Corotrope

Package Leaflet: Information for the Patient

Corotrope,1 mg/ml, solution for injection
Milrinone

Read the package leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• In case of any doubts, consult a doctor.
• This medicine has been prescribed specifically for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If the patient experiences any side effects, including any possible side effects not listed in this leaflet, they should inform their doctor or nurse. See section 4.

Table of Contents of the Leaflet

• 1. What is Corotrope and what is it used for
• 2. Important information before using Corotrope
• 3. How to use Corotrope
• 4. Possible side effects
• 5. How to store Corotrope
• 6. Contents of the pack and other information

1. What is Corotrope and what is it used for

Corotrope contains the active substance milrinone. Milrinone is a synthetic compound with a positive inotropic effect, increasing the contractile force of the heart muscle, and vasodilating properties.
Corotrope is intended for short-term intravenous therapy of cardiac failure, including low output syndrome after cardiac surgery.
Children and adolescents

• Short-term treatment (up to 35 hours) of severe congestive heart failure (when the heart is unable to pump enough blood to the rest of the body), when other medications have been ineffective;
• Short-term treatment (up to 35 hours) of acute heart failure after heart surgery, i.e., when the heart has difficulty pumping blood throughout the body.

2. Important information before using Corotrope

When not to use the medicine:

• if the patient is hypersensitive to milrinone or any of the other ingredients of this medicine (listed in section 6),

Warnings and precautions

Before starting Corotrope, discuss it with your doctor. Particular caution should be exercised:

• in patients with severe aortic or pulmonary valve stenosis and with hypertrophic subaortic stenosis,
• in patients in the acute phase of myocardial infarction,
• in patients who have developed excessive hypotension before or during milrinone treatment,
• in patients at high risk of ventricular and supraventricular arrhythmias,
• in patients taking diuretics. The doctor may recommend monitoring blood pressure, heart rate, and clinical symptoms,
• in patients taking digitalis glycosides,
• in patients with severe renal failure,
• in patients with decreased platelet count or hemoglobin,
• in patients with decreased potassium levels in the blood.

During milrinone treatment, the doctor will closely monitor blood pressure, heart rate, clinical condition, ECG, fluid balance, electrolytes, and kidney function (e.g., serum creatinine levels). In case of disorders, medical personnel will take corrective action.
As a result of Corotrope's action, there is an increase in urine output. This may lead to potassium deficiency in the blood. In such cases, medical personnel will administer potassium.
There are no data from clinical trials on the use of milrinone in infusion for more than 48 hours.
Cases of reactions at the injection site have been observed (see section "Possible side effects"). Therefore, the injection site should be carefully monitored to avoid extravascular administration.
There are no special recommendations for elderly patients.
Dosing in patients with renal impairment should be modified (see section 3).

Children and adolescents

Before administering Corotrope in infusion, the doctor will check several parameters, such as heart rate and blood pressure. The doctor will also order blood tests.
Infusion will not be started if the child's heart rate and blood pressure are not stable.
Tell your doctor if:

• the child has kidney problems,
• the child is premature or has low birth weight,
• the child has a heart defect - persistent ductus arteriosus: a connection between the two major blood vessels (aorta and pulmonary artery) that should be closed. In such cases, the doctor will decide whether the child will be treated with Corotrope.

Corotrope and other medicines

Tell your doctor about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take.
Administering furosemide or bumetanide and milrinone in the same infusion set can cause precipitation. Therefore, furosemide or bumetanide should not be administered with milrinone in the same infusion set.
Milrinone should not be diluted with sodium bicarbonate solution.
Due to limited data on interactions, the Corotrope medicinal product should not be mixed with other medicines.
Administration of Corotrope may result in the need to reduce the dose of diuretics.
During Corotrope treatment, the doctor will closely monitor fluid and electrolyte balance and serum creatinine levels. If cardiac function improves, the doctor may reduce the dose of diuretics.
Patients treated with Corotrope and digitalis glycosides should be closely monitored for potassium levels in the blood and supplemented if necessary, as potassium deficiency can cause arrhythmias, especially in these patients.
Concomitant use of Corotrope and other medicines with positive inotropic effects, i.e., increasing the contractile force of the heart, results in enhanced effects of Corotrope.
The doctor may adjust the dosage as needed during concomitant use of Corotrope and other blood pressure-lowering treatments.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, consult your doctor before using this medicine.

Driving and using machines

The effect of Corotrope on the ability to drive and use machines is not known.

Corotrope contains sodium

The medicine contains less than 1 mmol (23 mg) of sodium per ampoule, i.e., the medicine is considered "sodium-free".

3. How to use Corotrope

For intravenous use only.
Before administration, check that the solution in the ampoule is colorless and clear.
Milrinone treatment starts with a loading dose, followed by a maintenance dose administered as a continuous infusion according to the following scheme.

Adults

Loading dose: 50 μg/kg body weight, administered slowly intravenously over at least 10 minutes.
The following table shows the loading dose of milrinone (for a concentration of 1 mg/ml) in milliliters, calculated based on the patient's body weight (kg).

The loading dose can be administered undiluted, but dilution to a rounded total volume of 10 ml or 20 ml may facilitate monitoring of the infusion rate (over 10 minutes).
The following solutions can be used for dilution: 0.45% sodium chloride, 0.9% sodium chloride, or 5% glucose solution.
Corotrope should not be diluted with sodium bicarbonate. The diluted solution should be used within 24 hours.
Maintenance dose: 0.375 to 0.75 μg/kg body weight/min. The infusion rate should be adjusted according to the hemodynamic and clinical response.
The daily dose should not exceed 1.13 mg/kg body weight. Solutions of different concentrations can be administered, depending on the patient's fluid requirements.
MAINTENANCE DOSE

Patients with renal impairment

In patients with renal impairment, the dosage of Corotrope should be adjusted. Data from studies in patients with severe renal impairment but without signs of cardiac failure showed that the elimination half-life of milrinone in plasma is significantly prolonged.
There is no need to change the initial dose, but the maintenance dose should be reduced according to the following table:
The duration of treatment should be adjusted according to the observed improvement in the patient's condition.
Do not use for more than 5 days.

Use in children and adolescents

• The doctor should administer the first dose to the child in the range of 50 to 75 micrograms per kilogram of the child's body weight, over a period of 30 to 60 minutes.
• Then, a dose of 0.25 to 0.75 micrograms per kilogram of body weight per minute is administered, depending on the child's clinical response to treatment and the occurrence of side effects. Corotrope can be administered for up to 35 hours.

During infusion, the child will be closely monitored. The doctor will check several parameters, such as heart rate and blood pressure. A blood sample will also be taken to assess the response to treatment and the occurrence of side effects.

Elderly patients

There are no special recommendations for elderly patients. No relationship has been observed between the frequency of side effects and the patient's age. Controlled pharmacokinetic studies have not revealed any age-related differences in the distribution and elimination of milrinone.

Using a higher dose of Corotrope than recommended

Using high doses of milrinone may cause hypotension and arrhythmias.
In such cases, milrinone administration should be discontinued until the patient's clinical condition stabilizes.
There is no specific antidote. Treatment is symptomatic and supportive of the circulatory system.

Missing a dose of Corotrope

Do not take a double dose to make up for a missed dose or take two doses of the medicine in a short period.
If you have any further doubts about using this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, Corotrope can cause side effects, although not everybody gets them.
Side effects are presented in order of decreasing frequency.

Frequent(may affect up to 1 in 10 patients):

• ventricular extrasystoles, transient or sustained ventricular tachycardia, supraventricular arrhythmias, arterial hypotension, headaches, usually mild or moderate.

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

• ventricular fibrillation, angina pectoris - chest pain, thrombocytopenia, abnormal liver function test results, tremors, decreased potassium levels in the blood.

Rare(may affect up to 1 in 10,000 patients):

• torsades de pointes(polymorphic ventricular tachycardia), anaphylactic shock, bronchospasm, skin reactions such as rash.

Frequency not known(cannot be estimated from the available data):

• decreased red blood cell count and/or hemoglobin,
• reaction at the injection site,
• renal failure, secondary to concomitant hypotension. The following side effects have been reported in children:

Frequency not known(cannot be estimated from the available data):

• bleeding into fluid-filled areas (ventricles) surrounding the brain (intraventricular hemorrhage),
• persistent ductus arteriosus - a heart defect where the connection between the two major blood vessels (aorta and pulmonary artery) remains open, which can lead to excess fluid in the lungs, bleeding, intestinal damage, or part of the intestine, and can be fatal.

Compared to adults, a decrease in platelet count appears to occur more frequently in children, and the risk of this side effect increases with the duration of Corotrope infusion.
It appears that rhythm disorders occur less frequently in children than in adults.
Some people may experience other side effects while using Corotrope.

Reporting side effects

If you experience any side effects, including any side effects not listed in the leaflet, tell your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Monitoring of Adverse Reactions to Medicinal Products, Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products.
Jerozolimskie Avenue 181 C, 02-222 Warsaw, Tel.: +48 22 49 21 301, Fax: +48 22 49 21 309, Website: https://smz.ezdrowie.gov.pl Side effects can also be reported to the marketing authorization holder or its representative in Poland. Reporting side effects will help gather more information on the safety of the medicine.

• Sanofi Sp. z o.o., ul. Marcina Kasprzaka 6, 01-211 Warsaw, Tel.: +48 22 280 00 00

5. How to store Corotrope

Store in a temperature below 25°C. Do not freeze.
Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the month.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the pack and other information

What Corotrope contains

• The active substance of Corotrope is milrinone. 1 ml of the solution for injection contains 1 mg of milrinone. The other ingredients are: lactic acid, anhydrous glucose, water for injection, sodium hydroxide, and/or lactic acid (to adjust pH).

What Corotrope looks like and contents of the pack

The pack contains 10 ampoules of 10 ml each.

Marketing authorization holder and manufacturer

Marketing authorization holder:
Sanofi Winthrop Industrie
82, Avenue Raspail
94250 Gentilly
France
Manufacturer:
Delpharm Dijon
6, boulevard de l’Europe
21800 Quetigny
France

For more information, contact the representative of the marketing authorization holder in Poland:

Sanofi Sp. z o.o.
ul. Marcina Kasprzaka 6
01-211 Warsaw
Tel.: +48 22 280 00 00

Date of last revision of the leaflet: