Prospecto: information for the user

Terlipresina acetate EVER Pharma 1 mg injectable solution

terlipresina acetate

Read this prospectus carefully before starting to use this medicine, as it contains important information for you.

• Keep this prospectus, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• If you experience adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this prospectus. See section 4.

Content of theprospectus

1. What isTerlipresina acetate EVER Pharmaand for what it is used

2. What you need to know before starting to useTerlipresina acetate EVER Pharma

3. How to useTerlipresina acetate EVER Pharma

4. Possible adverse effects

5. Storage ofTerlipresina acetate EVER Pharma

6. Contents of the package and additional information

Terlipresina acetate EVER Pharmacontains the active ingredient terlipressin, which is a synthetic pituitary hormone (this hormone is normally produced by the pituitary gland located in the brain).

It will be administered via an injection into a vein.

Terlipresina acetate EVER Pharmais used for the treatment of:

• bleeding from dilated (enlarged) veins in the tube that carries food to your stomach (called bleeding esophageal varices).

• emergency treatment of type 1 hepatorenal syndrome (rapidly progressive kidney failure) in patients with liver cirrhosis (liver scarring) and ascites (abdominal fluid accumulation).

No useTerlipresina acetato EVER Pharma:

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

-if you are pregnant.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before receivingTerlipresina acetato EVER Pharma:

-if you have a severe infection known as septic shock

-if you have asthma or other respiratory diseases

-if you have uncontrolled high blood pressure, insufficient blood flow to the heart (e.g. angina pectoris)

-if you have previously had a heart attack (myocardial infarction), or if you havehardening of the arteries (arteriosclerosis)

-if you have seizures (attacks)

-if you have irregular heartbeats (cardiac arrhythmias) or a history ofprolongation of the QT interval (alterations in heart rhythm)

-if you have poor blood circulation to the brain (e.g. stroke) or to your extremities (peripheral vascular disease)

-if you have impaired kidney function (renal insufficiency)

-if you have altered levels of salts (electrolytes) in the blood

-if you have a decrease in the amount of fluid in the circulation or have lost a large amount of blood

-if you are over 70 years old.

If you have any of these conditions (or are unsure), inform your doctor, pharmacist, or nurse before receiving Terlipresina acetato EVER Pharma.

During treatment with Terlipresina acetato EVER Pharma, ensure that your heart function and fluid and electrolyte balance are controlled.

Terlipresina acetato EVER Pharma may increase the risk of developing severe respiratory failure(severe breathing difficulties)that can be fatal. If you experience breathing difficulties, or symptoms of fluid overload, before or during treatment with Terlipresina acetato EVER Pharma, inform your doctor immediately.

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

If you are receiving treatment for a severe liver and kidney disease, Terlipresina acetato EVER Pharma 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.

Children and adolescents

Terlipresina acetato EVER Pharma is not recommended for use in children and adolescents due to insufficient experience.

Use ofTerlipresina acetato EVER Pharmawith other medications

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

Inform your doctor immediately if you are taking any of the following medications:

• medications that affect heart rate (e.g. beta-blockers, sufentanil, or propofol)
• medications that can cause irregular heartbeats (arrhythmias) such as the following:

• antiarrhythmic medications known as class IA (quinidine, procainamide, disopyramide) and class III (amiodarone, sotalol, ibutilide, dofetilide)

• erythromycin (an antibiotic)

• antihistamines (used primarily to treat allergies, but also present in certain cough and cold preparations)

• tricyclic antidepressants used to treat depression

• medications that can alter the level of salt or electrolytes in the blood, especially diuretics (used to eliminate fluids, in the treatment of hypertension and heart failure)

Pregnancy and breastfeeding

Inform your doctor if you are pregnant or breastfeeding, think you may be pregnant, or intend to become pregnant.

Terlipresina acetato EVER Pharma should not be usedduring pregnancy.

The presence of Terlipresina acetato EVER Pharma in breast milk is unknown. Therefore, the potential effects on the infant are unknown. Consult your doctor to determine the potential risk to the infant.

Driving and operating machinery

No studies have been conducted on the effects on the ability to drive or operate machinery.However, if you do not feel well after receiving the injection, do not drive or operate machinery.

Terlipresina acetato EVER Pharma contains sodium

This medication contains 3.68 mg of sodium (main component of table salt/for cooking) in each ml. This is equivalent to 0.18% of the recommended daily maximum sodium intake for an adult.

This medication is injected or infused intravenously by your doctor. Your doctor will decide on the most appropriate dose for you and will continuously monitor your heart and blood circulation during administration. Consult your doctor for additional information on its use.

Use in adults

1. Short-term management of bleeding esophageal varices.

Initially, 1-2 mg of terlipressin acetate (5-10 ml of Terlipressin acetate EVER) is administered via injection into a vein. The dose will depend on your body weight.

After the initial injection, the dose may be reduced to 1 mg of terlipressin acetate (5 ml) every 4-6 hours.

2. Type 1 hepatorenal syndrome

The normal injection dose is 1 mg of terlipressin acetate every 6 hours, for at least 3 days. If the serum creatinine reduction is less than 30% after 3 days of treatment, your doctor should consider doubling the dose to 2 mg every 6 hours.

You may also be administered Terlipressin acetate EVER Pharma as a drip (intravenous continuous infusion) starting with a normal dose of 2 mg of terlipressin acetate per day and increasing gradually to a maximum of 12 mg of terlipressin acetate per day.

If there is no response to Terlipressin acetate EVER Pharma, or if patients have a complete response, treatment with Terlipressin acetate EVER should be discontinued.

When a reduction in serum creatinine is observed, treatment with Terlipressin acetate EVER Pharma should be continued for a maximum of 14 days.

Use in elderly individuals

If you are over 70 years old, consult your doctor before receiving Terlipressin acetate EVER Pharma.

Use in patients with kidney problems

Terlipressin acetate EVER Pharma should be used with caution in patients with long-term renal insufficiency.

Use in patients with liver problems

No dose adjustment is required in patients with hepatic problems.

Use in children and adolescents

Terlipressin acetate EVER Pharma is not recommended for use in children and adolescents due to insufficient experience.

Duration of treatment

The use of this medication is limited to 2 – 3 days for the short-term management of bleeding esophageal varices and a maximum of 14 days for the treatment of type 1 hepatorenal syndrome, depending on the progression of your disease.

If you are administered more Terlipressin acetate EVER Pharma than you should

Since this medication is administered by a healthcare professional, it is unlikely that you will receive a dose greater than the recommended amount. If you receive an excessive amount, you may experience a rapid increase in blood pressure (this will be detected during continuous monitoring), especially if you already have hypertension. If this occurs, you will be administered another medication called an alpha blocker (e.g., clonidina) to control blood pressure.

If you experience dizziness, fainting, or a sensation of fainting, consult your doctor as these may be symptoms of a slow heart rate. This can be treated with another medication called atropine.

If you discontinue treatment with Terlipressin acetate EVER Pharma

Your doctor will indicate when you should stop receiving this medication.

If you have any other questions 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.

Important side effects that require immediate attention:

In rare cases, there is a possibility of severe side effects when Terlipresina acetate EVER Pharma is administered. If you experience any of the following side effects, inform your doctor immediately if possible. Your doctor should stop administering Terlipresina acetate EVER Pharma.

• Severe difficulty breathing due to an asthma attack

• Acute chest pain (angina)

• Severe and persistent irregular heartbeats

• Dead skin around the injection area (necrosis)

• Convulsions (seizures)

Inform your doctor or another healthcare professional immediately:

• If you develop breathing difficulties or experience a worsening of respiratory capacity (signs or symptoms of respiratory failure). 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 at different frequencies depending on the disease you have:

Very frequent (may affect more than 1 in 10 people)

If you have type 1 hepatorenal syndrome:

• Difficulty breathing (dyspnea)

Frequent (may affect up to 1 in 10 people)

• Very slow heart rate
• Signs of insufficient blood circulation in the heart vesselsin the electrocardiogram
• High or low blood pressure
• Insufficient blood circulation in arms, legs, and skin
• Pale face
• Pale skin
• Headache
• Temporary abdominal cramps
• Temporary diarrhea
• Abdominal cramps (in women)

Inform your doctor or another healthcare professional immediately:

If you have type 1 hepatorenal syndrome:

• Liquid in the lungs (pulmonary edema)
• Difficulty breathing (respiratory difficulty)

Frequent (may affect up to 1 in 100 people)

• Chest pain
• Rapid increase in blood pressure
• Heart attack
• Too fast heart rate (palpitations)
• Swelling of body tissues or liquid in the lungs
• Blue discoloration of the skin or lips
• Seizures
• Temporary nausea
• Temporary vomiting
• Insufficient blood flow to the intestinal system
• Inflammation of lymphatic vessels (fine red lines under the skin that extend from the affected area to the armpit or groin and fever, chills, headache, and muscle pain
• Too low sodium levels in the blood (hyponatremia)

Inform your doctor or another healthcare professional immediately:

If you have dilated veins (that widen) in the digestive tract:

• Liquid in the lungs (pulmonary edema)
• Difficulty breathing (respiratory difficulty)

Rare (may affect up to 1 in 1000 people)

• Stroke
• Too high sugar levels in the blood (hyperglycemia)

Inform your doctor or another healthcare professional immediately:

If you have dilated veins (that widen) in the digestive tract:

• Difficulty breathing (dyspnea)

Unknown (frequency cannot be estimated from available data)

• Heart failure
• Torsade de Pointes
• Dead skin (necrosis) in areas unrelated to the injection site
• Decreased blood flow to the uterus
• Uterine contractions

Reporting side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Use: https://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 and on the vial after CAD. The expiration date is the last day of the month indicated.

Store in refrigerator between 2°C and 8°C. Do not freeze.

The solution must be visually inspected to detect if there are particles or discoloration before administration. Do not use the medication if discoloration is observed.

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

Composition of Terlipresin acetate EVER Pharma

- The active ingredient is terlipresin acetate.

5 ml of injectable solution contains 1 mg of terlipresin acetate, corresponding to 0.85 mg of terlipresin.
This is equivalent to 0.2 mg of terlipresin acetate per ml, corresponding to 0.17 mg of terlipresin per ml.

- The other components are: sodium chloride, acetic acid, sodium hydroxide (for pH adjustment), hydrochloric acid (for pH adjustment) and water for injection preparations.

Appearance of the product and contents of the package

This medicine is presented in transparent glass vials containing 5 ml of transparent and colorless solution.

This medicine is available in package sizes: 1 x 5 ml and 5 x 5 ml.

Only some package sizes may be commercially available.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

EVER Valinject GmbH

Oberburgau 3

4866 Unterach am Attersee

Austria

Responsible for manufacturing

EVER Pharma Jena GmbH

Otto-Schott-Strasse 15

07745 Jena

Germany

EVER Pharma Jena GmbH

Brüsseler Str. 18

07747 Jena

Germany

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

EVER Pharma Therapeutics Spain, S.L.

C/Toledo 170

28005 Madrid

Spain

This medicine is authorized in the member states of the European Economic Area and in the United Kingdom (Northern Ireland) with the following names:s:

Last review date of this leaflet: May 2023

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

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This information is intended solely for healthcare professionals

Dosage

1) Short-term treatment of bleeding esophageal varices:

Initial dose: 1 to 2 mg of terlipresin acetate#(equivalent to 5 to 10 ml of solution) administered intravenously over 1 minute.

Dose adjustment according to patient weight:

• Weight less than 50 kg: 1 mg of terlipresin acetate (5 ml)

• Weight between 50 kg and 70 kg: 1.5 mg of terlipresin acetate (7.5 ml)

• Weight greater than 70 kg: 2 mg of terlipresin acetate (10 ml).

Maintenance dose: after the initial injection, the dose can be reduced to 1 mg of terlipresin acetate every 4 to 6 hours.

#1 to 2 mg of terlipresin acetate corresponding to 0.85 to 1.7 mg of terlipresin

The approximate maximum daily dose of Terlipresin acetate EVER Pharma is 120 micrograms of terlipresin acetate per kilogram of body weight.

The treatment should be limited to 2 to 3 days according to the response to treatment in the course of the disease.

Terlipresin acetate EVER Pharma is administered intravenously and should be administered over 1 minute.

2) Type 1 hepatorenal syndrome:

A single intravenous injection of 1 mg of terlipresin acetate every 6 hours for a minimum of 3 days. If after 3 days of treatment, the decrease in serum creatinine is less than 3% compared to the initial value, consider doubling the dose to 2 mg every 6 hours.

Alternatively to the bolus injection, terlipresin can be administered as a continuous intravenous infusion (IV) with an initial dose of 2 mg of terlipresin acetate/24 hours and can be increased to a maximum of 12 mg of terlipresin acetate/24 hours. The administration of terlipresin as a continuous intravenous infusion can be associated with lower rates of severe adverse reactions compared to the intravenous bolus administration.

The treatment with terlipresin should be discontinued if no response is obtained (defined as a decrease in serum creatinine of less than 30% in the 7th day 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 showed an incomplete response (decrease in serum creatinine of at least 30% compared to the initial value, but without reaching a value below 1.5 mg/dl in the 7th day), the treatment with terlipresin should be continued until a maximum of 14 days.

In most clinical trials that support the use of terlipresin in the treatment of hepatorenal syndrome, human albumin was administered simultaneously at a dose of 1 g/kg PC on the first day and then at a dose of 20-40 g/day.

The usual duration of treatment of hepatorenal syndrome is 7 days, with a maximum duration of 14 days.

Terlipresin acetate EVER Pharma should be used with caution in patients over 70 years of age and in patients with chronic renal insufficiency.

Type 1 hepatorenal syndrome:

Terlipresin should be avoided in patients with advanced renal dysfunction, i.e. serum creatinine ≥ 442 μmol/l (5.0 mg/dl), unless it is considered that the benefit outweighs the risks.

Terlipresin acetate EVER Pharma is not recommended for use in children and adolescents due to insufficient experience of safety and efficacy.

No dose adjustment is necessary in patients with liver insufficiency.

Type 1 hepatorenal syndrome:

The use of terlipresin should be avoided in patients with severe liver disease defined as Acute-on-Chronic Liver Failure (ACLF) grade 3 and/or a MELD score ≥ 39, unless it is considered that the benefit outweighs the risks.

Preparation of the injection or infusion

To administer, the required volume should be extracted from the vial with a syringe.

Store in refrigerator (2°C-8°C). Do not freeze.

For single use only. Discard unused solution.