Pharmacological Considerations in Neonatal Cardiac Care: A Narrative Review of Dosing, Safety, and Efficacy

Abstract

Neonatal cardiac care presents unique therapeutic challenges due to the distinct physiological characteristics of the newborn, including immature hepatic and renal function, altered drug absorption and distribution, and rapidly changing hemodynamic parameters. Pharmacological interventions in this population demand heightened caution, precise dosing strategies, and rigorous evaluation of safety and efficacy to prevent adverse outcomes. Neonates with congenital or acquired heart disease often require complex medication regimens involving inotropes, vasodilators, diuretics, antiarrhythmics, and prostaglandin analogues, among others. However, limited clinical trial data, heterogeneous patient profiles, and ethical barriers to research significantly constrain evidence-based pharmacotherapy in this critical group. This review highlights essential pharmacological considerations for optimizing neonatal cardiac drug therapy. A literature search was performed across major electronic databases, including PubMed, Scopus, Web of Science, and Google Scholar. The search covered publications from 1987 to 2025. Data were extracted manually and synthesized thematically. Dosing regimens must be individualized by gestational age, birth weight, organ maturity, and concomitant morbidities to avoid toxicity or subtherapeutic exposure. Pharmacokinetic variables such as increased total body water, reduced plasma protein binding, and variable enzymatic activity necessitate careful titration and therapeutic drug monitoring for agents such as digoxin, milrinone, and amiodarone. Safety evaluation remains central, as neonates face increased risk of complications including arrhythmias, hypotension, electrolyte disturbances, and nephrotoxicity. Efficacy assessment must extend beyond immediate cardiovascular stabilization to include long-term neurodevelopmental and organ function outcomes. Emerging pharmacologic strategies, including precision dosing models, pharmacogenomics, and physiologically based pharmacokinetic (PBPK) modeling, show promise in enhancing therapeutic accuracy for neonatal cardiac care. Collaborative neonatal–cardiology drug registries and adaptive clinical trial methodologies are also essential to strengthen the evidence base. Ultimately, a multidisciplinary approach integrating cardiology, neonatology, pharmacy, and nursing is critical to ensure safe, effective, and individualized medication management. While recent literature highlights major advances in cardiovascular drug monitoring and support, the need for robust clinical trials and model-informed precision dosing remains urgent. Improving pharmacologic precision will contribute significantly to reducing morbidity, mortality, and long-term complications in this vulnerable population.