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Arsenic Trioxide Accord

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

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

This medicine does not require any special storage conditions.

After first opening: once opened, the product must be used immediately.

Stability after dilution: Chemical and physical in-use stability has been demonstrated for 168 hours at 25 °C and at 2°C to 8°C. From a microbiological standpoint, the product should be used immediately. If not used immediately, the storage conditions and duration prior to use are the responsibility of the user and should normally not exceed 24 hours at 2°C–8°C, unless the dilution has been carried out under validated, controlled aseptic conditions.

After dilution, if not used immediately, the storage conditions and duration prior to use are the responsibility of the physician and should normally not exceed 24 hours at 2°C–8°C, unless the dilution has been performed 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 dispose of medicines and containers you no longer need. This will help protect the environment.

6. Contents of the container and other information

Composition of Arsenic Trioxide Accord

• The active substance is arsenic trioxide. 1 mL of concentrate contains 1 mg of arsenic trioxide. One vial contains 10 mg of arsenic trioxide.
• The other components are sodium hydroxide, concentrated hydrochloric acid (to adjust pH), and water for injection. See Section 2: "Arsenic Trioxide Accord contains sodium".

Appearance of the product and contents of the container

Arsenic Trioxide Accord is a concentrate for solution for infusion. Arsenic Trioxide Accord is supplied in glass vials as a concentrated, sterile, aqueous, colourless, clear solution.

Each carton contains 1, 5, or 10 glass vials.

Only certain pack sizes may be marketed.

Marketing Authorization Holder

Accord Healthcare S.L.U.

World Trade Center, Moll de Barcelona s/n,

Edifici Est, 6th floor,

08039 Barcelona,

Spain

Manufacturer

Accord Healthcare Polska Sp. z o.o.,

ul. Lutomierska 50,

95-200 Pabianice,

Poland

More information about this medicinal product can be requested from the local representative of the Marketing Authorization Holder:

AT / BE / BG / CY / CZ / DE / DK / EE / ES / FI / FR / HR / HU / IE / IS / IT / LT / LV / LU / MT / NL / NO / PL / PT / RO / SE / SI / SK

Accord Healthcare S.L.U.

Tel: +34 93 301 00 64

EL

Win Medica A.E.

Tel: +30 210 74 88 821

Date of the most recent review of this summary:

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

This information is intended for medical or healthcare professionals only:

A STRICT ASEPTIC TECHNIQUE MUST BE FOLLOWED DURING HANDLING OF ARSENIC TRIOXIDE ACCORD AS IT DOES NOT CONTAIN PRESERVATIVES.

Dilution of Arsenic Trioxide Accord

Arsenic Trioxide Accord must be diluted before administration. Plastic bags without PVC should be used.

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 through the vial stopper and withdraw the entire contents. Arsenic Trioxide Accord should be immediately diluted with 100 to 250 mL of 50 mg/mL (5%) glucose injection solution or 9 mg/mL (0.9%) sodium chloride injection solution.

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

Use of Arsenic Trioxide Accord

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

Arsenic Trioxide Accord will be administered intravenously over 1–2 hours, although 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. Parenteral solutions should be inspected visually for particulate matter and discoloration prior to administration. Do not use the preparation if particulate matter is observed.

After dilution in intravenous solutions, Arsenic Trioxide Accord is chemically and physically stable for 24 hours at 25°C and for 48 hours under refrigeration (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 was carried out under validated, controlled aseptic conditions.

Procedure for correct disposal

The disposal of unused medicine and of all materials that have been in contact with it must be carried out in accordance with local regulations.