Prostin VR

Package leaflet: Information for the user

PROSTIN VR 500 mcg/1 ml injectable solution

Alprostadil
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

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

1. What Prostin VR is and what it is used for

Prostin VR contains the active substance alprostadil, which belongs to a group of medicines called prostaglandins and works by dilating blood vessels.
This medicine is used in newborns who are born with heart problems, to temporarily keep open the ductus arteriosus until surgical intervention can be performed.
The ductus arteriosus (or ductus arteriosus of Botallo) is a blood vessel present in all newborns and normally closes after birth, when the lungs begin to breathe. However, sometimes it is necessary to keep it open with medicines (such as Prostin VR) when a newborn is born with heart problems, while awaiting surgical correction of these conditions.

2. What you need to know before using Prostin VR

Do not use Prostin VR if the child:

• is allergic to alprostadil or to any of the other ingredients of this medicine (listed in section 6). Warnings and precautions Talk to the doctor, pharmacist, or nurse before using Prostin VR.

Tell the doctor before using Prostin VR if your child:

• has a tendency to bleed easily;
• has difficulty breathing due to a lung condition called “respiratory distress syndrome/hyaline membrane disease”. This condition occurs shortly after birth, especially if your child was born prematurely.

During treatment with Prostin VR, your child may develop one of the following conditions:

• temporary stop in breathing ( apnea );
• bone problems that tend to resolve after stopping treatment;
• weakening of the wall of certain blood vessels (ductus arteriosus and pulmonary artery), which could make surgical intervention more difficult;
• stomach problems, which may cause an obstruction in the passage of food from the stomach to the intestine (antral hyperplasia).

Laboratory tests
Careful and regular monitoring will be performed during treatment with Prostin VR to determine the most appropriate dose of this medicine.
Other medicines and Prostin VR
Tell the doctor, pharmacist, or nurse if your child is taking, has recently taken, or might take any other medicines.
Inform the doctor if your child is taking insulin (a medicine used in diabetes), as concomitant use with Prostin VR could cause an excessive decrease in blood glucose levels.
Prostin VR contains alcohol
This medicine contains small amounts of ethanol (alcohol), less than 100 mg per dose.

3. How to use Prostin VR

This medicine must be administered to your child only by experienced doctors within suitable healthcare facilities equipped with a paediatric intensive care unit.
Prostin VR will be administered to your child via injection into a large vein, or alternatively into the umbilical artery or directly into the ductus arteriosus of Botallo.
The recommended initial dose is 0.05–0.1 micrograms per kg of body weight per minute.
During treatment with Prostin VR, the doctor will carefully monitor your child's condition in order to determine the most appropriate dose.
If more Prostin VR has been administered than intended
If you think your child has been given more Prostin VR than necessary, inform the doctor, pharmacist, or nurse immediately, as the following symptoms may occur (see also section 4 "Possible side effects"):
temporary cessation of breathing (apnoea);
reduction in heart rate (bradycardia);
fever (pyrexia);
decrease in blood pressure (hypotension);
flushing.
The doctor will take the most appropriate measures depending on your child's condition.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The following side effects may occur:
Very common (may affect more than 1 in 10 people):

• interruption of breathing (apnea)
• transient fever

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

• seizures
• decreased or increased heart rate (bradycardia/tachycardia)
• decrease in blood pressure (hypotension)
• diarrhoea
• hot flushes

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

• obstruction blocking the passage of food from the stomach to the intestine (gastric obstruction)
• thickening of the stomach wall (hypertrophy of gastric mucosa)
• formation of bony protrusions, especially on the legs and arms (exostoses)
• fragility of blood vessels

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system at www.agenziafarmaco.gov.it/it/responsabili. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Prostin VR

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and vial after "Exp.".
The expiry date refers to the last day of that month.
Store in a refrigerator (2°C – 8°C).
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Prostin VR contains
The active substance is alprostadil.
Each vial contains 500 micrograms of alprostadil.
The other component is: dehydrated alcohol (see section 2, "Prostin VR contains alcohol").

Description of the appearance of Prostin VR and package contents
The Prostin VR injectable solution 500 micrograms/ml is available in a pack containing 1 glass vial of 1 ml with a safety pre-break point.

Marketing Authorization Holder
Pfizer Italia S.r.l.
Via Isonzo, 71
04100 Latina, Italy

Manufacturer
Pfizer Manufacturing Belgium N.V.
Rijksweg 12
Puurs, 2870 Belgium

The following information is intended exclusively for physicians or healthcare professionals

PROSTIN VR 500 mcg/1 ml injectable solution
Alprostadil
DOSAGE AND ADMINISTRATION
Prostin VR sterile solution must be diluted prior to administration.
It is preferable to administer Prostin VR sterile solution via continuous intravenous infusion using a large vein. Alternatively, Prostin VR may be administered through a catheter inserted into the umbilical artery and positioned at the level of the ductus arteriosus opening. In neonates where both of the above administration routes have been used, equivalent increases in blood pO₂ have been observed.
The infusion should begin at a rate of 0.05–0.1 micrograms of alprostadil per kilogram of body weight per minute. Good results have also been reported using lower initial doses; however, these data are largely anecdotal.
In most cases, an initial dose of 0.1 micrograms/kg/min has been used.
After achieving a therapeutic response (defined as an increase in pO₂ in neonates with restricted pulmonary blood flow, or an increase in systemic arterial pressure and pH in neonates with restricted systemic blood flow), the infusion rate should be reduced to reach the lowest effective dosage, practically decreasing the dosage stepwise from 0.1 to 0.05 to 0.025 to 0.001 micrograms per kilogram of body weight per minute.
If an adequate response is not achieved with an initial dose of 0.1 micrograms/kg/min, the dosage may be increased up to 0.4 micrograms/kg/min, although in general, higher infusion rates do not produce increased efficacy.

DILUTION INSTRUCTIONS
To prepare infusion solutions, dilute 1 ml of Prostin VR sterile solution with a sterile intravenous infusion solution of sodium chloride or dextrose to achieve the volume required by the available infusion system. Prepare fresh infusion solutions every 24 hours. Discard any solution older than 24 hours.

The table below provides guidance for determining the infusion rate of a diluted Prostin VR sample to deliver a dosage of 0.05 or 0.1 micrograms of alprostadil per kilogram of body weight per minute.

DILUTION AND INFUSION RATES FOR PROSTIN VR

| Dilution volume | Approximate concentration | Infusion rate (ml/min/kg) to | Infusion rate (ml/min/kg) to |
|---------------------|-------------------------------|----------------------------------|----------------------------------|
| of one vial | of solution (micrograms/ml) | administer 0.05 micrograms/kg/min | administer 0.1 micrograms/kg/min |
| (500 micrograms) | | of alprostadil | of alprostadil |
| 250 ml | 2 | 0.025 | 0.05 |
| 100 ml | 5 | 0.01 | 0.02 |
| 50 ml | 10 | 0.005 | 0.01 |
| 25 ml | 20 | 0.0025 | 0.005 |

Example: To administer 0.1 micrograms/kg/min of body weight to a neonate weighing 2.8 kg, when diluting one vial of Prostin VR in 100 ml of physiological saline or glucose solution, the infusion rate = 0.02 ml/min per kg × 2.8 kg = 0.056 ml/min, or 3.36 ml/h.