Giapreza 2.5 mg/ml concentrate for solution for infusion

Package leaflet: Information for the user

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 faster detection of new safety information. You can help by reporting any adverse reactions you may experience. Information on how to report adverse reactions is included at the end of section 4.

Read the entire leaflet carefully before you are administered this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor.
• If you experience any adverse reactions, consult your doctor, even if they are possible adverse reactions not listed in this leaflet. See section 4.

Contents of this leaflet

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

1. What Giapreza is and what it is used for

Giapreza contains the active substance angiotensin II, a compound normally produced by the body. It causes blood vessels to contract and narrow, thereby increasing blood pressure.

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

2. What you need to know before Giapreza is administered to you

Do not receive Giapreza:

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

Tell your doctor or nurse before you are given this medicine if any of these apply to you.

Warnings and precautions

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

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

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

When you first receive Giapreza, an increase in your blood pressure is expected. You will be closely monitored to ensure that your blood pressure reaches the appropriate level.

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

Children and adolescents

Giapreza must 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 need to take any other medicines.

Some medicines may affect how Giapreza works, such as:

• Angiotensin-converting enzyme (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), which may reduce the effect of Giapreza.

Your doctor may already be giving you other medicines to increase your blood pressure. Adding Giapreza to these medicines may require reducing 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 plan to become pregnant.

Information on the effects of Giapreza during pregnancy is limited. Use of this medicine during pregnancy should be avoided whenever possible. Your doctor will administer this medicine only if the potential benefit outweighs the potential risks.

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

Breastfeeding must be discontinued during treatment.

Sodium

This medicine contains less than 1 mmol of sodium (23 mg) per 2.5 mg/1 ml; therefore, it is essentially “sodium-free”.

3. How to use Giapreza

Giapreza will be administered to you in a hospital setting by a doctor or nurse. It is first diluted and then given as an intravenous infusion (drip), delivering a specific dose per minute.

The dose is based on 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 achieved. Your doctor will continue to monitor your response and adjust the dose accordingly, 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 administered at the lowest dose that helps you achieve or maintain your blood pressure. To minimize the risk of adverse effects from this medicine, Giapreza will be discontinued as soon as your condition improves.

Elderly patients

Giapreza has been studied in a small number of patients over 75 years of age. Dose adjustment is not necessary in patients over 75 years of age. Your doctor will monitor your blood pressure and adjust your dose as needed.

Hepatic or renal impairment

Dose adjustment is not 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 administered by a doctor or nurse, so it is unlikely that you will receive an incorrect dose. However, if you experience adverse effects or think you have received too much Giapreza, inform your doctor or nurse immediately. If you receive too much Giapreza, you may experience high blood pressure. In such a case, hospital staff will monitor your vital signs and provide supportive treatment.

Discontinuation of Giapreza treatment

Your doctor will gradually reduce the amount of Giapreza administered over time once your blood pressure has increased to adequate levels. If Giapreza administration is stopped suddenly or too early, you may experience a drop in blood pressure or worsening of your condition.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone 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 may travel through the blood vessels to the lungs and cause chest pain and difficulty breathing. If you notice any of these symptoms, consult a doctor immediately. These types of symptoms occur in more than 1 in 10 patients. Although not all of these symptoms lead to potentially life-threatening complications, you must inform your doctor immediately.

Other adverse effects are:

Very common adverse effects (may affect more than 1 in 10 people) are:

• blood pressure too high.

Common adverse 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 may be severe and cause tissue damage.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Giapreza

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the vial label after "EXP" and on the carton after "CAD". The expiry date refers to the last day of the month indicated.

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

The diluted solution should be used immediately. Chemical and physical stability has been demonstrated 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 colour.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and containers you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Giapreza

• The active substance is angiotensin II acetate. Each millilitre 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 components are mannitol and water for injectable preparations, with pH adjusted with sodium hydroxide and/or hydrochloric acid (see section 2 under “Sodium”).

Nature and contents of the container

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

Giapreza is supplied in a cardboard box containing 1 vial of 1 ml, 10 vials of 1 ml, or 1 vial of 2 ml, for single use. Only certain pack sizes may be marketed.

Marketing Authorization Holder

PAION Pharma GmbH

Heussstraße 25

52078 Aachen

Germany

Manufacturer responsible for batch release

PAION Deutschland GmbH

Heussstraße 25

52078 Aachen

Germany

PAION Pharma GmbH

Heussstraße 25

52078 Aachen

Germany

For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

Date of the most recent revision of this leaflet: MM/YYYY.

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

This information is intended for healthcare professionals only

Dosing and method of administration

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

Giapreza must only be administered by continuous intravenous infusion under close monitoring of haemodynamic and organ parameters.

Dilution instructions

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

Table 1: Preparation of the diluted solution

Administration

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

Once an infusion has been established, the dose may be adjusted at intervals 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 the target mean arterial pressure. In clinical trials, approximately one in four patients experienced transient hypertension with the initial angiotensin II dose of 20 ng/kg per minute, necessitating dose reduction. In critically ill patients, the usual target mean arterial pressure is 65–75 mm Hg. Doses exceeding 80 ng/kg per minute should not be used during the first three hours of treatment. Maintenance doses should not exceed 40 ng/kg per minute. Doses as low as 1.25 ng/kg per minute may be used.

It is important to administer Giapreza at the lowest compatible dose required 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).

To minimize the risk of adverse reactions due to prolonged vasoconstriction, Giapreza treatment should be discontinued once the underlying cardiocirculatory shock has sufficiently improved. The dose should be gradually reduced by up to 15 ng/kg per minute, as needed, based on blood pressure, to avoid hypotension due to abrupt withdrawal.

Storage conditions

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

The diluted solution may be stored at room temperature or under refrigeration. Discard the prepared solution after 24 hours, whether stored at room temperature or refrigerated.

Disposal of unused medication and of all materials that have come into contact with it must be carried out in accordance with local regulations.