Arsenic trioxide medac - patient leaflet, side effects, dosage

Patient leaflet - Arsenic trioxide medac

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

Arsenic trioxide medac contains the active substance arsenic trioxide which is an anticancer medicine. The mechanism of action of Arsenic trioxide medac is not completely understood.

Arsenic trioxide medac 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 medac

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

You will not be given Arsenic trioxide medac

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, pharmacist or nurse before you are given Arsenic trioxide medac, 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 medac.
You should have an electrical recording of the heart (electrocardiogram, ECG) performed before your first dose.
Blood tests (potassium, calcium, liver function) should be repeated during your treatment with Arsenic trioxide medac.
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 medac, 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 medac is not recommended in children and adolescents below 18 years of age.

Other medicines and Arsenic trioxide medac

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 or pharmacist

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 medac.

You must be sure to tell your doctor or pharmacist 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 or pharmacist.

Arsenic trioxide medac with food and drink

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

Pregnancy

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

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

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

Breast-feeding

Ask your doctor or pharmacist for advice before taking any medicine. The arsenic in Arsenic trioxide medac passes into breast milk.

Because Arsenic trioxide medac can harm breastfed children, do not breast-feed while on Arsenic trioxide medac.

Driving and using machines

Arsenic trioxide medac 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 an Arsenic trioxide medac injection, you should wait until the symptoms go away before driving or using machines.

Arsenic trioxide medac contains sodium

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

3. How Arsenic trioxide medac is used

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

Duration and frequency of treatment

Patients with newly diagnosed acute promyelocytic leukaemia

Your doctor will give you Arsenic trioxide medac 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 medac, you will be given 4 additional treatment cycles 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 medac.

Patients with acute promyelocytic leukaemia, whose disease has not responded to other therapies Your doctor will give you Arsenic trioxide medac 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 medac, 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 medac.

Method and route of administration

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

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

If you are given more Arsenic trioxide medac than you should

You may experience convulsions, muscle weakness and confusion. If this happens, treatment with Arsenic trioxide medac 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.

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 medac, 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. Y ou can also report side effects directly via the national reporting system listed in By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Arsenic trioxide medac

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. This medicinal product does not require any special storage conditions.

Once opened the product should be used immediately.

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 will not be used if it appears to contain 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 protect the environment.

6. Contents of the pack and other information

What Arsenic trioxide medac contains

– The active substance is arsenic trioxide. One ml of concentrate contains 1 mg arsenic trioxide.

One vial contains 10 mg of arsenic trioxide.

– The other ingredients are sodium hydroxide, hydrochloric acid and water for injections. See section 2 “Arsenic trioxide medac contains sodium”.

What Arsenic trioxide medac looks like and contents of the pack

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

Marketing Authorisation Holder and Manufacturer

medac

Gesellschaft für klinische Spezialpräparate mbH

Theaterstr. 6

22880 Wedel

Germany

This leaflet was last revised in {MM/YYYY}

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

There are also links to other websites about rare diseases and treatments.

The following information is intended for healthcare professionals only:

ASEPTIC TECHNIQUE MUST BE STRICTLY OBSERVED THROUGHOUT HANDLING OF ARSENIC TRIOXIDE MEDAC SINCE NO PRESERVATIVE IS PRESENT.

Dilution of Arsenic trioxide medac

Arsenic trioxide medac 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 medac 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 medac 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 medac

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

Arsenic trioxide medac 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.

Chemical and physical in-use stability has been demonstrated for 48 hours at 30 °C and 72 hours at 2 °C to 8 °C. 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.

In the CALGB study C9710, 2 cases of grade > 3 increased GGT were reported out of the

200 patients who received arsenic trioxide consolidation cycles (cycle 1 and cycle 2) versus none in the control arm.