Glipressin

Package leaflet: Information for the patient

GLIPRESSINA 1 mg/8.5 ml solution for intravenous injection

Terlipressin
Please read all of this leaflet carefully before you are given this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or nurse.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of this leaflet:

1. What Glipressina is and what it is used for
2. What you must know before you are given Glipressina
3. How Glipressina is given
4. Possible side effects
5. How to store Glipressina
6. Contents of the pack and other information

1. What Glipressin is and what it is used for

What Glipressin is
Glipressin contains the active substance terlipressin. Terlipressin is a synthetic substance similar to vasopressin, a hormone produced by the posterior pituitary gland. The pituitary gland is a gland located at the base of the brain.
What Glipressin is used for
Glipressin is used for:

• the treatment of oesophageal variceal bleeding (bleeding due to dilated blood vessels in the oesophagus)
• the prevention of bleeding following intravariceal sclerotherapy of oesophageal varices (bleeding due to hardening of the blood vessels in the oesophagus)
• the treatment of hepatorenal syndrome in patients with liver cirrhosis (deterioration of kidney function in patients with severe liver dysfunction, often rapidly progressive and fatal), in combination with the administration of human albumin.

After injection into the body, terlipressin is converted into vasopressin, which acts on the walls of blood vessels causing them to constrict, thereby reducing blood flow to the affected veins and controlling bleeding.

2. What you should know before being administered Glipressina

Glipressina will not be administered to you

• if you are allergic to terlipressin or to any of the other ingredients of this medicine (listed in section 6)
• if you are pregnant (see section "Pregnancy and breastfeeding").

Warnings and precautions
Glipressina will be administered to you with caution if you suffer from:

• hypertension (high blood pressure)
• advanced atherosclerosis (thickening of the inner layer of the artery with plaque formation)
• heart or circulatory disorders
• coronary insufficiency (a condition in which the coronary arteries are obstructed and do not allow adequate oxygen supply to the heart)
• previous myocardial infarction (death of part of the heart tissue due to lack of blood supply)
• heart rhythm disorders
• diabetes (a condition in which blood sugar levels are too high) or obesity (excess weight), because you have a higher risk of developing reduced blood flow to the skin (ischemia) and, in isolated cases, skin cell death (cutaneous necrosis)
• type 2 hepatorenal syndrome (gradual deterioration of kidney function in patients with severe liver dysfunction with slow onset and progression), as experience with Glipressina use is limited.

Glipressina will not be administered in case of septic shock with low cardiac output (acute circulatory failure originating from a systemic infection).
Glipressina may increase the risk of developing respiratory failure, which can be life-threatening. Before taking Glipressina or during treatment, if you experience breathing difficulties or symptoms of fluid overload, inform your doctor immediately.
If you are being treated for severe liver and kidney disease (type 1 hepatorenal syndrome), your doctor must ensure that cardiac function and fluid and electrolyte balance are monitored during treatment. If you have a history of heart or lung disease, you should pay particular attention, as Glipressina may cause cardiac ischemia (reduced blood flow to the heart) and respiratory failure (severe breathing difficulties). Treatment with Glipressina should be avoided if you have liver failure with multi-organ failure and/or kidney failure with high levels of creatinine (a waste product) in the blood, as this increases the risk of adverse events.
If you are being treated for liver and kidney diseases, Glipressina may increase the risk of developing sepsis (bacteria in the blood and an extreme 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 extra precautions if this applies to you.

Children and adolescents
The use of Glipressina is not recommended in children and adolescents, as there are no available data on efficacy and safety.

Elderly (age over 70 years)
The use of Glipressina is not recommended in the elderly, as there are no available data on efficacy and safety.

Other medicines and Glipressina
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
This is particularly important if you are taking medicines that affect the heart:

• drugs that lower blood pressure, known as beta-blockers
• drugs that slow the heart rate (such as propofol and sufentanil), as their effects may be enhanced when administered concomitantly with Glipressina.

Inform your doctor immediately if you are taking any of the following medicines:
Medicines that may trigger irregular heartbeats (arrhythmias), such as:

• antiarrhythmic drugs known as Class IA (quinidine, procainamide, disopyramide) and Class III (amiodarone, sotalol, ibutilide, dofetilide)
• erythromycin (an antibiotic)
• antihistamines (mainly used to treat allergies but also found in some cough and cold remedies)
• tricyclic antidepressants used to treat depression
• medicines that may alter salt or electrolyte levels in the blood, particularly diuretics (used to treat high blood pressure and heart failure).

Pregnancy and breastfeeding
Pregnancy
Glipressina must not be administered during pregnancy.
Breastfeeding
Your doctor will evaluate whether you should continue/stop breastfeeding or whether you should discontinue/continue treatment with terlipressin, taking into account the benefits of breastfeeding for the infant and the benefits of terlipressin therapy for you.

Driving and using machines
No studies have been conducted on the ability to drive or use machinery, as Glipressina is a medicine used exclusively in hospital settings.

For those engaged in sports
Using this medicine without therapeutic need constitutes doping and may result in a positive anti-doping test.

Glipressina contains sodium
Glipressina contains 1.33 mmol of sodium per vial. This should be taken into consideration if you have impaired kidney function or are on a low-sodium diet.

3. How to take Glipressina

This medicine is available only in a hospital setting. Therefore, it will be administered to you exclusively under the close supervision of qualified medical personnel.
Glipressina is administered by intravenous injection or intravenous infusion.
Type 1 hepatorenal syndrome
Glipressina may also be given to you by intravenous infusion (continuous intravenous infusion), usually starting at a dose of 2 mg of terlipressin acetate per day, gradually increasing the dose up to a maximum of 12 mg of terlipressin acetate per day.
Your doctor will determine the most appropriate dose for you, taking into account your age and overall health condition.
During treatment with Glipressina, certain parameters will be monitored, such as blood pressure, heart rate, and blood electrolytes (e.g. sodium, potassium, calcium).
If you are given more Glipressina than you should
It is highly unlikely that you will be given more Glipressina than required, as your doctor will closely monitor you during treatment.
However, if an overdose of Glipressina is administered, your doctor will initiate appropriate supportive therapy.
If you have any doubts about the use of Glipressina, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Immediately inform your doctor or a healthcare professional:

• if you develop difficulty breathing or worsening respiratory function (signs or symptoms of respiratory failure). This is a very common side effect if you are being treated for hepatorenal syndrome type 1 – it may occur in more than 1 in 10 people;
• if you develop signs or symptoms of a blood infection (sepsis/septic shock), which may include fever and chills or very low body temperature, pallor and/or bluish skin, severe shortness of breath, reduced urine output, rapid heartbeat, nausea and vomiting, diarrhoea, fatigue and weakness, and dizziness. This is a common side effect if you are being treated for hepatorenal syndrome type 1 – it may occur in up to 1 in 10 people. Other side effects may occur with varying frequencies depending on the condition you have.

The following side effects are listed according to the following frequency:
Very common (may affect more than 1 in 10 people)
If you have hepatorenal syndrome type 1:

• Shortness of breath (dyspnoea)
  Common (may affect up to 1 in 10 people)
• low levels of sodium in the blood (hyponatraemia)
• headache
• chest pain; bradycardia (slow heartbeat); tachycardia (very fast heartbeat)
• vasoconstriction, peripheral ischaemia (reduced or absent blood flow to organs), pallor, arterial hypertension (high blood pressure)
• cyanosis (bluish discolouration of peripheral tissues)
• abdominal pain, nausea, vomiting, diarrhoea

If you have hepatorenal syndrome type 1:

• Fluid in the lungs (pulmonary oedema)
• Difficulty breathing (respiratory distress)
  Uncommon (may affect up to 1 in 100 people)
• heart rhythm irregularities (such as atrial fibrillation, ventricular extrasystoles, torsade de pointes); heart attack; heart failure
• pulmonary oedema (fluid accumulation in the lungs)
• intestinal ischaemia (reduced or absent blood flow to the intestine)
• hot flushes
• respiratory problems such as respiratory distress (respiratory failure caused by various types of acute respiratory injury and characterised by pulmonary oedema, respiratory distress, and reduced oxygen levels in the blood) and respiratory failure
• nausea, vomiting
• death of skin cells and cells at the injection site

If you have conditions related to other approved indications for Glipressin besides hepatorenal syndrome type 1:
Not known (frequency cannot be estimated from the available data)

• contractions and reduced blood flow to the uterus

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Glipressin

Store in the refrigerator (2°C - 8°C) in the original packaging to protect the medicine from light.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton after Exp. The expiry date refers to the
last day of that month.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of
medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Glipressina contains

• The active substance is terlipressin. One 8.5 ml vial contains terlipressin acetate equivalent to 0.85 mg of terlipressin.
• The other components are: sodium chloride, sodium acetate trihydrate (see section “Glipressina contains sodium”), acetic acid, water for injections.

Description of the appearance of Glipressina and contents of the pack
Glipressina is a clear, transparent solution for intravenous injection.
It is available in a carton containing 5 vials of 8.5 ml each.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
Ferring S.p.A. - Via C. Imbonati 18, 20159 Milano, Italy
Manufacturer
Ferring GmbH, Wittland 11, D-24109 Kiel, Germany

The following information is intended exclusively for physicians or healthcare professionals:
P M
Oesophageal variceal bleeding
2 mg of terlipressin acetate (2 vials) as slow intravenous bolus every 4–6 hours until bleeding is controlled.
After cessation of bleeding, treatment should be continued for up to 24 hours, possibly reducing the dose.
Glipressina may also be used in combination with oesophageal tubes such as the Sengstaken-Blakemore or
Linton-Nachlas tubes.

Prevention of bleeding following oesophageal intravariceal sclerotherapy
2 mg of terlipressin acetate (2 vials) as slow intravenous bolus, 30–60 minutes before sclerotherapy procedure.

Treatment of hepatorenal syndrome in patients with liver cirrhosis, in combination with
administration of human albumin
Initial dose: 2–3 mg of terlipressin acetate (2–3 vials)/24 hours as continuous intravenous infusion (it is recommended to dilute the daily dose of terlipressin in 50 ml of 0.9% sodium chloride solution and administer via infusion pump at a rate of 2.1 ml/h) or as intravenous boluses of 0.5 mg terlipressin acetate (half a vial) every 4–6 hours. Therapeutic response should be assessed every 48 hours after initiation of treatment. If serum creatinine increases or decreases by less than 25% compared to pre-treatment baseline value, the dose of terlipressin may be gradually increased by 2–3 mg of terlipressin acetate (2–3 vials)/24 hours, up to a maximum dose of 12 mg of terlipressin acetate (12 vials)/24 hours.
Treatment with terlipressin should be maintained for at least 24 hours after recovery of renal function. There are no precise data on how to discontinue therapy, but a gradual reduction of the daily dose of terlipressin is recommended, especially after high-dose regimens.
In patients who partially respond or do not respond to treatment, the maximum duration of treatment is 14 days.
Supportive favorable studies on the use of terlipressin for the treatment of hepatorenal syndrome also include concomitant administration of human albumin at a dose of 1 g/kg body weight on the first day, followed by 20–40 g/day thereafter.

Following partial use of a vial (half a vial), which must be withdrawn under aseptic and controlled conditions, the storage time and conditions of the remaining solution fall under the responsibility of the user and must not exceed 4–6 hours at 2°C – 8°C (refrigerated).

S
The recommended dose (2 mg of terlipressin acetate (2 vials)/4 hours) must not be exceeded, as the risk of serious adverse effects on the circulatory system is dose-dependent.
Any increase in blood pressure due to overdose or occurring in patients who are already hypertensive can be managed with clonidine: 150 mcg intravenously.
Bradycardia requiring treatment should be managed with atropine.