Prospecto: information for thepatient

Trioxide of arsenic Stada 1 mg/ml concentrated solution for infusion EFG

Read this prospect carefully before this medicine is administered to you, because it contains important information for you.

-Keep this prospect, as you may need to read it again.

-If you have any doubts, consult your doctor, pharmacist or nurse.

- This medicine has been prescribed only to you, and you must not give it to other people, even if they have the same symptoms as you, as it may harm them.

-If you experience any adverse effects, consult your doctor, pharmacist or nurse, even if they are not listed in this prospect. See section 4.

1.What is Trioxide of arsenic Stada and what it is used for

2.What you need to know before Trioxide of arsenic Stada is administered to you

3.How to administer Trioxide of arsenic Stada

4.Possible adverse effects

5.Storage of Trioxide of arsenic Stada

6.Contents of the package and additional information

This medication is used in adult patients with acute promyelocytic leukemia (APL) of low to intermediate risk at initial diagnosis, and in adult patients whose disease has not responded to other treatments. APL is a unique type of acute myeloid leukemia, a disease that produces abnormal white blood cells, bleeding, and bruising.

Inform your doctor or pharmacist if you are taking or have recently taken other medications, including those purchased without a prescription.

This medication should be administered under the supervision of a doctor experienced in the treatment of acute leukemias.

Do not receive Trióxido de arsénico Stada

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

Warnings and precautions

You should consult your doctor or nurse before receiving arsenic trioxide if

-You have kidney failure.

-You have any liver problems.

Your doctor will take the following precautions:

-Blood tests will be performed to analyze the levels of potassium, magnesium, calcium, and creatinine in your blood before the first dose of arsenic trioxide.

-You will need to have an electrocardiogram (ECG) before the first dose.

-Blood tests (potassium, calcium, liver function) will be repeated while you continue treatment with arsenic trioxide.

-You will also have an electrocardiogram twice a week.

-If you are at risk of a certain type of heart rhythm anomaly (e.g. ventricular tachycardia in "torsades de pointes" or prolongation of the QT interval), your heart will be continuously monitored.

-Your doctor may also monitor your health during and after treatment, as arsenic trioxide, the active ingredient in this medication, may cause other cancers. You should report any new or unusual symptoms or circumstances to your doctor.

-Monitoring of cognitive functions and mobility if you are at risk of vitamin B1 deficiency.

Children and adolescents

Trióxido de arsénico is not recommended for children or adolescents under 18 years old.

Other medications andTrióxido de arsénico Stada

Inform your doctor or pharmacist if you are taking, have recently taken, or may need to take any other medication, including those purchased without a prescription.

In particular, inform your doctor

-If you are taking any medication that may cause a change in heart rhythm, including:

• Some types of antiarrhythmics (medications used to correct irregular heartbeats, e.g. quinidine, amiodarone, sotalol, dofetilide)
• Medications to treat psychosis (loss of contact with reality, e.g. thioridazine)
• Medications to treat depression (e.g. amitriptyline)
• Some types of medications to treat bacterial infections (e.g. erythromycin and ciprofloxacin)
• Some medications to treat allergies, such as pollen allergy, called antihistamines (e.g. terfenadine and astemizole)
• Any medication that reduces the level of magnesium or potassium in the blood (e.g. amphotericin B)
• Cisapride (medication used to alleviate certain stomach problems)

The effect of these medications on heart rhythm may worsen with arsenic trioxide. You should ensure that you inform your doctor about all the medications you are taking.

• If you are taking or have recently taken any medication that may affect the liver.

If you are unsure, show the bottle or packaging to your doctor.

Use of Trióxido de arsénico Stada with food and drinks

There are no restrictions on food or drink while receiving arsenic trioxide.

Pregnancy

Consult your doctor or pharmacist before using any medication. Arsenic trioxide may cause damage to the fetus if administered to pregnant women.

If you can become pregnant, you should use an effective contraceptive method during treatment with arsenic trioxide.

If you become pregnant or become pregnant during treatment with arsenic trioxide, consult your doctor.

Males should use effective contraceptive methods during treatment with arsenic trioxide.

Lactation

Consult your doctor or pharmacist before using any medication. Arsenic in arsenic trioxide passes into breast milk.

As arsenic trioxide may harm infants, avoid breastfeeding while on treatment with arsenic trioxide.

Driving and operating machinery

It is expected that the influence of arsenic trioxide on your ability to drive and operate machinery will be negligible or insignificant.

If you experience discomfort or do not feel well after an injection of arsenic trioxide, you should wait for the symptoms to subside before driving or operating machinery.

Trióxido de arsénico Stada contains sodium

This medication contains less than 1 mmol of sodium (23 mg) per dose; it is essentially "sodium-free".

Duration and Frequency of Treatment

Patients with Acute Promyelocytic Leukemia Newly Diagnosed

Your doctor will administer trioxide of arsenic once a day through infusion. In the first treatment cycle, you may receive treatment every day for a maximum of 60 days, or until your doctor considers that your condition has improved. If your condition responds to trioxide of arsenic, you will be administered an additional 4 treatment cycles of 20 doses, which will be administered 5 days a week (followed by 2 days of interruption) for 4 weeks (followed by a 4-week interruption). Your doctor will decide exactly how long you should continue with trioxide of arsenic treatment.

Patients with Acute Promyelocytic Leukemia Whose Condition Has Not Responded to Other Treatments

Your doctor will administer trioxide of arsenic once a day through infusion. In your first treatment cycle, you may receive treatment every day for a maximum of 50 days or until your doctor considers that your condition has improved. If your condition responds to trioxide of arsenic, you will be administered a second treatment cycle of 25 doses, which will be administered 5 days a week (followed by 2 days of interruption), for 5 weeks. Your doctor will decide exactly how long you should continue with trioxide of arsenic treatment.

Form and Route of Administration

Trioxide of arsenic must be diluted with a solution containing glucose or a solution containing sodium chloride.

Trioxide of arsenic is usually administered by a doctor or nurse. It is administered through a drip (infusion) inserted into a vein for 1-2 hours, but the infusion may last longer if side effects such as hot flashes and dizziness occur.

Trioxide of arsenic should not be mixed or injected through the same tube with other medications.

If Your Doctor Administers More Trioxide of Arsenic Stada Than Prescribed

You may experience convulsions, muscle weakness, and confusion. If this occurs, treatment with trioxide of arsenic should be stopped immediately, and your doctor will treat the arsenic overdose.

If you have any other questions about the use of this medication, ask your doctor, pharmacist, or nurse.

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

Inform your doctor or nurse immediately if you notice any of the following side effects, as they may be signs of a serious condition called "differentiation syndrome," which could be fatal:

-difficulty breathing

-coughing

-chest pain

-fever

Inform your doctor or nurse immediately if you notice one or more of the following side effects, as they may be signs of an allergic reaction:

-difficulty breathing

-fever

-rapid weight gain

-fluid retention

-loss of consciousness

-palpitations (strong heartbeat felt in the chest)

While taking arsenic trioxide, you may experience some of the following reactions:

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

-fatigue (tiredness), pain, fever, headache

-nausea, vomiting, diarrhea

-dizziness, muscle pain, numbness or tingling

-skin rash or itching, increased blood sugar, edema (inflammation due to excess fluid)

-shortness of breath, palpitations, electrocardiogram abnormalities

-decreased potassium or magnesium in the blood, liver or kidney function abnormalities, including excessive bilirubin or gamma-glutamyltransferase in the blood

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

-decreased blood cell count (platelets, red blood cells, and/or white blood cells), increased white blood cell count

-chills, weight gain

-fever due to infection and low white blood cell count, herpes zoster infection

-chest pain, pulmonary hemorrhage, hypoxia (low oxygen level), pericardial or pulmonary effusion, hypotension, arrhythmia

-seizures, bone or joint pain, vasculitis

-increased sodium or magnesium, presence of ketones in blood and urine (ketoacidosis), renal function abnormalities, renal insufficiency

-abdominal pain

-skin redness, facial swelling, blurred vision

Unknown frequency (cannot be estimated from available data):

-pulmonary infection, blood infection

-inflammatory lung disease with chest pain and difficulty breathing, heart failure,

-dehydration, confusion

-cerebral disease (Wernicke encephalopathy) with various manifestations, including difficulty using arms and legs, speech disorders, and confusion

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect not listed in this prospectus. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Use: https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

For ampoule presentation

Do not use this medication after the expiration date that appears on the ampoule label and on the box.

For vial presentation

Do not use this medication after the expiration date that appears on the vial label and on the box.

No special storage conditions are required.

After dilution with 0.9% sodium chloride solution or 5% glucose solution, arsenic trioxide is chemically and physically stable for 24 hours at 25°C and for 72 hours refrigerated (2-8°C). From a microbiological standpoint, the product should be used immediately. If not used immediately, storage conditions and times before use are the responsibility of the user and are normally not greater than 24 hours at 2-8°C, unless the dilution was carried out in validated and controlled aseptic conditions.

Do not use this medication if you observe foreign particles or if the solution is discolored.

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. This will help protect the environment.

Composition of Arsenic Trioxide Stada

-The active ingredient is arsenic trioxide (1 mg/1 ml).

-The other components are sodium hydroxide, hydrochloric acid (as pH adjuster) and water for injection.

Aspect of the product and content of the package

For the presentation in ampoules

Arsenic trioxide Stada is a concentrate for solution for infusion. Arsenic trioxide is supplied in glass ampoules in the form of a concentrated solution, sterile, transparent, colorless and aqueous, which is prepared and diluted in the hospital and administered through infusion in a blood vessel.

Each box contains 10 glass ampoules for single use. Each ampoule contains 10 mg of arsenic trioxide.

For the presentation in vials

Arsenic trioxide Stada is a concentrate for solution for infusion. Arsenic trioxide is supplied in glass vials in the form of a concentrated solution, sterile, transparent, colorless and aqueous, which is prepared and diluted in the hospital and administered through infusion in a blood vessel.

Each box contains 10 glass vials for single use. Each vial of 12 ml contains 12 mg of arsenic trioxide.

Holder of the marketing authorization

Stada, S.L.

Frederic Mompou, 5

08960 Sant Just Desvern (Barcelona)

Spain

[email protected]

Responsible for manufacturing

SVUS Pharma a.s.

Smetanovo nábreží 1238/20a

Hradec Králové 500 02

Czech Republic

or

STADA Arzneimittel AG

Stadastrasse 2 – 18

61118 Bad Vilbel

Germany

or

Centrafarm Services B.V.

Van de Reijtstraat 31-E

4814 NE Breda

Netherlands

Last review date of this prospectus:September 2023

The detailed and updated information of this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/

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This information is intended solely for doctors or healthcare professionals:

IT MUST BE FOLLOWED STRICTLY A TECHNIQUE ASPIRATION DURING HANDLING OF ARSENIC TRIOXIDE AS IT DOES NOT HAVE PRESERVATIVES.

Dilution of Arsenic Trioxide Stada

Arsenic Trioxide Stada must be diluted before administration.

The personnel must be properly trained to handle and dilute arsenic trioxide and must wear appropriate protective equipment.

For the presentation in ampoules

Opening the ampoule: Hold the arsenic trioxide ampoule with the colored tip facing upwards and in front of you. Shake it or tap it gently to allow any fluid in the nozzle to pass into the ampoule body. Now press the colored tip with your thumb and break the ampoule while holding the ampoule body firmly with your other hand.

Dilution: Carefully insert the needle of a syringe into the ampoule and extract all the contents. Arsenic trioxide must be diluted immediately with 100 to 250 ml of 50 mg/ml (5%) glucose injection solution or 9 mg/ml (0.9%) sodium chloride injection solution. Plastic polypropylene bags are used for the dilution of the final product.

The unused portions of each ampoule will be disposed of in the proper manner. Do not store any unused portion for subsequent administration.

For the presentation in vials

Dilution:Remove the transparent flip-off cap. Carefully insert the needle of a syringe into the vial through the rubber stopper and extract the required volume. Arsenic trioxide must be diluted immediately with 100 to 250 ml of 50 mg/ml (5%) glucose injection solution or 9 mg/ml (0.9%) sodium chloride injection solution. Plastic polypropylene bags are used for the dilution of the final product.

The unused portions of each vial will be disposed of in the proper manner. Do not store any unused portion for subsequent administration.

Use of Arsenic Trioxide Stada

Arsenic Trioxide Stada is for single use. It must not be mixed or administered concomitantly by the same intravenous route with other medications.

Arsenic trioxide will be injected intravenously for 1-2 hours, but the duration of the infusion may be prolonged up to 4 hours if vasomotor reactions are observed. A central venous catheter is not required.

The diluted solution must be transparent and colorless. Before administration, all parenteral solutions must be visually inspected for particles and discoloration. Do not use the preparation if there are signs of particles.

After dilution in intravenous solutions, arsenic trioxide is chemically and physically stable for 24 hours at 25°C and for 72 hours refrigerated (2-8°C). From a microbiological point of view, the product must be used immediately. If not used immediately, the storage conditions and times before use are the responsibility of the user and are normally not greater than 24 hours at 2-8°C, unless the dilution has been carried out in validated and controlled aseptic conditions.

Procedure for correct disposal

The disposal of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations.