Milrinone 1 Mg/Ml Solution For Injection Or Infusion

Package leaflet: Information for the user

Milrinone 1 mg/ml Solution for injection or infusion

Milrinone

The name of your medicine is Milrinone 1 mg/ml solution for injection or infusion, which will be referred to as Milrinone through out this leaflet.

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

• Keep this leaflet. You may need to read it again.

• If you have any further questions, ask your doctor, pharmacist or nurse.

• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their sign of illness are the same as yours.

• 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.

What is in this leaflet

1. What Milrinone is and what it is used for

2. What you need to know before you are given Milrinone

3. Howyouwill be given Milrinone

4. Possible side effects

5. Howto store Milrinone

6. Contents of the pack and other information

1. What Milrinone is and what it is used for

Milrinone works by making your heart muscle contract more strongly and your blood vessels become wider. This means blood can flow more easily making your heart pump blood more successfully.

Milrinone can be used in adults for:

- Short-term treatment of severe congestive heart failure (where the heart cannot pump enough blood to the rest of the body) when other medicines have not worked

Milrinone can be used in children for short term treatment (up to 35 hours! of:

- Severe congestive heart failure when other medicines have not worked

- Acute heart failure after a heart operation

2. What you need to know before you are given Milrinone

You should not be given Milrinone if:

- You are allergic (hypersensitive) to milrinone or any of the other ingredients of Milrinone (listed in Section 6)

Signs of an allergic reaction include: a rash, swallowing or breathing problems, swelling of your lips, face, throat or tongue.

- Youhavelostbodyfluidsandareseverelydehydrated

Do not have this medicine if any of the above apply to you. If you are not sure, talk to your doctor, nurse or pharmacist before having Milrinone

Warnings and precautions:

Take special care with Milrinone and tell your doctor if you have any of the following conditions:

- if you are having or have just had a heart attack

- if you have severe heart valve problems such as narrowing, thickening or blockage of your heart valves

- if you have uneven or uncontrolled fast heartbeats. You may also be experiencing pounding in your chest, light-headedness, fainting and shortness in breath

- if you have low blood pressure which may make you feel dizzy, light-headed or faint

- if you have previously taken water tablets (diuretics) which caused you to have heart problems

- if you have low levels of potassium in your blood. Your doctor may do blood tests to check this

- if you have an abnormal drop in the number of blood cells involved in forming blood clots (thrombocytopenia) and/or a reduced haemoglobin concentration

- if you have kidney problems

If you are not sure if any of the above apply to you, talk to your doctor, nurse or pharmacist before having Milrinone.

Children

The following should be considered in addition to warnings and precautions described for adults:

Before giving Milrinone infusion, your doctor will check a lot of parameters such as heart rhythm and blood pressure. He/she will order blood tests as well.

The infusion will not start if your child's heart rhythm and blood pressure is not stable.

Please tell your doctor if:

• yourchild has kidney problems

• yourchild is a preterm infant or has a low birth weight

• your child has a certain heart problem named Patent Ductus Arteriosus: a connection between 2 major blood vessels (aorta and pulmonary artery) which persists though it should be closed

In these cases, your doctor will decide if your child will be treated with Milrinone Injection

Other medicines and Milrinone

Please tell your doctor, nurse or pharmacist if you are taking or have recently taken any other medicines. This includes medicines you buy without a prescription, including herbal medicines. This is because Milrinone can affect the way some other medicines work. Also some medicines can affect the way Milrinone works.

In particular, tell yourdoctoror nurse if you are taking:

- Digoxin (used for heart problems)

- Other heart medication that affects the contractions of the heart muscle (inotropic agents)

- Water tablets (diuretics)

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, 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

In general you will be given Milrinone while you are hospitalised as careful clinical monitoring of the therapy is recommended. Thus the effect on the ability to drive and to use machines is not known.

Milrinone contains sodium

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. it is essentially ‘sodium-free’.

3. Howyouwill be given Milrinone

Milrinone will always be given by your doctor or nurse. This is because it needs to be given as an injection It is administered into a vein. Your doctor will decide on the correct dose, based on the nature of yoursymptoms. Milrinone Injection is intended for use in hospitals only.

Tests:

Your doctor or nurse will use an electrocardiogram (ECG) to check how well your heart works. They will also carry out blood tests and check your blood pressure and pulse rate.

How this medicine will be given to you

- This medicine is usually given in a “drip” after being diluted using either a sugar or a salt solution

- If you feel the effect of your medicine is too weak or to strong, tell your doctor ornurse

If you receive more Milrinone than you should

It is unlikely that your doctor or nurse will give you too much of this medicine. Your doctor and nurse will check your progress and the medicine that you are given. Always ask if you are not sure why you are getting a dose of medicine. The following effects may happen if you have too much Milrinone: feeling dizzy, lightheadedness and fainting (due to low blood pressure) and an uneven heartbeat.

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The following information is intended for healthcare professionals only:

Posology and method of administration.

For intravenous administration.

Posology Careful monitoring should be maintained during milrinone therapy including blood pressure, heart rate, clinical state, electro-cardiogram, fluid balance, electrolytes and renal function (i.e. serum creatinine) Facilities must be available for immediate treatment of potential adverse cardiac effects (e.g. life-threatening ventricular arrhythmias). The infusion rate should be adjusted according to haemodynamic response.

Adults: Milrinone 1 mg/ml Solution for injection or infusion should be given as a loading dose of 50pg/kg administered over a period of 10 minutes usually followed by a continuous infusion at a dosage titrated between 0.375pg/kg/min and 0.75pg/kg/min (standard 0.5 pg/kg/min) according to haemodynamic and clinical response and the possible onset of undesirable effects such as hypotension and arrhythmias.

The total dose should not exceed 1.13 mg/kg/day total dose which corresponds to an infusion rate of 45.0 pg/kg/hr.

The following provides a guide to maintenance infusion delivery rate based upon a solution containing milrinone 200pg/ml prepared by adding 40ml diluent per 10ml ampoule 0.45% saline, 0.9% saline or 5% glucose may be used as diluents.

Milrinone 1 mg/ml Solution for injection Dose (M9 /kg/min)	Maintenance Infusion (pg/kg/hr)	Infusion Delivery Rate (for a solution containing 200 pg milrinone per ml) (ml/kg/hr)
0.375	22.5	0.11
0.4	24	0.12
0.5	30	0.15
0.6	36	0.18
0.7	42	0.21
0.75	45	0.22

Solutions of different concentrations may be used according to patient fluid requirements. The duration of therapy should depend upon the patient's response, but should not exceed 48 hours due to lack of evidence of safety and efficacy in long-term treatment of congestive heartfailure.

Renal Impairment: Dosage adjustment required. Dosage adjustment in patients with renal impairment is based on data obtained from patients with common renal impairment but without congestive heart failure, who show significant increases to the terminal elimination half-life of milrinone. The loading dose is not affected, but a reduction in the maintenance infusion rates may be necessary depending on the severity (creatinine clearance) of the renal impairment (see table below):

Creatinine Clearance (ml/min/1,73m²)	Milrinone 1 mg/ml Solution for injection Dose (pg/kg/min)	Maintenance Infusion Delivery Rate (ml/kg/hr)
5	0.2	0.06
10	0.23	0.07
20	0.28	0.08
30	0.33	0.1
40	0.38	0.11
50	0.43	0.13

The infusion rate should be adjusted according to haemodynamic response.

Older people: Experience so far suggests that no special dosage recommendations are necessary in patients with normal renal function. Renal clearance may be reduced in older people, lower Milrinone 1 mg/ml Solution for injection or infusion doses may be required in such cases.

Paediatric population:

In published studies selected doses for infants and children were:

• Intravenous loading dose: 50 to 75 pg/kg administered over 30 to 60 minutes.

• Intravenous continuous infusion: To be initiated on the basis of hemodynamic response and the possible onset of undesirable effects between 0.25 to 0.75 pg/kg/min for a period up to 35 hours.

If you forget to have Milrinone

Your doctor or nurse will have instructions on when to give you this medicine. It is unlikely that you will not be given the medicine as it has been prescribed. However, if you do think you have missed a dose, tell yourdoctor or nurse.

If you stop having Milrinone

Keep having Milrinone until your doctor tells you to stop. Do not stop having Milrinone just because you feel better. If you stop, your illness may get worse.

4. Possible side effects

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

Stop having Milrinone and tell you doctor straight away if:

• You have an allergic reaction. The signs may include: a rash, swallowing or breathing problems, swelling of your lips, face, throat or tongue, fainting or losing consciousness. The chances of this happening are very rare

Tell a doctor or nurse straight away if you notice any of the following side effects:

Common (affects less than 1 in 10 people)

• Uneven, increased orfast heartbeats. You may also experience pounding in your chest, feel light-headed, faint or short of breath

Uncommon (affects less than 1 in 100 people)

• Ventricular fibrillation - a serious hearth rhythm problem. Signs of this include very fast, uneven or forceful heart beat (palpitations), dizziness and loss of consciousness. You may also feel sick, have cold sweats, shortness of breath and chest pain

• Thrombocytopenia - a blood problem. Signs of this are that you may bruise more easily than usual

• Chest pain

Very rare (affects less than 1 in 10,000 people)

• Torsades de Pointes - a serious heart rhythm problem. Signs of this include very fast, uneven or forceful heart beat (palpitations), dizziness and loss of consciousness. You may also feel sick, have cold sweats, shortness of breath, unusual pale complexion and chest pain

• Difficulty breathing, wheezing ortightness in the chest

Tell a doctor or nurse as soon as possible if you notice any of the following side effects:

Common (affects less than 1 in 10 people)

• Low blood pressure. Signs of this include feeling dizzy, lightheaded or fainting. If you also notice signs like a fast or uneven heart beat or chest pain this could be a more serious side effect (see above)

• Headache

Uncommon (affects less than 1 in 100 people)

• Feeling shaky

• Low levels of potassium in your blood. Signs of this are tiredness, confusion, muscle weakness and muscle cramps.This may be due to low levels of potassium in your body

Tell a doctor or nurse if any of the following side effects gets serious or lasts longer than a few days Very Rare (affects less than 1 in 10,000 people)

• Skin rashes including at the site of the injection Uncommon (affects less than 1 in 100 people)

• A blood test may show changes in the way the liver is working Talk to your doctor, nurse or pharmacist if any of the side effects gets serious or lasts longer than a few days, or if you notice any side effects not listed in this leaflet.

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

Frequency not known:

• Bleeding into the fluid-filled areas (ventricles) surrounded by the brain (intraventricular haemorrhage)

• A heart problem known as Patent Ductus Arteriosus: a connection between 2 major blood vessels (aorta and pulmonary artery) which persists though it should be closed. This can cause excess fluid in the lungs, bleedings, destruction of the bowel or part of the bowel and possibly be fatal

• Reduction of red blood count and/or haemoglobin concentration

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. You can also report any side effects directly (see details below). By reporting side effects you can help provide more information on the safety of this medicine.

United Kingdom

Yellow Card Scheme

Website: www.mhra.aov.uk/vellowcard

5. Howto store Milrinone

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

Do not use this medicine after the expiry date which is stated on the ampoule and the outer carton after “EXP”. The expiry date refers to the last day of that month.

Do not store above 25°C. Do not freeze. Discard any unused product.

After dilution:A diluted solution of Milrinone 1 mg/ml Solution for Injection should be used within 24 hours. From a microbiological point of view, unless the method of opening and dilution precludes the risk of microbial contamination, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user.

Do not use this medicine if you notice visible signs of deterioration or visible particles in the product.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Milrinone contains

The active substance is milrinone.

The other ingredients are lactic acid, glucose anhydrous, sodium hydroxide (for pH adjustment) and water for injections.

What Milrinone looks like and contents of the pack

Milrinone is a clear, colourless to pale yellow liquid and it comes in 10 ml clear glass ampoule (Ph. Eur. Type I), with a blister pack size of 5,10 and 25.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Claris Lifesciences UK Limited Crewe Hall, Crewe, Cheshire, CW16UL,

United Kingdom.

Manufacturer

Peckforton Pharmaceuticals Limited Crewe Hall, Crewe, Cheshire, CW16UL,

United Kingdom.

This Leaflet was last revised in 09/2014

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In clinical studies on low cardiac output syndrome in infants and children under 6 years of age after corrective surgery for congenital heart disease 75 pg/kg loading dose over 60 minutes followed by a 0.75 pg/kg/min infusion for 35 hours significantly reduced the risk of development of low cardiac output syndrome. Results of pharmacokinetic studies have to be taken into consideration.

Renal impairment:

Due to lack of data the use of milrinone is not recommended in paediatric population with renal impairment.

Patent ductus arteriosus:

If the use of milrinone is desirable in preterm or term infants at risk of/with patent ductus arteriosus, the therapeutic need must be weighed against potential risks.

Method of administration

For slow intravenous administration. To avoid local irritation, as large a vein as possible should be punctured. Extravascular injection must be avoided.

Milrinone 1 mg/ml Solution for injection or infusion may not be mixed with other diluents as stated above. Solutions of different concentrations may be used according to patient fluid requirements. After dilution the solution is a clear and colourless liquid free from visible particle.

The duration of therapy should depend upon the patient's response but should not exceed 48 hours due to a lack of evidence of safety and efficay in long-term treatment of congestive heart failure.

Incompatibilities

Furosemide or bumetanide should not be administered in intravenous lines containing Milrinone 1 mg/ml Solution for injection or infusion since precipitation occurs on admixture. Sodium Bicarbonate Intravenous infusion should not be used for dilution.

For single use only.

The (reconstituted) solution should be expected visually for particulate matter and discoloration prior to administration. Only clear and colourless or slightly yellow solution should be used.

Any unused product or waste material should be disposed of in accordance with local requirements.

Shelf life:

Unopened: 30 months.

Infusion solutions diluted as recommended with 0.45% saline, 0.9% saline or 5% glucose should be freshly prepared before use. Parenteral drug products should be examined visually and should not be used if particulate matter ordiscolorations are present.