PATIENT INFORMATION LEAFLET

Terlipresina Altan 1 mg injectable solution EFG

(Terlipresina acetate)

Read this leaflet carefully before you start taking this medicine, as it contains important information for you

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

6. Contents of the pack and additional information.

Terlipresina Altan is a solution for intravenous injection that is presented in a glass vial of 8.5 ml 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 medications that reduces 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). Terlipressin acts by constricting blood vessels (vasoconstriction) in this area, helping to control bleeding from esophageal and stomach varices (esophagogastroduodenal) when it occurs.

Terlipresina Altan also contributes to improving blood circulation in the kidney, 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:

• Digestive hemorrhages due to rupture of esophagogastroduodenal varices.

Emergency treatment of type 1 Hepatorenal Syndrome, defined according to the CIA (International Ascites Club) criterion.

No use Terlipresina Altan

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

Advertencias y precauciones

Consulte a su médico:

• if you have high blood pressure (hypertension).
• if you have heart problems, such as irregular heartbeat (arrhythmias), heart blood flow deficiency (coronary disease), or if 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 a blood flow deficiency in the brain (cerebral vascular disease), poor blood flow in the legs or arms (peripheral vascular disease), or intestinal blood vessel disease, as you have a higher risk of experiencing adverse effects related to blood flow deficiency in these locations.
• if you have swelling of the legs due to poor venous circulation or if you are overweight (obesity), as you have a higher risk of experiencing blood flow reduction in the skin (ischemia) and, in isolated cases, skin cell death (cutaneous necrosis).
• if you have a severe generalized infection with a drop in blood pressure (septic shock).
• if you have altered kidney function (renal insufficiency).
• if you have asthma or respiratory problems (respiratory insufficiency).
• in patients over 70 years with current cardiovascular disease or a history of the same.
• in children, as experience is limited in this age group.

Advertencias y precauciones

Consulte a su médico:

Consult your doctor, pharmacist, or nurse before starting to use Terlipresina Altan.

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

The injection must be administeredexclusively by intravenous routeto avoid skin cell death (cutaneous necrosis) due to the product leaking onto the skin.

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

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

If you receive treatment for severe liver and kidney disease, Terlipresina Altan may increase the risk of developing sepsis (bacteria in the blood and an extreme response of the body to an infection) and septic shock (a severe condition that occurs 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 medications

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication.

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

• Beta-blockers (medications to slow the heart rate), as their effects may be increased if you use them at the same time as Terlipresina Altan.
• Antiarrhythmics (used to treat irregular heartbeats), such as quinidine or amiodarone.
• Diuretics (used to increase urine elimination, such as furosemide).

Inform your doctor if you have had a sudden slowing of the heart rate with certain anesthetics (propofol, sulfentanil) in the past. Terlipresina Altan may increase the effect of these medications if they are administered again.

Embarazo, lactancia y fertilidad

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

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

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

Conducción y uso de máquinas

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

Uso en ancianos

Terlipresina Altan should be used with caution in patients over 70 years with current cardiovascular disease or a history of the same.

Niños

Special caution should be exercised in the treatment of children, as experience is limited in this age group.

Uso en personas con problemas en el hígado

In patients with liver problems, it is not necessary to adjust the dose of terlipressin.

Información importante sobre algunos de los componentes de Terlipresina Altan

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

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

The recommended dosein adults is:

Upper gastrointestinal bleeding due to esophageal variceal rupture

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 vial of 8.5 ml) will be administered every 4 hours. In patients with a body weight between 50 and 70 kilograms, 1.5 milligrams (1.5 vials of 8.5 ml) will be administered every 4 hours. In patients with a body weight of more than 70 kilograms, 2 milligrams (2 vials of 8.5 ml) will be administered every 4 hours.

The treatment must be continued 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 Terlipresin Altan when necessary, for example, due to the appearance of adverse reactions.

Heptorenal syndrome

It is recommended to start treatment with 1 mg of terlipresin (1 vial) every 6 hours for at least 3 days. If after 3 days of treatment the serum creatinine decrease is less than 30% compared to the baseline value, the dose should be evaluated to be doubled to 2 mg (2 vials) every 6 hours.

Treatment with terlipresin 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 2 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 terlipresin may be continued until a maximum of 14 days.

In the case of recurrence of heptorenal syndrome after a complete response, treatment with terlipresin may be restarted according to medical criteria.

In most clinical studies that support the use of terlipresin for the treatment of heptorenal syndrome, human albumin was administered simultaneously in doses of 1 g/kg of body weight on the first day and subsequent doses of 20-40 g/day.

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

Heptorenal syndrome type 1

Terlipresin Altan may also be administered in the form of a drip (intravenous continuous infusion) starting with 2 mg of terlipresin acetate per day and increasing in a stepwise manner to a maximum of 12 mg of terlipresin acetate per day.

Form of use and route of administration

Terlipresin Altan administration must be performed by qualified healthcare personnel.

Remove a vial from the packaging and ensure that no liquid remains in the vial head.

Once the vial is opened, extract the solution with a syringe and inject intravenously.

The drug once opened must be used immediately.

Terlipresin Altan is injected or infused intravenously.

If you use more Terlipresin Altan than you should

If you are administered more Terlipresin Altan than recommended, there is an increased risk of severe cardiovascular effects, including a hypertensive crisis.

In case of overdose or accidental ingestion, consult your doctor, pharmacist, or call the Toxicological Information Service, phone 915 620 420 indicating the medication and the amount ingested.

If you forgot to use Terlipresin Altan

Do not use a double dose to compensate for the missed doses.

If you have any other doubts about the use of this medication, ask your doctor, pharmacist, or nurse.

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

Inform your doctor or another healthcare professional immediately:

- If you develop respiratory difficulties or experience a worsening of respiratory capacity (signs or symptoms of respiratory insufficiency). This side effect is very frequent if you are 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 blue skin, severe shortness of breath, urinating less than usual, rapid heartbeats, nausea and vomiting, diarrhea, fatigue and weakness, and a feeling of dizziness. This side effect is frequent if you are being treated for type 1 hepatorenal syndrome: it may affect up to 1 in 10 people.

Other side effects that may appear with varying frequency depending on the disease you have.

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

If you have type 1 hepatorenal syndrome:

• Difficulty breathing (dyspnea)

Frequent 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 (ischemia)) resulting in pallor.
• Transient stomach pain.
• Transient diarrhea.

If you have type 1 hepatorenal syndrome:

• Pulmonary edema (fluid in the lungs)
• Difficulty breathing (respiratory difficulty)

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

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

If you have esophageal and gastric variceal hemorrhages:

• Pulmonary edema (fluid in the lungs)
• Difficulty breathing (respiratory difficulty)

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

If you have esophageal and gastric variceal hemorrhages:

Difficulty breathing (dyspnea)

Unknown frequency(cannot be estimated from available data)

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

The diuretic effect of the drug (decreased urine production) may cause decreased sodium in the blood unless fluid balance is controlled.

Patients with hepatorenal syndrome treated with terlipressin presented a higher risk of experiencing cardiovascular side effects, such as myocardial ischemia, arrhythmia, intestinal ischemia, or circulatory overload (may manifest as increased blood pressure, headache, difficulty breathing, or increased size of the neck veins) during clinical trials.

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

During post-marketing experience, several cases of cutaneous ischemia and skin cell death (necrosis) in areas of the skin other than the injection site of Terlipressin Altan have been reported.

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear 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 contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the packaging after "Cad." The expiration date is the last day of the month indicated.

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

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications you no longer need. This will help protect the environment.

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, acid, acetate sodium trihydrate, and water for injectable preparations.

Appearance of the product and contents of the packaging

Terlipresina Altan is a clear and colorless solution.

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

Holder of the Marketing Authorization

Altan Pharmaceuticals S.A.

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

Las Rozas, 28230 Madrid

Responsible for manufacturing

Altan Pharmaceuticals S.A.

Constitution Avenue 198-199. Monte Boyal Industrial Park

45950 Casarrubios del Monte (Toledo)

Last review date of this leaflet: March 2023

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