Medications for Premature and Newborn Infants

The administration of medications to premature and newborn infants presents unique challenges in medical practice. Many drug compounds lack substantial clinical trial data regarding their safety and efficacy in this vulnerable population. Often, dosages are determined empirically or based on anecdotal evidence rather than systematic research. A review conducted in Europe revealed that nearly 99.5% of patients in neonatal intensive care units received at least one medication through off-label use, raising concerns about the safety of pharmacotherapy and the potential for adverse drug reactions (ADRs) and medication errors.

This article provides an overview of the preventive medication practices and the most common treatment situations encountered in premature and newborn infants. It also highlights the vital role pharmacists can play in ensuring safe and evidence-based care.

Pharmacokinetic Considerations

The pharmacokinetics of drug absorption, distribution, metabolism, and excretion significantly differ in infants, especially in premature newborns, who undergo rapid developmental changes. These variations necessitate careful consideration in dosage calculations--simply scaling down from adult dosages is not appropriate.

Understanding Newborn Classification

Newborns are categorized into five developmental groups based on their age and growth milestones. The first four weeks of life define the neonatal phase, with the adjustment to life outside the womb as the primary focus. Following this period, infants from 28 days to 12 months are classified as infants, with growth being the primary concern. Newborns can also be classified based on gestational age at birth: premature (born before 36 weeks), term (36 to 42 weeks), and post-term (over 42 weeks). Additionally, birth weight categorizes them as low-birth-weight, very-low-birth-weight, or extremely-low-birth-weight infants.

Impact of Gastric Acid and Absorption

The lower gastric acid production in newborns results in a higher gastric pH, affecting the bioavailability of orally administered medications. Acid-sensitive drugs, such as penicillins, are absorbed more effectively, whereas the absorption of weakly acidic drugs, such as phenobarbital, is decreased. Furthermore, delayed gastric emptying in newborns leads to slower absorption rates, extending the time required to reach peak plasma concentrations.

Skin Barrier and Drug Distribution

The skin barrier in newborns, particularly in premature infants, is underdeveloped, characterized by a thinner stratum corneum and increased vascularity and hydration of the epidermis. This immaturity enhances the percutaneous absorption of topical medications, leading to a higher risk of systemic exposure and potential ADRs, especially with corticosteroids, antihistamines, and iodine-containing antiseptics.

Differences in Drug Distribution

Newborns exhibit distinct distribution characteristics compared to adults. Both extracellular and total body water proportions are higher, resulting in an increased volume of distribution for hydrophilic drugs (e.g., vancomycin, tobramycin) and a decreased volume for lipophilic drugs (e.g., diazepam, propofol). Consequently, higher doses of hydrophilic medications are often necessary to achieve similar plasma concentrations. Conversely, the reduced muscle mass in newborns requires lower dosages of lipophilic drugs.

Metabolic Enzyme Activity

Newborns demonstrate a significantly reduced expression of cytochrome P450 enzymes involved in phase I metabolism, such as CYP3A4, CYP1A2, and CYP2D6, as well as phase II enzymes responsible for glucuronidation. This decreased enzymatic activity persists into early childhood and influences the metabolism of various drugs, necessitating careful dose adjustments. For instance, caffeine, a substrate of CYP1A2, has a markedly extended half-life in newborns compared to older children.