PATIENT INFORMATION LEAFLET

GLYPRESSIN 1mg powder and solvent for injectable solution

Terlipressin acetate

Read this leaflet carefully before you start using the medicine.

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

Glypressin is presented in the form of powder and solvent for injectable solution, containing terlipressin acetate, which 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 (esophagogastric) when it occurs.

Glypressin 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 function alteration).

Glypressin is indicated for the treatment of:

• Digestive hemorrhages due to rupture of esophagogastric varices.
• Emergency treatment of type 1 Hepatorenal Syndrome, defined according to the CIA (International Ascites Club) criterion.

No use Glypressin:

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

Advertencias and precautions:

Consult your doctor or pharmacist before starting to use Glypressin:

• If you have high blood pressure (hypertension).
• If you have heart problems, such as irregular heartbeat (arrhythmias), heart blood flow deficiency (coronary 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 brain blood flow deficiency (cerebrovascular disease), poor blood flow in the legs or arms (peripheral vascular disease), or intestinal blood vessel disease, as you have a higher chance of experiencing adverse effects related to lack of blood flow in these locations.
• If you have swelling of the legs due to poor venous circulation or obesity, as you have a higher risk of experiencing decreased blood flow in the skin (ischemia) and even, in isolated cases, skin cell death (cutaneous necrosis).
• If you have a severe generalized infection with blood pressure drop (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 because the experience is limited in this age group.

Glypressin must be used under the supervision of a specialist in units with availability to regularly monitor blood pressure, cardiac 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.

Glypressin may increase the risk of developing respiratory insufficiency that can be fatal. If you experience breathing difficulties or symptoms of fluid overload, before or during treatment with Glypressin, inform your doctor immediately.

If you receive treatment for severe liver and kidney disease (type 1 hepatorenal syndrome), your doctor must ensure that your cardiac 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 Glypressin may induce cardiac ischemia (decreased blood flow to the heart) and respiratory insufficiency (severe breathing difficulties). Treatment with Glypressin should be avoided if you have liver insufficiency with multiple organ failures and/or renal insufficiency with very high creatinine levels (a waste product) in the blood, as it increases the risk of adverse effects.

If you receive treatment for severe liver and kidney disease, Glypressin 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 Glypressin 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 Glypressin.
• 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. Glypressin may increase the effect of these medications 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 medication.

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

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

Driving and operating machines

No studies have been conducted on the effects on the ability to drive or operate machines.

Use in children and people over 65 years

Glypressin should be used with caution in people over 70 years with current cardiovascular disease or a history of the same.

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

Use in people with liver problems

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

Important information about some of the components of Glypressin

Once reconstituted with the solvent provided, this medication contains less than 1 mmol (23 mg) of sodium per 5 ml, making the product essentially "sodium-free".

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubts, consult your doctor or pharmacist again.

Administration form and route

Glypressin administration should be performed by qualified healthcare personnel following the following recommendations:

Reconstitute the lyophilized Glypressin powder by introducing the sterile solvent into the vial. The transparent solution obtained should only be administered intravenously. The reconstituted medication should be used immediately.

Glypressin is injected or infused intravenously.

The normal dose in 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 will be administered every 4 hours. In patients with a body weight between 50 and 70 kilograms, 1.5 milligrams will be administered every 4 hours. In patients with a body weight over 70 kilograms, 2 milligrams will be administered every 4 hours.

Treatment should be continued for 24 consecutive hours until bleeding has been controlled. Treatment should be limited to 2-3 days depending on the patient's condition. After the initial injection, subsequent doses may be reduced to 1 milligram of Glypressin as needed, for example, due to the appearance of adverse reactions.

Heptorenal syndrome

It is recommended to initiate treatment with 1 mg of terlipressin 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 doubled to 2 mg every 6 hours.

Treatment with terlipressin 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 terlipressin may be continued for a maximum of 14 days.

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

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

Heptorenal syndrome type 1

Glypressin may also be administered in the form of a drip (intravenous continuous infusion) starting with 2 mg of terlipressin per day and increasing gradually to a maximum of 12 mg of terlipressin per day.

If you use more Glypressin than you should:

If you are administered more Glypressin 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 have any other doubts about the use of this medication, ask your doctor or pharmacist.

Like all medicines, this medicine may 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 suffer from.

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.

• 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)

Not very frequent: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)
• Pulmonary edema
• Torsades de pointes (serious cardiac event)
• Cardiac failure. Symptoms include shortness of breath, fatigue, and swelling of the ankles
• Inadequate blood flow to the intestines
• Peripheral cyanosis (blue discoloration of the skin caused by lack of oxygen)
• Syncope
• Difficulty breathing and respiratory failure (breathing difficulties)
• Transient nausea
• Transient vomiting
• Skin necrosis (tissue damage)
• Uterine contraction (contraction of the uterus)
• Decreased uterine blood flow
• Necrosis at the injection site (tissue damage)

If you have esophageal-gastric variceal hemorrhages:

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

Rare:may affect up to 1 in 1,000 people.

If you have esophageal-gastric variceal hemorrhages:

• Difficulty breathing (dyspnea)

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

Patients with Hepatorenal Syndrome treated with Glypressin 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.

Several cases of severe cardiac arrhythmias have been reported during clinical trials and post-marketing experience.

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

Reporting of 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 Pharmacovigilance of Medicines for Human Use: http;//www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep out of the sight and reach of children

Do not use Glypressin after the expiration date indicated on the packaging, after “CAD”. The expiration date is the last day of the month indicated.

Store in the original packaging to protect it from light.

The reconstituted solution must be used immediately after reconstitution.

Medicines should not be disposed of through drains, or in the trash. Ask your pharmacist how to dispose of the containers and medicines that you no longer need. This will help protect the environment

Composition of Glypressin:

The active ingredient is terlipressin acetate. Each vial contains 1 milligram of terlipressin acetate, corresponding to 0.86 milligrams of terlipressin. The concentration of the reconstituted solution is 0.2 milligrams/milliliter of terlipressin acetate.

The other components are:

Powder: mannitol (E421) and hydrochloric acid.

Solvent: sodium chloride, hydrochloric acid, and injection quality water.

Appearance of the product and contents of the packaging

The product is a powder and solvent for injectable solution.

The powder is white. When dissolved in the provided solvent, a transparent and colorless solution should be obtained.

It is marketed in packaging of 1 vial and 1 ampoule of solvent and packaging with 5 vials and 5 ampoules of solvent.

Only some sizes of packaging may be marketed.

Holder of the marketing authorization and responsible manufacturer

Holder of the Marketing Authorization

FERRING S.A.U.

C/ del Arquitecto Sánchez Arcas nº3, 1º

28040 Madrid

-. Spain

Responsible Manufacturer:

FERRING GmbH

Wittland 11, 24109 Kiel,

Germany

Date of the last review of this prospectus January 2023

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