Arsenic trioxide Medac

Patient Information Leaflet: Information for the User

Triossido di arsenico medac 1 mg/mL concentrate for solution for infusion

Generic medicine
arsenic trioxide
Please read this leaflet carefully before this medicine is administered to you 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, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

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

1. What Triossido di arsenico medac is and what it is used for

Triossido di arsenico medac contains the active substance arsenic trioxide, which is an antitumour medicinal product.
The mechanism of action of Triossido di arsenico medac has not been fully elucidated.
Triossido di arsenico medac is used in adult patients with newly diagnosed low/intermediate-risk acute promyelocytic leukaemia (APL), and in adult patients whose disease has not responded to other therapies. APL is a distinct variant of myeloid leukaemia, a disease characterised by abnormalities in blood white cells and abnormalities in bleeding and bruising.

2. What you should know before being administered Triossido di arsenico medac

Inform your doctor, pharmacist, or nurse if you are taking or have recently taken any other
medicines, including those without a prescription.
You will not be administered Triossido di arsenico medac
if you are allergic to arsenic trioxide or to any of the other ingredients of this medicine
(listed in section 6).
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before being administered Triossido di arsenico medac if

• you have impaired kidney function;
• you have liver problems.

Your doctor will take the following precautions:

• before administering the first dose of Triossido di arsenico medac, blood tests will be performed to check levels of potassium, magnesium, calcium, and creatinine in your blood;
• before the first dose is administered, you will undergo an electrocardiogram (ECG);
• during treatment with Triossido di arsenico medac, blood tests (potassium, calcium, liver function) will be repeated;
• an electrocardiogram will also be performed twice a week;
• if you are at risk of developing certain types of heart rhythm disorders (e.g., torsades de pointes or QTc prolongation), your heart will be continuously monitored;
• your doctor may monitor your health during and after treatment, as arsenic trioxide, the active substance in Triossido di arsenico medac, may cause other tumours. Report any new or unusual symptoms or conditions to your doctor at every visit;
• if you are at risk of vitamin B1 deficiency, cognitive and motor function tests will be performed.

Children and adolescents
Triossido di arsenico medac is not recommended for children and adolescents under 18 years of age.
Other medicines and Triossido di arsenico medac
Inform your doctor or pharmacist if you are taking, have recently taken, or might take
any other medicines, including those without a prescription.
In particular, inform your doctor or pharmacist

• if you are taking any medicine that may cause changes in heart rhythm. These include:
  • certain types of antiarrhythmics (medicines used to correct irregular heartbeats, e.g., quinidine, amiodarone, sotalol, dofetilide)
  • medicines for the treatment of psychosis (loss of contact with reality, e.g., thioridazine)
  • medicines for depression (e.g., amitriptiline)
  • certain types of medicines for 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 magnesium or potassium in the blood (e.g., amphotericin B)
  • cisapride (a medicine used for certain stomach problems). The effect of these medicines on your heartbeat may be worsened by Triossido di arsenico medac. Make sure you have informed your doctor or pharmacist 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 doctor or pharmacist the vial or packaging.

Triossido di arsenico medac with food and drink
There are no restrictions on food and drink while taking Triossido di arsenico medac.
Pregnancy
Ask your doctor or pharmacist for advice before taking any medicine.
Triossido di arsenico medac may harm the foetus if used during pregnancy.
If you are of childbearing age, you must use an effective method of contraception during treatment with Triossido di arsenico medac and for 6 months after the end of treatment.
If you are pregnant or become pregnant during treatment with Triossido di arsenico medac,
ask your doctor or pharmacist for advice.
Men must use effective contraception and must be advised not to father a child during treatment with Triossido di arsenico medac and for 3 months after the end of treatment.
Breast-feeding
Ask your doctor or pharmacist for advice before taking any medicine.
Arsenic contained in Triossido di arsenico medac passes into breast milk.
Since Triossido di arsenico medac may harm breastfed infants, do not breast-feed during treatment with Triossido di arsenico medac and for at least two weeks after the last dose.
Driving and using machines
Triossido di arsenico medac does not affect or has negligible effect on the ability to drive or use machines. If you experience discomfort or feeling unwell after an injection of Triossido di arsenico medac, wait until symptoms have disappeared before driving or using machines.
Triossido di arsenico medac contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e., essentially 'sodium-free'.

3. How Triossido di arsenico medac is used

Triossido di arsenico medac must be administered under the supervision of a physician experienced in
the treatment of acute leukemias.
Duration and frequency of treatment
Patients with newly diagnosed acute promyelocytic leukemia
Your doctor will administer Triossido di arsenico medac once daily, every day, by infusion. During the first treatment cycle, you may be treated daily for up to
60 days, or until your doctor determines that your disease has improved. If
your disease responds to Triossido di arsenico medac, you will receive an additional 4 treatment cycles of 20 doses each, 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 treatment with Triossido di arsenico medac.
Patients with acute promyelocytic leukemia whose disease has not responded to other treatments
Your doctor will administer Triossido di arsenico medac once daily, every day, by infusion. During the first treatment cycle, you may be treated daily for up to
50 days, or until your doctor determines that your disease has improved. If
your disease responds to Triossido di arsenico medac, you will receive 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 treatment with
Triossido di arsenico medac.
Method and route of administration
Triossido di arsenico medac must be diluted with a glucose-containing solution or a sodium chloride-containing solution.
Triossido di arsenico medac is generally administered by a physician or nurse. It is given by intravenous infusion over 1-2 hours. However, the infusion may take longer if adverse effects such as flushing or dizziness occur.
Triossido di arsenico medac must not be mixed with other medicinal products nor infused through the same tubing used for other medicinal products.
If you are given more Triossido di arsenico medac than you should
You may experience seizures, muscle weakness, and confusion. In such a case, treatment
with Triossido di arsenico medac must be stopped immediately, and your doctor will manage the arsenic overdose.
If you have any questions about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
Immediately tell your doctor or nurse if you notice any of the following side effects, which may be signs of a serious condition called "differentiation syndrome", which can be life-threatening:

• difficulty breathing
• cough
• chest pain
• fever

Immediately tell your doctor or nurse if you notice one or more of the following side effects, which may be signs of an allergic reaction:

• difficulty breathing
• fever
• sudden weight gain
• fluid retention
• fainting
• palpitations (strong or rapid heartbeats that you can feel in your chest)

During treatment with Triossido di arsenico medac, you may experience some of the following reactions:
Very common (may affect more than 1 in 10 people)

• fatigue, pain, fever, headache
• nausea, vomiting, diarrhoea
• dizziness, muscle pain, numbness or tingling
• skin rash or itching, increased blood sugar levels, oedema (swelling due to excess fluid)
• shortness of breath, rapid heartbeat, abnormal ECG
• decreased potassium or magnesium levels in the blood, abnormal liver function tests including increased blood levels of bilirubin or gamma-glutamyltransferase

Common (may affect up to 1 in 10 people)

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

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

• lung infections, blood infections
• lung inflammation causing chest pain and breathlessness, heart failure
• dehydration, confusion
• brain disease (encephalopathy, Wernicke's encephalopathy) with various symptoms including difficulty using arms and legs, speech disorders and confusion

Reporting of side effects
If you get any side effects, including ones not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via the national reporting system referred to in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Triossido di arsenico medac

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 on the carton.
This medicine requires no special storage conditions.
Once opened, the product must be used immediately.
After dilution, if the medicine is not used immediately, the storage times and conditions prior to use are the responsibility of the physician and will normally not exceed 24 hours at a temperature between 2 °C and 8 °C, unless the dilution has been carried out under sterile conditions.
This medicine must not be used if it contains foreign particles or if the solution appears discoloured.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Triossido di arsenico medac contains

• The active substance is arsenic trioxide. One mL of concentrate contains 1 mg of arsenic trioxide. One vial contains 10 mg of arsenic trioxide.
• The other components are sodium hydroxide, hydrochloric acid and water for injections. See section 2 “Triossido di arsenico medac contains sodium”.

Description of the appearance of Triossido di arsenico medac and package contents
Triossido di arsenico medac is a concentrate for solution for infusion (sterile concentrate). It is supplied in glass vials as a sterile, clear, colourless, aqueous concentrated 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
More detailed information on this medicinal product is available on the website of the European Medicines Agency, http://www.ema.europa.eu.
In addition, links to other websites on rare diseases and related therapeutic treatments are provided.

The following information is intended exclusively for healthcare professionals:
A STRICTLY ASEPTIC TECHNIQUE MUST BE OBSERVED FOR ALL PROCEDURES INVOLVING THE HANDLING OF TRIOSSIDO DI ARSENICO MEDAC, DUE TO THE ABSENCE OF A PRESERVATIVE IN THE PRODUCT.
Dilution of Triossido di arsenico medac
Triossido di arsenico medac must be diluted before administration.
Personnel must be trained in the handling and dilution of arsenic trioxide and must wear appropriate protective clothing.
Dilution: carefully insert the needle of a syringe into the vial and withdraw the entire contents. Immediately dilute Triossido di arsenico medac with 100–250 mL of glucose 50 mg/mL (5%) solution for injection or sodium chloride 9 mg/mL (0.9%) solution for injection.
Triossido di arsenico medac is for single use only. Any unused portions from each vial must be appropriately disposed of. Do not store unused portions for subsequent administration.
Use of Triossido di arsenico medac
Triossido di arsenico medac must not be mixed with other medicinal products nor administered simultaneously through the same intravenous line.
Triossido di arsenico medac must be administered intravenously over 1–2 hours. The infusion duration may be extended up to a maximum of 4 hours if vasomotor reactions occur. A central venous catheter is not required.
The diluted solution must be clear and colourless. All parenteral solutions should be inspected visually for particulate matter and discolouration prior to administration. Do not use the preparation if it contains foreign particulate matter.
Chemical and physical in-use stability has been demonstrated for 48 hours at 30 °C and for 72 hours at 2 °C–8 °C.
From a microbiological standpoint, the product should be used immediately. If not used immediately, the duration and conditions of in-use storage prior to use are the responsibility of the user and normally should not exceed 24 hours at 2 °C–8 °C, unless dilution has been carried out under controlled and validated aseptic conditions.
Procedure for proper disposal
Unused medicine, items that have come into contact with the product, and waste materials arising from this medicine must be disposed of in accordance with local regulations.