Arsenic trioxide Sandoz

Leaflet attached to the packaging: patient information

Arsenic trioxide Sandoz, 1 mg/ml, concentrate for solution for infusion

Arsenic trioxide

You should read the contents of the leaflet before using the medicine, as it contains important information for the patient.

• You should keep this leaflet, so that you can read it again if you need to.
• If you have any doubts, you should consult your doctor, pharmacist, or nurse.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet:

• 1. What Arsenic trioxide Sandoz is and what it is used for
• 2. Important information before using Arsenic trioxide Sandoz
• 3. How to use Arsenic trioxide Sandoz
• 4. Possible side effects
• 5. How to store Arsenic trioxide Sandoz
• 6. Contents of the packaging and other information

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

Arsenic trioxide Sandoz is used in adult patients with newly diagnosed acute promyelocytic leukemia (APL) with low or intermediate risk and in adult patients who have not responded to other therapies. APL is a unique type of blood cancer in which abnormal white blood cells and abnormal bleeding and bruising occur.

2. Important information before using Arsenic trioxide Sandoz

Arsenic trioxide Sandoz should be administered under the supervision of a doctor with experience in treating acute leukemias.

When not to use Arsenic trioxide Sandoz

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

Warnings and precautions

Before receiving Arsenic trioxide Sandoz, the patient should discuss it with their doctor or nurse if:

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

The doctor will take the following precautions:

• Before administering the first dose of Arsenic trioxide Sandoz, a blood test will be performed to check the levels of potassium, magnesium, calcium, and creatinine.
• Before administering the first dose, the patient should have an electrocardiogram (ECG) performed.
• During treatment with Arsenic trioxide Sandoz, the patient should have regular blood tests (potassium, magnesium, calcium, liver function).
• In addition, the patient should have electrocardiograms performed twice a week.
• In patients at risk of developing a certain type of heart rhythm disorder (e.g., torsades de pointes or QTc prolongation), heart function will be continuously monitored.
• The doctor may monitor the patient's health during and after treatment, as the active substance of Arsenic trioxide Sandoz, arsenic trioxide, may cause the development of other tumors. During each medical visit, all new or unusual symptoms or circumstances should be reported.
• Cognitive function and motor skills should be monitored if the patient is at risk of vitamin B1 deficiency.

Children and adolescents

Arsenic trioxide Sandoz is not recommended for use in children under 18 years of age.

Arsenic trioxide Sandoz and other medicines

The patient should tell their doctor or pharmacist about all medicines they are taking or have recently taken, as well as any medicines they plan to take, including those that are available without a prescription.

• In particular, the patient should inform their doctor
• about all medicines that may affect heart rhythm. These include:
• certain types of anti-arrhythmic medicines (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 (e.g., erythromycin and sparfloxacin)
• certain antihistamines (e.g., terfenadine and astemizole)
• any medicines that may decrease potassium or magnesium levels in the blood (e.g., amphotericin B)
• cisapride (a medicine used to relieve certain stomach disorders). The action of these medicines on the heart may worsen with the use of Arsenic trioxide Sandoz. The patient should remember to inform their doctor about all medicines they are taking.
• if the patient is currently taking or has recently taken medicines that may affect liver function. In case of doubt, the patient should show the bottle or packaging to their doctor.

Using Arsenic trioxide Sandoz with food and drink

There are no restrictions on eating and drinking during treatment with Arsenic trioxide Sandoz.

Pregnancy

Before using any medicine, the patient should consult their doctor or pharmacist. Arsenic trioxide Sandoz may be harmful to the fetus if taken by pregnant women. If the patient is of childbearing age, they should use effective contraception during treatment with Arsenic trioxide Sandoz.

Breast-feeding

Before using any medicine, the patient should consult their doctor or pharmacist. Arsenic in Arsenic trioxide Sandoz passes into breast milk. Since Arsenic trioxide Sandoz may be harmful to breast-fed infants, breast-feeding should be avoided during treatment with this medicine.

Driving and using machines

Arsenic trioxide Sandoz is expected to have no or negligible influence on the ability to drive and use machines. If the patient experiences discomfort or their condition worsens after receiving Arsenic trioxide Sandoz, they should wait until the symptoms resolve before driving or operating machinery.

Driving and using machines

Arsenic trioxide Sandoz may cause drowsiness, especially when taken with alcohol. The patient should not drive or operate machinery until they are sure that Arsenic trioxide Sandoz does not cause drowsiness.

Arsenic trioxide Sandoz contains sodium

Arsenic trioxide Sandoz contains less than 1 mmol of sodium (23 mg) per vial, which means the medicine is considered "sodium-free".

3. How to use Arsenic trioxide Sandoz

Duration of treatment and frequency of administration

Patient with newly diagnosed acute promyelocytic leukemia

The doctor will administer Arsenic trioxide Sandoz daily, by infusion. During the first cycle, treatment may be given daily for up to 60 days or until the doctor determines that there has been an improvement. If the patient responds to treatment with Arsenic trioxide Sandoz, they will receive 4 additional cycles of treatment. Each cycle consists of 20 doses, administered 5 days a week (with 2 days of rest) for 4 weeks, followed by 4 weeks of rest. The doctor will decide how long the treatment with Arsenic trioxide Sandoz should last.

Patient with acute promyelocytic leukemia who have not responded to other treatments

The doctor will administer Arsenic trioxide Sandoz daily, by infusion. During the first cycle, treatment may be given daily for up to 50 days or until the doctor determines that there has been an improvement. If the patient responds to treatment with Arsenic trioxide Sandoz, they will receive a second cycle of treatment, consisting of 25 doses, administered 5 days a week (with 2 days of rest) for 5 weeks. The doctor will decide how long the treatment with Arsenic trioxide Sandoz should last.

Method and route of administration

Arsenic trioxide Sandoz must be diluted before administration.

Arsenic trioxide Sandoz is usually administered by a doctor or nurse as an intravenous infusion over 1 to 2 hours. If side effects such as flushing or dizziness occur, the infusion may be prolonged.

Arsenic trioxide Sandoz should not be mixed with other medicines or administered through the same infusion set.

Administration of a higher dose of Arsenic trioxide Sandoz by a doctor

The patient may experience seizures, muscle weakness, and confusion. In such cases, administration of Arsenic trioxide Sandoz should be stopped immediately. The doctor will provide appropriate treatment, as in the case of arsenic overdose.

If there are any further doubts about the use of this medicine, the patient should consult their doctor or pharmacist.

4. Possible side effects

Like all medicines, Arsenic trioxide Sandoz can cause side effects, although not everybody gets them.

If any of the following symptoms occur, the patient should contact their doctor or nurse immediately, as they may be symptoms of a serious condition called "differentiation syndrome", which can be life-threatening:

• -difficulty breathing
• -cough
• -chest pain
• -fever

If any of the following symptoms occur, the patient should contact their doctor or nurse immediately, as they may be symptoms of an allergic reaction:

• -difficulty breathing
• -fever
• -sudden weight gain
• -water retention in the body
• -fainting
• -palpitations (strong heartbeats felt in the chest)

During treatment with Arsenic trioxide Sandoz, the following side effects may occur:

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

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

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

• -decreased blood cell count (platelets, red or white blood cells), increased white blood cell count
• -chills, weight gain
• -fever due to infection and low white blood cell count, shingles
• -chest pain, bleeding in the lungs, tissue hypoxia (low oxygen levels), fluid accumulation around the heart or lungs, low blood pressure, abnormal heart rhythm
• -muscle, joint, or bone pain, blood vessel inflammation
• -increased sodium or magnesium levels, ketone bodies in the blood and urine (ketoacidosis), abnormal kidney function tests, kidney failure
• -abdominal pain
• -flushing, facial swelling, blurred vision

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

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

Reporting side effects

If the patient experiences any side effects, including any side effects not listed in the leaflet, they should tell their doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Monitoring of Adverse Reactions to Medicinal Products of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products: Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +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 authorization holder.

By reporting side effects, more information can be gathered on the safety of the medicine.

5. How to store Arsenic trioxide Sandoz

The medicine should be stored out of sight and reach of children.

The medicine should not be used after the expiry date, which is stated on the carton and on the label after EXP. The expiry date refers to the last day of the month.

The medicine should not be stored above 25°C, with permissible variations between 15-30°C.

Stability after dilution

Dilution in 0.9% NaCl solution

The chemical and physical stability of Arsenic trioxide Sandoz infusion solutions has been demonstrated for 28 days at room temperature (20°C - 25°C) without protection from light and at a temperature between 2°C and 8°C without light.

Dilution in 5% glucose solution

The chemical and physical stability of Arsenic trioxide Sandoz infusion solutions has been demonstrated for 3 days at a temperature between 2°C and 8°C and for 24 hours at a temperature below 25°C.

From a microbiological point of view, the product should be used immediately after dilution.

If the product is not used immediately, the responsibility for the storage time and conditions before use lies with the user. Generally, the storage time should not exceed 24 hours at a temperature between 2°C and 8°C, unless the dilution was performed under controlled and validated aseptic conditions.

The medicine should not be used if particles or discoloration are visible.

Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Arsenic trioxide Sandoz contains

• -The active substance is arsenic trioxide.
• -The other ingredients are sodium hydroxide, hydrochloric acid 10% (for pH adjustment), and water for injections.

What Arsenic trioxide Sandoz looks like and contents of the pack

Arsenic trioxide Sandoz is a concentrate for solution for infusion.

It is available in glass vials as a sterile, clear, colorless solution without particles. The glass vials are closed with a bromobutyl rubber stopper and an aluminum seal with a polypropylene flip-off cap.

The pack contains 1 vial with 10 ml of concentrate for solution for infusion.

Marketing authorization holder:

Sandoz GmbH

Biochemiestrasse 10

6250 Kundl

Austria

Manufacturer:

EBEWE Pharma GmbH

Mondseestrasse 11

4866 Unterach am Attersee

Austria

Fareva Unterach GmbH

Mondseestraße 11

4866 Unterach

Austria

For further information about the medicine, please contact:

Sandoz Polska Sp. z o.o.

ul. Domaniewska 50 C

02-672 Warszawa

tel. 22 209 70 00

This medicinal product is authorized in the Member States of the European Economic Area (EEA) under the following names:

Austria

Arsentrioxid Sandoz 1 mg/ml – Konzentrat zur Herstellung einer Infusionslösung

Czech Republic

Arsenic Trioxide Sandoz

Germany

Arsentrioxid HEXAL 1 mg/ml

Spain

Trióxido de Arsénico Sandoz 1 mg/ml concentrado para solución para perfusión EFG

Italy

Arsenico triossido Sandoz

Netherlands

Arseentrioxide Sandoz 1 mg/ml, concentraat voor oplossing voor infusie.

Poland

Arsenic trioxide Sandoz

Date of last revision of the leaflet:06/2021

Sandoz logo

Information intended for healthcare professionals only

STRICTLY FOLLOW ASEPTIC PROCEDURES WHEN PREPARING ARSENIC TRIOXIDE SANDOZ, AS IT DOES NOT CONTAIN PRESERVATIVES.

Dilution of Arsenic trioxide Sandoz

Arsenic trioxide Sandoz must be diluted before administration.

Personnel should be trained in the handling and dilution of arsenic trioxide and should wear appropriate protective clothing.

Dilution: The contents of the ampoule should be drawn into a syringe. Arsenic trioxide Sandoz should then be immediately diluted in 100 ml to 250 ml of glucose 50 mg/ml (5%) solution for injection or sodium chloride 9 mg/ml (0.9%) solution for injection.

Stability after dilution

Dilution in 0.9% NaCl solution

The chemical and physical stability of Arsenic trioxide Sandoz infusion solutions has been demonstrated for 28 days at room temperature (20°C - 25°C) without protection from light and at a temperature between 2°C and 8°C without light.

Dilution in 5% glucose solution

The chemical and physical stability of Arsenic trioxide Sandoz infusion solutions has been demonstrated for 3 days at a temperature between 2°C and 8°C and for 24 hours at a temperature below 25°C.

From a microbiological point of view, the product should be used immediately after dilution.

If the product is not used immediately, the responsibility for the storage time and conditions before use lies with the user. Generally, the storage time should not exceed 24 hours at a temperature between 2°C and 8°C, unless the dilution was performed under controlled and validated aseptic conditions.

Administration of Arsenic trioxide Sandoz

For single use only. Arsenic trioxide Sandoz should not be mixed or administered simultaneously in the same infusion set with other medicinal products.

Arsenic trioxide Sandoz should be administered intravenously over 1 to 2 hours. If vascular reactions are observed, the infusion time can be extended to 4 hours. It is not necessary to insert a central venous catheter.

The diluted solution must be clear and colorless. Before administration, all parenteral solutions should be inspected for particulate matter and discoloration. The medicine should not be used if particles are present.

Procedure for proper disposal

Arsenic trioxide Sandoz is intended for single use only. Any unused residue of each vial should be properly disposed of. Unused residues of the product should not be stored for later administration.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.