What it is and what it is used for

for The name of your medicine is Primacor 1mg/ml Solution for Injection (called Primacor in this leaflet). Primacor contains a medicine called milrinone. This belongs to a group of medicines called phosphodiesterase inhibitors. It 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. Primacor can be used 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.
• Treatment after a heart operation for when your heart is having difficulty pumping blood around your body. Primacor can be used in children for:
• Short term treatment (up to 35 hours) of severe congestive heart failure (where the heart cannot pump enough blood to the rest of the body) when other medicines have not worked.

Do not use Primacor if: × You are allergic (hypersensitive) to milrinone or any of the other ingredients of Primacor (listed in section 6) Signs of an allergic reaction include: a rash, swallowing or breathing problems, swelling of your lips, face, throat or tongue. × You have lost body fluids and are severely dehydrated. Do not use this medicine if any of the above apply to you. If you are not sure, talk to your doctor, nurse or pharmacist before using Primacor.

The following provides a guide to maintenance infusion delivery rate based upon a solution containing milrinone 200 μg/ml prepared by adding 40 ml diluent per 10 ml ampoule (400 ml diluent per 100 ml Primacor Injection). 0.45% saline, 0.9% saline or 5% glucose may be used as diluents. Primacor Injection Dose (μg/kg/min) 0.375 0.400 0.500 0.600 0.700 0.750

Infusion Delivery Rate (ml/kg/hr) 0.11 0.12 0.15 0.18 0.21 0.22

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Code AC / Item : 710686 Description AC : Notice Primacor inj. 10 ml Grande Bretagne Destination : Date / Version : 18/09/2023 V1 210×148 mm Dimension : Double Pliée Type :

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• This is then followed by a smaller dose between 0.375 and 0.75 micrograms for every kilogram of body weight per minute as needed.
• The medicine is usually given for 2-3 days, but it may be given for up to 5 days.
• If you are using this medicine after a heart operation, it will usually only be given for up to 12 hours. Children and adolescents
• Your doctor should give your child a first dose ranging between 50 and 75 micrograms for every kilogram of his/her weight, over a period of 30-60 minutes.
• This is then followed by a dose ranging from 0.25-0.75 micrograms for every kilogram of his/her weight per minute according to your child's response to the treatment and occurrence of side effects. Primacor can be given for up to 35 hours. During infusion, your child will be closely monitored. Your doctor will check a lot of parameters such as heart rhythm and blood pressure, and blood will be taken to evaluate the response to therapy and occurrence of side effects. If you use more Primacor 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 use too much Primacor: feeling dizzy, light-headedness and fainting (due to low blood pressure) and an uneven heartbeat. If you forget to use Primacor 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 your doctor or nurse. If you stop using Primacor Keep using Primacor until your doctor tells you to stop. Do not stop using Primacor just because you feel better. If you stop, your illness may get worse. 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. If you have any further questions on the use of this medicine, ask your doctor or nurse.

Please tell your doctor if:

• Your child has kidney problems.
• Your child 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 Primacor. Other medicines and Primacor 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 Primacor can affect the way some other medicines work. Also some medicines can affect the way Primacor works. In particular, tell your doctor, nurse or pharmacist if you are taking:
• Digoxin – used for heart problems.
• Water tablets (diuretics).
• Medicines used to treat high blood pressure or angina (chest pain) such as amlodipine, nifedipine or felodipine. Pregnancy and breast-feeding Talk to your doctor, nurse or pharmacist before having this medicine if you are pregnant, might become pregnant, or think you may be pregnant. If you are breast-feeding or planning to breast-feed, talk to your doctor or pharmacist before taking any medicine. 3. How to use Primacor Primacor will normally be given by your doctor or nurse. This is because it needs to be given as an injection. Using this medicine
• This medicine is usually given in a 'drip' after being diluted using either a sugar or salt solution.
• If you feel the effect of your medicine is too weak or too strong, tell your doctor or nurse.

What you need to know before you take it

e Primacor 3. How to use Primacor 4. Possible side effects 5. How to store Primacor 6. Contents of the pack and other information

How to take it

to you

• Your doctor will decide how much medicine you should have based on your body weight.
• If you have problems with your kidneys, you may be given a lower dose. Adults (including the elderly)
• Your doctor should give you a first dose of 50 micrograms for every kilogram of your weight over 10 minutes.

Injection Creatinine Clearance Primacor Dose (ml/min/1.73m2) (μg/kg/min) 5 0.20 10 0.23 20 0.28 30 0.33 40 0.38 50 0.43

Maintenance Infusion Delivery Rate (ml/kg/hr) 0.06 0.07 0.08 0.10 0.11 0.13

The infusion rate should be adjusted according to haemodynamic response. Elderly Experience so far suggests that no special dosage recommendations 2 are necessary.

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Solutions of different concentrations may be used according to patient fluid requirements. The duration of therapy should depend upon the patient's response. In congestive cardiac failure, patients have been maintained on the infusion for up to 5 days, although the usual period is 48 – 72 hours. In acute states following cardiac surgery, it is unlikely that treatment need be maintained for more than 12 hours. Renal impairment Dosage adjustment required. Data obtained from patients with severe renal impairment but without heart failure have demonstrated that the presence of renal impairment significantly increases the terminal elimination half-life of milrinone. For patients with clinical evidence of renal impairment, the loading dose is not affected, but the following maintenance infusion rates are recommended using the infusion solution described above.

Code AC / Item : 710686 Description AC : Notice Primacor inj. 10 ml Grande Bretagne Destination : Date / Version : 18/09/2023 V1 210×148 mm Dimension : Double Pliée Type :

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Tell a doctor or nurse if any of the following side effects gets serious or lasts longer than a few days: Uncommon (affects less than 1 in 100 people)

• A blood test may show changes in the way the liver is working. Very rare (affects less than 1 in 10,000 people)
• Skin rashes including at the site of the injection. 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. Additional side effects in children and adolescents: Not known (frequency cannot be estimated from the available data)
• 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.
• Changes in the way the kidneys are working if you already have low blood pressure. Moreover, compared to adults, decrease in the number of platelets in the blood seems to occur more often in children and the risk of this side effect is increased with the duration of the Primacor infusion. Heart rhythm troubles seem to occur less often in children than in adults. Reporting of side effects If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.

Possible side effects

Like all medicines, Primacor can cause side effects, although not everybody gets them. Stop using Primacor 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 or fast 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 heart rhythm problem. Signs of this include very fast, uneven or forceful heartbeat (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 heartbeat (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 or tightness 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 heartbeat 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.

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Paediatric population Renal impairment: Due to lack of data the use of milrinone is not recommended in In published studies selected doses for infants and children were:

• Intravenous loading dose: 50 – 75 μg/kg administered over 30 – paediatric population with renal impairment. 60 minutes. Patent ductus arteriosus:
• Intravenous continuous infusion: To be initiated on the basis of If the use of milrinone is desirable in preterm or term infants at risk haemodynamic response and the possible onset of undesirable of/with patent ductus arteriosus, the therapeutic need must be effects between 0.25 – 0.75 μg/kg/min for a period up to weighed against potential risks. 35 hours. Overdose In clinical studies on low cardiac output syndrome in infants and Overdose of intravenous Primacor may produce hypotension children under 6 years of age after corrective surgery for congenital (because of its vasodilatory effect) and cardiac arrhythmia. If this heart disease 75 μg/kg loading dose over 60 minutes followed by a occurs, Primacor Injection administration should be reduced or 0.75 μg/kg/min infusion for 35 hours significantly reduced the risk temporarily discontinued until the patient's condition stabilises. No of development of low cardiac output syndrome. specific antidote is known, but general measures for circulatory Results of pharmacokinetic studies have to be taken into support should be taken. consideration. 3

Code AC / Item : 710686 Description AC : Notice Primacor inj. 10 ml Grande Bretagne Destination : Date / Version : 18/09/2023 V1 210×148 mm Dimension : Double Pliée Type :

Polices / Fonts : Ocean Sans Pro Texte corps mini / Text size mini : 9 pt

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Code actuel / Current code : 705239 Couleur (s) / Color(s) : 1 Noir Plan N° : N 100

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How to store it

Primacor This medicine will be kept by your doctor or pharmacist in a safe place where children cannot see or reach it. Do not use Primacor after the expiry date, which is stated on the ampoule and the carton. The expiry date refers to the last day of the month. Primacor should be stored below 25°C. Do not freeze. Do not throw away any medicines via wastewater or household waste. Your doctor or nurse will throw away medicines you no longer use. These measures will help protect the environment.

Contents of the pack and other information

What Primacor contains

• Each 1 ml of injection contains 1 mg of the active substance, milrinone.
• The other ingredients are lactic acid, glucose anhydrous, water for injection and sodium hydroxide (for pH adjustment). What Primacor looks like and contents of the pack Primacor is a clear, colourless to pale yellow liquid and is available as 10 ml or 20 ml glass ampoules in boxes of 10. Not all pack sizes may be marketed. Marketing Authorisation Holder Sanofi, 410 Thames Valley Park Drive, Reading, Berkshire, RG6 1PT, UK. Tel: 0800 035 2525 email: [email protected] Manufacturer Delpharm Dijon, 6 Boulevard de l'Europe, 21800 Quetigny, France This leaflet does not contain all the information about your medicine. If you have any questions or are not sure about anything, ask your doctor or pharmacist. This leaflet was last revised in July 2020 © Sanofi, 1989 – 2020

Special precautions for disposal 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 or discolouration are present.

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Incompatibilities Furosemide or bumetanide should not be administered in intravenous lines containing Primacor Injection since precipitation occurs on admixture. Sodium Bicarbonate Intravenous infusion should not be used for dilution. Other drugs should not be mixed with Primacor Injection until further compatibility data are available. Shelf life 36 months when unopened. A diluted solution of Primacor Injection should be used within 24 hours. Special precautions for storage Store below 25°C. Do not freeze.

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