"Inactive" Ingredients in Pharmaceutical Products

Abstract

Pharmaceuticals often contain agents that have a variety of purposes including improvement of the appearance, bioavailability, stability, and palatability of the product. Excipients frequently make up the majority of the mass or volume of oral and parenteral drug products. These pharmaceutical adjuvants are usually considered to be inert and do not add to or affect the intended action of the therapeutically active ingredient. Some 773 chemical agents have been approved by the Food and Drug Administration for use as inactive ingredients in drug products.1 Inasmuch as these compounds are classified as "inactive," manufacturers are not presently required to list them on the product label. These ingredients are used for a variety of different purposes (Table 1). Because of the large number of these agents and their frequency of use, practicing physicians have recently become concerned about their possible physiologic effects. The increasing number of reports of adverse effects associated with pharmaceutical excipients2 has led to professional and consumer organizations formally requesting the FDA (Food and Drug Administration) to require complete disclosure on the product label of all substances contained in pharmaceuticals. Problems encountered with "inactive" ingredients, include the following. ADVERSE EFFECTS OF PHARMACEUTICAL EXCIPIENTS Benzyl Alcohol This antimicrobial agent is commonly used as a preservative in many injectable drugs and solutions. A number of neonatal deaths and severe respiratory and metabolic complications in infants have been associated with use of this agent.3-5 In a controlled study, intraventricular hemorrhage, metabolic acidosis, and increased mortality were positively correlated with substantial benzoic acid and benzyl alcohol levels in neonates.6