TERLIPRESSINI 0.2 mg/ml Solution

Contents of the leaflet

1. Package Leaflet: Information for the User
2. Terlipressin acetate EVER Pharma, 0.2 mg/mL, solution for injection
   1. Read all of this leaflet carefully before using this medicine because it contains important information for you.
   2. Contents of the pack
3. What Terlipressin acetate EVER Pharma is and what it is used for
4. What you need to know before you are given Terlipressin acetate EVER Pharma
   1. When not to use Terlipressin acetate EVER Pharma:
   2. Warnings and precautions
   3. Children and adolescents
   4. Terlipressin acetate EVER Pharma and other medicines
   5. Pregnancy and breastfeeding
   6. Driving and using machines
   7. Terlipressin acetate EVER Pharma contains sodium
5. How Terlipressin acetate EVER Pharma is given
   1. Administration in adults
   2. Administration in the elderly
   3. Administration in patients with renal impairment
   4. Administration in patients with hepatic impairment
   5. Administration in children and adolescents
   6. Duration of treatment
   7. Overdose of Terlipressin acetate EVER Pharma
   8. Discontinuation of Terlipressin acetate EVER Pharma
6. Possible side effects
   1. Severe side effects that require immediate medical attention:
   2. Other side effects that may occur with varying frequency, depending on the patient's disease.
   3. Very common (may affect more than 1 in 10 people)
   4. Common (may affect up to 1 in 10 people)
   5. Uncommon (may affect up to 1 in 100 people)
   6. Rare (may affect up to 1 in 1000 people)
   7. Frequency not known: frequency cannot be estimated from the available data
   8. Reporting of side effects
7. How to store Terlipressin acetate EVER Pharma
8. Contents of the pack and other information
   1. What Terlipressin acetate EVER Pharma contains
   2. What Terlipressin acetate EVER Pharma looks like and contents of the pack
   3. Marketing authorisation holder
   4. Manufacturer
   5. This medicine is authorised in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:
   6. Information intended for healthcare professionals only:
   7. Dosage
   8. Preparation of the injection or intravenous infusion

Package Leaflet: Information for the User

Terlipressin acetate EVER Pharma, 0.2 mg/mL, solution for injection

Terlipressin acetate

Read all of this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

• 1. What Terlipressin acetate EVER Pharma is and what it is used for
• 2. What you need to know before you are given Terlipressin acetate EVER Pharma
• 3. How Terlipressin acetate EVER Pharma is given
• 4. Possible side effects
• 5. How to store Terlipressin acetate EVER Pharma
• 6. Contents of the pack and other information

1. What Terlipressin acetate EVER Pharma is and what it is used for

Terlipressin acetate EVER Pharma 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).
The medicine will be administered to you by injection into a vein.
Terlipressin acetate EVER Pharma is used to treat:

• bleeding from enlarged veins in the part of the digestive tract that leads to the stomach (called bleeding from oesophageal varices);
• sudden cases of hepatorenal syndrome type 1 (rapidly progressive renal failure) in patients with liver cirrhosis (scarring of the liver) and ascites (swelling of the abdomen).

2. What you need to know before you are given Terlipressin acetate EVER Pharma

When not to use Terlipressin acetate EVER Pharma:

• if you are allergic to terlipressin or any of the other ingredients of this medicine (listed in section 6);
• if you are pregnant.

Warnings and precautions

Before starting treatment with Terlipressin acetate EVER Pharma, you should discuss this with your doctor, pharmacist or nurse:

• if you have a severe infection, called septic shock;
• if you have asthma or other diseases that affect breathing;
• if you have high blood pressure that is not effectively treated, inadequate blood circulation in the blood vessels of the heart (e.g. angina pectoris);
• if you have had a heart attack (myocardial infarction) or have narrowing of the blood vessels (atherosclerosis);
• if you have seizures (convulsions);
• if you have irregular heart rhythm (arrhythmia) or prolonged QT interval in your medical history (arrhythmia);
• if you have poor blood circulation in the brain (e.g. you have had a stroke) or in the limbs (peripheral vascular disease);
• if you have kidney problems (renal failure);
• if you have electrolyte disturbances (e.g. low sodium levels in the blood);
• if you have decreased fluid volume in the circulatory system or have lost a lot of blood;
• if you are over 70 years old.

If any of these conditions apply to you (or if you are not sure), you should discuss this with your doctor, pharmacist or nurse before starting treatment with Terlipressin acetate EVER Pharma.
During treatment with Terlipressin acetate EVER Pharma, your heart rate and fluid and electrolyte balance should be constantly monitored.
Terlipressin acetate EVER Pharma may increase the risk of developing respiratory failure (severe breathing difficulties), which can be life-threatening. If you experience breathing difficulties or signs of excessive fluid in the body before or during treatment with Terlipressin acetate EVER Pharma, you should inform your doctor immediately.
If you are being treated for severe liver and kidney disease (hepatorenal syndrome type 1), your doctor should ensure that your heart rate and fluid and electrolyte balance are monitored during treatment.
Particular caution should be exercised in patients with a history of heart or lung disease, as Terlipressin acetate EVER Pharma may cause heart ischemia (reduced blood flow to the heart) and respiratory failure.
Treatment with Terlipressin acetate EVER Pharma should be avoided if you have liver failure with multi-organ failure and (or) renal failure with very high creatinine levels in the blood (a product of metabolism in the body), as this increases the risk of adverse reactions.
If you are being treated for severe liver and kidney disease, Terlipressin acetate EVER Pharma may increase the risk of developing sepsis (bacteria in the blood and extreme reaction of the body to 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 you, your doctor will take additional precautions.

Children and adolescents

Terlipressin acetate EVER Pharma is not recommended for use in children and adolescents due to lack of experience in this age group.

Terlipressin acetate EVER Pharma and other medicines

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

• medicines that affect heart rhythm (e.g. so-called beta-blockers, sufentanil or propofol);
• medicines that may cause irregular heart rhythm (arrhythmia), such as:
• anti-arrhythmic medicines of class IA (quinidine, procainamide, disopyramide) and class III (amiodarone, sotalol, ibutilide, dofetilide);
• erythromycin (an antibiotic);
• antihistamines (used mainly to treat allergies, but also as ingredients in some anti-cough and cold medicines);
• tricyclic antidepressants, used to treat depression;
• medicines that may cause electrolyte disturbances, mainly diuretics (water pills used to treat high blood pressure and heart failure).

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.
Terlipressin acetate EVER Pharma must not be used during pregnancy.
It is not known whether Terlipressin acetate EVER Pharma passes into breast milk, so the possible effect on the baby is not known. You should discuss the possible risk to the baby with your doctor.

Driving and using machines

No studies on the effects on the ability to drive and use machines have been performed. However, if you feel unwell after injection, you should not drive or operate machinery.

Terlipressin acetate EVER Pharma contains sodium

This medicine contains 3.68 mg of sodium (the main component of common salt) per mL. This corresponds to 0.18% of the maximum recommended daily intake of sodium in the diet for adults.

3. How Terlipressin acetate EVER Pharma is given

This medicine is given by injection or infusion into a vein by a doctor. Your doctor will decide what dose is most suitable for you. During administration of the medicine, your doctor will constantly monitor your heart and blood circulation. For further information on the use of this medicine, you should consult your doctor.

Administration in adults

• 1. Short-term treatment of bleeding from oesophageal varices:

Initially 1 to 2 mg of terlipressin acetate (5 to 10 mL of Terlipressin acetate EVER Pharma), administered in a slow intravenous injection. The dose depends on the patient's body weight.
After administration of the initial injection, the dose may be reduced to 1 mg of terlipressin acetate (5 mL) every 4 to 6 hours.

• 2. Hepatorenal syndrome type 1:

In the case of slow intravenous injection, the usual dose is 1 mg of terlipressin acetate every 6 hours, for at least 3 days. If after 3 days of treatment the serum creatinine level has decreased by less than 30% compared to the initial value, the doctor will consider increasing the dose to 2 mg every 6 hours.
Terlipressin acetate EVER Pharma may also be administered to the patient in a drip (continuous intravenous infusion), usually at an initial dose of 2 mg of terlipressin acetate per day, which will then be gradually increased to a maximum dose of 12 mg of terlipressin acetate per day.
If there is no response to treatment with Terlipressin acetate EVER Pharma or if the response is incomplete, treatment should be discontinued.
If the serum creatinine level has decreased, treatment with Terlipressin acetate EVER Pharma can be continued for a maximum of 14 days.

Administration in the elderly

If you are over 70 years old, you should talk to your doctor before using Terlipressin acetate EVER Pharma.

Administration in patients with renal impairment

Terlipressin acetate EVER Pharma should be used with caution in patients with chronic renal failure.

Administration in patients with hepatic impairment

No dose adjustment is required in patients with liver failure.

Administration in children and adolescents

Terlipressin acetate EVER Pharma is not recommended for use in children and adolescents due to lack of experience in this age group.

Duration of treatment

The use of this medicine is limited to 2-3 days in the case of short-term treatment of bleeding from oesophageal varices and up to a maximum of 14 days in the case of treatment of hepatorenal syndrome, depending on the course of the disease.

Overdose of Terlipressin acetate EVER Pharma

Since the medicine will be administered to you by a qualified medical professional, it is unlikely that you will receive a dose higher than recommended. In the event of an overdose, a sudden increase in blood pressure (detected during continuous monitoring) may occur, especially in patients with pre-existing hypertension. In such cases, the patient will receive another medicine, called an alpha-blocker (e.g. clonidine), to lower blood pressure.
Tell your doctor if you experience dizziness, dizziness or fainting, as these may be symptoms of slow heart rate. This can be treated with the administration of another medicine, called atropine.

Discontinuation of Terlipressin acetate EVER Pharma

Your doctor will tell you when you can stop using the medicine.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

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

Severe side effects that require immediate medical attention:

Rarely, severe side effects may occur during treatment with Terlipressin acetate EVER Pharma. You should immediately contact your doctorif you experience any of the following symptoms. Your doctor will advise you to stop using Terlipressin acetate EVER Pharma.

• severe shortness of breath due to an asthma attack
• severe chest pain (angina pectoris)
• severe and persistent arrhythmia
• skin necrosis at the injection site
• seizures (convulsions). You should immediately inform your doctor or another qualified medical professional:
• if you experience breathing difficulties or worsening of breathing (signs or symptoms of respiratory failure). These side effects are very common in patients treated for hepatorenal syndrome type 1 – they may affect more than 1 in 10 people;

if you experience signs or symptoms of blood infection (sepsis and (or) septic shock), which may include fever and chills or very low body temperature, paleness 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 are common in patients treated for hepatorenal syndrome type 1 - they 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 people)

If you have hepatorenal syndrome type 1:

• shortness of breath (dyspnoea)

Common (may affect up to 1 in 10 people)

• very slow heart rate
• symptoms of inadequate blood circulation in the heart vessels, visible on ECG
• high or low blood pressure
• poor blood circulation in the arms, legs and skin
• paleness of the face
• paleness of the skin
• headache
• transient abdominal cramps
• transient diarrhea
• abdominal cramps (in women)

You should immediately inform your doctor or another qualified medical professional:
If you have hepatorenal syndrome type 1:

• fluid in the lungs (pulmonary oedema)
• breathing difficulties (acute respiratory failure)

Uncommon (may affect up to 1 in 100 people)

• chest pain
• sudden increase in blood pressure
• heart attack
• rapid heart rate (palpitations)
• fluid in the tissues or lungs
• blue discoloration of the skin or lips
• hot flushes
• transient nausea
• transient vomiting
• reduced blood flow to the digestive tract
• inflammation of the lymphatic vessels - visible as small red streaks under the skin running from the affected area to the armpit or groin, and fever, chills, headache, and muscle pain
• low sodium levels in the blood (hyponatraemia)

You should immediately inform your doctor or another qualified medical professional:
If you have bleeding from oesophageal varices:

• fluid in the lungs (pulmonary oedema)
• breathing difficulties (acute respiratory failure)

Rare (may affect up to 1 in 1000 people)

• stroke
• high blood sugar levels (hyperglycaemia)

You should immediately inform your doctor or another qualified medical professional:
If you have bleeding from oesophageal varices:

• shortness of breath (dyspnoea)

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

• heart failure
• arrhythmia of the torsade de pointes type
• skin necrosis in areas other than the injection site
• reduced blood flow to the uterus
• uterine contractions

Reporting of side effects

If you experience any side effects, including any not listed in this leaflet, you should tell your doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products.
Al. Jerozolimskie 181 C, 02-222 Warsaw
Phone: +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 authorisation holder.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Terlipressin acetate EVER Pharma

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton and vial after “Expiry date (EXP)”. The expiry date refers to the last day of the month.
Store in a refrigerator (2°C – 8°C). Do not freeze.
Before administration, the solution should be inspected to ensure that it does not contain particles and that the colour has not changed. Do not use this medicine if you notice any change in colour.
Medicines should not be disposed of via wastewater or household waste. Your doctor will dispose of any unused medicine. This will help protect the environment.

6. Contents of the pack and other information

What Terlipressin acetate EVER Pharma contains

• The active substance is terlipressin acetate. 5 mL of the solution for injection contains 1 mg of terlipressin acetate, which corresponds to 0.85 mg of terlipressin. 10 mL of the solution for injection contains 2 mg of terlipressin acetate, which corresponds to 1.7 mg of terlipressin. This is equivalent to 0.2 mg of terlipressin acetate per mL, which corresponds to 0.17 mg of terlipressin per mL.
• The other ingredients are: sodium chloride, acetic acid, sodium hydroxide (for pH adjustment), hydrochloric acid (for pH adjustment) and water for injections.

What Terlipressin acetate EVER Pharma looks like and contents of the pack

This medicine is supplied in transparent glass vials containing 5 mL or 10 mL of a clear, colourless solution.
The medicine is available in the following packs: 5 x 5 mL, 5 x 10 mL.
Not all pack sizes may be marketed.

Marketing authorisation holder

EVER Valinject GmbH
Oberburgau 3
4866 Unterach am Attersee
Austria

Manufacturer

This medicine is authorised in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

AT
Terlipressinacetat EVER Pharma 0,2 mg/ml Injektionslösung

BG
Терлипресин ацетат EVER Pharma 0,2 mg/ml инжекционен разтвор
CZ
Terlipresin acetát EVER Pharma
DE
Terlipressinacetat EVER Pharma 0,2 mg/ml Injektionslösung
ES
Terlipresina acetato EVER Pharma 1 mg solución inyectable
Terlipresina acetato EVER Pharma 2 mg solución inyectable
FR
ACETATE DE TERLIPRESSINE EVER PHARMA 0,2 mg/ml, solution injectable
IE
Terlipressin acetate EVER Pharma 0.2 mg/ml solution for injection
IT
Terlipressina acetato EVER Pharma
PL
Terlipressini acetas EVER Pharma
PT
Terlipressina EVER Pharma, 0,2 mg/ml, Solução injetável
RO
Acetat de Terlipresină EVER Pharma 0,2 mg/ml soluţie injectabilă
SK
Terlipresín EVER Pharma 0,2 mg/ml injekčný roztok
UK
Terlipressin acetate EVER Pharma 0.2 mg/ml solution for injection
Date of last revision of the leaflet:01.07.2023
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Information intended for healthcare professionals only:

Dosage

• 1) Short-term treatment of bleeding from oesophageal varices: Initial dose: the recommended initial dose is 1 to 2 mg of terlipressin acetate * (corresponding to 5 to 10 mL of the solution), administered in a slow intravenous injection over one minute.

Depending on the patient's body weight, the dose can be adjusted as follows:
Maintenance dose: after administration of the initial injection, the dose of terlipressin acetate can be reduced to 1 mg every 4 to 6 hours.
* 1 to 2 mg of terlipressin acetate corresponds to 0.85 mg to 1.7 mg of terlipressin.
The approximate maximum daily dose of Terlipressin acetate EVER Pharma is 120 micrograms of terlipressin acetate per kg of body weight.
Treatment should be limited to 2 to 3 days, depending on the course of the disease.
Terlipressin acetate EVER Pharma is administered intravenously, and the intravenous injection should be performed over one minute.

• 2) Hepatorenal syndrome type 1:

1 mg of terlipressin acetate in an intravenous injection every 6 hours, for at least 3 days. If after 3 days of treatment the serum creatinine level has decreased by less than 30% compared to the initial value, the doctor will consider increasing the dose to 2 mg every 6 hours.
As an alternative to slow intravenous injection (bolus), terlipressin can be administered in a continuous intravenous infusion (iv.), starting at a dose of 2 mg of terlipressin acetate per day, which will then be gradually increased to a maximum dose of 12 mg of terlipressin acetate per day.
Administration of terlipressin in a continuous intravenous infusion may be associated with a lower frequency of severe side effects than administration in a slow intravenous injection (bolus).
Treatment with terlipressin should be discontinued in the absence of response to treatment (defined as a decrease in serum creatinine level on day 7 of less than 30% compared to the initial value), or in patients with a complete response (serum creatinine level less than 1.5 mg/dL for at least two consecutive days). In patients with a partial response (decrease in serum creatinine level of at least 30% compared to the initial value, but without reaching a value below 1.5 mg/dL on day 7), treatment with terlipressin can be continued for a maximum of 14 days.

In most clinical trials supporting the use of terlipressin in the treatment of hepatorenal syndrome, human albumin was also administered at a dose of 1 g/kg body weight on the first day, and then at a dose of 20-40 g/day.
Usually, the duration of treatment of hepatorenal syndrome is 7 days, and the maximum recommended duration of treatment is 14 days.
Terlipressin acetate EVER Pharma should be used with caution in patients over 70 years old and in patients with chronic renal failure.
Hepatorenal syndrome type 1
Terlipressin should be avoided in patients with advanced renal impairment, i.e. with a baseline serum creatinine level ≥ 442 µmol/L (5.0 mg/dL), unless the expected benefits of treatment outweigh the risks.
Terlipressin acetate EVER Pharma is not recommended for use in children and adolescents due to lack of studies on safety and efficacy.
No dose adjustment is required in patients with liver failure.
Hepatorenal syndrome type 1
Terlipressin should be avoided in patients with severe liver disease, defined as acute-on-chronic liver failure (ACLF) grade 3 and (or) with a MELD score ≥ 39, unless the expected benefits of treatment outweigh the risks.

Preparation of the injection or intravenous infusion

The required volume should be drawn from the vial using a syringe.
Store in a refrigerator (2°C – 8°C). Do not freeze.
For single use only. Any unused solution should be discarded.