Enalapril (Paediatric Heart Failure / Hypertension)

PAGE SCOPE: this is a PAEDIATRIC page — the clinically important content is in paedDose. The adult figures here exist only because the page carries an adult dose field; they come from the US generic enalapril maleate label, because the UK SPC in this bundle (AQUMELDI 0.25 mg orodispersible tablets) is a paediatric heart-failure product and contains no adult posology at all. Do NOT read the paediatric mg/kg protocol into this field and do not read these adult milligram figures into the paediatric one. HEART FAILURE VERBATIM: 'The recommended initial dose is 2.5 mg. The recommended dosing range is 2.5 to 20 mg given twice a day. Doses should be titrated upward, as tolerated, over a period of a few days or weeks. The maximum daily dose administered in clinical trials was 40 mg in divided doses.' 'After the initial dose of enalapril maleate, the patient should be observed under medical supervision for at least two hours and until blood pressure has stabilized for at least an additional hour.' HEART FAILURE WITH HYPONATRAEMIA OR RENAL IMPAIRMENT: 'In patients with heart failure who have hyponatremia (serum sodium less than 130 mEq/L) or with serum creatinine greater than 1.6 mg/dL, therapy should be initiated at 2.5 mg daily under close medical supervision... The dose may be increased to 2.5 mg b.i.d., then 5 mg b.i.d. and higher as needed, usually at intervals of four days or more.' ASYMPTOMATIC LEFT VENTRICULAR DYSFUNCTION: 'patients were started on 2.5 mg twice daily and were titrated as tolerated to the targeted daily dose of 20 mg (in divided doses).' HYPERTENSION VERBATIM: 'The recommended initial dose in patients not on diuretics is 5 mg once a day... The usual dosage range is 10 mg to 40 mg per day administered in a single dose or two divided doses.' If a diuretic cannot be discontinued, 'an initial dose of 2.5 mg should be used under medical supervision for at least two hours and until blood pressure has stabilized for at least an additional hour'; the label advises discontinuing the diuretic for two to three days before starting enalapril where possible.

INDICATION SPLIT — READ THE LABEL ON EACH REGIMEN. The UK SPC regimen below is licensed for PAEDIATRIC HEART FAILURE (its section 4.8 adverse-reaction table is headed 'List of adverse reactions in children with heart failure'). The US paediatric regimen further down is for HYPERTENSION. They are different indications with different figures and must not be blended. PAEDIATRIC HEART FAILURE (UK SPC 4.2, verbatim): 'Starting/test dose 0.01 to 0.04 mg/kg (max 2 mg) as a single initial dose.' 'Before giving a test dose, blood pressure (BP) and renal function should be checked. If the BP is below the 5th percentile or creatinine is above normal limit for age, then enalapril should not be given.' 'Test dose should be at the lower end of the range for less stable patients and in infants <30 days of age.' 'Blood pressure should be monitored at intervals for 1-2 hours after the initial dose. If systolic BP is below the 5th percentile enalapril should be stopped and appropriate clinical care given.' Then: 'Target/maintenance dose 0.15 to 0.3 mg/kg (max 20 mg) per day in one or two divided doses 8 hours after test dose. The dose should be individualised according to blood pressure, serum creatinine and potassium response.' WHY dosePerKg IS NULL: both the test dose and the maintenance dose are stated as RANGES, not single figures, and the maintenance range is a DAILY TOTAL that must be divided into one or two doses and reached only after an individually assessed test dose. Publishing a single computed number for a drug that requires a supervised test dose, with hypotension and renal-function stopping rules, would misrepresent the protocol — so no figure is fed to the calculator. Calculate each patient's dose against the SPC protocol above and a children's formulary. TITRATION RULES (UK SPC 4.2, verbatim): 'If systolic blood pressure (SBP) is greater than or equal to the 5th percentile and serum creatinine is no more than 1.5 x baseline, consider enalapril dose up-titration. If SBP is below the 5th percentile and serum creatinine is more than 2 x baseline, enalapril should be stopped. If systolic blood pressure is below the 5th percentile and serum creatinine is between 1.5 and 2 x baseline, enalapril dose should be titrated down. If SBP is above the 5th percentile and serum creatinine is more than 2 x baseline, enalapril dose should be titrated down. If systolic blood pressure is greater than or equal to the 5th percentile and serum creatinine is between 1.5 to 2 x baseline the enalapril should be continued at the same dose.' POTASSIUM RULE: 'At any stage if potassium >= 5.5 mmol/l pause enalapril treatment. Once hyperkalaemia has resolved, restart enalapril on the same or a lower dose level. If hyperkalaemia recurs, repeat the above and restart at a lower level. If potassium is repeatedly above 5.5 mmol/l, despite multiple dose decreases, discontinue enalapril.' MISSED DOSE: 'If a dose of AQUMELDI is missed the next dose should be given as usual. Do not give a double dose to make up for a forgotten dose.' INFANTS UNDER 30 DAYS: 'Treatment of infants < 30 days of age should only be conducted with rigorous monitoring, including blood pressure, serum potassium levels and renal function.' PAEDIATRIC HYPERTENSION (US label, a DIFFERENT indication, verbatim): 'The usual recommended starting dose is 0.08 mg/kg (up to 5 mg) once daily. Dosage should be adjusted according to blood pressure response. Doses above 0.58 mg/kg (or in excess of 40 mg) have not been studied in pediatric patients.' The same label states: 'Antihypertensive effects of enalapril maleate have been established in hypertensive pediatric patients age 1 month to 16 years' and 'Enalapril maleate is not recommended in neonates and in pediatric patients with glomerular filtration rate less than 30 mL/min/1.73 m2, as no data are available.' LIQUID FORM: concentration is null because the UK source product is an orodispersible TABLET, not a liquid. The US label does describe an extemporaneous preparation — 'Preparation of Suspension (for 200 mL of a 1.0 mg/mL suspension)' from ten 20 mg tablets in sodium citrate and citric acid oral solution plus Ora-Sweet SF, refrigerated at 2 to 8 C — but that is a US extemporaneous product, not the UK licensed one, so it has not been entered as the page concentration. Confirm any suspension strength with pharmacy. Verify all under-18 dosing against a children's formulary.