Review: Lisinopril in paediatric medicine: a retrospective chart review of long-term treatment in children

Abstract

Objective. To investigate the antihypertensive efficacy, dosing, tolerability and effects on growth of lisinopril (off label-use) in paediatric patients during long-term treatment. Design. We conducted a retrospective analysis of data from 123 patients treated with lisinopril in a paediatric nephrology clinic over a 9.3-year period. Patients were categorised by age group and predominant clinical diagnosis: hypertension (n=59), renal parenchymal disease (n=27), diabetes mellitus (n=33) and miscellaneous (n=4).Results. The vast majority were Caucasian (93%) and boys (66%). Mean duration of treatment was 2.0 years.Age at start of treatment ranged from two months to 17.7 years. Mean lisinopril starting and final doses were 0.105 mg/kg/day for hypertensive patients and 0.108 mg/kg/day for patients with renal disease, respectively.The most common adverse event was hypotension (8.6% of the patients). Haematology and serum biochemistry profiles were unaffected by lisinopril. Growth was not different from data recorded by Belgian population studies. In 29 of the 47 hypertensive patients who received lisinopril monotherapy, comparing blood pressure (BP) at baseline and after six months' treatment, mean reductions in systolic/diastolic BP were 19/18 mmHg. Conclusions. Lisinopril was well tolerated in paediatric patients. Doses of 0.1 mg/kg/day produced clinically significant BP reduction in hypertensive patients. IntroductionA survey on unlicensed and off-label drug use found that over two thirds of children admitted in European hospitals received unlicensed or off-label medicines.

Therapeutic efficacy and safety of ACE inhibitors in the hypertensive paediatric population: a review

“…Two of the studies defined hypertension as a DBP of ≥95th percentile for age, gender and height on repeated measurements, according to the ‘Fourth Report’ 1 15 17. In contrast, an SBP of ≥95th percentile was used in two studies, and an SBP or a DBP of ≥95th percentile was used in three studies 14 16 18–20. Soergel et al ,21 Seeman et al 25 and Wühl et al 22,24 defined hypertension as 24-hour mean systolic or diastolic arterial pressure ≥95th percentile for age, gender and height.…”

“…Lisinopril administration in hypertensive children has also been evaluated in a retrospective study and was found to result in a decrease in both SBP and DBP 16. The efficacy of lisinopril has also been evaluated in children with a renal transplant in a 30-day pharmacokinetic study and was also found to decrease both SBP and DBP with ≥6 mm Hg in 85% and 77%, respectively 23…”

Therapeutic Options for the Treatment of Hypertension in Children and Adolescents

“…Enalapril and lisinopril both produce a dose-dependent reduction in blood pressure. Minimum effective dosages range from 0.08 mg/kg/day to 0.6 mg/kg/day and were well tolerated 12,27,28. However, fosinopril did not produce the same dose response reduction in blood pressure as that seen in the enalapril and lisinopril studies, but did demonstrate a significant reduction in SBP and DBP.…”

“…One study found that children between 2–16 years of age receiving enalapril or captopril developed neutrophilic hypersegmentation 30. One retrospective study of lisinopril found no effect on age-specific growth patterns despite the varying medical conditions of the participants 28. A meta-analysis of studies evaluating ethnic differences in children treated with ACEI suggested a difference between black and white children to the antihypertensive effects of ACEI.…”

Lisinopril Dihydrate: Single-Crystal X-Ray Structure and Physicochemical Characterization of Derived Solid Forms

“…Lisinopril (LIS), (S)‐1‐[N 2 ‐(1‐carboxy‐3‐phenylpropyl)– l ‐lysyl]– l ‐proline, (Fig. S1, Supporting Information) is a long‐acting angiotensin‐converting enzyme (ACE) inhibitor, widely used in therapy for the treatment of many disorders including hypertension, heart failure, acute myocardial infarction, and diabetic nephropathy …”