ARSENIC TRIOXIDE STADA 1 mg/ml CONCENTRATE FOR INFUSION SOLUTION

2. What you need to know before you are given Arsenic Trioxide Stada

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

This medicine should be administered under the supervision of a doctor with experience in the treatment of acute leukemias.

You should not be given Arsenic Trioxide Stada

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

Warnings and precautions

You should consult your doctor or nurse before being given arsenic trioxide, if

• you have kidney problems.
• you have any liver problems.

Your doctor will take the following precautions:

• Tests will be carried out to analyze the amount of potassium, magnesium, calcium, and creatinine in your blood before the first dose of arsenic trioxide.
• An electrocardiogram (ECG) will be performed before the first dose.
• Blood tests (potassium, calcium, liver function) will be repeated while you are being treated with arsenic trioxide.
• An electrocardiogram will be performed twice a week.
• If you are at risk of a certain type of heart rhythm disorder (e.g., ventricular tachycardia in "torsades de pointes" or QT interval prolongation), your heart will be continuously monitored.
• Your doctor may monitor your health during and after treatment, as arsenic trioxide, the active substance of this medicine, may cause other cancers. You should report any new or unusual symptoms or circumstances whenever you visit your doctor.
• Monitoring of cognitive and motor functions if you are at risk of vitamin B1 deficiency.

Children and adolescents

Arsenic Trioxide is not recommended for children and adolescents under 18 years of age.

Other medicines and Arsenic Trioxide Stada

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those obtained without a prescription.

In particular, tell your doctor

• if you are taking any medicine that may cause a change in heart rhythm, including:
  • certain types of anti-arrhythmics (medicines used to correct irregular heartbeats, e.g., quinidine, amiodarone, sotalol, dofetilide)
  • medicines for treating psychosis (loss of contact with reality; e.g., thioridazine)
  • medicines for treating depression (e.g., amitriptyline)
  • certain types of medicines for treating bacterial infections (e.g., erythromycin and sparfloxacin)
  • certain medicines for treating allergies, such as hay fever, called antihistamines (e.g., terfenadine and astemizole)
  • any medicine that causes a decrease in magnesium or potassium levels in the blood (e.g., amphotericin B)
  • cisapride (a medicine used to relieve certain stomach problems).

The effect of these medicines on the heartbeat may worsen with arsenic trioxide. You must ensure that you inform your doctor about all the medicines you are taking.

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

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

Using Arsenic Trioxide 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 medicine. Arsenic trioxide may harm 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 are pregnant or become pregnant during treatment with arsenic trioxide, consult your doctor.

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

Breast-feeding

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

As arsenic trioxide may harm breast-fed infants, you should avoid breast-feeding while being treated with arsenic trioxide.

Driving and using machines

The influence of arsenic trioxide on your ability to drive and use machines is expected to be negligible or non-existent.

If you experience discomfort or do not feel well after an injection of arsenic trioxide, you should wait until the symptoms disappear before driving or using machines.

Arsenic Trioxide Stada contains sodium

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

3. How Arsenic Trioxide Stada is administered

Duration and frequency of treatment

Patient with newly diagnosed acute promyelocytic leukemia

Your doctor will administer arsenic trioxide once a day by infusion. In the first treatment cycle, you may receive treatment every day for up to 60 days, or until your doctor considers that your disease has improved. If your disease responds to arsenic trioxide, you will receive 4 additional treatment cycles of 20 doses, 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 treatment with arsenic trioxide.

Patient with acute promyelocytic leukemia whose disease has not responded to other treatments

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

Form and route of administration

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

Arsenic trioxide is normally administered by a doctor or nurse. It is administered through a drip (infusion) inserted into a vein over 1-2 hours, but the infusion may last longer if side effects such as flushing and dizziness occur.

Arsenic trioxide should not be mixed or injected through the same tube with other medicines.

If your doctor administers more Arsenic Trioxide Stada than you should

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

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Tell your doctor or nurse immediately if you notice one of the following side effects, as they could be signs of a serious condition called "differentiation syndrome", which can be life-threatening:

• difficulty breathing
• cough
• chest pain
• fever

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

• difficulty breathing
• fever
• sudden weight gain
• water retention
• fainting
• palpitations (strong heartbeat that can be felt in the chest)

While being treated with 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, high blood sugar, edema (swelling due to excess fluid)
• shortness of breath, palpitations, electrocardiogram abnormalities
• low potassium or magnesium levels in the blood, liver or kidney function test abnormalities, including high bilirubin or gamma-glutamyltransferase levels 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 bleeding, hypoxia (low oxygen level), fluid accumulation in the pericardium or lung, hypotension, heart rhythm disorder
• seizures, bone or joint pain, blood vessel inflammation
• high sodium or magnesium levels, presence of ketones in blood and urine (ketoacidosis), kidney function test abnormalities, kidney failure
• stomach pain (abdomen)
• skin redness, facial swelling, blurred vision

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

• pulmonary infection, blood infection
• pulmonary inflammation with chest pain and difficulty breathing, heart failure
• dehydration, confusion
• brain disease (encephalopathy, Wernicke's encephalopathy) with various manifestations, including difficulty using arms and legs, speech disorders, and confusion

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Medicines Monitoring System for Human Use: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Arsenic Trioxide Stada

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

For the ampoule presentation

Do not use this medicine after the expiry date which is stated on the ampoule label and carton.

For the vial presentation

Do not use this medicine after the expiry date which is stated on the vial label and carton.

No special storage conditions are required.

After dilution with sodium chloride 0.9% solution or glucose 5% 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 point of view, the product should be used immediately. If not used immediately, the storage conditions and times before use are the responsibility of the user and are normally not more than 24 hours at 2-8°C, unless the dilution has been carried out under validated and controlled aseptic conditions.

Do not use this medicine if you notice any foreign particles or if the solution is discolored.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Container Content and Additional Information

Composition of Trióxido de arsénico Stada

• The active ingredient is trióxido de arsénico (1 mg/1 ml).
• The other components are sodium hydroxide, hydrochloric acid (as a pH adjuster) and water for injectable preparations.

Appearance of the Product and Container Content

For the ampoule presentation

Trióxido de arsénico Stada is a concentrate for solution for perfusion. Trióxido de arsénico is supplied in glass ampoules in the form of a concentrated, sterile, transparent, colorless, and aqueous solution that is prepared and diluted in the hospital and administered by perfusion into a blood vessel.

Each box contains 10 single-use glass ampoules. Each ampoule contains 10 mg of trióxido de arsénico.

For the vial presentation

Trióxido de arsénico Stada is a concentrate for solution for perfusion. Trióxido de arsénico is supplied in glass vials in the form of a concentrated, sterile, transparent, colorless, and aqueous solution that is prepared and diluted in the hospital and administered by perfusion into a blood vessel.

Each box contains 10 single-use glass vials. Each 12 ml vial contains 12 mg of trióxido de arsénico.

Marketing Authorization Holder

Laboratorio Stada, S.L.

C/Frederic Mompou, 5

08960 Sant Just Desvern (Barcelona)

Spain

[email protected]

Manufacturer

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

Date of the Last Review of this Prospect:September 2023

Detailed and updated information on this medication is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

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This information is intended solely for doctors or healthcare professionals:

STRICT ASEPTIC TECHNIQUE MUST BE FOLLOWED DURING THE HANDLING OF TRIÓXIDO DE ARSÉNICO SINCE IT HAS NO PRESERVATIVES.

Dilution of Trióxido de arsénico Stada

Trióxido de arsénico Stada must be diluted before administration.

Personnel must be properly trained to handle and dilute trióxido de arsénico and must wear adequate protective equipment.

For the ampoule presentation

Ampoule opening: Hold the trióxido de arsénico ampoule with the colored tip facing upwards and in front of you. Shake it or tap it gently so that any fluid in the nozzle passes into the body of the ampoule. Now press the colored tip with your thumb and break the ampoule while holding the body of the ampoule firmly with your other hand.

Dilution: Carefully insert the needle of a syringe into the ampoule and withdraw all the contents. Trióxido de arsénico must be diluted immediately thereafter with 100 to 250 ml of injectable glucose solution 50 mg/ml (5%) or injectable sodium chloride solution 9 mg/ml (0.9%). Polypropylene plastic bags are used for the dilution of the finished product.

Unused portions of each ampoule will be discarded in an appropriate manner. Do not store any unused portion for later administration.

For the vial presentation

Dilution: Remove the transparent flip-off cap. Carefully insert the needle of a syringe into the vial through the rubber stopper and withdraw the necessary volume. Trióxido de arsénico must be diluted immediately thereafter with 100 to 250 ml of injectable glucose solution 50 mg/ml (5%) or injectable sodium chloride solution 9 mg/ml (0.9%). Polypropylene plastic bags are used for the dilution of the finished product.

Unused portions of each vial will be discarded in an appropriate manner. Do not store any unused portion for later administration.

Use of Trióxido de arsénico Stada

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

Trióxido de arsénico will be injected intravenously over 1-2 hours, but the duration of the perfusion may be extended 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, trióxido de arsénico 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 conditions and storage times before use are the responsibility of the user and will normally not exceed 24 hours at 2-8°C, unless the dilution has been carried out in validated and controlled aseptic conditions.

Procedure for Correct Elimination

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