GIAPREZA Concentrate for solution for infusion Ref.[51552] Active ingredients: Angiotensin II

GIAPREZA should be prescribed by a physician experienced in the treatment of shock and is intended for use in an acute and hospital setting.

Posology

The recommended starting dosage of GIAPREZA is 20 nanograms (ng)/kg per minute via continuous intravenous infusion.

GIAPREZA must be diluted in sodium chloride 9 mg/ml (0.9%) solution for injection prior to use. One or two millilitres of GIAPREZA must be diluted in sodium chloride 9 mg/ml (0.9%) solution for injection to achieve a final concentration of 5,000 ng/ml or 10,000 ng/ml (see Table 1).

Table 1. Preparation of diluted solution:

When initiating GIAPREZA, it is important to closely monitor blood pressure response and adjust dose accordingly.

Once an infusion has been established, the dose may be titrated as frequently as every 5 minutes in steps of up to 15 ng/kg per minute, as needed, depending on the patient’s condition and target mean arterial pressure. Approximately one in every four patients experienced transient hypertension with the angiotensin II 20 ng/kg per minute starting dose in clinical trials (see section 4.8), thus needing dose down-titration. For critically ill patients, the usual target mean arterial pressure is 65-75 mmHg. Do not exceed 80 ng/kg per minute during the first 3 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 to achieve or maintain adequate arterial blood pressure and tissue perfusion (see section 4.4). The median duration of treatment in clinical trials was 48 hours (range: 3.5 to 168 hours).

In order to minimise the risk of adverse events derived from prolonged vasoconstriction, treatment with GIAPREZA should be withdrawn once underlying shock is sufficiently improved (see section 4.4 and 4.8). Down-titrate by gradual decrements of up to 15 ng/kg per minute, as needed, based on blood pressure, in order to avoid hypotension due to abrupt withdrawal (see section 4.4).

Special populations

Elderly

There are limited efficacy and safety data of GIAPREZA in patients >75 years. No special dose adjustment is required in patients over 75 years. As for other age groups, it is important to closely monitor blood pressure response and adjust dose accordingly.

Renal or hepatic impairment

No special dose adjustment is required in patients with renal insufficiency or those with hepatic impairment (see section 5.2). As for other patient populations, it is important to closely monitor blood pressure response and adjust dose accordingly.

Paediatric population

The safety and efficacy of GIAPREZA in children less than 18 years old has not yet been established. No data are available.

Method of administration

GIAPREZA should only be administered by continuous intravenous infusion under close monitoring of haemodynamics and end-organ perfusion.

For intravenous use only after dilution. GIAPREZA is recommended to be administered via a central venous line.

For instructions on dilution of the medicinal product before administration, see section 6.6.

Overdose may result in severe hypertension. Down-titration of therapy, careful observation, and initiation of appropriate supportive measures are the indicated treatment of overdose of angiotensin II. Hypertensive effects are expected to be brief because the half-life of angiotensin II is less than one minute.

Unopened vial:

3 years.

Diluted solution:

Chemical and physical in-use stability has been demonstrated for 24 hours at room temperature and 2°C–8°C. From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C–8°C or 25°C.

Store in a refrigerator (2°C–8°C).

For storage conditions after dilution of the medicinal product, see section 6.3.

1 ml vial: 1 ml solution in a Type I glass vial with an aluminium over-seal, stopper (elastomeric), and plastic cap. Pack size of 1 or 10 vials per carton.

2 ml vial: 2 ml solution in a Type I glass vial with an aluminium over-seal, stopper (elastomeric), and plastic cap. Pack size of 1 vial per carton.

Not all pack sizes may be marketed.

For single dose only.

Instructions for preparation of the medicinal product before administration:

1. Inspect each vial for particulate matter prior to dilution.
2. Dilute 1 or 2 ml of GIAPREZA in sodium chloride 9 mg/ml (0.9%) solution for injection to achieve a final concentration of 5,000 ng/ml or 10,000 ng/ml.
3. Diluted solution should be clear and colourless.
4. Discard the vial and any unused portion of the medicinal product after use.

Diluted solution may be stored at room temperature or under refrigeration. Discard prepared solution after 24 hours at room temperature or under refrigeration.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.