Arsenic trioxide Mylan - patient leaflet, side effects, dosage

B. PACKAGE LEAFLET

Package leaflet: Information for the patient

Arsenic trioxide Mylan 1 mg/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 further questions, please ask your doctor or your pharmacist or nurse.

• – If you get any side effects, talk to your doctor or pharmacist or nurse. This includes any possible

side effects not listed in this leaflet. See section 4.

What is in this leaflet

• 1. What Arsenic trioxide Mylan is and what it is used for

• 2. What you need to know before you are given Arsenic trioxide Mylan

• 3. How to use Arsenic trioxide Mylan

• 4. Possible side effects

• 5. How to store Arsenic trioxide Mylan

• 6. Contents of the pack and other information

1. What Arsenic trioxide Mylan is and what it is used for

Arsenic trioxide Mylan is used in adult patients with newly diagnosed low-to-intermediate risk acute promyelocytic leukaemia (APL), and in adult patients, 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.

2. What you need to know before you are given Arsenic trioxide Mylan

Arsenic trioxide Mylan must be given under the supervision of a physician experienced in the treatment of acute leukaemias.

You must not receive Arsenic trioxide Mylan

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

Warnings and precautions

You must talk to your doctor or nurse before you are given Arsenic trioxide Mylan, if – you have impaired kidney function.

• – you have any liver problems.

Your doctor will take the following precautions:

• – Tests will be performed to check the amount of potassium, magnesium, calcium and creatinine in your blood before your first dose of Arsenic trioxide Mylan.

• – You should have an electrical recording of the heart (electrocardiogram ECG) performed before your first dose.

• – Blood tests (potassium, magnesium, calcium, liver function) should be repeated during your treatment with Arsenic trioxide Mylan.

• – 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.

• – Your doctor may monitor your health during and after treatment, since arsenic trioxide, the active substance in Arsenic trioxide Mylan, may cause other cancers. You should report any new and exceptional symptoms and circumstances whenever you see your doctor.

• – Follow-up of your cognitive and mobility functions if you are at risk for vitamin B1 deficiency.

Children and adolescents

Arsenic trioxide Mylan is not recommended in children and adolescents below 18 years of age.

Other medicines and Arsenic trioxide Mylan

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

In particular 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 (medicines used to correct irregular heart beats, e.g. quinidine, amiodarone, sotalol, dofetilide)
• medicines to treat psychosis (loss of contact with reality, e.g. thioridazine)
• medicines for depression (e.g. amitriptyline)
• some types of medicines to treat bacterial infections (e.g. erythromycin and sparfloxacin)
• some medicines to treat allergies such as hayfever, called 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 Arsenic trioxide Mylan.

You must be sure to tell your doctor about all medicines you are taking.

• – if you are taking or have recently taken any medicine which may affect your liver. If you are not sure, show the bottle or pack to your doctor.

Arsenic trioxide Mylan with food and drink

There are no restrictions on your food or drink while you are receiving Arsenic trioxide Mylan.

Pregnancy

Ask your doctor or pharmacist for advice before taking any medicine.

Arsenic trioxide Mylan 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 Arsenic trioxide Mylan.

If you are pregnant or you become pregnant during the treatment with Arsenic trioxide Mylan, you must ask your doctor for advice.

Men should also use effective contraception during treatment with Arsenic trioxide Mylan.

Breast-feeding

Ask your doctor or pharmacist for advice before taking any medicine.

The arsenic in Arsenic trioxide Mylan passes into breast milk.

Because Arsenic trioxide Mylan can harm nursing infants, do not breast-feed while on Arsenic trioxide Mylan.

Driving and using machines

Arsenic trioxide Mylan is expected to have no or negligible influence on your ability to drive and use machines.

If you experience discomfort or if you feel unwell after a Arsenic trioxide Mylan injection, you should wait until the symptoms go away before driving or using machines.

Arsenic trioxide Mylan contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially ‘sodium-free’.

3. How to use Arsenic trioxide Mylan

Duration and frequency of treatment

Patients with newly diagnosed acute promyelocytic leukaemia

Your doctor will give you Arsenic trioxide Mylan once every day as an infusion. In your first treatment cycle, you may be treated every day up to 60 days at most or until your doctor determines that your disease is better. If your disease responds to Arsenic trioxide Mylan, you will be given 4 additional treatment cycles. Each cycle consists of 20 doses given 5 days per week (followed by 2 days interruption) for 4 weeks followed by 4 weeks interruption. Your doctor will decide exactly how long you must continue on therapy with Arsenic trioxide Mylan.

Patients with acute promyelocytic leukaemia, whose disease has not responded to other therapies Your doctor will give you Arsenic trioxide Mylan once every day as an infusion. 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 Arsenic trioxide Mylan, you will be given a second treatment cycle of 25 doses given 5 days per week (followed by 2 days interruption) for 5 weeks. Your doctor will decide exactly how long you must continue on therapy with Arsenic trioxide Mylan.

Method and route of administration

Arsenic trioxide Mylan must be diluted with a solution containing glucose or a solution containing sodium chloride.

Arsenic trioxide Mylan is normally given by a doctor or a nurse. It is given as a drip (infusion) into a vein over 1–2 hours, but the infusion may last longer if side effects like flushing and dizziness occur.

Arsenic trioxide Mylan must not be mixed with or infused through the same tube with other medicines.

If your doctor or nurse gives you more Arsenic trioxide Mylan than he/she should

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

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

4. 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 these may be signs of a severe condition called “differentiation syndrome”, which might be fatal : – difficulty in breathing

• – coughing

• – chest pain

• – fever

Tell your doctor or nurse straight away if you notice one or more of the following side effects, as these may be signs of allergic reaction: – difficulty in breathing – fever

• – sudden weight gain

• – water retention

• – fainting

• – palpitations (strong heartbeat you can feel in your chest)

While on treatment with Arsenic trioxide Mylan, you may experience some of the following reactions:

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

• – fatigue (weariness), pain, fever, headache

• – nausea, vomiting, diarrhoea

• – dizziness, muscle pain, numbness or tingling

• – rash or itching, increased blood sugar, oedema (swelling due to excess fluid)

• – shortness of breath, fast heart beat, abnormal ECG heart tracing

• – reduced potassium or magnesium in the blood, liver function tests abnormal including presence of excess bilirubin or gamma-glutamyltransferase in the blood

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

• – reduction in blood cell counts (platelets, red and/or white blood cells), increased white blood cells

• – chills, increased weight

• – a fever due to an infection and low levels of white blood cells, herpes zoster infection

• – chest pain, bleeding in the lung, hypoxia (low oxygen level), collection of fluid around the heart

or the lung, low blood pressure, abnormal heart rhythm

• – fit, joint or bone pain, inflammation of the blood vessels

• – increased sodium or magnesium, ketones in the blood and urine (ketoacidosis), renal function tests abnormal, kidney failure

• – stomach (abdominal) ache

• – redness of the skin, swollen face, blurred vision

Not known (frequency cannot be estimated from the available data):

• – lung infection, infection in the blood

• – inflammation of the lungs which causes chest pain and breathlessness, cardiac failure

• – dehydration, confusion

• – Cerebral disease (Encephalopathy, Wernicke encephalopathy) with various manifestations including difficulties to use arms and legs, speech disorders and confusion

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed inBy reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Arsenic trioxide Mylan

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

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

Do not freeze.

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

This medicine must not be used if you notice foreign particulate matter or if the solution is discoloured.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help to protect the environment.

6. Contents of the pack and other information

What Arsenic trioxide Mylan contains

• – The active substance is arsenic trioxide. Each ml of concentrate contains 1 mg of arsenic trioxide. Each vial of 10 ml contains 10 mg of arsenic trioxide.

• – The other ingredients are sodium hydroxide, hydrochloric acid and water for injections. See section 2 ‘Arsenic trioxide Mylan contains sodium ’.

What Arsenic trioxide Mylan looks like and contents of the pack

Arsenic trioxide Mylan is a concentrate for solution for infusion (sterile concentrate). It is supplied in glass vials as a concentrated, clear, colourless, aqueous solution. Each carton contains 1 or 10 single-use glass vials.

Marketing Authorisation Holder

Mylan Ireland Limited

Unit 35/36 grange Parade

Baldoyle Industrial Estate

Dublin 13

Ireland

Manufacturer

Haupt Pharma Wolfratshausen GmbH

Pfaffenrieder Straße 5

82515 Wolfrat­shausen

Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgiqu­e/Belgien Mylan bvba/sprl Tél/Tel: + 32 (0)2 658 61 00	Lietuva Mylan Healthcare UAB Tel: +370 5 205 1288
Efc^rapufl Maw.iaH EOO4 Ten: +359 2 44 55 400	Luxembourg/Lu­xemburg Mylan bvba/sprl Tel: + 32 (0)2 658 61 00 (Belgique/Belgien)
Česká republika Mylan Healthcare CZ s.r.o. Tel: + 420 222 004 400	Magyarország Mylan EPD Kft Tel: + 36 1 465 2100
Danmark Mylan Denmark ApS Tlf: +45 28 11 69 32	Malta V.J. Salomone Pharma Ltd Tel: + 356 21 22 01 74
Deutschland Mylan Healthcare GmbH Tel: + 49– 800 0700 800	Nederland Mylan BV Tel: +31 (0)20 426 3300

Eesti BGP Products Switzerland GmbH Eesti filiaal

Norge Mylan Healthcare Norge AS Tel: + 47 66 75 33 00

Tel: + 372 6363 052

EXÀàôa Generics Pharma Hellas EnE TnX: +30 210 993 6410	Österreich Arcana Arzneimittel GmbH Tel: +43 1 416 2418
España Mylan Pharmaceuticals, S.L. Tel: + 34 900 102 712	Polska Mylan Healthcare Sp. z o.o. Tel: + 48 22 546 64 00
France Mylan S.A.S Tel: +33 4 37 25 75 00	Portugal Mylan, Lda. Tel: + 351 21 412 72 56
Hrvatska Mylan Hrvatska d.o.o. Tel: +385 1 23 50 599	România BGP Products SRL Tel: +40 372 579 000
Ireland Mylan Ireland Limited Tel: +353 (0) 87 1694982	Slovenija Mylan Healthcare d.o.o. Tel: + 386 1 23 63 180
Ísland Icepharma hf Tel: +354 540 8000	Slovenská republika Mylan s.r.o. Tel: +421 2 32 199 100
Italia Mylan Italia S.r.l. Tel: + 39 02 612 46921	Suomi/Finland Mylan Finland OY Puh/Tel: +358 20 720 9555
Kùnpoç Varnavas Hadjipanayis Ltd TnX: +357 2220 7700	Sverige Mylan AB Tel: + 46 855 522 750
Latvija Mylan Healthcare SIA Tel: +371 676 055 80	United Kingdom (Northern Ireland) Mylan IRE Healthcare Limited Tel: +353 18711600

This leaflet was last revised in

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site:

.

This leaflet is available in all EU/EEA languages on the European Medicines Agency website.

The following information is intended for healthcare professionals only

ASEPTIC TECHNIQUE MUST BE STRICTLY OBSERVED THROUGHOUT HANDLING OF Arsenic trioxide Mylan SINCE NO PRESERVATIVE IS PRESENT.

Dilution of Arsenic trioxide Mylan

Arsenic trioxide Mylan must be diluted before administration.

Personnel should be trained to handle and dilute arsenic trioxide and should wear appropriate protective clothing.

Dilution: Carefully insert the needle of a syringe into the vial and draw up all of the content. Arsenic trioxide Mylan must then be diluted immediately with 100 to 250 ml of glucose 50 mg/ml (5%) solution for injection or sodium chloride 9 mg/ml (0.9%) solution for injection.

Arsenic trioxide Mylan is for single use only. Unused portions of each vial must be discarded properly. Do not save any unused portions for later administration.

Use of Arsenic trioxide Mylan

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

Arsenic trioxide Mylan 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, Arsenic trioxide Mylan is chemically and physically stable for 30 days at 15–25°C and 30 days 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.

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