Comparative risks of non-prescription analgesics: a structured topic review and research priorities.
OBJECTIVE
The aims of this report are to quantify and compare competing risks associated with the use of non-prescription analgesics (daily doses of acetaminophen ≤ 4000 mg, aspirin ≤ 4000 mg, ibuprofen ≤ 1200 mg, naproxen ≤ 660 mg and ketoprofen ≤ 75 mg) and identify research needs.


METHODS
Literature was searched and organized by medication, adverse effect and direction of effect. Causality was determined using structured consensus, using IOM and GRADE nomenclature. Magnitude of risk data were extracted from primary sources. Structured consensus were used to construct a list of research priorities.


RESULTS
The available data favor acceptance of a causal relationship between each of the five analgesics studied and at least one specific form of harm. Dosing in excess of the non-prescription limits is associated with increased risk. Existing data do not support precise estimates of population or individual patient attributable risks for most analgesic and organ system combinations, and as a result competing risks cannot be adequately assessed. The highest priority research needs included understanding 'real world' dosing and how co-morbidities and prodromal symptoms modify exposure.


CONCLUSIONS
Although generally safe, all non-prescription analgesics are associated with some harm, particularly when recommended dosing limits are exceeded. Research to quantify the competing risks of different analgesic strategies is urgently needed.
Denver Health and Hospital Authority, Rocky Mountain Poison and Drug Center, 777 Bannock Street, MC 0180, Denver, CO 80204, USA. eric.lavonas@rmpdc.org
Eric J
EJ
Lavonas
James F
JF
Fries
Daniel E
DE
Furst
Kenneth J
KJ
Rothman
Andy
A
Stergachis
Allen J
AJ
Vaida
Daniel
D
Zelterman
Kate M
KM
Reynolds
Jody L
JL
Green
Richard C
RC
Dart
D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D004366:Nonprescription Drugs / Q000008:administration & dosage / Q000009:adverse effects*; D012306:Risk
D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004366:Nonprescription Drugs