COROTROPE 1 mg/ml INJECTABLE SOLUTION

Introduction

Package Leaflet: Information for the User

Corotrope 1 mg/ml Solution for Injection

Milrinone Lactate

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the Package Leaflet

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

1. What is Corotrope and what is it used for

Corotrope belongs to a group of medicines known as cardiac stimulants (used to increase the force with which the heart contracts).

Corotrope is used in the short-term treatment of acute congestive heart failure (the heart cannot pump enough blood to the whole body).

Corotrope may be used in children for:

• short-term treatment (up to 35 hours) of severe congestive heart failure (the heart cannot pump enough blood to the rest of the body) when other medicines have not worked.
• short-term treatment (up to 35 hours) of acute heart failure after heart surgery, i.e., when the heart has problems pumping blood to the whole body.

2. What you need to know before you use Corotrope

Do not use Corotrope

• if you are allergic to the active substance or to any of the other ingredients of this medicine (listed in section 6).
• if your total blood volume has decreased (hypovolemia)

Warnings and Precautions

Talk to your doctor before starting to use Corotrope:

• if you are pregnant or breastfeeding (see section "Pregnancy and Breastfeeding").
• if you have had a heart attack.
• if you have an abnormal heart rhythm.
• if you have severe heart problems.
• if you have low blood pressure (tension).

Tell your doctor if you have any severe kidney disease.

When you are given Corotrope, your doctor will continuously monitor your blood pressure, heart rate, general clinical condition, electrocardiogram, fluid levels in your body, and/or kidney function. Blood tests may also be performed to check your platelet levels (elements in the blood that contribute to blood clotting) and hemoglobin levels (component of red blood cells).

Children

The following information should be taken into account in addition to the warnings and precautions described above for adults.

Before administering the Corotrope infusion, your doctor will perform checks on many parameters such as heart rate and blood pressure. Blood tests will also be performed.

The infusion will not be started if the heart rate and blood pressure are not stable.

Please inform your doctor if:

• your child has kidney problems
• your child is premature or has a low birth weight
• your child has a heart problem called patent ductus arteriosus: a connection between 2 major blood vessels (aorta and pulmonary artery) that persists although it should be closed.

In these cases, your doctor will decide if your child will be treated with Corotrope.

Using Corotrope with other medicines

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

When furosemide (a diuretic: a medicine used to eliminate fluid) is administered intravenously together with milrinone, an immediate chemical interaction occurs, forming a precipitate. Therefore, furosemide should not be administered together with milrinone intravenously. Milrinone lactate should not be diluted in solutions for intravenous infusion that contain sodium bicarbonate.

Pregnancy and Breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.

There are no adequate controlled studies in pregnant or breastfeeding women. Milrinone lactate may be used during these periods at the doctor's discretion and only when the potential benefit justifies the potential risks to the fetus. The conditions for use, as well as the interest of milrinone in acute myocardial infarction in children, have not yet been determined, so the use of milrinone in these cases is not recommended.

Corotrope contains glucose

This medicine contains glucose. Patients with diabetes mellitus should note that this medicine contains 0.47 g of glucose per 10 ml ampoule.

Corotrope contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per ml of injectable solution; this is, essentially "sodium-free".

3. How to use Corotrope

Follow exactly the administration instructions of this medicine indicated by your doctor. If in doubt, ask your doctor or pharmacist.

Treatment with Corotrope will only be carried out in hospitalized patients in the intensive care unit and under continuous hemodynamic monitoring. The medicine will be administered by a healthcare professional.

It can be administered directly or diluted in sterile 5% glucose solution, 0.45% sodium chloride, or 0.9% sodium chloride. The infusion (form of administration of the medicine) will be performed through a constant flow pump, connected to a needle or catheter placed in a vein as large as possible. Before administration, the solution should be examined in the light and should not be used if discoloration is observed.

The diluted solution should be used before 24 hours after preparation.

Treatment with milrinone lactate should be started with a loading dose, followed by a continuous infusion (maintenance dose), according to the following guidelines:

Loading dose: 50 micrograms/kg, administered slowly over 10 minutes.

Maintenance dose: 0.375 to 0.75 micrograms/kg/minute. The infusion rate will be adjusted according to the patient's clinical and hemodynamic response.

Do not exceed the maximum dose of 1.13 mg/kg/day.

Dose adjustments in patients with renal impairment: results obtained in patients with severe renal impairment but without heart failure have shown that the presence of renal impairment significantly increases the terminal elimination half-life of milrinone, so it may be necessary to reduce the dose.

The duration of treatment will depend on the patient's response: the usual period is 48 to 72 hours.

If you think the action of Corotrope is too strong or too weak, tell your doctor or pharmacist.

Use in children

• Your doctor will administer an initial dose to your child between 50-75 micrograms per kilogram of weight, over a period of 30 to 60 minutes.
• Then, a dose between 0.25-0.75 micrograms per kilogram of weight and per minute will be administered, according to your child's response to treatment and the appearance of side effects. Corotrope can be administered for up to 35 hours.

During the infusion, your child will be continuously monitored: your doctor will perform checks on many parameters such as heart rate and blood pressure, and blood tests will be performed to evaluate the response to treatment and the appearance of side effects.

Use in elderly patients

If the patient does not have renal impairment, no dose adjustment is necessary.

If you use more Corotrope than you should

High doses of milrinone can cause hypotension (abnormally low blood pressure) and cardiac arrhythmias (change in heart rhythm). In case of overdose, the administration of Corotrope will be reduced or temporarily suspended. There is no known antidote, and general measures will be taken to stabilize the patient.

In case of overdose or accidental ingestion, contact the Toxicological Information Service at 91 562 04 20, indicating the medicine and the amount taken.

If you forget to use Corotrope

Do not use a double dose to make up for forgotten doses.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The side effects observed, according to their frequency of presentation: very common (may affect more than 1 in 10 patients); common (may affect up to 1 in 10 patients); uncommon (may affect up to 1 in 100 patients); rare (may affect up to 1 in 1,000 patients); very rare (may affect up to 1 in 10,000 patients); frequency not known (cannot be estimated from the available data), have been:

Cardiovascular side effects:

• Common:

• Ventricular ectopic activity (heartbeats outside the appropriate place).
• Sustained or non-sustained ventricular tachycardia (abnormally fast heart rate).
• Supraventricular arrhythmia (change in heart rhythm).
• Hypotension (abnormally low blood pressure).

• Uncommon:

• Ventricular fibrillation (very rapid uncontrolled irregular heartbeats).
• Angina/ chest pain.
• Very rare: "Torsades de pointes" (a form of ventricular tachycardia: abnormally fast heart rate).

The occurrence of ventricular and supraventricular arrhythmias has not been related to the dose or plasma levels (in the blood) of milrinone. Severe arrhythmias that can threaten the patient's life are often associated with certain factors such as a history of arrhythmias, metabolic disorders (e.g., hypokalemia: low potassium levels), abnormal digoxin levels (a medicine indicated for heart problems), and catheter insertion.

Hematological side effects:

• Uncommon: Thrombocytopenia (reduction in the number of platelets).

General and administration site side effects:

• Frequency not known: Administration site reactions.
  • Very rare: Anaphylactic shock (a severe allergic reaction that can put your life in danger).

Respiratory side effects:

• Very rare: Bronchospasm (contraction of the bronchial muscles).

Hepatic side effects:

• Uncommon: Abnormalities in liver function tests.

Nervous system side effects:

• Common: Headaches.
• Uncommon: Tremor.

Dermatological side effects:

• Very rare: Skin reactions such as rash (skin eruption).

Renal and urinary side effects:

• Frequency not known: Renal failure, as a consequence of hypotension that occurs at the same time.

Metabolic side effects:

• Uncommon: Hypokalemia (low potassium levels).

Other side effects in children

In addition to the side effects observed in adults, the following have been reported in children:

Frequency not known:

• bleeding in areas containing fluids (ventricles) surrounding the brain (intraventricular hemorrhage)
• a heart problem known as patent ductus arteriosus: a connection between 2 major blood vessels (aorta and pulmonary artery) that persists although it should be closed. This can cause excess fluid in the lungs, bleeding, destruction of the intestine, or part of the intestine that could cause death.

Additionally, compared to adults, a decrease in platelet count in the blood appears to occur more frequently in children, and the risk of this side effect increases with the duration of the Corotrope infusion. Heart rhythm problems appear to occur less frequently in children than in adults.

Reporting of side effects:

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Corotrope

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

Store below 25°C.

Do not use this medicine after the expiry date which is stated on the packaging and on the ampoules after EXP. The expiry date is the last day of the month stated.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

Composition of Corotrope

• The active substance is milrinone lactate. Each milliliter of solution contains 1 mg of milrinone.
• The other ingredients (excipients) are: lactic acid, anhydrous glucose, and water for injectable preparations.

Appearance of the product and contents of the pack

The injectable solution is a clear, colorless to pale yellow liquid.

Each pack contains 10 colorless glass ampoules.

Standard pack with 10 ampoules of 10 ml.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder:

sanofi-aventis, S.A.

C/ Roselló i Porcel, 21

08016 Barcelona

Spain

Manufacturer:

Delpharm Dijon

6, Boulevard L’Europe

F-21800 Quétigny (France)

Date of last revision of this leaflet: October 2022

Detailed information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/