Arsenic trioxide tillomed

Package leaflet: Information for the patient

Arsenic trioxide Tillomed, 2 mg/mL, concentrate for solution for infusion
Arsenii trioxidum
For use in adults
Please read all of this leaflet carefully before using this medicine because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any side effects not listed in this leaflet. See section 4.

Contents of the leaflet

1. What Arsenic trioxide Tillomed is and what it is used for
2. What you need to know before you use Arsenic trioxide Tillomed
3. How to use Arsenic trioxide Tillomed
4. Possible side effects
5. How to store Arsenic trioxide Tillomed
6. Contents of the pack and other information

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

Arsenic trioxide Tillomed is used in adult patients with newly diagnosed acute promyelocytic leukaemia (APL) with low or intermediate risk, and in adult patients who have not responded to other treatments. APL is a unique type of myeloid leukaemia characterized by the presence of abnormal white blood cells and abnormal bleeding and bruising.

2. Important information before using Arsenic trioxide Tillomed

Arsenic trioxide Tillomed should be administered only under the supervision of a physician experienced in the treatment of acute leukemias.
When not to use Arsenic trioxide Tillomed
If the patient is allergic to arsenic (III) oxide or to any of the other ingredients of this medicine (listed in section 6).
Warnings and precautions
Before receiving Arsenic trioxide Tillomed, discuss with the doctor or nurse if:

• the patient has impaired kidney function,
• the patient has any liver function disorders.

The physician will take the following precautions:

• Prior to the first dose of Arsenic trioxide Tillomed, blood levels of potassium, magnesium, calcium, and creatinine should be assessed.
• An electrocardiogram (ECG) should be performed before the first dose.
• During treatment with Arsenic trioxide Tillomed, blood tests (potassium, magnesium, calcium, liver function) should be repeated regularly.
• Additionally, an electrocardiogram should be performed twice weekly.
• In patients at risk of developing a specific type of cardiac arrhythmia (e.g., torsade de pointes or QTc interval prolongation), continuous cardiac monitoring should be performed.
• The physician may monitor the patient's health status during and after treatment, as the active substance in Arsenic trioxide Tillomed, arsenic (III) oxide, may cause the development of other tumors. Any new or unusual symptoms or circumstances should be reported during every medical visit.
• Cognitive function and motor performance should be monitored if the patient is at risk of vitamin B deficiency. Children and adolescents Arsenic (III) oxide is not recommended for use in children and adolescents under 18 years of age.

Arsenic trioxide Tillomed with other medicines
Inform the doctor or pharmacist about all medicines the patient is currently taking or has recently taken, including medicines the patient plans to use, even those available without a prescription.
In particular, inform the doctor:

• about all medicines the patient is taking that may alter heart rhythm. These include:
  • certain types of antiarrhythmic drugs (used to treat irregular heartbeat, e.g., quinidine, amiodarone, sotalol, or dofetilide)
  • medicines used to treat psychosis (loss of contact with reality, e.g., thioridazine)
  • medicines used to treat depression (e.g., amitriptyline)
  • certain types of antibiotics used to treat bacterial infections (e.g., erythromycin and sparfloxacin)
  • certain antiallergic medicines used to treat conditions such as hay fever, known as antihistamines (e.g., terfenadine and astemizole)
  • any medicines causing decreased blood levels of magnesium or potassium (e.g., amphotericin B)
  • cisapride (a medicine used to relieve certain gastrointestinal symptoms). The effects of these medicines on heart function may be worsened by the use of arsenic (III) oxide. It is important to inform the doctor about all medicines being taken.
• if the patient is currently taking or has recently taken any medicines that may affect liver function. In case of doubt, show the medicine container or packaging to the doctor. Arsenic trioxide Tillomed and food and drink There are no dietary restrictions regarding food and drink while receiving arsenic (III) oxide. Pregnancy Before using any medicine, consult a doctor or pharmacist.

Arsenic (III) oxide taken by pregnant women may be harmful to the fetus.
If the patient is of childbearing potential, effective contraception must be used during treatment with Arsenic trioxide Tillomed and for 6 months after completion of treatment.
If the patient is pregnant or becomes pregnant during treatment with Arsenic trioxide Tillomed, consult a doctor.
Men should also use effective contraception and are advised not to father a child during treatment with Arsenic trioxide Tillomed and for 3 months after completion of treatment.
Breast-feeding
Before using any medicine, consult a doctor or pharmacist.
Arsenic (III) oxide passes into human milk.
Arsenic (III) oxide may be harmful to breastfed infants; therefore, breast-feeding must be avoided during treatment with this medicine and for two weeks after the last dose of arsenic (III) oxide.
Driving and operating machinery
Arsenic (III) oxide is expected to have no effect or a negligible effect on the ability to drive vehicles and operate machinery.
If, after injection of Arsenic trioxide Tillomed, the patient experiences discomfort or worsening of well-being, the patient should wait until symptoms subside before driving or operating machinery.
Arsenic trioxide Tillomed contains sodium
Arsenic trioxide Tillomed contains less than 1 mmol sodium (23 mg) per dose, i.e., the medicine is considered "sodium-free".

3. How to use Arsenic trioxide Tillomed

Duration of treatment and frequency of administration
Patients with newly diagnosed acute promyelocytic leukemia
Your doctor will administer Arsenic trioxide Tillomed daily by infusion. During the first cycle, treatment may continue daily for up to 60 days or until your doctor determines that improvement has occurred. If a response to treatment with Arsenic trioxide Tillomed is achieved, the patient will receive 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 how long treatment with Arsenic trioxide Tillomed should continue.

Patients with acute promyelocytic leukemia who have not responded to other treatments
Your doctor will administer Arsenic trioxide Tillomed daily by infusion. During the first cycle, treatment may continue daily for up to 50 days or until your doctor determines that improvement has occurred. If a response to treatment with Arsenic trioxide Tillomed is achieved, the patient will receive a second cycle of treatment consisting of 25 doses administered 5 days per week (followed by 2 days off) for 5 weeks. Your doctor will decide how long treatment with Arsenic trioxide Tillomed should continue.

Method and route of administration
Arsenic trioxide Tillomed must be diluted in a solution containing glucose or a solution containing sodium chloride.
Arsenic trioxide Tillomed is usually administered by a doctor or nurse as an intravenous infusion (drip) over 1 to 2 hours. If adverse effects occur, such as hot flushes or dizziness, the infusion may be prolonged.
Do not mix Arsenic trioxide Tillomed with other medicines, and do not administer through the same infusion set.

Overdose of Arsenic trioxide Tillomed administered by a doctor or nurse
The patient may experience seizures, muscle weakness, and confusion. In such a case, administration of Arsenic trioxide Tillomed must be stopped immediately. The doctor will initiate appropriate treatment, as in cases of arsenic overdose.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
If any of the symptoms listed below occur, contact your doctor or nurse immediately,
as they may be signs of a serious condition called "differentiation syndrome," which may be fatal:

• difficulty breathing
• cough
• chest pain
• fever

If one or more of the following symptoms occur, contact your doctor or nurse immediately,
as they may be signs of an allergic reaction:

• difficulty breathing
• fever
• sudden weight gain
• fluid retention in the body
• fainting
• palpitations (strong, noticeable heartbeats in the chest)

During treatment with arsenic trioxide, some of the following side effects may occur:

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

• fatigue (weakness), pain, fever, headache
• nausea, vomiting, diarrhoea
• dizziness, muscle pain, numbness or tingling
• rash or itching, increased blood glucose levels, oedema (caused by excess fluid in the body)
• shortness of breath, rapid heartbeat, abnormal ECG (electrocardiogram) readings
• decreased blood potassium or magnesium levels, abnormal liver function test results, including elevated bilirubin or gamma-glutamyl transferase levels in the blood

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

• decreased number of blood cells (platelets, red and/or white blood cells), increased number of white blood cells
• chills, weight gain
• fever due to infection and low white blood cell count, shingles
• chest pain, lung haemorrhage, tissue hypoxia (low oxygen levels), fluid accumulation around the heart or lungs, hypotension, irregular heartbeat
• muscle, joint or bone pain, inflammation of blood vessels
• increased sodium or magnesium levels, ketone bodies in blood and urine (ketoacidosis), abnormal kidney function test results, kidney failure
• stomach (abdominal) pain
• facial flushing, facial swelling, blurred vision

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

• pneumonia, blood infection
• pneumonia causing chest pain and shortness of breath, heart failure
• dehydration, confusion
• brain disorders (encephalopathy, Wernicke's encephalopathy) with various symptoms, including difficulty moving arms and legs, speech disorders and confusion

Reporting of side effects
If any side effects occur, including any not listed in this leaflet, inform your doctor, pharmacist or nurse. Side effects can also be reported directly to the Department of Monitoring Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorisation holder.
Reporting side effects helps provide more information on the safety of the medicine.

5. How to store Arsenic trioxide Tillomed
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and on the vial label after: EXP. The expiry date refers to the last day of the stated month.
No special storage conditions apply.
If the medicine is not used immediately after dilution, the user is responsible for the storage time and conditions prior to administration. Generally, the storage time should not exceed 24 hours at a temperature of 2°C to 8°C, unless the dilution was performed under controlled and validated aseptic conditions.
Do not use this medicine if visible solid particles are present or if the solution has changed colour.
Medicines must not be disposed of via the sewage system or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Arsenic trioxide Tillomed contains

• The active substance is arsenic (III) oxide. Each mL contains 2 mg of arsenic (III) oxide. Each 6 mL vial contains 12 mg of arsenic (III) oxide.
• Other components of the medicine: sodium hydroxide, hydrochloric acid and water for injections.

What Arsenic trioxide Tillomed looks like and contents of the pack
Arsenic trioxide Tillomed is a clear, colourless concentrate for solution for infusion. The 6 mL concentrate is contained in a vial made of colourless type I glass, closed with a dark grey chlorobutyl rubber stopper coated with Teflon and sealed with a white flip-off cap. Filled vials are labelled and placed in a plastic overwrap made of heat-shrinkable film. The bottom of the vial is additionally protected with a plastic foil.
The pack contains 1 vial or 10 vials.

Marketing Authorisation Holder
Tillomed Malta Ltd.
Tower Business Centre 2nd floor
Tower Street, SWATAR
Birkirkara, BKR4013
Malta
tel: +48 509 368 531
e-mail: [email protected]

Importer
Tillomed Malta Ltd.
Malta Life Sciences Park
LS2.01.06 Industrial Estate
San Gwann, SGN 3000
Malta

This medicinal product is authorised in the European Economic Area countries under the following names:
Austria Arsentrioxid Tillomed 2 mg/ml Konzentrat zur Herstellung einer Infusionslösung
Bulgaria Арсенов триоксид Tillomed 1 mg/ml концентрат за инфузионен разтвор
Arsenic trioxide Tillomed 2 /ml concentrate for solution for infusion
Croatia Arsenov trioksid Tillomed 2 /ml koncentrat za otopinu za infuziju
Cyprus Arsenic trioxide Tillomed 2 /ml πυκνό διάλυμα για παρασκευή διαλύματος προς έγχυση
Denmark Arsentrioxid Tillomed
Estonia Arsenic trioxide Tillomed
Finland Arsenic trioxide Tillomed
France Arsenic trioxide Tillomed 2 /mL solution à diluer pour perfusion
Greece Arsenic trioxide/ Tillomed
Spain Trióxido de arsénico Tillomed 2 /ml concentrado para solución para perfusión
Lithuania Arsenic trioxide Tillomed 2 /ml koncentratas infuziniam tirpalui
Latvia Arsenic trioxide Tillomed 2 /ml koncentrāts infūziju šķīduma pagatavošanai
Malta Arsenic trioxide Tillomed 2 /ml concentrate for solution for infusion
Germany Arsenic Trioxide 2 /ml Konzentrat zur Herstellung einer Infusionslösung
Norway Arsenic trioxide Tillomed
Poland Arsenic trioxide Tillomed
Czech Republic ARSENIC TRIOXIDE TILLOMED
Slovakia Arsenic trioxide Tillomed 2 /ml infúzny koncentrát
Slovenia Arzenov trioksid Tillomed 2 /ml koncentrat za raztopino za infundiranje
Sweden Arsenic trioxide Tillomed
Romania Trioxid de arsen Tillomed 2 /ml concentrat pentru soluție perfuzabilă
Hungary Arsenic trioxide Tillomed 2 /ml koncentrátum oldatos infúzióhoz
Italy ARSENICO TRIOSSIDO TILLOMED

Information intended solely for medical professionals:
THE ASEPTIC PROCEDURES MUST BE STRICTLY FOLLOWED DURING THE PREPARATION OF THE MEDICINAL PRODUCT ARSENIC TRIOXIDE TILLOMED, AS IT DOES NOT CONTAIN ANY PRESERVATIVES.

Dilution of the medicinal product Arsenic trioxide Tillomed
The medicinal product Arsenic trioxide Tillomed must be diluted before administration.
Personnel should be trained in handling and diluting arsenic trioxide and should wear appropriate protective clothing.
Dilution: Carefully insert the syringe needle into the vial and withdraw the required volume of concentrate. The medicinal product Arsenic trioxide Tillomed should then be immediately diluted in 100 to 250 mL of 5% glucose solution (50 mg/mL) for injection or 0.9% sodium chloride solution (9 mg/mL) for injection.
Any unused content of each vial should be properly discarded. Do not store unused content for later administration.

Administration of the medicinal product Arsenic trioxide Tillomed
The medicinal product Arsenic trioxide Tillomed is for single use only. It must not be mixed or administered simultaneously in the same intravenous infusion set with other medicinal products.
The medicinal product Arsenic trioxide Tillomed should be administered intravenously by infusion lasting from 1 to 2 hours. If vascular reactions are observed, the infusion duration may be extended up to 4 hours. A central venous catheter is not required.
The diluted solution must be clear and colourless. Before administration, all parenteral solutions should be inspected visually for particulate matter and discoloration.
Do not use the medicinal product if particulate matter is present.
After dilution in infusion solutions, chemical and physical stability of the medicinal product Arsenic trioxide Tillomed has been demonstrated for 48 hours at temperatures from 15°C to 30°C and for 96 hours when stored refrigerated (2°C – 8°C). From a microbiological point of view, the product should be used immediately after preparation. If not used immediately, the responsibility for storage conditions and duration prior to use lies with the user. Generally, the storage time should not exceed 24 hours at 2°C to 8°C, unless dilution has been carried out under controlled and validated aseptic conditions.

Proper disposal procedure
All unused residues of the medicinal product, materials that have come into contact with it, and waste materials must be disposed of in accordance with local regulations.