Trisenox

Package leaflet: Information for the patient

TRISENOX 1 mg/mL concentrate for solution for infusion

arsenic trioxide
Please read this leaflet carefully before you are given this medicine 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 get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of this leaflet

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

1. WHAT TRISENOX IS AND WHAT IT IS USED FOR

TRISENOX is used in adult patients with newly diagnosed low-to-intermediate risk acute promyelocytic leukemia (APL) and in adult patients whose disease has not responded to other therapies.
APL is a distinct variant of myeloid leukemia, a disease characterized by abnormalities in blood white cells and abnormalities in bleeding and bruising.

2. WHAT YOU SHOULD KNOW BEFORE YOU ARE GIVEN TRISENOX

TRISENOX must be administered under the supervision of a physician experienced in the treatment of acute leukemias.

Do not take TRISENOX
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 or nurse before you are given TRISENOX if:

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

Your doctor will take the following precautions:

• Before administering the first dose of TRISENOX, blood tests will be performed to check your levels of potassium, magnesium, calcium, and creatinine.
• An electrocardiogram (ECG) will be performed before the first dose is administered.
• During treatment with TRISENOX, blood tests (for potassium, calcium, magnesium, and liver function) must be repeated regularly.
• In addition, an electrocardiogram will be performed twice weekly.
• If you are at risk of a certain type of heart rhythm disorder (e.g., torsades de pointes or QTc prolongation), your heart will be continuously monitored.
• Your doctor may monitor your health status during and after treatment, as arsenic trioxide, the active substance in TRISENOX, may cause other tumors. You must report any new or unusual symptoms or conditions whenever you see your doctor.
• If you are at risk of vitamin B1 deficiency, your cognitive and motor functions will be monitored.

Children and adolescents
TRISENOX is not recommended for children and adolescents under 18 years of age.

Other medicines and TRISENOX
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those not requiring a prescription.

In particular, inform your doctor:

• 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., amitriptyline)
  • 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 heart rhythm may be worsened by TRISENOX. Make sure you inform your doctor 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 container or packaging to your doctor.

TRISENOX with food and drink
There are no restrictions on food or drink while receiving TRISENOX.

Pregnancy
Ask your doctor or pharmacist for advice before taking any medicine.
TRISENOX may harm the fetus if used in pregnant women.
If you are of childbearing age, you must use an effective method of contraception during treatment with TRISENOX and for 6 months after the end of treatment.
If you are pregnant or become pregnant during treatment with TRISENOX, consult your doctor.
Men must use effective contraception and must be advised not to father a child during treatment with TRISENOX and for 3 months after the end of treatment.

Breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine.
The arsenic contained in TRISENOX passes into breast milk.
Because TRISENOX may harm breastfed infants, do not breastfeed during treatment with TRISENOX and for up to two weeks after the last dose.

Driving and using machines
TRISENOX has no effect or has a negligible effect on the ability to drive and use machines.
If you experience discomfort or illness after a TRISENOX injection, wait until symptoms have resolved before driving or using machinery.

TRISENOX contains sodium
TRISENOX contains less than 1 mmol (23 mg) of sodium per dose. This means the medicine is essentially 'sodium-free'.

3. HOW TRISENOX IS ADMINISTERED

Duration and frequency of treatment
Patients with newly diagnosed acute promyelocytic leukemia
Your doctor will administer TRISENOX once daily, every day, as an 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 TRISENOX, you will receive an additional 4 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 treatment break. Your doctor will decide exactly how long you should continue
treatment with TRISENOX.

Patients with acute promyelocytic leukemia whose disease has not responded to other treatments
Your doctor will administer TRISENOX once daily, every day, as an 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 TRISENOX, you will receive a second treatment cycle
consisting 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 TRISENOX.

Method and route of administration
TRISENOX must be diluted with a glucose-containing solution or a sodium chloride-containing solution.
TRISENOX is usually administered by a doctor 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.
TRISENOX must not be mixed with other medicinal products nor infused through the same line used
for other medicinal products.

If the doctor or nurse gives you more TRISENOX than you should receive
You may experience seizures, muscle weakness, and confusion. In this case, treatment with TRISENOX
must be stopped immediately, and your doctor will treat the arsenic overdose.

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

4. POSSIBLE ADVERSE REACTIONS

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.

Immediately inform your doctor or nurse if you notice any of the following adverse reactions, which may be signs of a serious condition called "differentiation syndrome", which can be fatal:

• difficulty breathing
• cough
• chest pain
• fever

Immediately inform your doctor or nurse if you notice one or more of the following adverse reactions, which may be signs of an allergic reaction:

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

During treatment with TRISENOX, you may experience some of the following reactions:

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

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

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
• seizure, 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 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 manifestations, including difficulty using arms and legs, speech disorders and confusion

Reporting of adverse reactions
If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor, pharmacist or nurse. You can also report adverse reactions directly via the national reporting system detailed in Annex V. Reporting adverse reactions can help provide more information on the safety of this medicine.

5. HOW TO STORE TRISENOX

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 box.
This medicine does not require any special storage conditions.
After dilution, if the medicinal product is not used immediately, the times and conditions of storage prior to use are the responsibility of the physician, pharmacist, or nurse, and normally shall not exceed 24 hours at 2 to 8°C, unless the dilution has been carried out under sterile conditions.
Do not use this medicine if you notice the presence of foreign particles or if the solution appears discolored.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer used. This will help protect the environment.

6. PACKAGING CONTENTS AND OTHER INFORMATION

What TRISENOX contains

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

Description of the appearance of TRISENOX and contents of the pack

• TRISENOX is a sterile concentrate for solution for infusion. TRISENOX is supplied in glass vials as a clear, colourless, concentrated aqueous solution.
• Each carton contains 10 single-use glass vials.

Marketing Authorisation Holder
Teva B.V., Swensweg 5, 2031 GA Haarlem, The Netherlands
Manufacturer
Almac Pharma Services Limited, Almac House, 20 Seagoe Industrial Estate, Craigavon, BT63 5QD,
United Kingdom
Almac Pharma Services (Ireland) Limited; Finnabair Industrial Estate, Dundalk, Co. Louth,
A91 P9KD, Ireland
Teva Pharmaceuticals Europe B.V., Swensweg 5, 2031 GA Haarlem, The Netherlands
More detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu.
In addition, links to other websites on rare diseases and their therapeutic treatments are provided.

The following information is intended exclusively for physicians or healthcare professionals:
A STRICTLY ASEPTIC TECHNIQUE MUST BE OBSERVED FOR ALL PROCEDURES
INVOLVING THE HANDLING OF TRISENOX, DUE TO THE ABSENCE OF A PRESERVATIVE
IN THE PRODUCT.
Dilution of TRISENOX
TRISENOX must be diluted before administration.
Personnel must be trained in handling and diluting arsenic trioxide and must wear appropriate protective clothing.
Opening the vial: hold the TRISENOX vial in front of you with the coloured dot facing upwards. Shake or gently tap the vial to ensure any liquid in the neck falls back into the main body of the vial. Then press the thumb on the coloured dot and break the vial, holding the body of the vial firmly with the other hand.
Dilution: carefully insert the needle of a syringe into the vial and withdraw the entire contents.
Immediately dilute TRISENOX with 100–250 mL of 50 mg/mL (5%) glucose solution for injection or 9 mg/mL (0.9%) sodium chloride solution for injection.
Any unused portions from each vial must be properly disposed of. Do not store unused portions for subsequent administration.
Use of TRISENOX
TRISENOX is for single use only. It must not be mixed with other medicinal products nor administered simultaneously with them through the same intravenous line.
TRISENOX 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 visually inspected for particulate matter and discolouration prior to administration. Do not use the preparation if it contains foreign particulate matter.
After dilution in intravenous solutions, TRISENOX remains chemically and physically stable for 24 hours at 15–30°C and for 72 hours under refrigerated conditions (2–8°C). From a microbiological standpoint, the product should be used immediately. If not used immediately, in-use storage conditions and times prior to use are the responsibility of the user and normally should not exceed 24 hours at 2–8°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 applicable local regulations.

Patient information leaflet: information for the patient

TRISENOX 2 mg/mL concentrate for solution for infusion

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

1. WHAT TRISENOX IS AND WHAT IT IS USED FOR

TRISENOX is used in adult patients with newly diagnosed low-to-intermediate risk acute promyelocytic leukemia (APL) and in adult patients whose disease has not responded to other therapies.
APL is a distinct variant of myeloid leukemia, a disease characterized by abnormalities in blood white cells and abnormalities in bleeding and bruising.

2. WHAT YOU NEED TO KNOW BEFORE YOU ARE GIVEN TRISENOX

TRISENOX must be administered under the supervision of a physician experienced in the treatment of acute leukemias.
Do not take TRISENOX
If you are allergic to arsenic trioxide or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
You should speak with your doctor or nurse before being given TRISENOX if:

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

Your doctor will take the following precautions:

• Before administering the first dose of TRISENOX, blood tests will be performed to check the levels of potassium, magnesium, calcium, and creatinine in your blood.
• An electrocardiogram (ECG) must be performed before the first dose is administered.
• During treatment with TRISENOX, blood tests (for potassium, calcium, magnesium, and liver function) must be repeated regularly.
• In addition, an electrocardiogram will be performed twice weekly.
• If you are at risk of 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 status during and after treatment, as arsenic trioxide, the active substance in TRISENOX, may cause other tumors. You must report any new or unusual symptoms or conditions at every visit to your doctor.
• If you are at risk of vitamin B1 deficiency, checks of your cognitive and motor functions will be carried out.

Children and adolescents
TRISENOX is not recommended for children and adolescents under 18 years of age.

Other medicines and TRISENOX
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those not requiring a prescription.
In particular, inform your doctor:

• 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 antibiotics (e.g., erythromycin and sparfloxacin)
  • Certain antihistamines used to treat allergies such as hay fever (e.g., terfenadine and astemizole)
  • Any medicine that causes low magnesium or potassium levels in the blood (e.g., amphotericin B)
  • Cisapride (a medicine used for certain stomach problems)
    The effect of these medicines on your heart rhythm may be worsened by TRISENOX. Make sure you inform your doctor 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 the container or packaging of the medicine.

TRISENOX with food and drink
There are no restrictions on food or drink while taking TRISENOX.

Pregnancy
Ask your doctor or pharmacist for advice before taking any medicine.
TRISENOX may harm the fetus if used during pregnancy.
If you are of childbearing age, you must use an effective method of contraception during treatment with TRISENOX and for 6 months after the end of treatment.
If you are pregnant or become pregnant during treatment with TRISENOX, consult your doctor.
Men must use effective contraception and must be advised not to father a child during treatment with TRISENOX 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 TRISENOX passes into breast milk.
Because TRISENOX may harm breastfed infants, you must not breast-feed during treatment with TRISENOX and for up to two weeks after the last dose.

Driving and using machines
TRISENOX does not affect, or has a negligible effect on, the ability to drive vehicles or operate machinery.
If you experience discomfort or side effects after a TRISENOX injection, wait until symptoms have resolved before driving or using machinery.

TRISENOX contains sodium
TRISENOX contains less than 1 mmol (23 mg) of sodium per dose. This means the medicine is essentially 'sodium-free'.

3. HOW TRISENOX IS ADMINISTERED

Duration and frequency of treatment
Patients with newly diagnosed acute promyelocytic leukemia
Your doctor will administer TRISENOX once daily, every day, as an 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 TRISENOX, you will receive an additional 4 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 exactly how long you should continue
treatment with TRISENOX.

Patients with acute promyelocytic leukemia whose disease has not responded to other treatments
Your doctor will administer TRISENOX once daily, every day, as an 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 TRISENOX, you will receive a second treatment
cycle consisting 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 TRISENOX.

Method and route of administration
TRISENOX must be diluted with a glucose-containing solution or a sodium chloride-containing solution.
TRISENOX is usually administered by a doctor or nurse. It is given by intravenous infusion over 1–2
hours. However, the infusion may take longer if side effects such as flushing or dizziness occur.
TRISENOX must not be mixed with other medicinal products or infused through the same tubing used
for other medicinal products.

If the doctor or nurse gives you more TRISENOX than you should receive
You may experience seizures, muscle weakness, and confusion. In this case, treatment with TRISENOX
must be stopped immediately, and your doctor will treat the arsenic overdose.

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

4. POSSIBLE ADVERSE REACTIONS

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.
Contact your doctor or nurse immediately if you notice any of the following adverse reactions, which
may be signs of a serious condition called "differentiation syndrome," which can be fatal:

• difficulty breathing
• cough
• chest pain
• fever

Contact your doctor or nurse immediately if you notice one or more of the following adverse
reactions, which may be signs of an allergic reaction:

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

During treatment with TRISENOX, you may experience some of the following reactions:
Very common (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 (swelling due to fluid buildup)
• shortness of breath, rapid heartbeat, abnormal ECG
• decreased potassium or magnesium in the blood, abnormal liver function tests including increased blood levels of bilirubin or gamma-glutamyl transferase

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, 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
• inflammation of the lungs causing chest pain and shortness of breath, 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 adverse reactions
If you experience any adverse reaction, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You may also report adverse reactions directly via the national reporting system listed in Annex V. By reporting adverse reactions, you can help provide more information on the safety of this medicine.

5. HOW TO STORE TRISENOX

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 carton.
This medicine does not require any special storage conditions.
After dilution, if the medicinal product is not used immediately, the times and conditions of storage prior to use are the responsibility of the physician, pharmacist, or nurse and normally will not exceed 24 hours at 2 to 8°C, unless the dilution has been carried out in a sterile environment.
Do not use this medicine if you notice the presence of 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 no longer required. This will help protect the environment.

6. PACKAGING CONTENTS AND OTHER INFORMATION

What TRISENOX contains

• The active substance is arsenic trioxide. Each mL of concentrate contains 2 mg of arsenic trioxide. Each 6 mL vial contains 12 mg of arsenic trioxide.
• The other components are sodium hydroxide, hydrochloric acid, and water for injections. See section 2 “TRISENOX contains sodium”.

Description of the appearance of TRISENOX and contents of the pack

• TRISENOX is a sterile concentrate for solution for infusion. TRISENOX is supplied in glass vials, wrapped in a protective plastic overwrap, as a clear, colourless, aqueous concentrate.
• Each box contains 10 single-use glass vials.

Marketing Authorisation Holder
Teva B.V., Swensweg 5, 2031 GA Haarlem, The Netherlands
Manufacturer
Teva Pharmaceuticals Europe B.V., Swensweg 5, 2031 GA Haarlem, The Netherlands
Merckle GmbH, Graf-Arco-Str. 3, 89079 Ulm, Germany
S.C. Sindan-Pharma S.R.L., B-dul Ion Mihalache nr 11, sector 1, Cod 011171, Bucharest, Romania
More detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu.
In addition, links to other websites on rare diseases and their therapeutic treatments are provided.

The following information is intended exclusively for physicians or healthcare professionals:
ASEPTIC TECHNIQUE MUST BE STRICTLY FOLLOWED FOR ALL TRISENOX HANDLING PROCEDURES DUE TO THE ABSENCE OF A PRESERVATIVE IN THE PRODUCT.
Dilution of TRISENOX
TRISENOX must be diluted prior to administration.
Personnel handling and diluting arsenic trioxide must be properly trained and must wear appropriate protective clothing.
CAUTION: NEW CONCENTRATION (2 mg/mL)
Dilution: Carefully insert the needle of a syringe into the vial and withdraw the required volume.
Immediately dilute TRISENOX with 100–250 mL of glucose injection 50 mg/mL (5%) or sodium chloride injection 9 mg/mL (0.9%).
Any unused portion from each vial must be properly discarded. Do not store unused portions for subsequent administration.
Use of TRISENOX
TRISENOX is for single use only. It must not be mixed with other medicinal products or administered simultaneously with them through the same intravenous line.
TRISENOX must be administered by intravenous infusion 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 visually inspected for particulate matter and discoloration prior to administration. Do not use the preparation if it contains foreign particulate matter.
After dilution in intravenous solutions, TRISENOX remains chemically and physically stable for 24 hours at 15–30°C and for 72 hours under refrigerated conditions (2–8°C). From a microbiological standpoint, the product should be used immediately. If not used immediately, storage in use before administration is the responsibility of the user and normally should not exceed 24 hours at 2–8°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.