Terlipressin Altan 1 mg solution for injection EFG

Package leaflet: Information for the user

Introduction

PACKAGE LEAFLET: INFORMATION FOR THE USER

Terlipresina Altan 1 mg injection solution EFG

(Terlipressin acetate)

Read the entire leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only and must not be given to other people, even if they have the same symptoms, as it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are adverse effects not listed in this leaflet. See section 4.

Leaflet contents:

1. What Terlipresina Altan is and what it is used for.

2. What you need to know before using Terlipresina Altan.

3. How to use Terlipresina Altan.

4. Possible adverse effects.

5. How to store Terlipresina Altan.

6. Contents of the container and other information.

1. What Terlipresina Altan is and what it is used for

Terlipresina Altan is an intravenous solution supplied in an 8.5 ml glass ampoule containing 1 mg of terlipressin acetate (equivalent to 0.85 mg of terlipressin base). The concentration of the solution is 0.12 mg of terlipressin acetate/ml.

Terlipresina Altan belongs to a group of medicines that reduce pressure in the liver veins (portal venous pressure) in patients with high blood pressure in the vein carrying blood to the liver (portal hypertension). Terlipresin acts by narrowing the blood vessels (vasoconstriction) in this area, helping to control bleeding from oesophageal and gastric varices (oesophagogastric varices) when it occurs.

Terlipresina Altan also contributes to improving blood circulation in the kidney, thereby helping to restore kidney function in patients with Hepatorenal Syndrome (a type of kidney failure occurring in patients with severe liver dysfunction).

Terlipresina Altan is indicated for the treatment of:

• Gastrointestinal bleeding due to rupture of oesophagogastric varices.

• Emergency treatment of type 1 hepatorenal syndrome, as defined by the criteria of the International Ascites Club (IAC).

2. What you need to know before using Terlipresina Altan.

Do not use Terlipresina Altan

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

Warnings and precautions

Consult your doctor:

• if you have high blood pressure (hypertension).
• if you have heart problems, such as irregular heartbeat (arrhythmias), reduced blood supply to the heart (coronary artery disease), or your heart pumps less blood than it should (heart failure), as you have a higher risk of experiencing heart-related adverse effects.
• if you have reduced blood flow to the brain (cerebrovascular disease), poor blood circulation in the legs or arms (peripheral vascular disease), or intestinal blood vessel disorders, as you are more likely to experience adverse effects related to reduced blood flow in these areas.
• if you have leg swelling due to poor venous circulation or suffer from excess weight (obesity), as you have an increased risk of reduced blood flow to the skin (ischemia) and, in isolated cases, even death of skin cells (cutaneous necrosis).
• if you have a severe generalized infection with low blood pressure (septic shock).
• if you have impaired kidney function (renal failure).
• if you have asthma or respiratory problems (respiratory insufficiency).
• in patients over 70 years of age with current or past cardiovascular disease.
• in children, as experience is limited in this age group.

Consult your doctor, pharmacist, or nurse before starting treatment with Terlipresina Altan.

Terlipresina Altan must be used under the supervision of a specialist in units equipped to regularly monitor your blood pressure, cardiac function, blood parameters, and fluid balance.

The injection must be administered exclusively by intravenous route to avoid death of skin cells (cutaneous necrosis) at the injection site due to leakage of the drug into the skin.

Terlipresina Altan may increase the risk of developing respiratory failure, which can be fatal. If you experience difficulty breathing or symptoms of fluid overload before or during treatment with Terlipresina Altan, inform your doctor immediately.

If you are being treated for severe liver and kidney disease (type 1 hepatorenal syndrome), your doctor must ensure that your cardiac function and fluid and electrolyte balance are monitored during treatment. Special care is required if you have pre-existing heart or lung disease, as Terlipresina Altan may induce cardiac ischemia (reduced blood flow to the heart) and respiratory failure (severe breathing difficulties). Treatment with Terlipresina Altan should be avoided if you have liver failure with multiple organ dysfunction and/or renal failure with very high levels of creatinine (a waste product) in the blood, as this increases the risk of adverse outcomes.

If you are receiving treatment for severe liver and kidney disease, Terlipresina Altan may increase the risk of developing sepsis (bacteria in the blood and an extreme systemic response to infection) and septic shock (a serious condition occurring when a severe infection causes low blood pressure and reduced blood flow). Your doctor will take additional precautions in your case.

Use of Terlipresina Altan with other medicines

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

It is very important to inform your doctor if you are being treated with:

• Beta-blockers (medicines to slow the heart rate), as their effects may be increased when used together with Terlipresina Altan
• Antiarrhythmics (used to treat irregular heartbeats), such as quinidine or amiodarone.
• Diuretics (used to increase urine output, such as those in the furosemide group).

Inform your doctor if you have previously experienced sudden slowing of the heartbeat with certain anesthetics (propofol, sufentanil). Terlipresina Altan may enhance the effect of these drugs if they are administered again.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Terlipresina Altan must not be given if you are pregnant, as it may cause harm to your baby.

Terlipresina Altan must not be administered during breastfeeding, as it is unknown whether Terlipresina Altan passes into breast milk.

Driving and using machines

No studies on the effects of terlipressin on the ability to drive or operate machinery have been conducted.

Use in the elderly

Terlipresina Altan should be used with caution in patients over 70 years of age with current or past cardiovascular disease.

Children

Particular caution should be exercised when treating children, as experience is limited in this age group.

Use in patients with liver problems

In patients with liver problems, no dose adjustment of terlipressin is necessary.

Important information about some of the ingredients of Terlipresina Altan

Patients on low-sodium diets should be aware that this medicine contains 30.6 mg (1.33 mmol) of sodium per vial.

3. How to use Terlipresina Altan

Follow exactly the administration instructions for this medicine as given by your doctor. If in doubt, consult your doctor again.

Recommended dose in adults:

Gastrointestinal bleeding due to rupture of esophagogastric varices

The dose will be determined by the physician, depending on the patient's weight.

Generally, if the patient's weight is less than 50 kilograms, 1 milligram (1 vial of 8.5 ml) should be administered every four hours. In patients with a body weight between 50 and 70 kilograms, 1.5 milligrams (1.5 vials of 8.5 ml) should be administered every four hours. In patients with a body weight over 70 kilograms, 2 milligrams (2 vials of 8.5 ml) should be administered every four hours.

Treatment should continue for 24 consecutive hours until the bleeding has been controlled or for a maximum period of 48 hours. After the initial injection, subsequent doses may be reduced to 1 milligram (1 vial) of Terlipresina Altan when necessary, for example, due to the occurrence of adverse reactions.

Hepatorenal syndrome

It is recommended to initiate treatment with 1 mg of terlipressin (1 vial) every 6 hours for at least 3 days. If after 3 days of treatment the reduction in serum creatinine is less than 30% compared to baseline value, doubling the dose to 2 mg (2 vials) every 6 hours should be considered.

Treatment with terlipressin should be discontinued if there is no response to treatment (defined as less than a 30% reduction in serum creatinine by day 7 compared to baseline) or in patients who achieve a complete response (serum creatinine values below 1.5 mg/dl for at least two consecutive days).

In patients who show an incomplete response (a reduction in serum creatinine of at least 30% compared to baseline but not reaching a value below 1.5 mg/dl by day 7), treatment with terlipressin may be continued for up to a maximum of 14 days.

In case of recurrence of hepatorenal syndrome after a complete response, treatment with terlipressin may be restarted according to medical judgment.

In most clinical studies supporting the use of terlipressin for the treatment of hepatorenal syndrome, human albumin was administered concomitantly at a dose of 1 g/kg body weight on the first day, followed by doses of 20–40 g/day.

The usual duration of treatment for hepatorenal syndrome is 7 days, and the maximum recommended duration is 14 days.

Type 1 hepatorenal syndrome

Terlipresina Altan may also be administered as a continuous intravenous infusion, typically starting with 2 mg of terlipressin acetate per day, increasing stepwise up to a maximum of 12 mg of terlipressin acetate per day.

Method of use and route of administration

Administration of Terlipresina Altan must be performed by qualified healthcare personnel.

Remove one vial from the package and ensure that no liquid remains in the neck of the vial.

Once the vial is opened, withdraw the solution with a syringe and inject strictly by intravenous route.

The drug should be used immediately after opening.

Terlipresina Altan is injected or infused intravenously.

If you use more Terlipresina Altan than you should

If more Terlipresina Altan is administered than recommended, there is an increased risk of serious circulatory effects, including hypertensive crisis.

In case of overdose or accidental ingestion, contact your doctor, pharmacist, or call the Toxicology Information Service at telephone 915 620 420, indicating the medicine and the amount ingested.

If you forget to use Terlipresina Altan

Do not use a double dose to make up for missed doses.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

Immediately inform your doctor or another healthcare professional:

• If you develop breathing difficulties or experience a worsening of respiratory function (signs or symptoms of respiratory failure). This adverse effect is very common in patients being treated for type 1 hepatorenal syndrome – it may affect more than 1 in 10 people.

• If you develop signs or symptoms of blood infection (sepsis/septic shock), which may include fever and chills or very low body temperature, pale and/or bluish skin, severe shortness of breath, reduced urination, rapid heartbeat, nausea and vomiting, diarrhea, fatigue and weakness, or dizziness. This adverse effect is common in patients being treated for type 1 hepatorenal syndrome – it may affect up to 1 in 10 people.

Other adverse effects may occur with varying frequency depending on the condition being treated.

Very common adverse effects, which may affect more than 1 in 10 people:

If you have type 1 hepatorenal syndrome:

• Difficulty breathing (dyspnea)

Common adverse effects, which may affect up to 1 in 10 people:

• Headache
• Bradycardia (very slow heart rate)
• Increased blood pressure (hypertension)
• Peripheral constriction of blood vessels (inadequate blood flow to tissues [ischemia]), resulting in paleness
• Transient stomach pain
• Transient diarrhea

If you have type 1 hepatorenal syndrome:

• Fluid in the lungs (pulmonary edema)
• Breathing difficulties (respiratory distress)

Uncommon adverse effects, which may affect up to 1 in 100 people:

• Decreased sodium levels in the blood if fluid balance is not controlled
• Irregular heartbeat
• Increased heart rate
• Chest pain
• Myocardial infarction (heart attack)
• Inadequate blood flow to the intestines
• Peripheral cyanosis (bluish discoloration of the skin caused by lack of oxygen)
• Hot flushes
• Transient nausea
• Transient vomiting
• Skin necrosis (tissue damage) at the injection site

If you have gastrointestinal bleeding due to rupture of esophagogastric varices:

• Fluid in the lungs (pulmonary edema)
• Breathing difficulties (respiratory distress)

Rare adverse effects, which may affect up to 1 in 1,000 people:

If you have gastrointestinal bleeding due to rupture of esophagogastric varices:

• Difficulty breathing (dyspnea)

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

• Heart failure. Symptoms include shortness of breath, fatigue, and swelling of the ankles
• Torsade de pointes (a serious cardiac event)
• Skin necrosis (tissue damage)
• Uterine contractions
• Decreased uterine blood flow

The drug's antidiuretic effect (reduced urine output) may lead to decreased sodium levels in the blood (hyponatremia) unless fluid balance is controlled.

Patients with Hepatorenal Syndrome treated with terlipressin showed, during clinical trials, an increased risk of cardiovascular adverse effects such as reduced blood flow to the heart (myocardial ischemia), irregular heartbeat (arrhythmia), reduced blood flow to the intestine (intestinal ischemia), or circulatory overload (which may present as increased blood pressure, headache, difficulty breathing, or distended neck veins).

During clinical trials and post-marketing experience, several cases of serious irregular heartbeats (cardiac arrhythmias) have been reported.

During post-marketing experience, several cases of impaired blood supply to the skin (cutaneous ischemia) and death of skin cells (cutaneous necrosis) in areas of skin other than the terlipressin injection site have been reported.

Reporting of adverse effects

If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are possible adverse effects not listed in this leaflet. You can also report them directly via the national Pharmacovigilance System for Human Medicines: www.notificaRAM.es.

By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Terlipressin Altan

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

Do not use this medicine after the expiry date stated on the packaging following Exp. The expiry date refers to the last day of the month indicated.

Store in a refrigerator (between 2°C and 8°C). Keep in the original packaging to protect from light.

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

6. Contents of the pack and other information

Composition of Terlipresin Altan

• The active substance is: Terlipressin acetate. Each vial contains 1 mg of terlipressin acetate in 8.5 ml of injectable solution, equivalent to 0.85 mg of terlipressin. 1 ml of injectable 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, and water for injections.

Nature of the product and pack size

Terlipresin Altan is a clear, colourless solution.

Terlipresin Altan is supplied in packs containing 5 vials of 8.5 ml each.

Marketing Authorization Holder

Altan Pharmaceuticals S.A.

C/ Cólquide, Nº 6, Portal 2, 1st Floor, Office F. Edificio Prisma

Las Rozas, 28230 Madrid

Manufacturer

Altan Pharmaceuticals S.A.

Avda. Constitución 198-199. Pol. Industrial Monte Boyal

45950 Casarrubios del Monte (Toledo)

Date of the most recent revision of this summary: March 2023

Detailed and up-to-date information on this medicine is available on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es