Considering NSAID Risks

NSAIDs as a group are well known for their potential side effects on multiple clinical systems.
Individual NSAIDs, however, confer significantly different GI, renal, and cardiovascular risks.
Choosing the right NSAID for an individual patient requires that the relative risks for each type of
side effect be considered.

For patients at risk for Cardiovascular events, consider the following:

Lowest risk for adverse cardiovascular side effects: Naproxen

Highest risk for adverse cardiovascular side effects: Diclofenac* and Celecoxib*
The risk associated with celecoxib has been shown to increase in a dose dependent fashion (always use the
lowest effective dose for the shortest duration of time)

For patients at risk for GI Ulceration and/or Bleeding, consider the following:

All NSAIDs are associated with some level of increased risk for GI complications so it is best to use the
lowest effective dose for the shortest duration of time
Lowest risk for GI complications: Ibuprofen and celecoxib*
Relatively low risk for GI complications: Meloxicam, etodolac* and nabumetone*
High (i.e. twice the risk associated with ibuprofen) for GI complications: Naproxen, indomethacin and
diclofenac*
Highest risk for GI complications: Ketorolac and piroxicam*
GI Risk Factors1
Age > 65 years
High dose NSAID therapy
Previous history of uncomplicated ulcer Concurrent
aspirin, anticoagulant, or corticosteroid use

GI Risk Classification1
Low:
No risk factors
Moderate: 1-2 risk factors
High:
> 2 risk factors OR
Previous complicated ulcer

For patients at risk for Renal complication (e.g. elderly, hypovolemic, HF, diabetic patients or patients
taking an ACE-I or ARB) consider the following:

All NSAIDs inhibit renal vasodilating prostaglandins which can lead to decreases in renal blood flow and
renal perfusion
Ketorolac is contraindicated in advanced renal disease in patients at risk for renal failure due to volume
depletion
Ibuprofen, naproxen, piroxicam*, indomethacin, etodolac*, sulindac and diclofenac* are not
recommended in patients with advanced renal disease (CrCl<30 ml/min)
Meloxicam is not recommended in patients with CrCl<15 ml/min)
Celecoxib* has not been studied in patients with renal insufficiency
The recommended starting dose of nabumetone* in a patient with a CrCl 31-49 is 750mg QD (max
1500mg/day). For patients with CrCl <30 the recommended starting dose is 500mg QD (max 1000mg/day)

Prescribing NSAIDs in Patients with Certain Risk Factors

Patient Risk Factors
Low GI Risk
Moderate GI Risk
High GI Risk
Ibuprofen OR

Low CV Risk

1.
2.

other low-GI risk NSAID

High CV Risk

Naproxen

3.
1.
2.

Low-GI risk NSAID + generic PPI

Low-GI risk NSAID +generic double-dose H2nd
blocker (2 line)
Celecoxib* alone (most expensive choice)
Naproxen + PPI
Naproxen + double-dose H2 blocker (2nd line)

1.
2.

Avoid NSAIDs if
possible
Celecoxib*+ PPI

Avoid NSAIDs

High CV risk defined as patients requiring low-dose aspirin for prevention of serious CV events
* non-formulary drugs
1

Adapted from: Managing NSAID risks. Pharmacists Letter/Prescribers Letter. 2010;26(8):260810. (Full update December 2010; last modified October 2011). Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.;
2012. URL: http://cp.gsm.com.
Micromedex Healthcare Series. n.d. Thomson Reuters (Healthcare) Inc. , Greenwood Village, CO. 22 Feb. 2012 <http://www.thomsonhc.com>.