Formulary





Edward J. Baker

Clinical trials of medicines for children have been limited, and often therapeutic decisions are made on the basis of evidence of efficacy and safety in adult patients. Caution in the use of new, unlicensed medicines, without evidence in children is therefore inevitable. This means that the choice of medicines is much more limited than in adult practice. Here, I present a summary of medicines commonly used for cardiovascular disorders in children ( Table 67-1 ). This list does not attempt to be comprehensive, as practice will vary internationally, and some drugs in common use in one part of the world are hardly used elsewhere. The paucity of evidence makes this unavoidable. This summary, therefore, is not a replacement for local guidelines. To avoid confusion, I have used the recommended international non-proprietary names for the medicines covered. Where there is a common alternative name, I have included it, but I have not tried to include local or proprietary names, as these vary internationally.



TABLE 67-1

SUMMARY OF MEDICINES COMMONLY USED FOR CARDIOVASCULAR DISORDERS IN CHILDREN




































































































































































































































Drug Indications Contra-indications Major Side Effects Typical Dose and Frequency Comments
Adenosine Diagnosis of arrhythmias and termination of supraventricular arrhythmias Heart block, asthma Chest pain, dyspnoea, bronchospasm, severe bradycardia Fast intravenous bolus of 100 μg/kg to maximum of 300 μg/kg for the neonate, or 500 μg/kg for the older child


  • Electrocardiographic monitoring and recording during the administration of the bolus is essential.



  • The bolus can be repeated after 2 minutes with the dose increased progressively until electrocardiographic changes occur.

Alprostadil (prostaglandin E 1 ) Maintenance of the patency of the ductus arteriosus in the neonate Apnoea, tachycardia, hypotension, fever, cortical proliferation of long bones, necrotising enterocolitis Intravenous infusion of initially 10 ng/kg per minute, can be increased to 50 ng/kg per minute according to response


  • Monitor heart rate, respiration, and temperature.



  • Ventilation may be required for apnoea.

Amiloride Potassium sparing diuretic Hyperkalaemia, renal failure Hyponatraemia, hyperkalaemia, hypotension


  • Orally 200 μg/kg twice per day



  • Maximum of 20 mg per day

Weak diuretic used in combination with thiazide or loop diuretics
Amiodarone Supraventricular and ventricular arrhythmias Bradycardia, heart block, hypotension Bradycardia, thyroid disorders, hepatotoxicity, corneal microdeposits, photosensitivity, gray skin discolouration, neuropathy, anaemia


  • Orally initially 5 mg/kg two to three times per day,



  • reduce to maintenance dose after 7 days



  • Maintenance 5 mg/kg once per day or based on measurement of plasma levels



  • Intravenous infusion initially 25 μg/kg per hour for 4 hours then 5 to 15 μg/kg per minute.



  • Maximum of 1.2 g per day




  • Long-term administration should be avoided because of the incidence of side effects.



  • Careful monitoring of hepatic, thyroid and visual function is required.



  • Photosensitivity and skin discolouration can be severe, and sun block is required.



  • Monitor the heart rate during intravenous infusions, and adjust the dose as necessary.



  • Therapeutic plasma level of amiodarone and its active metabolite is 0.6 to 2.5 mg/L.

Aspirin


  • Low-dose antiplatelet prophylaxis against thrombosis



  • High dose anti-inflammatory agent for Kawasaki disease

Viral infections, with the risk of Reye’s syndrome, peptic ulceration bleeding disorders Reye’s syndrome, bleeding especially gastrointestinal, bronchospasm


  • Low-dose antiplatelet: orally 5 mg/kg (maximum of 75 mg) once per day



  • High-dose antiplatelet: orally 20 to 25 mg/kg 4 times per day for approximately 14 days, then reduce to low dose

High-dose aspirin is also used in acute rheumatic fever (see Chapter 54A ) and post-pericardectomy syndrome (see Chapter 53 ).
Atenolol Hypertension, supraventricular and ventricular tachycardias Asthma, heart block, hypotension, depressed myocardial function Bradycardia, heart failure, bronchospasm, heart block, peripheral vasoconstriction, fatigue


  • Orally 1 to 2 mg/kg once per day



  • Maximum of 100 mg per day

Use smaller doses in renal and hepatic impairment.
Captopril Cardiac failure, hypertension Renal impairment, renovascular disease, coarctation, left ventricular outflow or inflow obstruction Hypotension particularly with initial doses, renal impairment, tachycardia, photosensitivity, persistent dry cough Orally initially 100 μg/kg three times per day, increasing to 1 mg/kg three times per day


  • ACE inhibitor, in heart failure usually combined with a loop diuretic



  • Do not give with potassium sparing diuretics.



  • Initiate carefully under close supervision, usually in an in-patient to ensure close monitoring of blood pressure and renal function.

Carvedilol Cardiac failure Asthma, heart block, hypotension, depressed myocardial function Bradycardia, cardiac failure, bronchospasm, heart block, peripheral vasoconstriction, fatigue


  • Orally initially 50 μg/kg (maximum of 3.125 mg) twice per day.



  • Increase at 2-week intervals eventually up to 350 μg/kg (maximum of 25 mg) twice per day




  • Used as a third-line treatment for chronic cardiac failure as an adjunct to diuretics and inhibitors of angiotensin-converting enzyme



  • As yet, there is no evidence of long-term benefit in children.

Clopidogrel Antiplatelet prophylaxis against thrombosis as an alternative to low-dose aspirin Haemorrhage, neutropenia Orally 1 mg/kg once per day (maximum of 75 mg) Used as a second-line treatment after aspirin
Digoxin Supraventricular arrhythmias, cardiac failure Heart block, renal failure, Wolff-Parkinson-White syndrome, ventricular tachycardia Anorexia, abdominal pain, heart block, arrhythmias


  • Orally, neonates to 5 years: 10 μg/kg/day



  • Children 5 to 10 years: 6 μg/kg/day

Maximum 250 μg/day


  • In urgent circumstances, loading doses (digitalisation) may be needed over first 24 hours.



  • Dose should be reduced in preterm neonates and renal failure.



  • Is of limited value in cardiac failure, and rarely used as first choice



  • Intravenous administration is rarely justified.



  • Therapeutic plasma digoxin concentration 0.8 to 2.0 μg/L

Dinoprostone (prostaglandin E 2 ) Maintaining the patency of the ductus arteriosus in the neonate Apnoea, tachycardia, hypotension, fever, cortical proliferation of long bones, necrotising enterocolitis Intravenous infusion of initially 5 ng/kg/min, can be increased to 20 ng/kg/min according to response


  • Monitor heart rate, respiration, and temperature.



  • Ventilation may be required for apnoea.

Dipyridamole Antiplatelet prophylaxis against thrombosis as an alternative to low-dose aspirin Heart failure, aortic stenosis Hypotension, tachycardia, bronchospasm


  • Orally 2.5 mg/kg twice per day



  • Over age 12 years: 100 to 200 mg three times per day




  • Dipyridamole has also been used to treat pulmonary hypertension.



  • Antiplatelet action may be synergistic with aspirin.

Dobutamine Inotropic support in low cardiac output Left ventricular outflow obstruction Tachycardia, hypotension Intravenous infusion 2 to 20 μg/kg/min
Dopamine Hypotension and low cardiac output Tachycardia, arrhythmia Hypertension, tachycardia, arrhythmias Intravenous infusion 2 to 20 μg/kg/min There is little evidence that low doses have beneficial vasodilatory effects in clinical practice.
Enalapril Heart failure, hypertension Renal impairment, renovascular disease, coarctation, left ventricular outflow or inflow obstruction Hypotension particularly with initial doses, renal impairment, tachycardia, Raynaud’s syndrome, Stevens-Johnson syndrome, alopecia, muscle cramps, persistent dry cough Orally initially 0.1 mg/kg/day, increasing according to response up to a maximum of 1.0 mg/kg/day


  • ACE inhibitor, in heart failure usually combined with a loop diuretic.



  • Do not give with potassium sparing diuretics.



  • Initiate carefully under close supervision, usually as an in-patient to ensure close monitoring of blood pressure and renal function.

Epinephrine (adrenaline) Acute hypotension Hypertension Tachycardia, hypertension, arrhythmias Intravenous infusion of 100 ng/kg/min, up to 1.5 μg/kg/min
Esmolol Emergency management of arrhythmias and hypertension, cyanotic spells in tetralogy of Fallot Asthma, heart block, hypotension, depressed myocardial function Bradycardia, heart failure, bronchospasm, heart block


  • Intravenously initial dose of 500 μg/kg administered over 1 to 2 minutes



  • Can be followed by an infusion of 25 to 50 μg/kg/min



  • Can be increased to a maximum of 200 μg/kg/min in resistant cases




  • Relatively cardioselective β-blocker



  • Reduce dose if hypotension or bradycardia occurs.



  • Higher dose of infusion may be required to terminate severe cyanotic spells in tetralogy of Fallot.

Flecainide Ventricular tachycardia, arrhythmias in Wolff-Parkinson-White syndrome, atrioventricular re-entry tachycardias Heart failure, heart block, hypokalaemia


  • Precipitation of life-threatening arrhythmias particularly in structural heart disease



  • Depression of myocardial function especially when used with β-blockers or calcium-channel blockers




  • Orally 2 mg/kg two to three times per day



  • Adjust dose according to plasma levels



  • Intravenously 2 mg/kg per dose



  • Infusion of 100 to 250 μg/kg/hr until arrhythmia controlled (maximum total dose of 600 mg in first day)




  • Monitor electrocardiogram during slow intravenous administration.



  • If intravenous infusion lasts more than 24 hours, monitor plasma levels (therapeutic range 200 to 800 μg/L).

Furosemide (frusemide) Cardiac failure, pulmonary oedema, hypertension Hypokalaemia, hypotension Hyponatraemia, hypokalaemia, hypomagnesaemia, nephrocalcinosis, hypotension, deafness (with rapid intravenous infusion)


  • Orally 0.5 to 2 mg/kg two to three times per day (maximum of 12 mg/kg/day or 80 mg/day in total, whichever is lower)



  • Intravenously 0.5 to 1 mg/kg up to four times per day, or continuous infusion of 0.1 to 2 mg/kg/hr

In oliguria, much higher doses may be needed, titrated against the urine output.
Ibuprofen Closure of the patent arterial duct in preterm neonates Hepatic impairment, pulmonary hypertension, bleeding disorders, necrotising enterocolitis, infection Bleeding especially intracranial bleeding, renal impairment, necrotising enterocolitis


  • Slow intravenous infusion of 10 mg/kg



  • Second and third doses at 24 and 48 hours of 5 mg/kg

Reduce dose with renal impairment, and monitor hepatic function.
Indomethacin Closure of the patent arterial duct in preterm neonates Renal impairment, infection, bleeding, especially intracranial bleeding, necrotising enterocolitis Haemorrhage, including intracranial bleeding, oliguria or anuria, fluid retention


  • Intravenous infusion over 30 minutes



  • Neonate under 48 hours: 200 μg, followed by two doses of 100 μg separated by 12 to 24 hours



  • Neonate 2 to 7 days: 200 μg, followed by two doses of 200 μg separated by 12 to 24 hours



  • Neonate over 7 days: 200 μg, followed by two doses of 250 μg separated by 12 to 24 hours




  • Monitor urinary output, and delay second and third doses until it recovers.



  • Indomethacin is also used as an anti-inflammatory agent in post-pericardiectomy syndrome.

Isoprenaline Bradycardia, complete heart block Hypotension Hypotension, tachycardia, arrhythmias 0.02 μg/kg/min increasing to a maximum of 0.5 μg/min (neonate maximum of 0.2 μg/kg/min)
Lidocaine (lignocaine) Ventricular fibrillation, ventricular tachycardia Heart block, myocardial dysfunction, hepatic failure, renal failure Central nervous system depression, respiratory depression, hypotension bradycardia


  • Intravenous bolus of 500 μg to 1 mg/kg over 1 minute



  • Repeat at 5-minute intervals up to a maximum of 3 mg/kg, followed by an intravenous infusion of 1 to 3 mg/kg/hr




  • Monitor electrocardiogram during administration.



  • Reduce dose in presence of hepatic or renal impairment.

Lisinopril Heart failure, hypertension Renal impairment, renovascular disease, coarctation, left ventricular outflow or inflow obstruction Hypotension particularly with initial doses, renal impairment, tachycardia, alopecia, persistent dry cough Orally initially 0.1 mg/kg/day, increasing according to response to 0.5 to 1.0 mg/kg/day. Maximum 40 mg/day


  • ACE inhibitor, in heart failure usually combined with a loop diuretic.



  • Do not give with potassium sparing diuretics.



  • Initiate carefully under close supervision, usually as an in-patient to ensure close monitoring of blood pressure and renal function.

Losartan Heart failure, hypertension Renal impairment, renovascular disease, coarctation, left ventricular outflow or inflow obstruction First-dose hypotension, hyperkalaemia Orally 0.5 mg/kg once per day, increasing to a maximum of 2 mg/kg once per day


  • Angiotensin II receptor antagonist with similar effects to inhibitors of angiotensin-converting enzyme, but it does not cause the characteristic dry cough of the inhibitors of the enzyme and is a useful alternative.



  • Use a lower dose in renal or hepatic impairment.



  • Introduce with caution because of the risk of hypotension

Milrinone Heart failure, low cardiac output, shock Renal failure, hypotension Arrhythmias, hypotension Intravenous infusion of 30 to 45 μg/kg/hr


  • Phosphodiesterase inhibitor with positive inotropic and vasodilator effects



  • Loading dose of 50 to 75 μg/kg for first hour, omit if hypotension occurs



  • Reduce dose in renal failure.



  • Short-term use only

Norepinephrine (noradrenaline) Hypotension secondary to severe vasodilation Hypertension Hypertension, severe vasoconstriction and peripheral ischaemia, arrhythmias 20 to 100 ng/kg/min up to maximum of 1 μg/kg/min
Propranolol Hypertension, supraventricular and ventricular tachycardias, cyanotic spells in tetralogy of Fallot Asthma, heart block, hypotension, depressed myocardial function Bradycardia, heart failure, bronchospasm, heart block, peripheral vasoconstriction, fatigue


  • Tetralogy of Fallot: intravenously 15 to 20 μg/kg, increasing to 100 to 200 μg/kg given slowly under electrocardiographic control



  • Arrhythmias: orally 250 to 500 μg/kg three times per day



  • Can increase up to 1 mg/kg three times per day



  • Intravenously 10 to 50 μg/kg slowly under electrocardiographic control




  • Do not give with verapamil.



  • Use smaller doses in renal and hepatic impairment.

Sildenafil Pulmonary hypertension Hypotension Dyspepsia, headache, visual disturbances, priapism Orally 0.5 mg/kg every 4 to 6 hours, increasing according to response to a maximum of 2 mg/kg every 4 hours


  • Reduce dose in hepatic or renal impairment.



  • Used to treat pulmonary hypertension following cardiac surgery and to wean from inhaled nitric oxide

Sotalol Atrial flutter, supraventricular and ventricular tachycardias Asthma, heart block, hypotension, depressed myocardial function, hypokalaemia, hypomagnesaemia, prolonged QT interval Bradycardia, heart failure, bronchospasm, heart block, arrhythmias, prolongation of QT interval, torsades de pointes Orally 1 mg/kg twice daily, increasing as needed every 3 to 4 days to maximum of 4 mg/kg twice per day (maximum of 80 mg twice per day)


  • Monitor the QT interval.



  • Do not administer with other drugs that prolong the QT interval.



  • Therapeutic range is 0.04 to 2.0 mg/L

Spironolactone Potassium sparing diuretic (aldosterone antagonist) Hyperkalaemia, hyponatraemia Hyperkalaemia, hyponatraemia, hepatotoxicity, gynaecomastia, osteomalacia Orally 0.5 to 1 mg/kg up to three times per day


  • Typically used with loop diuretics



  • Should not be given simultaneously with inhibitors of angiotensin-converting enzyme

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Apr 6, 2019 | Posted by in CARDIOLOGY | Comments Off on Formulary

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