TERLIPRESSIN 0.12 mg/ml Solution

Contents of the leaflet

1. Package Leaflet: Information for the Patient
2. Terlipressin acetate Altan, 0.12 mg/1 mL, solution for injection
   1. Read the package leaflet carefully before using the medicine, as it contains important information for the patient.
   2. Table of Contents of the Leaflet
3. What is Terlipressin acetate Altan and what is it used for
4. Important information before using Terlipressin acetate Altan
   1. When not to use Terlipressin acetate Altan:
   2. Warnings and precautions
   3. Terlipressin acetate Altan should be used under specialist supervision in facilities equipped with appropriate equipment to continuously monitor blood pressure, heart rate, blood parameters, and electrolyte levels.
   4. Terlipressin acetate Altan and other medicines
   5. Pregnancy and breastfeeding
   6. Driving and using machines
   7. Elderly patients
   8. Use in children and adolescents
   9. Use in patients with liver function disorders
   10. Terlipressin acetate Altan contains sodium
5. How to use Terlipressin acetate Altan
   1. Use in adults
   2. Method and route of administration
   3. Using a higher dose of Terlipressin acetate Altan than recommended
   4. Missing a dose of Terlipressin acetate Altan
6. Possible side effects
   1. Reporting side effects
7. How to store Terlipressin acetate Altan
8. Contents of the pack and other information
   1. What Terlipressin acetate Altan contains
   2. What Terlipressin acetate Altan looks like and contents of the pack
   3. Marketing authorization holder:
   4. Manufacturer:
   5. Date of revision of the leaflet:

Package Leaflet: Information for the Patient

Terlipressin acetate Altan, 0.12 mg/1 mL, solution for injection

Terlipressin acetate

Read the package leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including those not listed in this leaflet, please inform your doctor, pharmacist, or nurse. See section 4.

Table of Contents of the Leaflet

• 1. What is Terlipressin acetate Altan and what is it used for
• 2. Important information before using Terlipressin acetate Altan
• 3. How to use Terlipressin acetate Altan
• 4. Possible side effects
• 5. How to store Terlipressin acetate Altan
• 6. Contents of the pack and other information

1. What is Terlipressin acetate Altan and what is it used for

Terlipressin acetate Altan contains the active substance terlipressin, which is a synthetic hormone of the pituitary gland (this hormone is normally produced by the pituitary gland, located in the brain).
Terlipressin acetate Altan is used to treat:

• bleeding from enlarged veins in the part of the digestive tract leading to the stomach (bleeding from esophageal varices). Terlipressin works on the walls of blood vessels, causing them to narrow and reduce blood flow to the varices, thereby reducing bleeding.
• emergency treatment of renal failure in patients with severe liver function disorders (hepatorenal syndrome type 1). Terlipressin reduces pressure in the liver veins (portal vein pressure) in patients with high blood pressure (portal hypertension), and also contributes to improved blood circulation in the kidneys, helping to restore kidney function.

2. Important information before using Terlipressin acetate Altan

When not to use Terlipressin acetate Altan:

Warnings and precautions

Using Terlipressin acetate Altan should be discussed with your doctor:

• as there is an increased risk of adverse cardiac events;
• as there is a higher likelihood of adverse effects related to poor blood flow in these areas;
• as there is an increased risk of skin ischemia, and in single cases, even skin necrosis;
• in children, as experience in these age groups is limited.
• in pregnant women.

Before starting treatment with Terlipressin acetate Altan, discuss it with your doctor, pharmacist, or nurse.

Terlipressin acetate Altan should be used under specialist supervision in facilities equipped with appropriate equipment to continuously monitor blood pressure, heart rate, blood parameters, and electrolyte levels.

To avoid skin necrosis due to the drug getting into the skin, the injection should be administered intravenously only.
Terlipressin acetate Altan may increase the risk of developing respiratory failure, which can be life-threatening for the patient. If before administration of Terlipressin acetate Altan or during treatment, breathing difficulties or symptoms of excessive fluid in the body occur, the doctor should be informed immediately.
If the patient is being treated for very severe liver and kidney disease (hepatorenal syndrome type 1), the doctor should ensure that heart rate and water-electrolyte balance are monitored during treatment. Particular caution should be exercised in cases of past heart or lung disease, as Terlipressin acetate Altan may cause cardiac ischemia (reduced blood flow to the heart) and respiratory failure (severe breathing difficulties). Treatment with Terlipressin acetate Altan should be avoided if the patient has liver failure with multi-organ failure and (or) renal failure with very high creatinine levels in the blood (a product resulting from metabolism in the body), as this increases the risk of adverse effects.
If the patient is being treated for very severe liver and kidney disease, Terlipressin acetate Altan may increase the risk of developing sepsis (presence of bacteria in the blood and a strong reaction of the body to the infection) and septic shock (a severe disease that occurs when a severe infection leads to decreased blood pressure and low blood flow). If these situations apply to the patient, the doctor will take additional precautions.

Terlipressin acetate Altan and other medicines

Tell your doctor, pharmacist, or nurse about all medicines you are taking or have recently taken, as well as any medicines you plan to take.
Immediately inform your doctor if you are taking any of the following medicines:

• medicines that affect heart rhythm (e.g., so-called beta-blockers, as their effect may be enhanced if used simultaneously with Terlipressin acetate Altan;
• anti-arrhythmic medicines (used to treat irregular heart rhythm, such as quinidine or amiodarone;
• diuretics (increasing urine excretion, e.g., from the furosemide group).

Inform your doctor if in the past you have experienced sudden slowing of heart rate after using certain anesthetics (propofol, sufentanil). Terlipressin acetate Altan may enhance the effect of these medicines if they are administered again.

Pregnancy and breastfeeding

Terlipressin acetate Altan can only be used when your doctor considers it necessary.
If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, ask your doctor for advice before using this medicine.
Terlipressin acetate Altan should not be used during breastfeeding, as it is not known whether it passes into breast milk.

Driving and using machines

No studies have been conducted on the effect of the medicine on the ability to drive and use machines. However, if you feel unwell after receiving the injection, you should not drive or operate machinery.

Elderly patients

Terlipressin acetate Altan should be used with caution in patients over 70 years old with cardiovascular disease present or past.

Use in children and adolescents

Terlipressin Acetate is not recommended for use in children and adolescents due to insufficient experience in this age group.

Use in patients with liver function disorders

No dose adjustment is required in patients with liver failure.

Terlipressin acetate Altan contains sodium

This medicine contains 30.6 mg of sodium (the main component of common salt) in each 8.5 ml ampoule.
This corresponds to 1.53% of the recommended daily sodium intake in the diet for adults.

3. How to use Terlipressin acetate Altan

This medicine should always be used as directed by your doctor. If you are unsure, ask your doctor or pharmacist.

Use in adults

Bleeding from enlarged veins (varices) in the part of the digestive tract leading to the stomach
Your doctor will determine the dose based on your body weight.
Usually, patients with a body weight below 50 kg are given 1 mg (1 ampoule of 8.5 ml) every 4 hours.
Patients with a body weight between 50 and 70 kg should be given 1.5 mg (1.5 ampoules of 8.5 ml) every 4 hours.
Patients with a body weight above 70 kg should be given 2 mg (2 ampoules of 8.5 ml) every 4 hours.
Treatment should be continued for a further 24 hours, until bleeding is controlled.
Treatment should not exceed 48 hours.
After the initial dose, if necessary, e.g., in case of adverse effects, subsequent doses of Terlipressin acetate Altan can be reduced to 1 mg (1 ampoule).
Hepatorenal syndrome
The usual dose is 1 mg (1 ampoule of terlipressin) every 6 hours, for at least 3 days. If after 3 days of treatment, the decrease in serum creatinine is less than 30% compared to the initial value, the dose should be increased to 2 mg (2 ampoules) every 6 hours.
Terlipressin treatment should be discontinued in case of no response to treatment (defined as a decrease in serum creatinine less than 30% compared to the initial value on day 7) or in patients with a full response (serum creatinine less than 1.5 mg/dl for at least two consecutive days).
In patients showing a partial response (decrease in serum creatinine of at least 30% compared to the initial value, but without achieving a value below 1.5 mg/dl on day 7), terlipressin treatment can be continued for a maximum of 14 days.
In case of recurrence of hepatorenal syndrome after a complete response, terlipressin treatment can be restarted according to medical advice.
Treatment of hepatorenal syndrome usually lasts 7 days, and the maximum recommended duration is 14 days.
Hepatorenal syndrome type 1
Terlipressin acetate Altan can also be administered to the patient by infusion (continuous intravenous infusion), usually at an initial dose of 2 mg of terlipressin per day, which will then be gradually increased to a maximum dose of 12 mg of terlipressin per day.

Method and route of administration

Administration of Terlipressin acetate Altan should be performed by qualified medical personnel.
Remove the ampoule from the packaging and ensure that no liquid remains in the top part of the ampoule.
After opening the ampoule, draw up the solution with a syringe and administer by intravenous injection.
The medicine should be used immediately after opening.
Terlipressin acetate Altan is administered by injection or intravenous infusion.

Using a higher dose of Terlipressin acetate Altan than recommended

In case of using too high a dose, a sudden increase in blood pressure may occur.

Missing a dose of Terlipressin acetate Altan

Do not take a double dose to make up for a missed dose.
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 other healthcare professional immediately:

• If you experience breathing difficulties or worsening of breathing ability (symptoms of respiratory failure). These side effects occur very frequently in patients treated for hepatorenal syndrome type 1. – may affect more than 1 in 10 people.

if you experience symptoms of blood infection (sepsis and/or septic shock), which may include fever and chills or very low body temperature, pallor and/or cyanosis, severe shortness of breath, less frequent urination, rapid heart rate, nausea and vomiting, diarrhea, fatigue and weakness, and dizziness. These side effects occur frequently in patients treated for hepatorenal syndrome type 1. - may affect up to 1 in 10 people.

Other side effects that may occur with varying frequency, depending on the patient's disease.
Very common(may affect more than 1 in 10 treated patients):
If you have hepatorenal syndrome type 1:

• Shortness of breath (dyspnea)

Common(may affect up to 1 in 10 patients)

• headache
• bradycardia (very slow heart rate)
• increased blood pressure
• peripheral vascular spasm (insufficient blood flow to tissues) causing pallor
• transient abdominal pain
• transient diarrhea

If you have hepatorenal syndrome type 1:

• fluid in the lungs (pulmonary edema)
• difficulty breathing (acute respiratory distress syndrome)

Uncommon(may affect up to 1 in 100 patients)

• low sodium levels in the blood if fluid balance is not controlled
• irregular heart rhythm
• rapid pulse
• chest pain
• heart attack (myocardial infarction)
• insufficient blood flow to the intestines (intestinal ischemia)
• peripheral cyanosis (blue discoloration of the skin due to lack of oxygen)
• hot flashes
• transient nausea
• transient vomiting
• skin necrosis (tissue damage) at the injection site

If you experience bleeding from the digestive tract with ruptured esophageal-gastric varices:

• fluid in the lungs (pulmonary edema)
• difficulty breathing (acute respiratory distress syndrome)

Rare(may affect up to 1 in 1000 patients)
If you experience bleeding from the digestive tract with ruptured esophageal-gastric varices:

• shortness of breath (dyspnea)

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

• heart failure. Symptoms include shortness of breath, fatigue, and swelling of the ankles
• arrhythmia of the torsade de pointes type
• skin necrosis (tissue damage)
• uterine contractions
• reduced blood flow to the uterus

The antidiuretic effect of the medicine (reduced urine excretion) may cause decreased sodium levels in the blood (hyponatremia), if fluid balance is not controlled.
During clinical trials in patients with hepatorenal syndrome treated with terlipressin, the risk of adverse effects on the cardiovascular system, such as reduced blood flow to the heart (myocardial ischemia), irregular heart rhythm (arrhythmia), reduced blood flow to the intestines (intestinal ischemia), or overload of the circulatory system (manifested by increased blood pressure, headache, difficulty breathing, or jugular venous distension), increased.
During clinical trials and after the marketing of the medicinal product, several cases of arrhythmia have been reported.
After the marketing of the medicinal product, several cases of ischemia and skin necrosis not related to the injection site have been reported

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, please inform your doctor or pharmacist. 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, you can help provide more information on the safety of this medicine.

5. How to store Terlipressin acetate Altan

Keep this medicine out of the sight and reach of children.
Store in a refrigerator (2°C – 8°C).
Store in the original packaging to protect from light.
Do not freeze.
Do not use this medicine after the expiry date stated on the packaging after EXP.
The expiry date refers to the last day of the month stated.
After first opening, the product should be used immediately.
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. Contents of the pack and other information

What Terlipressin acetate Altan contains

• The active substance of the medicine is terlipressin. One 8.5 ml ampoule of solution for injection contains 1 mg of terlipressin, which corresponds to 0.85 mg of terlipressin.

1 ml of solution for injection contains 0.12 mg of terlipressin, which corresponds to 0.1 mg of terlipressin.

• The other ingredients are: sodium chloride, glacial acetic acid, sodium acetate trihydrate, water for injections.

What Terlipressin acetate Altan looks like and contents of the pack

Terlipressin acetate Altan is a clear, colorless solution for injection.
One pack contains 5 ampoules of colorless glass (type I) of 8.5 mL of solution, in a cardboard box.

Marketing authorization holder:

Altan Pharma Ltd
The Lennox Building, 50 South Richmond Street
Dublin 2, D02FK02
Ireland

Manufacturer:

Altan Pharmaceuticals S.A.
Avda. de la Constitución, 198-199
Polígono Industrial Monte Boyal
45950 Casarrubios del Monte (Toledo)
Spain

Date of revision of the leaflet: