Empesin

Package leaflet: Information for the user

Empesin, 40 IU/2 mL, concentrate for solution for infusion
Argipressinum
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet as you may need to read it again.
• If you have any further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm other people, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the leaflet

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

1. What Empesin is and what it is used for

Empesin is a synthetic active substance identical to the natural hormone vasopressin. It regulates the body's water balance and reduces urine excretion. Empesin is used in septic shock conditions, after unsuccessful application of other appropriate therapies, to achieve target arterial blood pressure values as determined by the physician.

2. Important information before using Empesin

When not to use Empesin

• if the patient is allergic to argipressin or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Precautions when using Empesin are necessary:

• if it is used to increase blood pressure after other methods have been applied. Administration must be performed under strict monitoring of vital parameters;
• if it is used in patients with cardiovascular diseases;
• if it is administered to patients with epilepsy, migraine, asthma, heart failure, or conditions where a sudden increase in extracellular water volume poses a risk;
• if the patient suffers from chronic kidney inflammation.

Children and adolescents
The use of Empesin for this indication is not recommended in children and newborns.
Empesin and other medicines
Caution is advised when administering Empesin together with carbamazepine,
chlorpropamide, clofibrate, urea, fludrocortisone, or tricyclic
antidepressants, as they may enhance the effect of Empesin. Caution is also advised when administering Empesin together with demeclocycline, noradrenaline, lithium compounds,
heparin, or alcohol, as they may weaken its effect. Concurrent use of Empesin with drugs affecting blood pressure may increase or decrease the blood pressure rise caused by Empesin.
Inform your doctor or pharmacist about all medicines currently taken or recently used, as well as any medicines the patient plans to take. This also includes medicines available without a prescription.
Taking Empesin with food and drink
Empesin must not be taken with alcohol.
Pregnancy and breastfeeding
Empesin may cause uterine contractions and increased intrauterine pressure during
pregnancy and may reduce uterine blood flow. Empesin should not be used during pregnancy
unless absolutely necessary.
It is unknown whether Empesin passes into human milk.
The use of Empesin is not recommended during pregnancy and breastfeeding.
Before taking any medicines, consult a doctor or pharmacist.
Driving and operating machinery
Studies on the influence of Empesin on the ability to drive and operate machinery have not been conducted.
Important information about certain excipients in Empesin
This medicine contains less than 1 mmol of sodium (23 mg) per dose, meaning the medicine is considered "sodium-free".

3. How to use Empesin

Empesin is administered by a doctor.
Empesin should be used only as an additional treatment to the usual therapy. Initially,
0.01 IU of Empesin per minute should be administered as an infusion. The dose may be increased every
15–20 minutes up to a maximum of 0.03 IU of Empesin per minute. Higher doses should be used
only in emergency situations.
Empesin is administered as a long-term infusion and must be diluted with physiological saline solution.
Use in children and adolescents
Empesin has been used to treat certain shock conditions in infants, young children,
and older children in intensive care units and operating rooms. However, the use of Empesin for this indication is not recommended in children and newborns.
Administration of a higher than recommended dose of Empesin
This medicine is administered by a doctor. If the patient believes that an excessive dose has been administered, medical advice should be sought immediately.
Discontinuation of Empesin treatment
Discontinuation of treatment with this medicine must be done gradually, meaning that treatment must not be stopped abruptly. If the patient believes that treatment has been discontinued too early, medical advice should be sought immediately. If there are any further doubts regarding the use of this medicine, consult a doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everybody will experience them.

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

• heart rhythm disorders,
• chest tightness,
• circulatory disturbances in the heart muscle, intestines or fingertips,
• peripheral vasoconstriction,
• tissue necrosis,
• abdominal cramps,
• perioral pallor,
• skin tissue necrosis.

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

• low blood sodium levels,
• tremor,
• dizziness,
• headache,
• reduced cardiac output,
• life-threatening change in heart rhythm,
• circulatory arrest,
• breathing difficulties due to airway constriction,
• nausea,
• vomiting,
• bloating,
• intestinal tissue necrosis,
• sweating,
• rash,
• changes in certain blood laboratory test results.

Rare (may occur in up to 1 in 1000 people):

• severe, life-threatening allergic reaction.

Unknown frequency (cannot be estimated from available data):

• water intoxication,
• transient diabetes insipidus after discontinuation.

Reporting of adverse reactions
If any adverse reactions occur in a patient, including any adverse reactions not listed in this leaflet, they should be reported to a doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products: Al. Jerozolimskie 181C, 02-222 Warsaw; tel.: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl.
Reporting adverse reactions helps to provide more information on the safety of the medicine. Adverse reactions may also be reported to the marketing authorization holder.

5. How to store Empesin

Keep the medicine out of the sight and reach of children.
Store in a refrigerator (2°C - 8°C).
Do not use this medicine after the expiry date stated on the label and carton following: EXP.
The expiry date refers to the last day of the stated month.
After opening, dilute and use immediately.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the package and other information

What Empesin contains

• The active substance is argipressin. One 2 mL vial of concentrate for solution for infusion contains 40 IU argipressin (equivalent to 133 micrograms), in the form of argipressin acetate.
• The other ingredients are: sodium chloride, glacial acetic acid (for pH adjustment), water for injections.

What Empesin looks like and contents of the pack
Empesin is a clear, colourless concentrate for solution for infusion.
Each pack contains 5 or 10 vials.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Orpha-Devel Handels und Vertriebs GmbH
Wintergasse 85/1B
3002 Purkersdorf
Austria

Manufacturer
AOP Orphan Pharmaceuticals GmbH
Leopold-Ungar-Platz 2
1190 Vienna
Austria

For further information about this medicine, please contact the local representative of the Marketing Authorisation Holder:
AOP Orphan Pharmaceuticals Poland Sp. z o.o.
[email protected]
Tel. +48 22 542 81 80

This medicine has been authorised in the countries of the European Economic Area under the following names:
Austria: Empesin 40 I.E./2 ml Konzentrat zur Herstellung einer Infusionslösung
Belgium: Reverpleg 40 I.E./2 ml concentraat voor oplossing voor infusie
Bulgaria: Емпресин 40 IU/2ml Концентрат за инфузионен разтвор
Croatia: Empressin 40 IU/ 2 ml koncentrat za otopinu za infuziju
Czech Republic: Embesin
Denmark: Empressin
Estonia: Empesin
Finland: Empressin 40 I.U./2 ml infuusiokonsentraatti, liuosta varten
France: Reverpleg 40 U.I./2ml solution à diluer pour perfusion
Greece: Empressin 40 I.U./2 ml Πυκνό διάλυμα για παρασκευή διαλύματος προς έγχυση
Spain: Empressin 40 I.U./2 ml concentrado para solución para perfusión
Netherlands: Empressine 40 I.E./2ml, concentraat voor oplossing voor infusie
Ireland: Embesin
Lithuania: Empesin
Luxembourg: Reverpleg 40 I.U./2 ml solution à diluer pour perfusion
Latvia: Empesin 40 SV/2 ml koncentrāts infūziju šķīduma pagatavošanai
Germany: Empressin 40 I.E./2 ml Konzentrat zur Herstellung einer Infusionslösung
Norway: Empressin
Poland: Empesin
Portugal: Empressin 40 U.I./2ml concentrado para solução para perfusão
Romania: Reverpleg
Slovakia: Embesin 40 I.U./2 mL infúzny koncentrát
Slovenia: Empesin 40 I.E./2 ml koncentrat za raztopino za infundiranje
Sweden: Empressin 40 I.E./2 ml koncentrat till infusionsvätska, lösning
Hungary: Embesyn 40 N.E./2ml koncentrátum oldatus infúzióhoz
Italy: Empressin 40 U.I. /2 ml concentrato per soluzione per infusione

Information intended exclusively for healthcare professionals:

Dosage and method of administration
Treatment with argipressin in patients with catecholamine-resistant hypotension should ideally be initiated within the first six hours after onset of septic shock or within three hours in patients receiving high-dose catecholamines (see section 5.1 of the SmPC). Argipressin should be administered as a continuous intravenous infusion at a dose of 0.01 IU per minute using an infusion/mechanical pump. Depending on the clinical response, the dose may be increased every 15–20 minutes up to 0.03 IU per minute. In intensive care patients, the target blood pressure is usually 65–75 mmHg. Argipressin should only be used as an adjunct to conventional catecholamine vasopressor therapy. Doses exceeding 0.03 IU per minute should only be used as rescue therapy, as they may cause intestinal and skin necrosis and increase the risk of circulatory arrest (see section 4.4 of the SmPC). The duration of treatment should be determined according to the individual clinical picture, but should ideally last at least 48 hours. Argipressin must not be discontinued abruptly; tapering should be performed gradually according to the patient's clinical condition. The total duration of argipressin treatment depends on the decision of the attending physician.

Prepare the infusion solution by diluting 2 mL of concentrate in 48 mL of sodium chloride 9 mg/mL (0.9%) solution (resulting in 0.8 IU of argipressin per mL). The total volume after dilution should be 50 mL.

Infusion rate according to recommended doses:

Children and adolescents
Vasopressin has been used for the treatment of vasodilatory shock in children and infants in intensive care units and during surgical procedures. Since vasopressin did not improve survival compared to standard treatment and showed higher rates of adverse events, its use in children and infants is not recommended.
Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 of the SmPC.
Special warnings and precautions for use
This product must not be used interchangeably with other medicinal products containing vasopressin expressed in different units (e.g. Pressor Units P.U.).
Vasopressin must not be administered as a bolus injection in the treatment of catecholamine-resistant shock.
Vasopressin must be administered only under strict and continuous monitoring of hemodynamic and organ-specific parameters.
Treatment with vasopressin should be initiated only when adequate perfusion pressure cannot be maintained despite appropriate volume replacement and administration of catecholaminergic vasopressors.
Particular caution is required when using vasopressin in patients with heart or vascular diseases. Reports indicate that administration of high doses of vasopressin in other indications may cause myocardial and intestinal ischemia, myocardial and intestinal infarction, and reduced limb perfusion.
Vasopressin may rarely cause water intoxication. Early signs such as drowsiness, apathy, and headache should be promptly recognized to prevent terminal coma and seizures.
Vasopressin should be used with caution in patients with epilepsy, migraine, asthma, heart failure, or any other condition where a sudden increase in extracellular water volume may pose a risk to an already overloaded system.
In the pediatric population, a positive benefit-risk ratio has not been demonstrated. The use of vasopressin for this indication in children and newborns is not recommended (see section 5.1 of the SmPC).