Drug-Drug Interactions of Infectious Disease Treatments in Low-Income Countries: A Neglected Topic?

Abstract

Despite recent advances in recognizing and reducing the risk of drug-drug interactions (DDIs) in developed countries, there are still significant challenges in managing DDIs in low-income countries (LICs) worldwide. In the treatment of major infectious diseases in these regions, multiple factors contribute to ineffective management of DDIs that lead to loss of efficacy or increased risk of adverse events to patients. Some of these difficulties, however, can be overcome. This review aims to evaluate the inherent complexities of DDI management in LICs from pharmacological standpoints and illustrate the unique barriers to effective management of DDIs, such as the challenges of co-infection and treatment settings. A better understanding of comprehensive drug-related properties, population-specific attributes, such as physiological changes associated with infectious diseases, and the use of modeling and simulation techniques are discussed, as they can facilitate the implementation of optimal treatments for infectious diseases at the individual patient level.

Figure 1

Therapeutic areas for reported drug–drug interactions (DDI)s with rifampin. Distribution of therapeutic areas with reported interactions (≥ 25% change in victim area under the curve (AUC)) with rifampin as the perpetrator for both induction and inhibition studies. Data were retrieved from the University of Washington Metabolism and Transport Drug Interaction Database on or before December 18, 2018. (a) The “miscellaneous” group includes drug categories, such as endogenous compounds and cannabinoids; “other” is a summation of the following therapeutic areas with less than five compounds tested (% of total): respiratory agents (1.9%), skin agents (1.2%), erectile dysfunction treatments (1.2%), dietary supplements and vitamins (0.6%), Parkinson's disease treatments (0.6%), antigout and uricosuric agents (0.5%), drug addiction treatments (0.5%), beta3‐adrenoreceptor agonist (0.5%), osteoporosis treatment (0.5%), muscle relaxants (0.5%), and migraine treatments (0.5%). (b,c). Interactions with rifampin by selected therapeutic area. Percentage indicates the relative contribution by that class to the overall number of observed interactions; the contribution from the primary drugs evaluated is included in parenthesis for the fractional contribution to interactions for that class. CCR5, C‐C chemokine receptor type 5; CNS, central nervous system; INSTI, HIV‐integrase strand transfer inhibitor; NRTI, nucleoside reverse‐transcriptase inhibitor; NNRTI, non‐nucleoside reverse‐transcriptase inhibitor; RIF, rifampin.