Milrinone parenteral
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Solution for injection containing milrinone.
Drugs List
Therapeutic Indications
Uses
Acute heart failure
Congestive heart failure (resistant to other treatment)
Heart failure associated with cardiac surgery
Dosage
Adults
Loading dose: 50microgram/kg intravenous injection over 10 minutes.
Maintenance dose: Continuous intravenous infusion at a dosage titrated between 375 and 750nanograms/kg/minute according to patient's response.
Maximum dose: 1.13mg/kg daily.
Duration of therapy depends on patient's response.
Usual maintenance period is 48 to 72 hours. However, in congestive cardiac failure, patients have been maintained on infusion for up to five days.
In acute states following cardiac surgery treatment is unlikely to be required for longer than 12 hours.
Solutions of different concentrations may be used according to patient's fluid requirements.
Children
Loading dose: 50 to 75micrograms/kg by intravenous infusion over 30 to 60 minutes.
Maintenance dose: Intravenous continuous infusion, to be initiated on the basis of haemodynamic response and the possible onset of undesirable effects, between 250 to 750nanograms/kg/minute for a period of up to 35 hours.
Clinical studies in low cardiac output syndrome in infants and children under 6 years after corrective surgery for congenital heart disease loading dose 75microgram/kg over 60 minutes followed by a 750nanogram/kg/minute infusion for 35 hours significantly reduced the risk of development of low cardiac output syndrome.
Studies have shown that milrinone clearance rate is faster in children than adults, but infants have a significantly lower clearance rate than children, and preterm infants have an even lower clearance rate.
The following alternative dosing schedule may be suitable:
Congestive heart failure; Low cardiac output following cardiac surgery; Shock
Initial dose: 50 to 75micrograms/kg by intravenous infusion over 30 to 60 minutes. Reduce or omit initial dose if at risk of hypotension. Dose may be given undiluted if fluid restricted.
Maintenance dose: 30 to 45micrograms/kg/hour by continuous intravenous infusion for two to three days. Give for 12 hours after cardiac surgery.
Patients with Renal Impairment
In adults
Dosage should be reduced in patients with renal impairment based on creatinine clearance.
Loading dose
50microgram/kg intravenous injection over 10 minutes.
Reduced maintenance dose based on patient's creatinine clearance
Based on a solution containing 200microgram/ml prepared by adding 40ml diluent per 10ml of milrinone solution (400ml diluent per 100ml milrinone injection), the following doses (nanogram/kg/minute) are equivalent to the corresponding infusion delivery rate (ml/kg/hour):
Creatinine clearance 50ml/minute/1.73 square metres: 430nanogram/kg/minute milrinone at a delivery rate of 0.13ml/kg/hour
Creatinine clearance 40ml/minute/1.73 square metres: 380nanogram/kg/minute milrinone at a delivery rate of 0.11ml/kg/hour
Creatinine clearance 30ml/minute/1.73 square metres: 330nanogram/kg/minute milrinone at a delivery rate of 0.1ml/kg/hour
Creatinine clearance 20ml/minute/1.73 square metres: 280nanogram/kg/minute milrinone at a delivery rate of 0.08ml/kg/hour
Creatinine clearance 10ml/minute/1.73 square metres: 230nanogram/kg/minute milrinone at a delivery rate of 0.07ml/kg/hour
Creatinine clearance 5ml/minute/1.73 square metres: 200nanogram/kg/minute milrinone at a delivery rate of 0.06ml/kg/hour
Adjust the infusion rate according to haemodynamic response.
In children
Due to lack of data the use of milrinone is not recommended in children with renal impairment.
Administration
For intravenous administration.
Contraindications
Breastfeeding
Hypertrophic cardiomyopathy
Hypertrophic subaortic stenosis
Recent myocardial infarction (until stabilised)
Renal impairment in children under 18 years
Severe hypovolaemia
Severe obstructive aortic valve disease
Severe obstructive pulmonary valve disease
Ventricular aneurysm
Precautions and Warnings
Children under 18 years
Haemoglobin concentration below 10g/dL
Low cardiac filling pressures
Hypokalaemia
Hypotension
Patent ductus arteriosus
Pregnancy
Renal impairment - creatinine clearance below 51ml/minute/1.73m sq
Thrombocytopenia
Uncontrolled atrial flutter / fibrillation
Ventricular arrhythmias
Reduce dose in patients with renal impairment
Consider need for prior digitalisation
Do not use in place of surgical relief of obstructive cardiac disease
If extravasation occurs follow local policy & seek expert help immediately
Correct hypokalaemia before or during treatment
Monitor blood pressure regularly
Monitor central venous pressure
Monitor ECG
Monitor fluid balance
Monitor haemoglobin levels
Monitor heart rate
Monitor hepatic enzymes
Monitor platelets
Monitor renal function
Monitor serum electrolytes
Increased risk of thrombocytopenia in children
Reduce dose if arterial blood pressure falls significantly
Discontinue treatment if arrhythmias occur
Supraventricular and ventricular arrhythmias may occur with treatment.
An increase in ventricular ectopy including non-sustained ventricular tachycardia may occur but this has not been shown to affect patient safety or outcome. The potential for arrhythmia, present in heart failure itself, may be increased by many drugs or a combination of drugs.
Milrinone produces a slight enhancement in atrioventricular (A-V) node conduction and may increase ventricular response rate in patients with uncontrolled atrial flutter or fibrillation.
In the event of decreased cardiac filling pressures, suspend treatment with milrinone until ventricular filling pressures have been corrected.
Correct for hypokalaemia in advance of, or during therapy due to resultant diuresis following improved cardiac output with milrinone use. Potassium loss due to excessive diuresis may predispose digitalised patients to arrhythmias.
In addition to the monitoring described for adults: In neonates, following open heart surgery during milrinone therapy, monitoring should include heart rate and rhythm, systemic arterial blood pressure via umbilical artery catheter or peripheral catheter, central venous pressure, cardiac index, cardiac output, systemic vascular resistance, pulmonary artery pressure and atrial pressure. Laboratory monitoring of platelet count, serum potassium, liver function and renal function should be conducted. The frequency of assessment is determined by baseline values and it is necessary to evaluate the neonate's response to change in therapy.
In paediatric patients, milrinone therapy should be initiated only if the patients is haemodynamically stable.
Caution should be exercised in neonates with risk factors of intraventricular haemorrhage (i.e. preterm infants, low birth weight) since milrinone may induce thrombocytopenia. In clinical studies, risk of thrombocytopenia increased significantly with duration of infusion. Studies suggest that milrinone related thrombocytopenia is more common in children than adults.
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 risk.
There is no experience in controlled trials with infusions of milrinone for periods exceeding 48 hours.
Pregnancy and Lactation
Pregnancy
Use milrinone with caution during pregnancy.
The manufacturer does not recommend using milrinone during pregnancy. Animal studies have not shown teratogenic effects. Human data is limited and as such, a potential risk cannot be ruled out. It should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus.
Lactation
Milrinone is contraindicated during breastfeeding.
The manufacturer advises that the patient either discontinues milrinone or discontinues breastfeeding taking into account the benefit of breastfeeding for a child and the benefit of the woman. It is not known whether milrinone is present in human breast milk. Effects on exposed infants are unknown.
Side Effects
Abnormal liver function tests
Anaphylactic shock
Angina
Bronchospasm
Chest pain
Decrease in haemoglobin
Ectopic beats
Enhanced AV node conduction
Headache
Hypokalaemia
Hypotension
Intraventricular haemorrhage
Local reaction at injection site
Persistent patent ductus arteriosus
Rash
Renal failure
Skin reactions
Supraventricular arrhythmias
Thrombocytopenia
Torsades de pointes
Tremor
Ventricular fibrillation
Ventricular tachycardia
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: May 2016
Reference Sources
Summary of Product Characteristics: Milrinone 1mg/ml Solution for injection/infusion. Tillomed Laboratories Ltd. Revised May 2021.
Summary of Product Characteristics: Milrinone 1mg/ml solution for Injection. Wockhardt UK Ltd. Revised March 2017.
Summary of Product Characteristics: Primacor 1mg/ml solution for Injection. Sanofi. Revised January 2016.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 13 September 2017
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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