Significant interactions with new antiretrovirals and psychotropic drugs

To provide an update on relevant antiretroviral interactions and psychotropic medications for healthcare practitioners managing complex HIV-related pharmacotherapy.

Information was retrieved via a MEDLINE search (January 1966-September 1998) using MeSH headings human immunodeficiency virus, drug interactions, psychiatry, psychotropics, psychiatric illness, and names of medications commonly prescribed for the management of HIV infection. Abstracts of international and national conferences (until February 1999), review articles, textbooks, and references of all articles also were searched.

Literature on pharmacokinetic interactions was considered for inclusion. Pertinent information was selected and summarized for discussion. In the absence of specific data, pharmacokinetic and pharmacodynamic properties were considered in order to predict the likelihood of potential drug interactions.

All protease inhibitors and nonnucleoside reverse transcriptase inhibitors are substrates of the cytochrome P450 system and possess enzyme-inhibiting and/or -inducing properties. Psychotropic medications also possess similar metabolic characteristics and may interact with antiretrovirals. Modifications in drug selection, dose, or dosing regimen may be needed to ensure adequate antiretroviral concentrations and thus minimize the risk of incomplete viral suppression and/or development of drug resistance. In the absence of specific data, consideration of metabolic characteristics may assist practitioners in predicting the likelihood of possible interactions.

The incidence and implications of antiretroviral drug interactions are reviewed. Practical management strategies are also discussed. Comprehensive tables on clinically significant interactions with antiretroviral combinations and with psychiatric medications are provided.

Given the increasing use of multiple-drug therapy, the potential for drug interactions is extremely high. Drug interactions may lead to undesirable outcomes including subtherapeutic drug concentrations and risk of antiretroviral resistance. Practitioners need to consider pharmacokinetic, pharmacologic, therapeutic, and adherence factors when managing interactions with complex antiretroviral therapy.