Corotrope

Package leaflet: Information for the patient

Corotrope, 1 mg/ml, solution for injection
Milrinone
Please read all of this leaflet carefully before the medicine is administered, as it contains
important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, please consult your doctor.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm other people, even if their symptoms are the same.
• If the patient experiences any adverse reactions, including any possible adverse reactions not listed in this leaflet, inform the doctor or nurse immediately. See section 4.

Contents of the leaflet

1. What Corotrope is and what it is 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 Corotrope is and what it is used for

Corotrope contains milrinone as the active substance. Milrinone is a synthetic compound
that enhances the force of cardiac muscle contraction and causes vasodilation.
Corotrope is intended for short-term intravenous therapy of circulatory failure, including
low-output syndromes following cardiothoracic surgery.

Children and adolescents

• Short-term treatment (up to 35 hours) of severe congestive heart failure (when the heart cannot pump sufficient blood to the body), when other medications have proven ineffective;
• Short-term treatment (up to 35 hours) of acute heart failure following heart surgery, i.e. when the heart has difficulty pumping blood throughout the body.

2. Important information before using Corotrope

When not to use Corotrope:

• if the patient is allergic to milrinone or any of the other ingredients of this medicine (listed in section 6),
• in cases of severe hypovolemia (reduced circulating blood volume).

Warnings and precautions
Before starting treatment with Corotrope, discuss this with your doctor. Special caution is required:

• in patients with severe aortic or pulmonary valve stenosis or hypertrophic subaortic stenosis,
• in patients during the acute phase of myocardial infarction,
• in patients who develop excessive drop in arterial blood pressure before and/or during milrinone treatment,
• ventricular and supraventricular arrhythmias have been observed in high-risk patients,
• in patients receiving diuretics. The doctor may recommend monitoring of blood pressure, heart rate, and clinical symptoms,
• in patients taking digitalis glycosides,
• in patients with severe renal insufficiency,
• in patients with low platelet or hemoglobin levels,
• in patients with low potassium levels in blood.

During milrinone treatment, the doctor will closely monitor blood pressure, heart rate, clinical status, ECG, fluid balance, electrolytes, and kidney function (e.g., serum creatinine concentration). If disturbances occur, medical staff will take corrective actions.

As a result of Corotrope's action, urine output increases. This may lead to potassium deficiency in the blood. In such cases, medical staff will administer potassium.

There are no clinical data on the use of milrinone infusion for longer than 48 hours.

Reactions at the infusion site have been observed (see section "Possible side effects"). Therefore, the infusion site should be carefully monitored to avoid extravasation.

No special recommendations exist for elderly patients.

Dosage adjustment is necessary in patients with renal impairment (see section 3).

Children and adolescents
Before starting Corotrope infusion, the doctor will assess several parameters, such as heart rhythm and blood pressure. The doctor will also order blood tests.

Infusion will not be initiated if the child's heart rhythm and blood pressure are unstable.

Inform the doctor if:

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

Corotrope and other medicines
Inform the doctor about all medicines currently used, recently taken, or planned for use.

Injecting furosemide or bumetanide together with milrinone into the same intravenous infusion set causes precipitation. Therefore, furosemide or bumetanide must not be administered through the same intravenous line as milrinone.

Milrinone must not be diluted in sodium bicarbonate solution.

Due to limited data on interactions, Corotrope medicinal product must not be mixed with other medicines.

Treatment with Corotrope may necessitate a reduction in the dose of diuretic medication.

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 diuretic dose.

Patients receiving both Corotrope and digitalis glycosides must be closely monitored for serum potassium levels, and potassium deficiency must be corrected, as hypokalemia may particularly in these patients lead to cardiac arrhythmias.

Concomitant use of Corotrope and other inotropic agents (which increase the force of heart contractions) may enhance the inotropic effect of Corotrope.

The doctor may adjust the dosage appropriately when Corotrope is used together with other antihypertensive treatments.

Pregnancy, breastfeeding, and fertility
If the patient is pregnant, breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor before using this medicine.

Driving and operating machinery
The effect of Corotrope on the ability to drive or operate machinery is unknown.

Corotrope contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per ampoule, meaning 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 colourless and clear.
Milrinone treatment begins with a loading dose, followed by a maintenance dose administered as a continuous infusion according to the scheme below.
Adults
Loading dose: 50 \μg/kg body weight, given slowly intravenously over at least 10 minutes.
The following table shows the milrinone loading dose (for a concentration of 1 mg/ml) in millilitres, adjusted according to patient body weight (kg).

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

Patients with renal function impairment
Dosage adjustment is required in patients with impaired renal function. Data obtained from studies
conducted in patients with severe renal insufficiency, but without signs of circulatory failure,
demonstrated that milrinone plasma half-life is significantly prolonged in renal failure.
There is no need to alter the initial dose; however, the maintenance dose should be reduced according
to the table below:

The duration of treatment should be adjusted according to the observed improvement in the patient's condition.
Do not use for longer 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.
• Subsequently, a dose of 0.25 to 0.75 micrograms per kilogram of the child's body weight per minute should be administered, depending on the child's clinical response to treatment and the occurrence of adverse effects. Corotrope may be administered for up to 35 hours.

During the infusion, the child will be closely monitored. The doctor will check various parameters,
such as heart rhythm and blood pressure. A blood sample will also be taken to assess
the response to treatment and the occurrence of adverse effects.
Elderly patients
There are no special recommendations for elderly patients. No relationship has been observed between
the frequency of adverse events and patient age. Controlled pharmacokinetic studies have not revealed age-related differences in the distribution and elimination of milrinone.
Overdose of Corotrope
Administration of high doses of milrinone may cause a decrease in arterial blood pressure and cardiac rhythm disturbances.
In such cases, milrinone administration should be discontinued until the patient's clinical condition stabilizes.
No specific antidote is known. Symptomatic treatment and circulatory support measures are used.
Missed dose of Corotrope
Do not administer a double dose to make up for a missed dose or administer two doses in short succession.
If you have any further doubts regarding the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.
Adverse reactions are listed below in order of decreasing frequency.
Common (may occur in up to 1 in 10 patients):

• Ventricular extrasystoles, non-sustained or sustained ventricular tachycardia, supraventricular arrhythmias, hypotension, headache, usually mild or of moderate intensity.

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

• Ventricular fibrillation, angina pectoris – chest pain, thrombocytopenia, abnormal liver function tests, tremor, decreased blood potassium levels.

Very rare (may occur in up to 1 in 10,000 patients):

• Torsades de pointes-type arrhythmias (polymorphic ventricular tachycardia), anaphylactic shock, bronchospasm, skin reactions such as rash.

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

• Decreased concentration of red blood cells and (or) hemoglobin,
• Local reaction at the site of administration,
• Renal failure secondary to concomitant arterial hypotension.

The following adverse reactions have been reported in children:

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

• Bleeding into fluid-filled spaces (ventricles) surrounding the brain (intraventricular hemorrhage),
• Patent ductus arteriosus – a heart defect characterized by persistence of the connection between two major blood vessels (aorta and pulmonary artery) that should have closed after birth. This may lead to fluid accumulation in the lungs, bleeding, intestinal damage or necrosis of part of the intestine, and may result in death.

Compared to adults, decreased platelet count appears to occur more frequently in children, and the risk of this adverse reaction increases with the duration of Corotrope infusion.
Cardiac rhythm disturbances seem to occur less frequently in children than in adults.
Other adverse reactions may occur in some individuals during treatment with Corotrope.
Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor, pharmacist or nurse. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products.
Al. Jerozolimskie 181 C
02 - 222 Warsaw
Tel.: + 48 22 49 21 301
Fax: + 48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder or its representative in Poland.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Corotrope

Store 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 stated month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Corotrope contains

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

What Corotrope looks like and contents of the pack
The pack contains 10 ampoules of 10 ml each.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Sanofi Winthrop Industrie
82, Avenue Raspail
94250 Gentilly
France
Manufacturer:
Delpharm Dijon
6, boulevard de l’Europe
21800 Quetigny
France
For further information, contact the local representative of the Marketing Authorisation Holder in Poland:
Sanofi Sp. z o.o.
ul. Marcina Kasprzaka 6
01-211 Warsaw
Tel.: +48 22 280 00 00