Glypressin 1 mg powder and solvent for solution for injection

Package leaflet: Information for the user

Introduction

PACKAGE LEAFLET: INFORMATION FOR THE USER

GLYPRESSIN 1mg powder and solvent for injection solution

Terlipressin acetate

Read the entire leaflet carefully before you start using this medicine.

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

Contents of the leaflet:

1. What Glypressin is and what it is used for
2. What you need to know before using Glypressin
3. How to use Glypressin
4. Possible side effects
5. How to store Glypressin
6. Contents of the pack and other information

1. What Glypressin is and what it is used for

Glypressin is supplied as a powder and solvent for injectable solution, containing terlipressin acetate, which 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 that carries blood to the liver (portal hypertension). Terlipressin acts by constricting the blood vessels (vasoconstriction) in this area, helping to control bleeding from oesophageal and gastric varices (oesophagogastric varices) when it occurs.

Glypressin also helps improve blood circulation in the kidney, thereby aiding recovery of renal function in patients with Hepatorenal Syndrome (a type of kidney failure occurring in patients with severe liver dysfunction).

Glypressin 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 Glypressin

Do not use Glypressin:

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

Warnings and precautions:

Talk to 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), reduced blood supply to the heart (coronary artery disease), or your heart pumps less blood than it should (heart failure), as you may have a higher risk of heart-related adverse effects.
• if you have reduced blood flow to the brain (cerebrovascular disease), poor blood circulation in the arms or legs (peripheral vascular disease), or intestinal blood vessel disease, as you may have an increased risk of adverse effects due to reduced blood flow in these areas.
• if you have leg swelling due to poor venous circulation or if you are overweight (obesity), as you may have a higher risk of reduced blood flow to the skin (ischaemia) and, in rare cases, even death of skin cells (cutaneous necrosis).
• if you have a severe systemic infection with low 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 of age with current or past cardiovascular disease.
• in children, as experience is limited in this age group.

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

The injection must be administered exclusively by intravenous route to avoid local skin cell death (cutaneous necrosis) due to leakage of the product into the skin.

Glypressin 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 Glypressin, inform your doctor immediately.

If you are being treated for severe liver and kidney disease (hepatorenal syndrome type 1), 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 Glypressin may induce cardiac ischaemia (reduced blood flow to the heart) and respiratory failure (severe breathing difficulties). Treatment with Glypressin 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 being treated for severe liver and kidney disease, Glypressin may increase the risk of developing sepsis (bacteria in the blood and a severe body 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 Glypressin 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 enhanced when used together with 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 previously experienced sudden slowing of the heartbeat with certain anaesthetics (propofol, sufentanil). Glypressin may enhance the effect of these drugs if they are administered again.

Pregnancy, breast-feeding and fertility

If you are pregnant, breast-feeding, think you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medicine.

Glypressin must not be given during pregnancy, as it may cause harm to your unborn baby.

Glypressin must not be administered during breast-feeding, as it is unknown whether Glypressin passes into breast milk.

Driving and using machines

No studies have been performed on the effects on the ability to drive or use machines.

Use in children and elderly people over 65 years

Glypressin should be used with caution in patients over 70 years of age who have current or past cardiovascular disease.

Particular caution should be taken 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 Glypressin

After reconstitution with the solvent supplied, this medicine contains less than 1 mmol (23 mg) of sodium per 5 ml, therefore the product is essentially “sodium-free”.

3. How to use Glypressin

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

Method of administration and route

Administration of Glypressin must be performed by qualified healthcare personnel following the recommendations below:

Reconstitute the lyophilized Glypressin powder by adding sterile solvent to the vial. The resulting clear solution must be administered exclusively by intravenous injection. The drug should be used immediately after reconstitution.

Glypressin is administered by intravenous injection or infusion.

Normal dosage in adults:

Gastrointestinal bleeding due to rupture of esophagogastric varices

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

Generally, if the patient's weight is less than 50 kilograms, 1 milligram should be administered every four hours. For patients weighing between 50 and 70 kilograms, 1.5 milligrams should be administered every four hours. For patients weighing more than 70 kilograms, 2 milligrams should be administered every four hours.

Treatment should continue for 24 consecutive hours until bleeding is 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 when necessary, for example, due to the occurrence of adverse reactions.

Hepatorenal 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 decrease in serum creatinine is less than 30% compared to baseline, 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 less than a 30% decrease 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 decrease in serum creatinine of at least 30% compared to baseline but not reaching values below 1.5 mg/dL by day 7), treatment with terlipressin may be continued for up to a maximum of 14 days.

In cases of relapse of hepatorenal syndrome after a complete response, treatment with terlipressin may be restarted at the physician's discretion.

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

Type 1 hepatorenal syndrome

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

If you use more Glypressin than you should:

If more Glypressin 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 immediately at telephone number 915 620 420, indicating the medicine and the amount ingested.

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

4. Possible adverse effects

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

Tell your doctor or another healthcare professional immediately:

• If you develop breathing difficulties or worsening respiratory function (signs or symptoms of respiratory failure). This adverse effect is very common 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 bluish skin, severe shortness of breath, urinating less than usual, rapid heartbeat, nausea and vomiting, diarrhea, fatigue and weakness, and dizziness. This adverse effect is frequent if you are 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: may affect more than 1 in 10 people.

If you have type 1 hepatorenal syndrome:

• Difficulty breathing (dyspnea)

Common: 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: may affect up to 1 in 100 people.

• Decreased sodium in the blood if fluid balance is not controlled
• Irregular heartbeat
• Increased heart rate
• Chest pain
• Myocardial infarction (heart attack)
• Pulmonary edema
• Torsade de pointes (serious cardiac event)
• Heart failure. Symptoms include shortness of breath, fatigue, and swelling of the ankles
• Inadequate blood flow to the intestines
• Peripheral cyanosis (bluish discoloration of the skin caused by lack of oxygen)
• Hot flushes
• Respiratory difficulty and respiratory failure (difficulty breathing)
• 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 gastrointestinal bleeding due to rupture of esophagogastric varices:

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

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

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

• Difficulty breathing (dyspnea)

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

Patients with hepatorenal syndrome treated with Glypressin 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 intestines (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 heartbeat (serious 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 skin areas other than the Glypressin injection site have been reported.

Reporting of adverse effects:

If you experience any adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines: http;//www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Glypressin

Keep out of the sight and reach of children.

Do not use Glypressin after the expiry date stated on the container, after “EXP”. The expiry date refers to the last day of the month indicated.

Store in the original container to protect from light.

The reconstituted solution must be used immediately after reconstitution.

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

6. Contents of the pack and other information

Composition of Glypressin:

The active substance is terlipressin acetate. Each vial contains 1 milligram of terlipressin acetate, equivalent 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, sodium hydroxide and water for injections.

Appearance of the product and contents of the pack

The product is a powder and solvent for injectable solution.

The powder is white. When dissolved in the provided solvent, a clear, colourless solution should be obtained.

It is marketed in packs containing 1 vial and 1 ampoule of solvent, and packs containing 5 vials and 5 ampoules of solvent.

Only certain pack sizes may be commercially available.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder:

FERRING S.A.U.

C/ del Arquitecto Sánchez Arcas nº3, 1º

28040 Madrid

Spain

Manufacturer:

FERRING GmbH

Wittland 11, 24109 Kiel,

Germany

Date of the most recent revision of this package leaflet: January 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.es/