A narrative review of papers published from January 2011 to December 2021, after a literature search in selected databases using the terms “pharmacokinetics”, “ibuprofen”, “diclofenac”, “acemetacin”, “naproxen”, “etodolac” and “etoricoxib” was performed. From 828 articles identified, only eight met the inclusion criteria. Selective COX-2 inhibitors are associated with higher cardiovascular risk, while non-selective COX inhibitors are associated with higher gastrointestinal risk. NSAIDs with lower renal excretion with phase 2 metabolism are less likely to induce adverse effects and drug-drug interactions. Patients with frequent NSAID use needs, such as elderly patients and patients with cardiovascular disease or impaired renal function, will benefit from lower renal excretion (e.g. acemethacin, diclofenac, and etodolac) (level of evidence 3). Polymedicated patients, elderly patients, and patients with chronic alcohol abuse will be at a lower risk for adverse effects with NSAIDs that undergo phase 2 liver biotransformation, namely, acemethacin and diclofenac (level of evidence 3). Young patients, patients dealing with acute pain, or with active and/or chronic symptomatic gastritis, selective COX-2 inhibitors (celecoxib or etoricoxib) may be a better option (level of evidence 2). Knowing the individual characteristics of the patients, combined with knowledge on basic pharmacology, offers greater safety and better adherence to therapy.

Although there are several NSAIDs options to treat pain, physicians usually take special care to its prescription regarding cardiovascular and gastrointestinal side effects, despite the age of the patient. In this paper, based on the best evidence, the authors present a review of the safest NSAIDs to use in the elderly.