Terlipressin acetate altan

Package leaflet: Information for the user

Terlipressin acetate Altan, 0.12 mg/1 mL, solution for injection
Terlipressini acetas
Please read all of 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 further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you personally. Do not pass it on to others. It may harm them even if their symptoms are the same as yours.
• 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 the leaflet

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

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

Terlipressin acetate Altan contains the active substance terlipressin, which is a synthetic
pituitary hormone (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 upper gastrointestinal tract leading to the stomach (oesophageal variceal bleeding). Terlipressin acts on the walls of blood vessels, causing them to constrict and reducing blood flow to the varices, thereby reducing bleeding.
• Acute treatment of kidney failure in patients with severe liver dysfunction (hepatorenal syndrome type 1). Terlipressin reduces pressure in the liver veins (portal pressure) in patients with high blood pressure in the portal vein (portal hypertension), and also helps improve blood circulation in the kidneys, aiding in the restoration of kidney function.

2. Important information before using Terlipressin acetate Altan

When not to use Terlipressin acetate Altan:

• if the patient is allergic to the active substance or to any of the other ingredients of this medicine (listed in section 6);

Warnings and precautions
The use of Terlipressin acetate Altan should be discussed with a doctor:

• if the patient has high blood pressure (hypertension)
• if the patient has irregular heart function (arrhythmia) or narrowing of blood vessels (atherosclerosis)
• because there is an increased risk of heart-related adverse events;
• if the patient has poor blood circulation in the brain (e.g. the patient has had a stroke) or in the limbs (peripheral vascular disease) or intestinal ischemia
• because there is a higher likelihood of adverse effects related to reduced blood flow in these areas;
• if the patient has leg swelling due to poor venous circulation or overweight (obesity)
• because there is an increased risk of skin ischemia, and in isolated cases, even skin necrosis;
• if the patient has a severe infection called septic shock
• if the patient has kidney function disorders (renal failure)
• if the patient has asthma or other conditions affecting breathing
• if the patient is over 70 years of age with existing or past cardiovascular disease
• in children, as experience in these age groups is limited.
• in pregnant women.

Before starting treatment with Terlipressin acetate Altan, discuss this with a doctor,
pharmacist, or nurse.
Terlipressin acetate Altan should be administered under specialist supervision in
facilities equipped with appropriate equipment allowing continuous monitoring of blood
pressure, heart function, blood parameters, and electrolyte levels.
To avoid skin necrosis due to leakage of the drug into the skin, the injection must be administered
intravenously only.
Terlipressin acetate Altan may increase the risk of developing respiratory failure, which may
be life-threatening. If breathing difficulties or symptoms of fluid overload occur before or during
treatment with Terlipressin acetate Altan, inform the doctor immediately.
If the patient is being treated for severe liver and kidney disease (hepatorenal syndrome type 1),
the doctor should ensure that heart function and fluid-electrolyte balance are monitored during
treatment. Particular caution is required in patients with a history of heart or lung disease, as
Terlipressin acetate Altan may cause myocardial 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 kidney failure with very
high serum creatinine levels (a product of metabolism in the body), as this increases the risk of
adverse reactions.
If the patient is being treated for severe liver and kidney disease, Terlipressin acetate Altan may
increase the risk of developing sepsis (presence of bacteria in the blood and a strong systemic
response to infection) and septic shock (a serious condition occurring when severe infection leads
to low blood pressure and poor blood flow). If any of these conditions apply to the patient, the
doctor will take additional precautions.

Terlipressin acetate Altan and other medicines
Inform the doctor, pharmacist, or nurse about all medicines currently taken or recently used, as well
as any medicines the patient plans to take.
Inform the doctor immediately if the patient is taking any of the following medicines:

• medicines affecting heart rhythm (e.g. so-called beta-blockers), as their effect may be enhanced when used concomitantly with Terlipressin acetate Altan;
• antiarrhythmic drugs (used to treat irregular heart rhythm, such as quinidine or amiodarone);
• diuretics (increasing urine output, e.g. furosemide group).

Inform the doctor if the patient previously experienced sudden slowing of heart rate after
administration of certain anesthetic agents (propofol, sufentanil). Terlipressin acetate Altan may
enhance the effect of these drugs if they are administered again.

Pregnancy and breastfeeding
Terlipressin acetate Altan should only be used if the doctor considers it necessary.
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to become
pregnant, she should consult a doctor before using this medicine.
Terlipressin acetate Altan should not be used during breastfeeding, as it is unknown whether it is
excreted in breast milk.

Driving and operating machinery
No studies have been conducted on the effect of the medicine on the ability to drive or operate
machinery. However, if the patient feels unwell after receiving the injection, he or she should not
drive or operate machinery.

Elderly patients
Terlipressin acetate Altan should be used with caution in patients over 70 years of age with
existing or past cardiovascular disease.

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 impaired liver function
Dose adjustment is not required in patients with liver impairment.

Terlipressin acetate Altan contains sodium
This medicine contains 30.6 mg of sodium (the main component of table salt) in each 8.5 ml vial.
This corresponds to 1.53% of the recommended daily sodium intake in the adult diet.

3. How to use Terlipressin acetate Altan

This medicine should always be used as directed by the physician. In case of doubt, consult your
doctor or pharmacist.
Use in adults
Variceal bleeding in the upper gastrointestinal tract
The physician will determine the most appropriate dose based on the patient's body weight.
Typically, patients with body weight below 50 kg receive 1 mg (1 vial of 8.5 ml) every 4 hours.
Patients with body weight between 50 and 70 kg should receive 1.5 mg (1.5 vials of 8.5 ml) every
four hours.
Patients with body weight above 70 kg should receive 2 mg (2 vials of 8.5 ml) every 4 hours.
Treatment should continue for an additional 24 hours after bleeding has been controlled.
Treatment should not exceed 48 hours in total.
After the initial dose, if necessary (e.g. due to adverse reactions), subsequent doses of Terlipressin acetate Altan may be reduced to 1 mg (1 vial).
Hepatorenal syndrome
The usual dose is 1 mg (1 vial) of terlipressin acetate every 6 hours for at least 3 days. If after 3 days of treatment the serum creatinine concentration has decreased by less than 30% compared to baseline, consider increasing the dose to 2 mg (2 vials) every 6 hours.
Terlipressin treatment should be discontinued in patients who show no response (defined as less than 30% reduction in serum creatinine concentration on day 7 compared to baseline), or in patients who achieve a complete response (serum creatinine concentration less than 1.5 mg/dL for at least two consecutive days).
In patients showing a partial response (reduction in serum creatinine concentration of at least 30% compared to baseline, but without achieving values below 1.5 mg/dL on day 7), terlipressin treatment may be continued for up to 14 days.
In case of recurrence of hepatorenal syndrome after a complete response, terlipressin treatment may be restarted as medically advised.
Treatment of hepatorenal syndrome typically lasts 7 days, with a maximum recommended duration of 14 days.
Type 1 hepatorenal syndrome
Terlipressin acetate Altan may also be administered via intravenous infusion (continuous intravenous infusion), usually starting at an initial dose of 2 mg terlipressin acetate per day, which may then be gradually increased up to a maximum dose of 12 mg terlipressin acetate per day.
Method and route of administration
Administration of Terlipressin acetate Altan should be performed by qualified medical personnel.
Remove the vial from the packaging and ensure that no liquid remains in the upper part of the vial.
After opening, withdraw the solution with a syringe and administer by intravenous injection.
After opening, the medicine should be used immediately.
Terlipressin acetate Altan is administered by intravenous injection or infusion.
Use of a higher than recommended dose of Terlipressin acetate Altan
If an overdose is administered, a sudden increase in arterial blood pressure may occur.
Missed dose of Terlipressin acetate Altan
Do not administer a double dose to make up for a missed dose.
If you have further 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.
Inform the doctor or another healthcare professional immediately:

• If the patient develops difficulty breathing or worsening ability to breathe (symptoms of respiratory failure). These adverse reactions occur very commonly in
  patients treated for hepatorenal syndrome type 1 – affecting more
  than 1 in 10 people.

• If the patient develops signs of blood infection (sepsis and/or septic shock), which may include fever and chills or very low body temperature, paleness and/or cyanosis (bluish discoloration) of the skin, severe shortness of breath, reduced urine output, rapid heartbeat, nausea and vomiting, diarrhoea, fatigue and weakness, and dizziness. These adverse reactions occur commonly in patients treated for hepatorenal syndrome type 1 – affecting up to 1 in 10 people.

Other adverse reactions which may occur with varying frequency depending on the patient's condition.
Very commonly (may affect more than 1 in 10 treated patients):
If the patient has hepatorenal syndrome type 1:

• Shortness of breath (dyspnoea)

Commonly (may affect up to 1 in 10 patients):

• headache
• bradycardia (very slow heart rate)
• increased blood pressure
• peripheral vasoconstriction (inadequate blood flow to tissues) causing paleness
• transient abdominal pain
• transient diarrhoea

If the patient has hepatorenal syndrome type 1:

• presence of fluid in the lungs (pulmonary oedema)
• breathing difficulties (acute respiratory distress syndrome)

Uncommonly (may affect up to 1 in 100 patients)

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

If the patient has gastrointestinal bleeding from ruptured oesophagogastric varices:

• presence of fluid in the lungs (pulmonary oedema)
• breathing difficulties (acute respiratory distress syndrome)

Rarely (may affect up to 1 in 1000 patients)
If the patient has gastrointestinal bleeding from ruptured oesophagogastric varices:

• shortness of breath (dyspnoea)

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

• heart failure. Symptoms include shortness of breath, fatigue and ankle swelling
• cardiac arrhythmias 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 output) may lead to decreased sodium levels in the blood (hyponatraemia), unless fluid balance is monitored and controlled.
During clinical trials in patients with hepatorenal syndrome treated with terlipressin, an increased risk of cardiovascular adverse reactions was observed, such as reduced blood flow to the heart (myocardial ischaemia), irregular heartbeat (arrhythmia), reduced blood flow to the intestines (intestinal ischaemia), or circulatory overload (manifested by increased blood pressure, headache, difficulty breathing, or distended neck veins).
During clinical trials and after marketing authorization, several cases of cardiac arrhythmias have been reported.
After marketing authorization, several cases of skin ischaemia and necrosis, unrelated to the injection site, have been reported.

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform a doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 4921 301, fax: +48 22 4921 309,
website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the responsible entity.
Reporting adverse reactions contributes to further enhancing medicine safety information.

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 stated month.
After first opening, the product should be used immediately.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the packaging and other information

What Terlipressin acetate Altan contains

• The active substance is terlipressin acetate. One 8.5 ml vial of injection solution contains 1 mg of terlipressin acetate, equivalent to 0.85 mg of terlipressin.

1 ml of injection solution contains 0.12 mg of terlipressin acetate, equivalent to 0.1 mg of terlipressin.

• The other components 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, colourless injection solution.
One pack contains 5 vials made of colourless glass (type I), each containing 8.5 mL of solution, in a cardboard box.
Marketing Authorisation Holder:
Altan Pharmaceuticals, S.A.
C/ Cólquide Nº 6, Portal 2, 1ª Planta, Oficina F. Edificio Prisma
Las Rozas, 28230 Madrid
Spain
Manufacturer:
Altan Pharmaceuticals S.A.
Avda. de la Constitución, 198-199
Polígono Industrial Monte Boyal
45950 Casarrubios del Monte (Toledo)
Spain