GLIPRESSINA 0.1 MG/ML Powder and solvent for injectable solution

Зміст інструкції

1. GLIPRESSINA 1 mg/8.5 ml injectable solution for intravenous use
   1. What is Glipressina and what is it used for
   2. What you need to know before you are given Glipressina
   3. How to take Glipressina
   4. Possible side effects
   5. How to store Glipressina
   6. Package Contents and Other Information

GLIPRESSINA 1 mg/8.5 ml injectable solution for intravenous use

Terlipressin

Read this leaflet carefully before you are given this medicine as 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 any side effects occur, 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 need to know before you are given Glipressina
• 3. How to administer Glipressina
• 4. Possible side effects
• 5. How to store Glipressina
• 6. Contents of the pack and other information

1. What is Glipressina and what is it used for

What is Glipressina
Glipressina contains the active substance terlipressin. Terlipressin is an artificial 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 is Glipressina used for
Glipressina is used for:

• the treatment of esophageal variceal bleeding (bleeding due to the dilation of blood vessels in the esophagus)
• the prevention of bleeding from esophageal sclerotherapy (bleeding from the hardening of blood vessels in the esophagus)
• the treatment of hepatorenal syndrome in patients with liver cirrhosis (deterioration of kidney function in subjects affected by severe liver dysfunction, often rapid and fatal), in association with the administration of human albumin.

Once injected into the body, terlipressin is converted into vasopressin, which acts
on the walls of blood vessels causing them to constrict and limiting blood flow to the
affected veins so that bleeding is reduced.

2. What you need to know before you are given Glipressina

You will not be given Glipressina

• if you are allergic to terlipressin or 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 given 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 and blood circulation disorders
• coronary insufficiency (a condition in which the coronary arteries become blocked and do not allow adequate oxygen supply to the heart)
• previous myocardial infarction (death of a part of heart tissue due to lack of blood supply)
• heart rhythm disturbances
• type 2 hepatorenal syndrome (deterioration of kidney function in subjects with severe liver dysfunction with slow onset and progression), as experience with the use of Glipressina is limited.

Glipressina will not be given to you in case of septic shock with low cardiac output
(acute circulatory failure originating from a widespread infection in the blood).
Glipressina may increase the risk of developing respiratory failure which may be
life-threatening. Before taking Glipressina or during treatment, in case of breathing difficulties or symptoms of fluid overload, inform your doctor immediately.
If you are being treated for very severe liver and kidney disease (type 1 hepatorenal syndrome),
your doctor must ensure that cardiac function and electrolyte and fluid 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
(reduction in the amount of blood flow to the heart) and respiratory failure (severe difficulty
in breathing). Treatment with Glipressina should be avoided if you suffer from hepatic
insufficiency with multi-organ failure and/or renal insufficiency with high levels of creatinine (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 response of the body to an infection) and septic
shock (a serious condition that occurs when a severe infection causes a drop
in blood pressure and 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 is no efficacy and safety data available.

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

Other medicines and Glipressina
Tell your doctor or pharmacist if you are taking, have recently taken or might take
any other medicine.
This is particularly important if you are using medicines that have an effect on the heart:

• medicines that can lower blood pressure, called beta-blockers
• medicines that can slow down the heartbeat (such as propofol and sufentanil) as their effect may be increased by simultaneous administration with Glipressina.

Tell your doctor immediately if you are taking any of the following medicines:
Medicines that can trigger an irregular heartbeat (arrhythmia) such as the following:

• 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 can alter the level of salt or electrolytes in the blood, in particular diuretics (used to treat high blood pressure and heart failure).

Pregnancy and breastfeeding

Pregnancy
Glipressina must notbe given during pregnancy.

Breastfeeding
The doctor will assess whether you should continue/interrupt breastfeeding or whether you should
suspend/continue therapy with terlipressin, taking into account the benefits of breastfeeding
for the baby and the therapy with terlipressin for you.

Driving and operating machinery
Studies on the ability to drive and operate machinery have not been conducted as
Glipressina is a medicine used only in hospitals.

For athletes
The use of the drug without therapeutic necessity constitutes doping and may still
result in positive anti-doping tests.

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

3. How to take Glipressina

This medicine is only available in hospital. Therefore, it will be administered to you only
under strict supervision of qualified medical personnel.
Glipressina is administered by injection or intravenous infusion.
Type 1 hepatorenal syndrome
Glipressina may also be administered with an intravenous drip (continuous intravenous infusion),
usually starting with 2 mg of terlipressin acetate per day and gradually increasing
the dose up to a maximum of 12 mg of terlipressin acetate per day.
The doctor will decide the most appropriate dose for you, taking into consideration your age and your
state of health.
During treatment with Glipressina, certain parameters will be monitored, such as blood
pressure, heart rate, electrolytes in the blood (e.g. sodium, potassium, calcium).

If you are given more Glipressina than you should
It is very unlikely that you will be given a higher dose of Glipressina than necessary,
as your doctor will monitor you during treatment.

However, if you are given an excessive dose of Glipressina, the doctor will adopt the
appropriate supportive therapy.
If you have any doubts about the use of Glipressina, ask your doctor or pharmacist.

4. Possible side effects

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

• if you develop difficulty breathing or a worsening of your ability to breathe (signs or symptoms of respiratory failure). This is a very common side effect if you are being treated for type 1 hepatorenal syndrome - it can 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, paleness and/or bluish skin, severe shortness of breath, reduced urine output, rapid heartbeat, nausea and vomiting, diarrhea, fatigue and weakness, and dizziness. This is a common side effect if you are being treated for type 1 hepatorenal syndrome - it can occur in up to 1 in
• 10. Other side effects may occur with varying frequencies depending on the condition you have.

Side effects are listed below according to the following frequency:

Very common (may affect more than 1 in 10 people)
If you suffer from type 1 hepatorenal syndrome:

• Shortness of breath (dyspnea) Common( may affect up to 1 in 10 people)
• headache
• bradycardia (slowed heartbeat)
• peripheral vasoconstriction, peripheral ischemia (reduced or decreased blood flow to the organs), pallor, high blood pressure (hypertension)
• transient abdominal cramps, transient diarrhea

If you suffer from type 1 hepatorenal syndrome:

• Fluid in the lungs (pulmonary edema)
• Difficulty breathing (respiratory distress) Uncommon( may affect up to 1 in 100 people)
• low levels of sodium in the blood (hyponatremia), especially when hydration status is not monitored
• irregular heartbeat (such as atrial fibrillation, ventricular extrasystoles, tachycardia, torsade de pointes); chest pain; heart attack; heart failure
• fluid retention with edema in the lungs (fluid accumulation in the lungs)
• intestinal ischemia (reduced or decreased blood flow to the intestine)
• peripheral cyanosis (bluish discoloration of peripheral tissues)
• hot flashes
• breathing problems such as respiratory distress (respiratory failure caused by various types of acute respiratory damage and characterized by pulmonary edema, respiratory distress and reduced blood oxygen) and respiratory failure
• transient nausea, transient vomiting
• death of skin cells and cells at the injection site
• contractions and reduced blood flow to the uterus

If you suffer from conditions related to other approved indications for Glipressina in addition to type 1
hepatorenal syndrome:

• Fluid in the lungs (pulmonary edema)
• Difficulty breathing (respiratory distress) Rare( may affect up to 1 in 1000 people) If you suffer from conditions related to other approved indications for Glipressina in addition to type 1 hepatorenal syndrome:
• Shortness of breath (dyspnea)

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through
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 Glipressina

Store in a refrigerator (2°C - 8°C) in the original package 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 which is stated on the pack after Exp. The
expiry date refers to the last day of that month.
Do not dispose of any medicine in 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 ingredient is terlipressin. One 8.5 ml vial contains terlipressin acetate corresponding to 0.85 mg of terlipressin.
• The other ingredients are: sodiumchloride, sodiumacetate trihydrate (see paragraph “Glipressina contains sodium”), acetic acid, water for injections.

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

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Ferring S.p.A. - Via C. Imbonati 18, 20159 Milano

Manufacturer
Ferring GmbH, Wittland 11, D-24109 Kiel, Germany
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The following information is intended exclusively for doctors or healthcare professionals:
PM
Esophageal variceal bleeding
2 mg of terlipressin acetate (2 vials) as a slow intravenous bolus every 4-6 hours until bleeding control is achieved.
After the bleeding has stopped, treatment should be continued for up to 24 hours, possibly reducing the dosage.
Glipressina can also be used in association with esophageal probes such as the Sengstaken-Blakemore and Linton-Nachlas probes.

Prevention of bleeding from esophageal variceal sclerotherapy
2 mg of terlipressin acetate (2 vials) as a slow intravenous bolus, 30-60 minutes before
the sclerosing procedure.

Treatment of hepatorenal syndrome in patients with cirrhosis, in association with the
administration of human albumin
Initial dose 2-3 mg of terlipressin acetate (2-3 vials)/24 hours as a continuous intravenous infusion (it
is recommended to dilute the daily dose of terlipressin in 50 ml of 0.9% physiological saline and to
administer it subsequently with an infusion pump at a rate of 2.1 ml/h) or as intravenous boluses of
0.5 mg of terlipressin acetate (half vial) every 4-6 hours. The therapeutic response must be
evaluated every 48 hours from the start of therapy. If serum creatinine increases or decreases
by less than 25% compared to the baseline pre-treatment 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 terlipessin acetate (12 vials)/24 hours.
Treatment with terlipressin should be maintained for at least 24 hours after recovery of
renal function. There is no precise data on how to discontinue therapy, but a gradual reduction in the daily dose of terlipressin is recommended, especially in cases of high doses.
In patients who respond partially or do not respond to treatment, the maximum duration of
treatment is 14 days.
Studies supporting the use of terlipressin for the treatment of hepatorenal syndrome also provide for the administration of human albumin at a dose of
1 g/kg of body weight on the first day and subsequently at a dose of 20-40 g/day.
Following the partial use of the vial (half vial), the removal of which must take place under aseptic and controlled conditions, the timing and methods of conservation of the remaining solution fall
within the responsibility of the user and in any case must not exceed 4-6 hours between 2°C – 8 °C (in
the refrigerator).

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 an overdose of the drug or in patients who are already
hypertensive can be controlled with clonidine: 150 mcg intravenously.
The onset of bradycardia requiring treatment must be treated with atropine.