Drug interactions between antibiotics and select maintenance medications: seeing more clearly through the narrow therapeutic window of opportunity.
OBJECTIVE
Infections often occur while treating patients with long-term medications for chronic illnesses. Treating these infections with systemic antibiotics often leads to pharmacokinetic and pharmacodynamic interactions between the antimicrobials and one or more of the maintenance medications. Previously optimized long-term regimens may become either subtherapeutic or super-therapeutic, with deleterious consequences. This article discusses some of the most significant and commonly encountered antibiotic drug interactions that may occur with medications with "narrow therapeutic windows" including warfarin, phenytoin, carbamazepine, theophylline, and the two calcineurin inhibitors. Given the logistics of many consultant pharmacists' practices, it may not always be possible for them to react prospectively when these combinations are prescribed at their facilities. Therefore, there are several things the pharmacist can do: provide regular and comprehensive inservice raining on this topic, be available as needed to answer patient-specific questions, and provide readily available charts and other educational materials that help identify and characterize these important interactions.


METHODS
A Medline search of the English literature was performed in October/November 2003, going back to 1980 for the commonly used antibiotics and drug interactions stated in this text. In some cases, cross referencing of articles reviewed also led to older publications. Textbooks dealing with drug interactions also were used as initial sources. However, whenever possible, any data quoted within the text were verified from the original research paper.


METHODS
Pharmacokinetic studies, case reports, and general review articles published in the English medical literature were all selected for review. In cases where review articles were cited that summarize groups of data from previous original research papers, the authors made the best possible effort to verify the accuracy by referring to the original research papers.


RESULTS
Because of the breadth of the topic in terms of all the antibiotics discussed, the interacting medications that pertained to each antibiotic, and the lack of homogeneity among the various types of papers (most of which were case reports), most analyses include broad-based summaries based on the aggregate findings of the authors.


CONCLUSIONS
The addition of antibiotics to a stabilized medical regimen can result in either potentiation or antagonism of the clinical effects of narrow-therapeutic-window medications such as warfarin, phenytoin, theophylline, calcineurin inhibitors, carbamazepine, and numerous other agents. As usual in the clinical arena, awareness is the first step in appropriate management of these encounters.
University of Michigan College of Pharmacy, Ann Arbor, MI 48109, USA. reregal@umich.edu
Randolph E
RE
Regal
Celina
C
Ong Vue