Editorials

Avoiding Drug Interactions



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Am Fam Physician. 2000 Mar 15;61(6):1628-1637.

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In this issue of American Family Physician, Ament and colleagues1 highlight several important drug interactions and also raise an ongoing health care concern: How can morbidity and mortality from drug interactions be reduced?

A recent study2 showed that although drug interactions are responsible for only 3.8 percent of emergency department visits, these patients usually have to be admitted to the hospital. Another study3 indicated that preventable drug interactions are responsible for approximately one third of all adverse events in hospitalized patients and account for one half of the costs attributed to adverse events.

Preventing undesirable drug interactions requires that family physicians make full use of available resources and keep current with recent changes in drug safety. Unfortunately, the safety profile of a drug (adverse reactions and drug interactions) is not static and can change as the drug is prescribed more frequently in varied patient populations.

In the past two and one half years, an unprecedented number of drugs have been withdrawn from the U.S. market for safety reasons discovered through postmarketing surveillance. These drugs include fenfluramine (Pondimin), dexfenfluramine (Redux), terfenadine (Seldane), bromfenac (Duract), astemizole (Hismanal), mibefradil (Posicor), grepafloxacin (Raxar) and, most recently, the rotavirus vaccine (Rotashield). Serious drug interactions were a factor in the withdrawal of at least three of these drugs (terfenadine, astemizole and mibefradil).

In addition, approximately one fifth of all safety notifications posted on the Web site of the U.S. Food and Drug Administration (FDA) in 1999 concerned new safety warnings about drug interactions.4 Included were interactions between celecoxib (Celebrex) and warfarin (Coumadin); methotrexate (Rheumatrex) and radiotherapy; pimozide (Orap) and cytochrome P450-3A (CYP3A) inhibitors; cisapride (Propulsid) and grapefruit juice; and nevirapine (Viramune) and methadone.

Because the FDA approves approximately 25 new molecular entities (drugs not previously marketed in the United States) each year, keeping abreast of new drug interactions is difficult. The article by Ament and colleagues1 lists a number of resources that are valuable in screening for drug interactions. At least one of these references should be available at every practice site. However, it is important to note that drug information references are merely tools and do not replace basic knowledge of pharmacology, clinical judgment and sound problem-solving skills.

In using any drug information resource, family physicians should keep a number of factors in mind. Knowing the capabilities and limitations of a particular resource is as important as knowing how to use it. It is important to select a resource that is updated several times a year to maximize the chance that the information in the resource is current. A good drug information resource provides information on the severity of interactions, their potential clinical significance, management suggestions and references if further information is desired.

Even with updates, information in any drug interaction resource is typically six months behind the published literature. Thus, the resource may not contain data on newly released products, information from recent FDA announcements or data released by pharmaceutical companies in the form of letters to health professionals.

It is important to access alternative sources when prescribing newly marketed drugs (less than one year old). A significant consideration is interactions with alternative or herbal medicines, in that the popularity of these therapies has increased the potential for previously unknown interactions.

In addition to the drug interaction resources mentioned by Ament and colleagues,1 journals, local pharmacists, drug information centers and the Internet are valuable avenues for keeping current. Pharmacists and drug information centers often use computerized drug interaction databases. These databases are efficient screening tools for a large number of drug interactions.

The FDA Web site for the year 2000 contains information on recent labeling changes related to safety.5 The information is organized by the brand and generic names of drugs. The Web site also includes summaries of letters to health care professionals from pharmaceutical companies, and other important safety notifications regarding drugs, biologics, dietary supplements and medical devices.

Family physicians who regularly access electronic mail (e-mail) can keep abreast of newly published or about-to-be-published information on drug interactions by receiving tables of contents from electronic journals. Most online journals currently offer this service free of charge to subscribers and non-subscribers. Some journals will e-mail only the specific topics of interest selected by the reader, thereby minimizing unnecessary correspondence.

Selecting medication regimens that optimize therapeutic benefits, minimize side effects and avoid detrimental drug interactions remains an essential component of patient care. Although keeping up with new drug safety information can be time-consuming, accessing various drug information resources may increase awareness and prevent drug interactions.

Joyce Generali, M.S., R.Ph., is clinical associate professor and director of the Drug Information Center at the University of Kansas Medical Center, Kansas City, Kan.

Address correspondence to Joyce Generali, M.S., R.Ph., Department of Pharmacy, Drug Information Center, University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, KS 66160-7231; e-mail address: jgeneral@kumc.edu.

REFERENCES

1. Ament PW, Bertolino JG, Liszewski JL. Clinically significant drug interactions. Am Fam Physician. 2000;61:1745–54.

2. Raschetti R, Morgutti M, Menniti-Ippolito F, Belisari A, Rossignoli A, Linghini P, et al. Suspected adverse drug events requiring emergency department visits or hospital admissions. Eur J Clin Pharmacol. 1999;54:959–63.

3. Bates DW, Spell N, Cullen DJ, Burdick E, Laird N, Petersen LA, et al. The costs of adverse drug events in hospitalized patients. Adverse Drug Events Prevention Study Group. JAMA. 1997;277:307–11.

4. New safety information summaries. FDA Web site 1999. Retrieved December 27, 1999 from the World Wide Web: http://www.fda.gov/medwatch/safety/1999/safety99.htm.

5. New safety information summaries. FDA Web site 2000. Retrieved January 11, 2000 from the World Wide Web: http://www.fda.gov/medwatch/safety/2000/safety00.htm.



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