Prospect: information for the patient

Giapreza 2.5 mg/ml concentrate for solution for infusion

angiotensin II

This medicine is subject to additional monitoring, which will expedite the detection of new information about its safety. You may contribute by reporting any adverse effects you experience. The final part of section 4 includes information on how to report these adverse effects.

Read this prospect carefully before this medicine is administered to you, because it contains important information for you.

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

Giaprezacontains the active ingredient angiotensin II, a compound normally produced by the body. It causes blood vessels to constrict and narrow, thereby increasing blood pressure.

Giaprezais used in emergency situations to increase blood pressure to normal levels in adult patients with severely low blood pressure that does not respond to treatment with fluids or other medications that elevate blood pressure.

You should not receive Giapreza:

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

Inform your doctor or nurse before this medication is administered to you if this is the case.

Warnings and precautions

Giaprezahas only been tested in people with septic and distributive shock.

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

This medication has been associated with the formation of blood clots.As part of your treatment, you will be given medications to prevent the formation of blood clots, unless your doctor does not consider it appropriate.

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

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

Children and adolescents

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

Other medications and Giapreza

Inform your doctor if you are using, have used recently, or may need to use any other medication.

Some medications may affect the functioning ofGiapreza, such as:

• Angiotensin-converting enzyme inhibitors (ACE inhibitors) such as enalapril (medications used to reduce blood pressure). ACE inhibitors may increase the effect ofGiapreza.
• Angiotensin II receptor antagonistssuch as candesartán(medications used to reduce blood pressure) may reduce the effect ofGiapreza.

Your doctor may already be giving you other medications to increase your blood pressure. The addition ofGiaprezato these medications may require a reduction in the dose of the other medications.

Pregnancy, breastfeeding, and fertility

Inform your doctor before this medication is administered to you if you are pregnant or breastfeeding, think you may be pregnant, or intend to become pregnant.

There is limited information available on the effects ofGiaprezaduring pregnancy. It should be avoided as much as possible during pregnancy.Your doctor will only give you this medication if the potential benefit outweighs the possible risks.

It is not known ifGiaprezais excreted in breast milk. Inform your doctor before this medication is administered to you if you are breastfeeding.

You should discontinue breastfeeding during treatment.

Sodium

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

Giapreza will be administered to you in a hospital by a doctor or nurse. First, it will be diluted and then administered through an intravenous infusion, 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 to reach the target blood pressure. Your doctor will continue to evaluate 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 of this medication, you will be removed from Giapreza as soon as your condition improves.

Patients with advanced age

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

Liver or kidney impairment

No dose adjustment is necessary for patients with liver or kidney dysfunction. 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 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 administered over time once your blood pressure has increased to acceptable levels. If treatment with Giapreza is stopped suddenly or too soon, you may experience a decrease in blood pressure or a worsening of your condition.

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

Like all medications, this medication may produce adverse effects,

although not all people will experience them.

Inform your doctorimmediatelyif you experience:

• Pain, redness, paleness, swelling, or coldness to the touch of the skin or extremities, as they may be symptoms of a blood clot in a vein. These clots can move 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 appear in more than 1 in 10 patients. Although not all these symptoms cause potentially fatal complications, you must inform your doctor immediately.

Other adverse effects are:

Adverse effectsvery frequent(may affect more than 1 in 10 people) are:

• Too high blood pressure.

Adverse effectscommon(may affect up to 1 in 10 people) are:

• Fast heart rate,
• Poor circulation in the hands, feet, or other areas of the body that can be severe and damage tissues.

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor, even if it is possible adverse effects that do not appear in this prospectus. You can also report them directly through thenational notification system included in theAppendix V. By reporting adverse effects, you can contribute to providing more information about the safety of this medication.

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

Do not use this medication after the expiration date that appears on the vial label after “EXP” and on the box after “CAD”. The expiration date is the last day of the month indicated.

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

The diluted solution must be used immediately. It has been demonstrated to have chemical and physical stability for 24 hours at room temperature and between 2 °C and 8 °C.

Do not use this medication if you observe any visible sign of damage or color change.

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. This will help protect the environment.

Composition of Giapreza

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

Appearance of the product and contents of the pack

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

Giaprezais supplied in a carton box containing 1 vial of 1 ml, 10 vials of 1 ml or 1 vial of 2 ml for single use. Only some pack sizes may be marketed.

Marketing Authorization Holder

PAION Pharma GmbH

Heussstraße 25

52078 Aachen

Germany

Responsible Person

PAION Deutschland GmbH

Heussstraße 25

52078 Aachen

Germany

PAION Pharma GmbH

Heussstraße 25

52078 Aachen

Germany

Further information on this medicinal product can be obtained from the local representative of the marketing authorization holder:

Last update of this leaflet: MM/AAAA.

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

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This information is intended solely for healthcare professionals

Dosage and administration

Only for intravenous use after dilution. It is recommended to administer Giapreza through a central venous access.

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

Instructions for dilution

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

Table 1:Preparation of the diluted solution

Administration

When starting treatment withGiapreza, it is essential to closely monitor blood pressure and adjust the dose accordingly.

Once the 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 the target mean arterial pressure. Approximately one in four patients experienced transient hypertension with the initial angiotensin II dose of 20 ng/kg per minute in clinical trials, so the dose had to be reduced. In critically ill patients, the usual target mean arterial pressure is 65-75 mm Hg. Do 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 essential to administerGiaprezaat 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: 3.5-168 hours).

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

Storage conditions

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

Dispose of unused medicinal product and all materials that have come into contact with it in accordance with local regulations.