Over the last 10+ years, the evidence supporting the dose-related risks of certain serious adverse events associated

with nonsteroidal anti-inflammatory drugs (NSAIDs) has piled up—the higher the dose, the higher the risk. 1-6 Using

NSAIDs in today’s complex therapeutic landscape requires more attention and thought than ever before.

The Climate of Pain Management Is Shifting

Recent concerns about opioid use have led to a decline in opioid prescriptions for

the first time since 1996, and may be the reason why NSAID prescriptions are on the rise. 7,8

$ $ $

$ $ $

$ $ $

$ $ $


White House asks for more than $1 billion

in new funding for opioid addiction treatment 9

11% 10%

Decrease in opioid


nationally since 2011 8






Increase in NSAID


from 2011 to 2015 8

NSAIDs may now be more on the radar than ever, especially since recent CDC

guidelines specifically recommend the use of nonopioid therapies as preferred

treatment options for chronic pain.

—Vijay Sikand, MD

Fellow, American Academy of Family Physicians

Adjunct Assistant Professor of Medicine, Tufts University School of Medicine

NSAIDilemma.com Page 1

Please see references on page 7

Risks: The Root of the Dilemma

Pain is very real and can often be managed effectively

with NSAIDs—but we must first consider the

dose-related risks.


28% 104% 35%

Percentage by which CV risk is

increased with high NSAID doses

compared to low-medium doses 2

Percentage by which upper GI risk

is increased with high NSAID doses

compared to low-medium doses 1

Percentage by which risk of

acute renal failure is increased

with high NSAID doses

compared to low-medium doses 3




16,500 DEATHS

from NSAID-related GI complications are estimated to occur

annually in people with rheumatic diseases 10

11 %

Of preventable drug-related

hospital admissions

are attributed to NSAID use 11

Certain serious adverse

events can occur in as little as


after initiating treatment

with an NSAID

—and that risk increases with duration of use 1-6,12,13


NSAIDilemma.com Page 2

Patients with rheumatic diseases are estimated to be

hospitalized for NSAID-related GI complications each year 10 Please see references on page 7

NSAID Doses in Excess

In an effort to ease their patients’ pain, doctors

have a tendency to prescribe NSAIDs at high doses.

80 % highest

Of prescriptions for the most commonly

prescribed NSAIDs are written at the

approved dosage 14

According to national surveys...


Of patients taking a prescription

NSAID reported frequently

consuming more than

the exact prescribed dosage 15


Of patients taking

prescription NSAIDs are also

taking OTC NSAIDs 15


Of patients said they believe

that their pain requires high

NSAID doses 14

Research has shown that after a certain dose threshold, the analgesic response of

NSAIDs reaches a ceiling effect, so patients won’t necessarily experience any greater

pain relief, but they may have greater potential risk for dose-related adverse events.

—James Scheiman, MD

Professor, Division of Gastroenterology

Dept of Internal Medicine, University of Michigan Medical School

NSAIDilemma.com Page 3

Please see references on page 7

Perception vs Reality

Your peers have taken notice of the NSAIDilemma

and are starting to change how they speak with

their patients and how they prescribe NSAIDs.

94 %

19 %


15 %

44 %


92 %

Of physicians believe

NSAIDs should

be prescribed at the

lowest effective dose

for the shortest duration 16

Of physicians have

prescribed NSAIDs

at high doses to patients

who were also taking


Of physicians say they

always follow FDA


for NSAID dosing 16

Of patients report

taking more than the

recommended dose

of OTC NSAIDs 15

55 %

Of physicians

believe it is always

necessary to talk to

their patients about

the risks of taking

prescription NSAIDs

and OTC NSAIDs 16


Of physicians always

discuss the increased

risks related to taking

NSAIDs at high doses

before prescribing 16


Page 4

Please see references on page 7

The FDA Role

Responsible NSAID dosing has been in the spotlight

since FDA first released a Public Health Advisory in 2005.


Required manufacturers of all marketed prescription NSAIDs to revise

product labeling to include a Boxed Warning and Medication Guide as well as

recommendations to use the lowest effective dose. 17


FDA strengthened the Boxed Warning to include statements that

nonaspirin NSAIDs increase the chance of a heart attack or stroke 18


FDA required manufacturers of all marketed prescription NSAIDs to include

revised safety language within their product labels to strengthen

warning of potential serious CV adverse events


Number of studies FDA reviewed that led to strengthening

cardiovascular label warnings for all nonaspirin NSAIDs 18,19

NSAIDilemma.com Page 5

Please see references on page 7

Professional Medical Organizations

Are in Agreement

Recommendations from professional medical organizations consistently

advise using the lowest effective dose for the shortest duration. 20-25

In all cases, the lowest effective dose

should be used for the shortest

possible time. 20

– American Heart Association (AHA)

If a patient and provider agree

to utilize an NSAID…then the lowest effective

dose of the least expensive agent should

be considered first line. 23

– American College of Rheumatology (ACR)

Even with normal kidney function,

you should use analgesics:

• At the lowest dose possible

• For the shortest period of time. 21

– National Kidney Foundation

…[NSAIDs] should be used at the lowest

effective dose but their long-term use

should be avoided if possible. 24

– Osteoarthritis Research Society International

GI risks may be decreased

through similar attention to risk factors

and use of cotherapy. Risk can be reduced

through the use of the lowest effective

dose for the shortest duration of time. 22

– American Gastroenterological Association

…dosing for most patients requires

initiation with low doses followed by

careful upward titration, including

frequent reassessment for dosage

adjustments and optimum pain relief

and for adverse effects. 25

– American Geriatrics Society

We need your help to truly make a difference.

Alert your colleagues and spread the word by sharing NSAIDilemma.com with your peers.


Page 6

Please see references on page 7


1. García Rodríguez LA, Hernández-Díaz S. Relative risk of upper gastrointestinal complications among users of acetaminophen and nonsteroidal

anti-inflammatory drugs. Epidemiology. 2001;12(5):570-576. 2. García Rodríguez LA, Tacconelli S, Patrignani P. Role of dose potency in the prediction of

risk of myocardial infraction associated with nonsteroidal anti-inflammatory drugs in the general population. J Am Coll Cardiol. 2008;52(20):1628-1636.

3. Huerta C, Castellsague J, Varas-Lorenzo C, García Rodríguez LA. Nonsteroidal anti-inflammatory drugs and risk of ARF in the general population. Am

J Kidney Dis. 2005;45(3):531-539. 4. Castellsague J, Riera-Guardia N, Calingaert B, et al; on behalf of the investigators of the Safety of Non-Steroidal

Anti-Inflammatory Drugs (SOS) Project. Individual NSAIDs and upper gastrointestinal complications: a systematic review and meta-analysis of

observational studies (the SOS Project). Drug Saf. 2012;35(12):1127-1146. 5. McGettigan P, Henry D. Cardiovascular risk with non-steroidal

anti-inflammatory drugs: systematic review of population-based controlled observational studies. PLoS Med. 2011;8(9):1-18. 6. Coxib and traditional

NSAID Trialists’ (CNT) Collaboration, Bhala N, Emberson J, Merhi A, Abramson S, Arber N, et al. Vascular and upper gastrointestinal effects of

non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet. 2013;382:769-779. 7. Goodnough A,

Tavernise S. Opioid prescriptions drop for first time in two decades. The New York Times. May 20, 2016. http://www.nytimes.com/2016/05/21/health/

opioid-prescriptions-drop-for-first-time-in-two-decades.html. Accessed August 15, 2016. 8. IMS National Prescription Audit, Total Prescriptions,

2011-2015. 9. White House Asks for More Than $1 Billion in New Funding for Opioid Addiction Treatment. NCADD. https://www.ncadd.org/blogs/

in-the-news/white-house-asks-for-more-than-1-billion-in-new-funding-for-opioid-addiction-treatment. Published February 11, 2016. Accessed August

15, 2016. 10. Singh G, Triadafilopoulos G. Epidemiology of NSAID induced gastrointestinal complications. J Rheumatol. 1999;56:18-24. 11. Howard RL,

Avery AJ, Slavenburg S, et al. What drugs cause preventable admissions to hospital? A systematic review. Br J Clin Pharmacol. 2007;63(2):136-147.

12. Helin-Salmivaara A, Virtanen A, Vesalainen R, et al. NSAID use and the risk of hospitalization for first myocardial infarction in the general population:

a nationwide case-control study from Finland. Eur Heart J. 2006;27(14):1657-1663. 13. Helin-Salmivaara A, Saarelainen S, Grönroos JM, Vesalainen R,

Klaukka T, Huupponen R. Risk of upper gastrointestinal events with the use of various NSAIDs: a case-control study in a general population. Scand J

Gastroenterol. 2007;42(8):923-932. 14. Data on file, Iroko Pharmaceuticals, LLC. 15. Wilcox CM, Cryer B, Triadafilopoulos G. Patterns of use and public

perception of over-the-counter pain relievers: focus on nonsteroidal antiinflammatory drugs. J Rheumatol. 2005;32(11):2218-2224. 16. Data on File. Iroko

Pharmaceuticals, LLC. 2016 HCP NSAID Survey. September 2016. 17. US Food and Drug Administration. Public health advisory - FDA announces

important changes and additional warnings for COX-2 selective and non-selective non-steroidal anti-inflammatory drugs (NSAIDs). http://www.fda.gov/

Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm150314.htm. Published April 7, 2005. Accessed August 15, 2016.

18. US Food and Drug Administration Drug Safety Communication: FDA strengthens warning that non-aspirin nonsteroidal anti-inflammatory drugs

(NSAIDs) can cause heart attacks or strokes. http://www.fda.gov/Drugs/DrugSafety/ucm451800.htm. Published July 9, 2015. Accessed August 15, 2016.

19. US Food and Drug Administration. Joint meeting of the Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee:

nonsteroidal anti-inflammatory drugs and cardiovascular thrombotic risk. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeeting-

Materials/Drugs/ArthritisAdvisoryCommittee/UCM383180.pdf. Published February 10-11, 2014. Accessed August 15, 2016. 20. Anderson JL, Adams CD,

Antman EM, et al. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction: a report of the

American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing committee to revise the 2002 guidelines for the

management of patients with unstable angina/non-ST-elevation myocardial infarction). Circulation. 2007;116:e148-e304. 21. National Kidney Foundation.

Pain medicines (analgesics). Available from: https://www.kidney.org/atoz/content/painMeds_Analgesics. Accessed August 15, 2016. 22. Wilcox CM,

Allison J, Benzuly K, et al. Consensus Development Conference on the Use of Nonsteroidal Anti-Inflammatory Agents, Including Cyclooxygenase-2

Enzyme Inhibitors and Aspirin. Clin Gastroenterol Hepatol. 2006;4(9):1082-1089. 23. American College of Rheumatology Ad Hoc Group on Use of Selective

and Nonselective Nonsteroidal Anti-inflammatory Drugs. Recommendations for use of selective and nonselective nonsteroidal anti-inflammatory drugs:

an American College of Rheumatology white paper. Arthritis Rheum. 2008;59(8):1058-1073. 24. Zhang W, Moskowitz RW, Nuki G, et al. OARSI

recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines. Osteoarthritis

Cartilage. 2008;16(2):137-162. 25. American Geriatrics Society Panel on the Pharmacological Management of Persistent Pain in Older Persons. J Am

Geriatr Soc. 2009;57(8):1331-1346.

The health care professionals that appear on this Web site are paid consultants of Iroko Pharmaceuticals, LLC.

Page 7

Iroko Pharmaceuticals LLC, One Kew Place, 150 Rouse Boulevard, Philadelphia, PA 19112 USA

©2016 Iroko Pharmaceuticals, LLC UNB-0229 10/2016

Similar magazines