GIAPREZA 2.5 mg/mL concentrate for infusion solution

Introduction

Package Leaflet: Information for the Patient

Giapreza 2.5 mg/ml Concentrate for Solution for Infusion

Angiotensin II

This medicinal product is subject to additional monitoring, which will allow for quick identification of new safety information. You can help by reporting any side effects you may get. See the end of section 4 for how to report side effects.

Read all of this leaflet carefully before this medicine is given to you because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or nurse.
• If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is Giapreza and what is it used for

Giapreza contains the active substance angiotensin II, a compound that is normally produced by the body. It makes blood vessels constrict and narrow, which increases blood pressure.

Giapreza is used in emergency situations to increase blood pressure to normal values in adult patients with severely low blood pressure who do not respond to treatment with fluids or other medicines that increase blood pressure.

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

You should not be given Giapreza:

• if you are allergic to angiotensin II or any of the other ingredients of this medicine (listed in section 6).

Tell your doctor or nurse before you are given this medicine if this applies to you.

Warnings and precautions

Giapreza has only been tested in people with septic and distributive shock.

It has not been tested in other types of cardiocirculatory shock.

This medicine has been associated with the formation of blood clots. As part of your treatment, you will be given medicines to prevent the formation of blood clots, unless your doctor considers it inappropriate.

When you first receive Giapreza, it is expected to increase your blood pressure. You will be closely monitored to ensure that your blood pressure is at the right level.

Tell your doctor or nurse immediately if you experience a change in color (redness or paleness), pain or numbness of any of the limbs or if any of the limbs are cold to the touch, as these could be signs that a blood clot has blocked the blood flow in a part of the body.

Children and adolescents

Giapreza should not be used in children or adolescents under 18 years of age, as it has not been studied in these age groups.

Other medicines and Giapreza

Tell your doctor if you are taking, have recently taken or might take any other medicines.

Some medicines may affect the way Giapreza works, such as:

• Angiotensin-converting enzyme inhibitors (ACE inhibitors) such as enalapril (medicines used to lower blood pressure). ACE inhibitors may increase the effect of Giapreza.
• Angiotensin II receptor antagonists such as candesartan (medicines used to lower blood pressure) may reduce the effect of Giapreza.

It is possible that your doctor is already giving you other medicines to increase your blood pressure. The addition of Giapreza to these medicines may make it necessary to reduce the dose of the other medicines.

Pregnancy, breastfeeding and fertility

Tell your doctor before you are given this medicine if you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby.

There is limited information on the effects of Giapreza during pregnancy. It should be avoided whenever possible during pregnancy. Your doctor will only give you this medicine if the possible benefit is greater than the possible risks.

It is not known whether Giapreza is excreted in breast milk. Tell your doctor before you are given this medicine if you are breastfeeding.

Breastfeeding should be discontinued during treatment.

Sodium

This medicine contains less than 1 mmol of sodium (23 mg) per 2.5 mg/1 ml, which is essentially "sodium-free".

3. How Giapreza is given

Giapreza will be given to you in a hospital by a doctor or nurse. It is first diluted and then given by drip (infusion) into a vein, providing a specific dose every minute.

The dose depends on your body weight. The recommended initial dose of Giapreza is 20 nanograms (ng) per kilogram of body weight per minute. After the initial dose, your doctor will adjust the dose every 5 minutes until the target blood pressure is reached. Your doctor will continue to evaluate your response and adjust the dose as needed up to a maximum of 80 ng per kilogram per minute during the first three hours of treatment. The maximum dose after the first three hours will be 40 ng per kilogram per minute.

Giapreza will be given to you at the lowest dose that helps you achieve or maintain your blood pressure. To minimize the risk of side effects from this medicine, Giapreza will be withdrawn as soon as your condition improves.

Elderly patients

Giapreza has been tested in a small number of patients over 75 years of age. No dose adjustment is necessary in patients over 75 years of age. Your doctor will monitor your blood pressure and adjust your dose as needed.

Liver or kidney problems

No dose adjustment is necessary in patients with impaired liver or kidney function. Your doctor will monitor your blood pressure and adjust your dose as needed.

If you receive more Giapreza than you should

Giapreza will be given to you by a doctor or nurse, so it is unlikely that you will receive an incorrect dose. However, if you experience side effects or think you have received too much Giapreza, tell your doctor or nurse immediately. If you receive too much Giapreza, you may experience high blood pressure. In this case, hospital staff will monitor your vital signs and provide supportive treatment.

Stopping treatment with Giapreza

Your doctor will gradually reduce the amount of Giapreza given to you over time once your blood pressure has increased to adequate levels. If Giapreza is stopped suddenly or too soon, you may experience a decrease in blood pressure or your condition may worsen.

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

4. Possible side effects

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

Tell your doctor immediately if you experience:

• Pain, redness or paleness, swelling or coldness to the touch of the skin or limbs, as these may be symptoms of a blood clot in a vein. These clots can travel through the blood vessels to the lungs and cause chest pain and difficulty breathing. If you notice any of these symptoms, see a doctor immediately. These types of symptoms occur in more than 1 in 10 patients. Although not all these symptoms cause potentially life-threatening complications, you should tell your doctor immediately.

Other side effects are:

The very common side effects (may affect more than 1 in 10 people) are:

• high blood pressure.

The common side effects (may affect up to 1 in 10 people) are:

• fast heartbeat,
• poor circulation in the hands, feet or other areas of the body which can be severe and damage tissues.

Reporting of side effects

If you experience any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Giapreza

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 vial label after "EXP" and on the carton after "CAD". The expiry date is the last day of the month shown.

Store in a refrigerator (between 2°C and 8°C).

The diluted solution should be used immediately. It has been shown to be chemically and physically stable for 24 hours at room temperature and between 2°C and 8°C.

Do not use this medicine if you notice any visible signs of damage or change in color.

Medicines should 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 pack and other information

What Giapreza contains

• The active substance is angiotensin II acetate. Each milliliter contains angiotensin II acetate equivalent to 2.5 mg of angiotensin II.
• A 1 ml vial of concentrate for solution for infusion contains 2.5 mg of angiotensin II.
• A 2 ml vial of concentrate for solution for infusion contains 5 mg of angiotensin II.
• The other ingredients are mannitol and water for injections with pH adjusted with sodium hydroxide and/or hydrochloric acid (see section 2 in "Sodium").

Appearance and pack size

Giapreza 2.5 mg/ml is presented as a concentrate for solution for infusion (sterile concentrate). The solution is a clear and colorless solution without visible particles.

Giapreza is supplied in a carton containing 1 vial of 1 ml, 10 vials of 1 ml or 1 vial of 2 ml for single use. Not all pack sizes may be marketed.

Marketing authorisation holder

PAION Pharma GmbH

Heussstraße 25

52078 Aachen

Germany

Manufacturer

PAION Deutschland GmbH

Heussstraße 25

52078 Aachen

Germany

PAION Pharma GmbH

Heussstraße 25

52078 Aachen

Germany

You can get more information about this medicine from the local representative of the marketing authorisation holder:

Date of last revision of this leaflet: MM/AAAA.

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu.

--------------------------------------------------------------------------------------------------------------

This information is intended only for healthcare professionals.

Dosage and administration

For intravenous use only after dilution. Administration of Giapreza through a central venous access line is recommended.

Giapreza should only be administered by continuous intravenous infusion under close monitoring of hemodynamic and organ function parameters.

Instructions for dilution

1. Inspect each vial for visible particles before dilution.
2. Dilute 1 or 2 ml of Giapreza in a 9 mg/ml (0.9%) sodium chloride injection solution to obtain a final concentration of 5,000 ng/ml or 10,000 ng/ml.
3. The diluted solution should be clear and colorless.
4. Discard the vial and any unused portion of the medicine after use.

Table 1:Preparation of the diluted solution

Administration

When starting treatment with Giapreza, it is important to closely monitor the blood pressure response and adjust the dose accordingly.

Once an infusion is established, the dose can be adjusted with a frequency of up to every 5 minutes in increments of up to 15 ng/kg per minute, as needed, depending on the patient's condition and mean arterial pressure target. Approximately one in four patients experienced transient hypertension with the initial dose of angiotensin II of 20 ng/kg per minute in clinical trials, so it was necessary to reduce the dose. In critically ill patients, the usual mean arterial pressure target is 65-75 mm Hg. The dose should not exceed 80 ng/kg per minute during the first three hours of treatment. Maintenance doses should not exceed 40 ng/kg per minute. Doses of up to only 1.25 ng/kg per minute can be used.

It is important to administer Giapreza at the lowest compatible dose to achieve or maintain adequate blood pressure and tissue perfusion. The median duration of treatment in clinical trials was 48 hours (range: 3.5 to 168 hours).

In order to minimize the risk of adverse reactions from prolonged vasoconstriction, treatment with Giapreza should be discontinued once the underlying cardiocirculatory shock has improved sufficiently. The dose should be reduced gradually in increments of up to 15 ng/kg per minute, as needed, based on blood pressure, to avoid withdrawal-induced hypotension.

Storage conditions

Store in a refrigerator (between 2°C and 8°C). Dilute before use. Administer as a diluted solution.

The diluted solution can be stored at room temperature or refrigerated. Discard the prepared solution after 24 hours at room temperature or refrigerated.

Disposal of unused medicine and all materials that have been in contact with it should be done in accordance with local regulations.