Adverse drug reactions and drug-drug interactions with over-the-counter NSAIDs

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen have a long history of safe and effective use as both prescription and over-the-counter (OTC) analgesics/antipyretics. The mechanism of action of all NSAIDs is through reversible inhibition of cyclooxygenase enzymes. Adverse drug reactions (ADRs) including gastrointestinal bleeding as well as cardiovascular and renal effects have been reported with NSAID use. In many cases, ADRs may occur because of drug-drug interactions (DDIs) between the NSAID and a concomitant medication. For example, DDIs have been reported when NSAIDs are coadministered with aspirin, alcohol, some antihypertensives, antidepressants, and other commonly used medications. Because of the pharmacologic nature of these interactions, there is a continuum of risk in that the potential for an ADR is dependent on total drug exposure. Therefore, consideration of dose and duration of NSAID use, as well as the type or class of comedication administered, is important when assessing potential risk for ADRs. Safety findings from clinical studies evaluating prescription-strength NSAIDs may not be directly applicable to OTC dosing. Health care providers can be instrumental in educating patients that using OTC NSAIDs at the lowest effective dose for the shortest required duration is vital to balancing efficacy and safety. This review discusses some of the most clinically relevant DDIs reported with NSAIDs based on major sites of ADRs and classes of medication, with a focus on OTC ibuprofen, for which the most data are available.

Keywords: adverse effects; cardiovascular; gastrointestinal; nonsteroidal anti-inflammatory drugs; renal.

Figure 1

Effect of dose (in week before index day) on ORs of upper GI bleeding: meta-analysis of three case-control studies. Notes: ^aAll ORs are relative to nonuse of any non-aspirin nonsteroidal anti-inflammatory drug or aspirin and are adjusted for use of aspirin, ketoprofen, anticoagulants, smoking, and history of upper GI problems. Copyright © 2002, John Wiley and Sons. Adapted with permission from Lewis SC, Langman MJ, Laporte JR, Matthews JN, Rawlins MD, Wiholm BE. Dose-response relationships between individual nonaspirin nonsteroidal anti-inflammatory drugs (NANSAIDs) and serious upper gastrointestinal bleeding: a meta-analysis based on individual patient data. Br J Clin Pharmacol. 2002;54(3):320–326. Abbreviations: CI, confidence interval; GI, gastrointestinal; OR, odds ratio.

Figure 2

Summary of changes in systolic ambulatory blood pressure when prescription ibuprofen (1,800 mg/d) and antihypertensives are coadministered. Notes: ^aAny use = monotherapy or free- and fixed-dose combinations. For the final “any agent” category, the “any use” data represent free- or fixed-dose combinations only. Data from MacDonald et al. Abbreviations: ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; CCB, calcium channel blocker; LSM, least squares mean; MSABP, mean systolic ambulatory blood pressure; SE, standard error.