Terlipressin acetate Ever Pharma

Patient Information Leaflet

Terlipressin Acetate EVER Pharma 0.2 mg/ml Injection Solution

terlipressin acetate
Read this entire leaflet carefully before you are administered 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, pharmacist, or nurse.
• If you experience any side effects, including those not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

1. What Terlipressin Acetate EVER Pharma is and what it is used for
2. What you need to know before you are administered Terlipressin Acetate EVER Pharma
3. How Terlipressin Acetate EVER Pharma will be administered to you
4. Possible side effects
5. How to store Terlipressin Acetate EVER Pharma
6. Contents of the pack and other information

1. What Terlipressin Acetate EVER Pharma is and what it is used for

Terlipressin Acetate EVER Pharma contains the active substance terlipressin, a synthetic pituitary hormone (this hormone is normally produced by the pituitary gland located in the brain).
It is administered by intravenous injection.
Terlipressin Acetate EVER Pharma is used for the treatment of:

• Bleeding from enlarged veins in the digestive tract connecting the pharynx to the stomach (known as oesophageal variceal bleeding).
• Emergency treatment of type 1 hepatorenal syndrome (rapidly progressive kidney failure) in patients with liver cirrhosis (liver scarring) and ascites (abdominal fluid accumulation).

2. What you need to know before you are given Terlipressin acetate EVER Pharma

Do not administer Terlipressin acetate EVER Pharma to you if:

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

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before you are given Terlipressin acetate EVER Pharma:

• if you have a severe infection known as septic shock;
• if you have bronchial asthma or other breathing disorders;
• if you have uncontrolled high blood pressure, or inadequate blood circulation in the heart vessels (e.g. angina);
• if you have previously had a heart attack (myocardial infarction) or hardened arteries (arteriosclerosis);
• if you suffer from seizures (convulsions);
• if you have irregular heartbeats (cardiac arrhythmias) or a history of prolonged QT interval (a heart rhythm disorder);
• if you have reduced blood circulation in the brain (e.g. if you have had a stroke) or in the limbs (peripheral vascular disease);
• if you have impaired kidney function (renal failure);
• if you have disorders affecting blood salts (electrolytes);
• if you have a reduced amount of fluid in the circulation or if you have already lost a large amount of blood;
• if you are over 70 years of age.

If any of the above conditions apply to you (or if you are unsure), inform your doctor, pharmacist, or nurse before you are given Terlipressin acetate EVER Pharma.
During treatment with Terlipressin acetate EVER Pharma, your blood pressure, heart rate, serum sodium and potassium levels, and fluid balance will be continuously monitored.

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

Other medicines and Terlipressin acetate EVER Pharma
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Inform your doctor immediately if you are taking any of the following medicines:

• medicines affecting heart rate (e.g. beta-blockers, sufentanil, or propofol);
• medicines that may cause irregular heartbeats (arrhythmias), such as:
• class IA and class III antiarrhythmic drugs (quinidine, procainamide, disopyramide) and class III (amiodarone, sotalol, ibutilide, dofetilide);
• erythromycin (an antibiotic);
• antihistamines (used mainly to treat allergies, but also present in some cough and cold remedies);
• tricyclic antidepressants used to treat depression;
• medicines that may alter the level of salts or electrolytes in the blood, particularly diuretics (used to treat high blood pressure and heart failure).

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor before taking this medicine.
Terlipressin acetate EVER Pharma must not be used during pregnancy.
It is not known whether terlipressin acetate EVER Pharma is excreted in breast milk; therefore, possible effects on the infant are unknown. Discuss with your doctor the potential risk to the infant.

Driving and using machines
No studies on the ability to drive vehicles or operate machinery have been conducted. However, if you feel unwell after the injection, you must not drive or operate machinery.

Terlipressin acetate EVER Pharma contains sodium
This medicine contains 3.68 mg of sodium (the main component of table salt) per ml. This corresponds to 0.18% of the maximum recommended daily dietary intake for an adult.

For those engaged in sports activities: using this medicine without a therapeutic need constitutes doping and may lead to a positive anti-doping test.

3. How to take Terlipressin acetate EVER Pharma

This medicine will always be administered to you by a healthcare professional via intravenous route. The doctor will determine the most appropriate dose, and during the injection your heart and blood circulation will be continuously monitored. Please consult your doctor for further information on the use of this medicine.

Use in adults

1. Short-term management of oesophageal variceal bleeding
   Initially, you will receive 1–2 mg of terlipressin acetate (5–10 ml of Terlipressin acetate EVER Pharma) administered intravenously. The dose depends 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 usual dose is 1 mg of terlipressin acetate every 6 hours for at least 3 days. If the reduction in serum creatinine is less than 30% after 3 days of treatment, the doctor should consider doubling the dose to 2 mg every 6 hours.

Treatment with terlipressin should be discontinued in case of non-response to treatment or in patients who have achieved a complete response.
When a reduction in serum creatinine is observed, treatment with terlipressin should be continued for up to a maximum of 14 days.

Use in elderly patients
If you are over 70 years of age, speak with your doctor before taking Terlipressin acetate EVER Pharma.

Use in patients with renal impairment
Terlipressin acetate EVER Pharma should be used with caution in patients with a history of renal insufficiency.

Use in patients with hepatic impairment
Dose adjustments are not required in patients with hepatic insufficiency.

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

Duration of treatment
The use of this medicine is limited to 2–3 days for the short-term management of oesophageal variceal bleeding and up to a maximum of 14 days for the treatment of type 1 hepatorenal syndrome, depending on the course of the disease.

If you are given more Terlipressin acetate EVER Pharma than you should
Since this medicine is administered by a healthcare professional, it is unlikely that you will receive more than the recommended dose. If an overdose occurs, you may experience a rapid increase in blood pressure (which will be detected during continuous monitoring), particularly if you already have high blood pressure (hypertension). If this occurs, you will be given another medicine called an alpha-blocker (e.g. clonidine) to control your blood pressure.

Inform your doctor if you experience a sensation of light-headedness, dizziness, or fainting, as these may be signs of a slow heart rate. This condition is treated with another medicine called atropine.

If you stop treatment with Terlipressin acetate EVER Pharma
Your doctor will advise you when to discontinue treatment with this medicine.

If you have any doubts about how to use this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.

Important side effects requiring immediate attention:
Very rarely, serious side effects may occur when Terlipressin acetate EVER Pharma is administered.
If any of the following side effects occur, inform your doctor immediately if you are able to do so. Your doctor must no longer administer Terlipressin acetate EVER Pharma if you experience:

• severe shortness of breath due to an asthma attack
• severe breathing difficulty or cessation of breathing
• severe chest pain (angina)
• persistent and severe irregular heartbeat
• areas of dead skin around the injection site (necrosis)
• seizures (epileptic fits)

Other possible side effects:

Common (may affect up to 1 in 10 people):

• very slow heartbeat
• ECG signs indicating inadequate blood circulation in the blood vessels of the heart
• high or low blood pressure
• inadequate blood circulation in the arms, legs, and skin
• paleness of the face
• paleness of the skin
• headache
• temporary abdominal cramps
• temporary diarrhoea
• abdominal cramps (in women)

Uncommon (may affect up to 1 in 100 people):

• chest pain
• rapid increase in blood pressure
• heart attack
• abnormally high heart rate (palpitations)
• swelling of tissues or presence of fluid in the lungs
• bluish discolouration of the skin or lips
• hot flushes
• excess fluid in the lungs
• temporary nausea
• temporary vomiting
• reduced blood supply to the intestinal tract
• inflammation of the lymphatic vessels – appears as thin red streaks on the skin radiating from the affected area towards the elbow or groin, accompanied by fever, chills, headache, and muscle pain
• low sodium levels in the blood (hyponatremia)

Rare (may affect up to 1 in 1,000 people):

• shortness of breath
• stroke
• high blood sugar (hyperglycaemia)

Not known: frequency cannot be estimated from the available data

• heart failure
• torsade de pointes
• dead skin (necrosis) in areas other than the injection site
• reduced blood flow to the uterus
• uterine cramps (cramps in the uterus)

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system at: 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 Terlipressin acetate EVER Pharma

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and vial after EXP. The expiry date refers to the last day of that month.
Store in a refrigerator (2°C–8°C). Do not freeze.
The solution should be inspected visually for the presence of particles and discoloration prior to administration. The medicine must not be used if any change in colour is observed.
Do not dispose of medicines via wastewater or household waste. Ask your doctor how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Terlipressina acetato EVER Pharma contains

• The active substance is terlipressin acetate.

5 ml of injectable solution contain 1 mg of terlipressin acetate, equivalent to 0.85 mg of
terlipressin.
10 ml of injectable solution contain 2 mg of terlipressin acetate, equivalent to 1.7 mg of
terlipressin.
This corresponds to 0.2 mg of terlipressin acetate per ml, equivalent to 0.17 mg of terlipressin
per ml.

• The other components are: sodium chloride, acetic acid, sodium hydroxide (for pH adjustment), hydrochloric acid (for pH adjustment), water for injections.

Description of the appearance of Terlipressina acetato EVER Pharma and contents of the pack
This medicinal product is supplied in clear glass vials containing 5 ml or 10 ml of a clear, colourless solution.
The medicine is available in pack sizes of 1 x 5 ml, 5 x 5 ml, 1 x 10 ml, 5 x 10 ml.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
EVER Valinject GmbH
Oberburgau 3
4866 Unterach
Austria

Manufacturer
EVER Pharma Jena GmbH
Otto-Schott-Strasse 15
07745 Jena
Germany

This medicinal product is authorised in the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:
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The following information is intended exclusively for physicians or healthcare professionals

Dosage

1. Short-term treatment of bleeding from oesophageal varices:
   Initial dose: 1–2 mg of terlipressin acetate (equivalent to 5–10 ml of solution) administered by intravenous injection over a period of one minute.
   The dose may be adjusted according to the patient's body weight as follows:

• body weight less than 50 kg: 1 mg of terlipressin acetate (5 ml)
• body weight between 50 kg and 70 kg: 1.5 mg of terlipressin acetate (7.5 ml)
• body weight over 70 kg: 2 mg of terlipressin acetate (10 ml).

Maintenance dose: after the initial injection, the dose may be reduced to 1 mg of terlipressin acetate every 4–6 hours.
1–2 mg of terlipressin acetate correspond to 0.85–1.7 mg of terlipressin.
The approximate maximum daily dose of Terlipressina acetato EVER Pharma is 120 micrograms of terlipressin per kg of body weight.
Treatment should be limited to 2–3 days, depending on the response to therapy and the clinical course.
Terlipressina acetato EVER Pharma is administered by intravenous injection and must be given over one minute.

2. In type 1 hepatorenal syndrome:
   An intravenous injection of 1 mg of terlipressin acetate every 6 hours for at least 3 days. If, after 3 days of treatment, the reduction 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 in case of non-response (defined as less than 30% reduction 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 showing an incomplete response (reduction in serum creatinine of at least 30% compared to baseline but not achieving values below 1.5 mg/dl by day 7), treatment with terlipressin may be continued for up to a maximum of 14 days.
   In the majority of clinical studies supporting the use of terlipressin for the treatment of hepatorenal syndrome, human albumin was administered concomitantly at a dose of 1 g/kg body weight on the first day, followed by 20–40 g/day thereafter.
   The usual duration of treatment for hepatorenal syndrome is 7 days; the maximum recommended duration is 14 days.

Terlipressina acetato EVER Pharma should be used with caution in patients over 70 years of age and in patients with chronic renal failure.
The use of Terlipressina acetato EVER Pharma is not recommended in children and adolescents due to insufficient data on safety and efficacy.
Dose adjustment is not required in patients with hepatic insufficiency.

Preparation of the injection
To administer the medicinal product, withdraw the required volume from the vial using a syringe.
Store in the refrigerator (2°C–8°C). Do not freeze.
For single use only. Dispose of any unused solution.