TERLIPRESINA ALTAN 1 mg INJECTABLE SOLUTION

Introduction

PACKAGE LEAFLET: INFORMATION FOR THE USER

Terlipresina Altan 1 mg solution for injection EFG

(Terlipresina acetate)

Read all of this leaflet carefully before you start 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, 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 signs of illness 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 pack and other information

1. What is Terlipresina Altan and what is it used for.
2. What you need to know before you use Terlipresina Altan.
3. How to use Terlipresina Altan.
4. Possible side effects.
5. Storing Terlipresina Altan.

1. Contents of the pack and further information.

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

Terlipresina Altan is a solution for intravenous injection that comes in a 8.5 ml glass ampoule containing 1 mg of terlipresina acetate (equivalent to 0.85 mg of terlipresina base). The concentration of the solution is 0.12 mg of terlipresina acetate/ml.

Terlipresina Altan belongs to a group of medicines that decrease the pressure in the liver veins (portal venous pressure) in patients with high blood pressure in the vein that carries blood to the liver (portal hypertension). Terlipresina acts by constricting the blood vessels (vasoconstriction) in this area, helping to control bleeding from esophageal and stomach varices (esophagogastic) when it occurs.

Terlipresina Altan also helps to improve blood circulation in the kidneys, helping to recover renal function in patients with Hepatorenal Syndrome (a type of kidney failure in patients with severe liver dysfunction).

Terlipresina Altan is indicated for the treatment of:

• Gastrointestinal bleeding due to rupture of esophagogastic varices.

Emergency treatment of hepatorenal syndrome type 1, defined according to the CIA (International Ascites Club) criteria.

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

Do not use Terlipresina Altan

• if you are allergic to terlipresina or 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), coronary artery disease, or your heart pumps less blood than it should (heart failure), as you are at greater risk of suffering from heart-related side effects.
• if you have cerebral vascular disease, peripheral vascular disease, or vascular disease of the intestines, as you are more likely to suffer from side effects related to lack of blood flow in these locations.
• if you have swelling of the legs due to poor circulation in the veins or if you are overweight (obesity), as you are at greater risk of suffering from decreased blood flow to the skin (ischemia) and even, in isolated cases, death of skin cells (necrosis).
• if you have a severe generalized infection with a drop in blood pressure (septic shock).
• if you have impaired kidney function (renal insufficiency).
• if you have asthma or respiratory problems (respiratory insufficiency).
• in patients over 70 years old with current or past cardiovascular disease.
• in children because experience is limited in this age group.

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

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

The injection should be administered exclusively by the intravenous routeto avoid local skin necrosis due to the product leaking into the skin.

Terlipresina Altan may increase the risk of developing respiratory failure that 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 (hepatorenal syndrome type 1), your doctor should 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 (decreased 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 failures and/or renal failure with very high creatinine levels in the blood, as it increases the risk of adverse outcomes.

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

Using Terlipresina Altan with other medicines

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

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

• Betablockers (medicines to slow down the heart rate), as their effects may increase if used at the same time as Terlipresina Altan
• Antiarrhythmics (used to treat irregular heartbeats), such as quinidine or amiodarone.
• Diuretics (used to increase urine production, such as furosemide).

Tell your doctor if you have previously experienced a sudden slowing of the heart rate with certain anesthetics (propofol, sufentanil). Terlipresina Altan may increase 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 should not be administered if you are pregnant, as it may harm your baby.

Terlipresina Altan should not be administered during breastfeeding, as it is not known whether Terlipresina Altan can pass into breast milk.

Driving and using machines

No studies have been conducted on the effects of terlipresina on the ability to drive or use machines.

Use in the elderly

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

Children

Special 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, it is not necessary to adjust the dose of terlipresina.

Important information about some of the ingredients of Terlipresina Altan

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

3. How to use Terlipresina Altan

Follow exactly the administration instructions of this medicine indicated by your doctor. In case of doubt, consult your doctor again.

The recommended dosein adults is:

Gastrointestinal bleeding due to rupture of esophagogastic varices

It will be established by the doctor, depending on the patient's weight.

Generally, if the patient's weight is less than 50 kilograms, 1 milligram (1 ampoule of 8.5 ml) will be administered every four hours. In patients with a body weight between 50 and 70 kilograms, 1.5 milligrams (1.5 ampoules of 8.5 ml) will be administered every four hours. In patients with a body weight of more than 70 kilograms, 2 milligrams (2 ampoules of 8.5 ml) will be administered every 4 hours.

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

Hepatorenal syndrome

It is recommended to start treatment with 1 mg of terlipresina (1 ampoule) 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 baseline value, it should be considered to double the dose to 2 mg (2 ampoules) every 6 hours.

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

In patients who present an incomplete response (decrease in serum creatinine of at least 30% compared to the baseline value but without reaching a value below 1.5 mg/dl on day 7), treatment with terlipresina may be maintained for up to a maximum of 14 days.

In the event of a relapse of hepatorenal syndrome after a complete response, treatment with terlipresina may be restarted according to medical criteria.

In most clinical studies that support the use of terlipresina for the treatment of hepatorenal syndrome, human albumin was administered simultaneously in doses of 1 g/kg body weight on the first day and then 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.

Hepatorenal syndrome type 1

Terlipresina Altan may also be administered as a drip (continuous intravenous infusion) starting normally with 2 mg of terlipresina acetate per day and increasing stepwise up to a maximum of 12 mg of terlipresina acetate per day.

Method of use and route of administration

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

Remove an ampoule from the packaging and ensure that no liquid remains in the head of the ampoule.

Once the ampoule is opened, extract the solution with a syringe and inject it strictly intravenously.

The drug, once opened, must be used immediately.

Terlipresina Altan is injected or infused intravenously.

If you use more Terlipresina Altan than you should

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

In case of overdose or accidental ingestion, consult your doctor, pharmacist, or call the Toxicology Information Service, phone 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 forgotten doses.

If you have any further questions about 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 another healthcare professional immediately:

• If you develop breathing difficulties or experience a worsening of your respiratory capacity (signs or symptoms of respiratory failure). This side effect is very common if you are being treated for hepatorenal syndrome type 1 - 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 or blue-tinged skin, severe shortness of breath, decreased urine production, rapid heart rate, nausea and vomiting, diarrhea, fatigue and weakness, and dizziness. This side effect is common if you are being treated for hepatorenal syndrome type 1: it may affect up to 1 in 10 people.

Other side effects that may occur with different frequencies depending on the disease being treated.

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

If you have hepatorenal syndrome type 1:

• Breathing difficulties (dyspnea)

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

• Headache
• Bradycardia (very slow heart rate)
• Increased blood pressure (hypertension)
• Peripheral vasoconstriction (inadequate blood flow to tissues) resulting in pallor
• Transient stomach pain
• Transient diarrhea

If you have hepatorenal syndrome type 1:

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

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

• Decreased sodium in the blood if fluid balance is not controlled
• Irrregular heart rhythm
• Increased heart rate
• Chest pain
• Myocardial infarction (heart attack)
• Inadequate blood flow to the intestines
• Peripheral cyanosis (blue-tinged skin due to lack of oxygen)
• Hot flashes
• Transient nausea
• Transient vomiting
• Skin necrosis (tissue damage) at the injection site

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

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

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

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

Difficulty breathing (dyspnea)

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

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

The antidiuretic effect of the drug (decrease in urine production) may cause a decrease in sodium in the blood (hyponatremia) unless fluid balance is controlled.

Patient with Hepatorenal Syndrome treated with terlipresina presented during clinical trials a higher risk of suffering from cardiovascular side effects, such as decreased blood flow to the heart (myocardial ischemia), irregular heart rhythm (arrhythmia), decreased blood flow to the intestine (intestinal ischemia), or circulatory overload (which may manifest as increased blood pressure, headache, difficulty breathing, or increased size of the neck veins).

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

During post-marketing experience, several cases of skin ischemia and skin necrosis have been reported in areas of the skin distinct from the injection site of Terlipresina Altan.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if it is possible side effects not listed in this leaflet. You can also report them directly through the national system of Pharmacovigilance of Medicines for Human Use: www.notificaRAM.es.

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

5. Storing Terlipresina Altan

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 packaging after Exp. The expiry date is the last day of the month stated.

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 no longer required. This will help protect the environment.

6. Packaging Contents and Additional Information

Composition of Terlipresina Altan

• The active ingredient is: Terlipresina acetate. Each ampoule contains 1 mg of terlipresina acetate in 8.5 ml of injectable solution, equivalent to 0.85 mg of terlipresina. 1 ml of injectable solution contains 0.12 mg of terlipresina acetate, equivalent to 0.1 mg of terlipresina.
• The other components are: sodium chloride, glacial acetic acid, sodium acetate trihydrate, and water for injectable preparations.

Appearance of the Product and Packaging Contents

Terlipresina Altan is a clear and colorless solution.

Terlipresina Altan is supplied in packages containing 5 ampoules of 8.5 ml each.

Marketing Authorization Holder

Altan Pharmaceuticals S.A.

C/ Cólquide, Nº 6, Portal 2, 1ª Planta, Oficina 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 Last Revision of this Leaflet: March 2023

Detailed and updated information on this medication is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS)http://www.aemps.gob.es