Special populations

Abstract

This chapter will consider selected populations that require special attention with regards to the administration of phenytoin. It is important for clinicians to be aware of the variables at play that make these populations unique in order for therapy to be tailored thus avoiding toxicity. The neonatal and pediatric populations will be the focus, with some remarks on patients with liver and/or kidney impairment. This chapter will focus primarily on the alterations of the pharmacokinetics in these populations since most of the susceptibility to toxicity are due to these differences. Differences in the pharmacokinetics of these populations as compared to the general population requires caution and special attention to dosing, drug level monitoring, focused history and examination, and the recognition/management of toxicity. Preceding the highlights of special considerations in the neonatal and pediatric populations will be a discussion on phenytoin's historical and present role in the management of childhood epilepsy. Trends in phenytoin's use as compared to other traditional antiepileptic drugs (AEDs) will be discussed in the context of the available literature. Focus will turn to the general physiological and pharmacological differences between the neonatal/pediatric populations as compared to the general population. This will highlight important principles necessary to understand how some of these differences pertain specifically to the administration of phenytoin in these populations. Age dependent adverse effects will be explored with regards to differences in incidence and presentation in these populations. Finally, special consideration relating to the history, physical and management primarily pertaining to the evaluation of phenytoin toxicity will be considered. A vast majority of medications are affected by alterations in hepatic and renal function. Phenytoin is a classic example of how impairments in either the liver or kidneys can dramatically alter phenytoin concentrations predisposing these populations at increased risk for toxicity. Unfortunately, evidence-based research is often scarce and limited in these special populations. This is not only true of phenytoin but a common limitation in the evaluation and understanding of many medications that are commonly used in these populations. Very few randomized trials are available in support of the information contained in this chapter. Rather, literature will often be dependent on available observational and case reports/series studies. While limitations in available literature is common, this chapter will provide information valuable to the health care provider in order to make cognizant decisions and recommendations to patients in these special populations.