ASICOR 1 mg /Ml Concentrate

Contents of the leaflet

1. Package Leaflet: Information for the User
2. Asicor, 1mg/ml, Concentrate for Solution for Infusion
   1. Read All of This Leaflet Carefully Before You Start Using This Medicine Because It Contains Important Information for You.
   2. Contents of the Pack
3. What Asicor is and what it is used for
4. What you need to know before you use Asicor
   1. Do not use Asicor:
   2. Warnings and precautions
   3. Before starting treatment with Asicor, tell your doctor or nurse:
   4. Children
   5. Asicor with other medicines
   6. Pregnancy, breastfeeding and fertility
   7. Driving and using machines
   8. Asicor contains sodium
5. How to use Asicor
   1. Recommended dose
   2. Overdose of Asicor
   3. Missed dose of Asicor
6. Possible side effects
   1. Stop the infusion and tell your doctor immediately if:
   2. Tell your doctor or nurse immediately if you experience any of the following side effects:
   3. Additional side effects in children
   4. Reporting of side effects
7. How to store Asicor
8. Contents of the pack and other information
   1. What Asicor contains
   2. What Asicor looks like and contents of the pack
   3. Marketing Authorisation Holder and Manufacturer
   4. This medicinal product is authorised in the Member States of the European Economic Area under the following names:
   5. Date of last revision of the package leaflet: -------------------------------------------------------------------------------------------------------------------------
   6. Information intended for healthcare professionals only:
   7. Preparation of the medicinal product for administration
   8. Safety information:
   9. Incompatibilities:
   10. Administration:
   11. Dosage
   12. Contraindications
   13. Overdose

Package Leaflet: Information for the User

Asicor, 1mg/ml, Concentrate for Solution for Infusion

Milrinone

Read All of This Leaflet Carefully Before You Start Using This Medicine Because It Contains Important Information for You.

• You should keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• If you get 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 Pack

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

1. What Asicor is and what it is used for

The name of your medicine is Asicor.
Asicor contains the active substance milrinone (as lactate). It belongs to a group of medicines called phosphodiesterase inhibitors.
The medicine works by making the heart muscle contract more strongly and the blood vessels wider.
This means that blood can flow more easily and the heart can pump more efficiently.
Asicor can be used in adults for:
Short-term (up to 48 hours) treatment of severe congestive heart failure (when the heart is not pumping enough blood to the rest of the body) when other medicines have not worked.
Asicor can be used in children for short-term treatment (up to 35 hours):

• Severe congestive heart failure (when the heart is not pumping enough blood to the rest of the body) when other medicines have not worked.
• Acute heart failure after heart surgery, i.e., when the heart has difficulty pumping blood to the whole body.

2. What you need to know before you use Asicor

Do not use Asicor:

• If you are allergic to milrinone or any of the other ingredients of this medicine (listed in section 6).
• If you have a significantly reduced volume of circulating blood.

Warnings and precautions

Before starting treatment with Asicor, tell your doctor or nurse:

• If you have recently had a heart attack.
• If you have severe heart valve diseases such as stenosis, fibrosis or valve regurgitation.
• If you have irregular or uncontrolled rapid heart rhythm. You may also feel palpitations, dizziness, weakness or shortness of breath.
• If you have low blood pressure, which causes dizziness, headaches or fainting.
• If you have taken diuretic medicines (which increase urine production) that have caused heart problems.
• If you have low potassium levels in your blood. Your doctor may do a blood test to check this.
• If you have a reduced number of blood cells involved in blood clotting (thrombocytopenia) and/or reduced hemoglobin levels.
• If you have kidney problems.
• If you have liver problems.

Children

In addition to the warnings and precautions described for adults, the following should also be considered:
Before starting the Asicor infusion, the doctor will check various parameters, such as heart rate and blood pressure. Blood tests will also be ordered.
The infusion should 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 a premature or low-birth-weight newborn.
• The child has a certain heart defect called patent ductus arteriosus: a connection between the two main blood vessels (aorta and pulmonary artery) that should be closed but remains open.

In these cases, the doctor will decide whether the child should receive Asicor.

Asicor with other medicines

Tell your doctor or nurse about all medicines you are taking, have recently taken, or might take, as milrinone may affect the action of other medicines. Also, some medicines may affect the action of milrinone.
Tell your doctor or nurse, especially if you are taking:

• Digoxin (used for heart problems).
• Other heart medicines that affect heart muscle contractions (inotropic agents).
• Diuretic medicines (which increase urine production).
• Medicines used to treat high blood pressure or angina (chest pain), such as amlodipine, nifedipine or felodipine.

Pregnancy, breastfeeding and fertility

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

Driving and using machines

You will usually receive Asicor in a hospital, as close clinical monitoring of treatment is recommended. Therefore, the effect on the ability to drive and use machines is not known.

Asicor contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per dose, which means it is essentially 'sodium-free'.

3. How to use Asicor

Asicor will always be given to you by a doctor or nurse, as it needs to be given by intravenous infusion. The correct dose will be decided by your doctor based on your symptoms. Asicor is only intended for use in hospitals.
Tests:
During treatment, an electrocardiogram (ECG) will be used to check your heart. Blood tests will also be done and your blood pressure and heart rate will be monitored.
How the medicine will be given.

• This medicine is usually given in a 'drip' after being diluted with a sugar or salt solution.
• Tell your doctor or nurse if you feel that the medicine is not working or is too strong.

Recommended dose

Adults

• Your doctor will decide how much medicine you should receive based on your body weight.
• If you have kidney problems, you may receive a lower dose. Asicor infusions are usually given for up to 48 hours.

Use in children

• The initial dose given to a child is 50 to 75 micrograms per kilogram of body weight, over 30 to 60 minutes.
• Subsequent doses are 0.25 to 0.75 micrograms per kilogram of body weight per minute, depending on the child's clinical response to treatment and the occurrence of side effects. Asicor can be given for up to 35 hours. During the infusion, the child's condition will be closely monitored: the doctor will check various parameters, such as heart rate and blood pressure. Blood tests will also be done to assess the response to treatment and the occurrence of side effects.

Overdose of Asicor

If you have any doubts about the dose you have received, talk to your doctor.
If you receive too much Asicor, you may experience symptoms such as dizziness, headaches, weakness (due to low blood pressure) and irregular heart rhythm.

Missed dose of Asicor

Tell your doctor or nurse if you think you have missed a dose of Asicor.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

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

Stop the infusion and tell your doctor immediately if:

You have an allergic reaction. Symptoms may include rash, difficulty swallowing or breathing, swelling of the face, lips, throat or tongue. This is very rare.

Tell your doctor or nurse immediately if you experience any of the following side effects:

Common(affects up to 1 in 10 people)

• Irregular, rapid or fast heart rhythm. You may also feel palpitations, dizziness, weakness or shortness of breath.
• Headache: usually mild to moderate.
• Low blood pressure: symptoms include dizziness, headaches or weakness. If you also experience symptoms such as rapid or irregular heart rhythm or chest pain, this may be a more serious side effect (see above).

Uncommon(affects up to 1 in 100 people)

• Atrial fibrillation - a serious heart rhythm disorder. Symptoms include very rapid, irregular or strong heart rhythm (palpitations), dizziness and fainting. You may also experience nausea; cold sweats, shortness of breath and chest pain.
• Thrombocytopenia - a blood disorder (low platelet count). Symptoms may include easy bruising.
• Chest pain.
• Hypokalemia, when there is a low level of potassium in the blood. Symptoms include fatigue, disorientation, muscle weakness and muscle cramps.
• Muscle spasms (tremors).
• Blood tests may show changes in liver function.

Rare(affects up to 1 in 10,000 people)

• Torsade de pointes- a serious heart rhythm disorder. Symptoms include very rapid, irregular or strong heart rhythm (palpitations), dizziness and fainting. You may also experience nausea, cold sweats, shortness of breath, pale appearance and chest pain.
• Breathing difficulties, wheezing, chest tightness.
• Skin reactions.

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

• Decreased red blood cell count and/or hemoglobin level.
• Reaction at the infusion site.

Additional side effects in children

In addition to the side effects seen in adults, the following have also been reported in children:
Frequency not known:

• Bleeding into fluid-filled spaces (compartments) surrounding the brain (intracranial hemorrhage).
• A heart defect known as patent ductus arteriosus: a connection between the two main blood vessels (aorta and pulmonary artery) that should be closed but remains open. This can cause fluid buildup in the lungs, bleeding, intestinal damage and can lead to death. Additionally, compared to adults, a low platelet count seems to occur more frequently in children, and the risk of this side effect increases with the duration of the Asicor infusion. Heart rhythm disorders seem to occur less frequently in children than in adults.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.
Side effects can be reported to the Medicines and Healthcare products Regulatory Agency (MHRA) using the Yellow Card Scheme (www.mhra.gov.uk/yellowcard). You can also report side effects directly to the manufacturer.

5. How to store Asicor

The medicine should be stored by your doctor or nurse in a safe place out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton and ampoule after EXP.
The expiry date refers to the last day of that month.
There are no special storage instructions for this medicine.
Do not freeze.
For single use only.
Chemical and physical in-use stability has been demonstrated for 72 hours at room temperature (15-25°C) or under refrigeration (2-8°C).
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

What Asicor contains

• Asicor is a sterile solution of milrinone lactate equivalent to 1 mg milrinone in 1 ml.
• The other ingredients are (S)-lactic acid, anhydrous glucose, water for injections and sodium hydroxide (for pH adjustment).

What Asicor looks like and contents of the pack

Asicor is a clear, colorless to pale yellow solution.
Asicor is available in packs containing 10 glass ampoules of 10 ml or 20 ml.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Pharmaselect International Beteiligungs GmbH
Ernst-Melchior-Gasse 20
1020 Vienna
Austria

This medicinal product is authorised in the Member States of the European Economic Area under the following names:

Austria, Poland:
Asicor
Hungary, Romania:
Unacor
Czech Republic, Slovakia:
Asicord

Date of last revision of the package leaflet: -------------------------------------------------------------------------------------------------------------------------

Information intended for healthcare professionals only:

Asicor, 1 mg/ml, concentrate for solution for infusion
To obtain full information, please consult the Summary of Product Characteristics (SmPC).

Preparation of the medicinal product for administration

Infusion solutions, diluted as recommended: with sodium chloride 4.5 mg/ml (0.45%), sodium chloride 9 mg/ml (0.9%) or glucose 50 mg/ml (5%), should be prepared immediately before administration.
For single use only.
The diluted solution for infusion should be inspected visually for particulate matter and discoloration prior to administration.
Shelf-life: 3 years, prior to opening.
Chemical and physical in-use stability has been demonstrated for 72 hours at room temperature (15-25°C) or under refrigeration (2-8°C).
From a microbiological point of view, the diluted solution for infusion 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 2-8°C, unless dilution has been made in controlled and validated aseptic conditions. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Safety information:

During treatment with Asicor, blood pressure, heart rate, clinical status, electrocardiogram, fluid balance, electrolytes and kidney function (i.e., serum creatinine) should be closely monitored.

Incompatibilities:

Furosemide or bumetanide should not be added to the infusion set of Asicor, as precipitation will occur.
Milrinone should not be diluted with sodium bicarbonate injection.
Asicor should not be mixed with other medicinal products, unless compatibility has been established.

Administration:

For intravenous use only.
Extravasation should be avoided. The medicine should be administered into a large vein to prevent reactions at the infusion site. During treatment with milrinone, blood pressure, heart rate, clinical status, electrocardiogram, fluid balance, electrolytes and kidney function (i.e., serum creatinine) should be closely monitored.
Equipment for treating potential cardiac side effects (e.g., life-threatening ventricular arrhythmias) should be available. The infusion rate should be adjusted according to the hemodynamic response. The duration of treatment should be based on clinical response. The infusion should not exceed 48 hours due to the lack of evidence of safety and efficacy in the treatment of congestive heart failure for a longer period.

Dosage

Adults
Asicor should be administered as a loading dose of 50 μg/kg body weight given over 10 minutes, followed by a maintenance infusion of 0.375 to 0.75 μg/kg body weight per minute (usually 0.5 μg/kg body weight per minute) adjusted to the hemodynamic response and taking into account the possible onset of side effects such as hypotension or heart rhythm disorders. The total dose should not exceed 1.13 mg/kg body weight per day.

The following is a guide to dosing and infusion rates for a solution containing 200 μg/ml milrinone, prepared by adding 400 ml of diluent to 100 ml of injection solution (40 ml of diluent per 10 ml ampoule or 80 ml of diluent per 20 ml ampoule).
Solutions of different concentrations may be used according to the patient's fluid requirements. The duration of treatment should be based on the patient's response.

Elderly patients
Experience to date suggests that no special dosage recommendations are necessary in patients with normal renal function. Renal clearance may be reduced in elderly patients, and in such cases, lower doses of Asicor may be required.

Patients with impaired renal function
Dosage adjustment is necessary. Dosage adjustment in patients with impaired renal function is based on data from patients with the most common type of renal impairment, but without congestive heart failure, which indicate a significant prolongation of the elimination half-life of milrinone. The loading dose remains unchanged, but it may be necessary to reduce the maintenance dose depending on the severity (creatinine clearance) of the renal impairment (see table below):

Children
In published studies in infants and children, the following doses have been used:

• Intravenous loading dose: 50 to 75 μg/kg body weight given over 30 to 60 minutes.
• Intravenous continuous infusion: started based on the hemodynamic response and taking into account the possible onset of side effects, between 0.25 and 0.75 μg/kg body weight per minute for up to 35 hours. In clinical studies of low cardiac output syndrome in infants and children under 6 years of age after corrective heart surgery, a loading dose of 75 μg/kg body weight given over 60 minutes, followed by an infusion of 0.75 μg/kg body weight per minute for 35 hours, significantly reduced the risk of developing low cardiac output syndrome. The results of pharmacokinetic studies should be taken into account.

Renal impairment
Due to the lack of data, the use of milrinone is not recommended in children and adolescents with renal impairment.
Patent ductus arteriosus:
If it is desired to use milrinone in premature or full-term newborns with patent ductus arteriosus or at risk of patent ductus arteriosus, the therapeutic benefits should be carefully weighed against the potential risks.

Contraindications

• Hypersensitivity to the active substance or to any of the excipients
• Severe hypovolemia

Overdose

Symptoms
High doses of Asicor may cause low blood pressure (due to its vasodilatory effect) and heart rhythm disorders.
Treatment
In such cases, the administration of Asicor should be stopped until the patient's clinical condition stabilizes. There is no specific antidote for milrinone, and supportive measures for cardiovascular disorders should be used.