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Antihistamines and decongestants rank highly among the top 40 prescription and nonprescription xenobiotics used in the United States. Inappropriate use and unrecognized dangers associated with their use have posed significant public health problems. Their ready availability, singly and in combination with each other and with analgesics and antipyretics, coupled with widespread public impression that nonprescription and herbal xenobiotics are "safe," contributes to their frequent use, misuse, and potential abuse.

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Recreational use of antihistamines and decongestants as "legal highs" has gained in notoriety over the past several years, and nonprescription sympathomimetics have been used as precursors in the synthesis of illegal stimulants. While the rates of potential adverse events are perceived as low, the issue takes on added significance when the magnitude of the exposure rates for these xenobiotics is considered: in a survey of 2590 participants distributed across the Unied States, 8.1% of adult participants reported taking pseudoephedrine within the past week, and 4.4% reported the use of diphenhydramine within the same time period47 (Table 50–1).

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Table 50–1. Antihistamines and Decongestants among the 40 Most Commonly Used Prescription and Nonprescription Drugs (Adult Use in the United States) in 1998 and 1999
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Despite well-designed and carefully monitored studies prior to US Food and Drug Administration (FDA) approval of medications, only half of newly discovered serious adverse drug events (ADEs) are detected and reported in the Physicians' Desk Reference within 7 years of drug approval.52 This suggests that increased efforts to detect and report ADEs via improved postmarketing surveillance are required. The quality and timeliness of current toxicovigilance efforts may be hampered by many variables including low reporting rates, variable data quality in reports, and the effects of media attention on spontaneous reporting systems—factors well-known to clinical toxicologists and poison centers. The potential impact of surveillance system inadequacies on public health is dramatically illustrated by the delayed recognition of the risk of intracranial hemorrhage associated with the use of phenylpropanolamine.48

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Recent information regarding potential hazards of antihistamine or decongestant use has catalyzed new review, regulations and withdrawal of some xenobiotics from the market. The Combat Methamphetamine Act signed into law in 2006 limiting methamphetamine precursor availability and additional precautions in pharmacies (such as dispensing limits for nonprescription quantities and storage of the medications behind pharmacy counters) has attempted to reduce potential harm associated with these xenobiotics.

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