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Which NSAID is the safest? Compare the relative safety data, particularly gastrointestinal safety, of commonly used NSAIDs

Digestion, Heart, Pain, General | October 20, 2015 | Author: The Super Pharmacist

heart, Digestion, Pain

Which NSAID is the safest? Compare the relative safety data, particularly gastrointestinal safety, of commonly used NSAIDs

Nonsteroidal anti-inflammatory drugs or NSAIDs are the most important non-opioid class of pain relieving medications physicians have in their arsenal. For short-term use, NSAIDs are considered both safe and effective. Unfortunately, people who suffer from chronic pain disorders are faced with choosing between various drugs with potentially serious side effects. We review the current information on NSAID safety.

Not all NSAIDs are the same

When discussing NSAID safety, one must consider the cyclooxygenase (COX) enzyme. Drugs that block cyclooxygenase enzymes, such as NSAIDs, are helpful in many ways. They reduce inflammation and fever, and modestly thin the blood (which can be helpful in certain patients and harmful in others). COX inhibitors also relieve mild to moderate pain by blocking pain pathways. NSAIDs can be divided into three categories by how they block COX1:

  1. COX-1 Selective – aspirin, (naproxen is relatively COX-1 selective)
  2. Nonselective – ibuprofen, naproxen
  3. COX-2 Selective – diclofenac, meloxicam, celecoxib

Which NSAID is the safest? Compare the relative safety data, particularly gastrointestinal safety, of commonly used NSAIDsWhy COX inhibition matters for NSAIDs

Unfortunately, blocking cyclooxygenase can also cause a number of serious side effects. Blocking COX-1 decreases the production of protective substances in the stomach and duodenum. This can, over time, cause damage to the lining of the stomach and small intestine. Damage to the gastrointestinal lining can lead to internal bleeding. If internal bleeding is severe or takes place over a long period, it can lead to anaemia. Initial hopes were that selectively blocking COX-2 would allow patients to enjoy pain relief without gastrointestinal side effects. Unfortunately, studies of COX-2 inhibitors showed significant increases in cardiovascular risk and some were pulled from the market as a result.

A side effect balancing act

Therefore, physicians and patients must balance the risks to the gastrointestinal tract and the cardiovascular system with the need for long-term pain relief. Nonselective NSAIDs are useful in people who do not have or who are not at risk for kidney or cardiovascular diseases. Selective NSAIDs, specifically celecoxib, may be useful in people who cannot tolerate NSAIDs because of gastrointestinal difficulties.

Which NSAID is the safest?

Unfortunately, countless people suffer from chronic daily pain and cannot avoid taking NSAIDs. In this case, a reasonable question is which NSAID is the safest? The answer to this question, it turns out, depends as much on how you use the NSAID as which one you choose.

Side effect risk of NSAIDs increases with the duration of use

NSAIDs are relatively safe drugs when used for a short periods, such as a few days. Conversely, NSAIDs are responsible for more than one in 10 adverse drug event hospitalisations.2 The risk of serious side effects increases significantly the longer that one takes daily doses of NSAIDs. The relative risk of serious upper gastrointestinal problems doubles in people taking an NSAID for greater than six months.3 Likewise, the risk of acute renal failure almost doubles when one takes NSAIDs for an entire year.4 Limiting the use of NSAIDs when possible is the best way to minimize side effects. Since the risk of side effects also increases with the dose of NSAIDs, patient should also take the lowest possible dose that provides the desired therapeutic action, e.g. pain relief.5

Which NSAID is the safest? Compare the relative safety data, particularly gastrointestinal safety, of commonly used NSAIDsPatients at risk of gastrointestinal side effects

Patients with a history of, or who are at risk for, gastrointestinal bleeding may need to be treated with paracetamol rather than an NSAID. If an NSAID is required in these patients, the gastrointestinal tract may be protected by simultaneously prescribing medications that reduce acid in the stomach, specifically proton pump inhibitors, such as omeprazole.6 It may also be best to select an NSAID that is relatively more selective for the COX-2 enzyme than COX-1. Reasonable choices may be diclofenac or celecoxib.5

Patients at risk for cardiovascular disease

People who have atherosclerosis, a history of unstable angina or myocardial infarction, or a history of stroke must use NSAIDs with caution. COX-2 selective NSAIDs increase the absolute risk for adverse cardiovascular events in these individuals.7 Therefore, nonselective or COX-1 favoring NSAIDs may be best for initial therapy.5 It is also important to realize that ibuprofen interferes with aspirin's ability to beneficially affect platelets.8 Therefore, no one taking daily aspirin therapy for a heart condition should take it at the same time as they take ibuprofen.9 For these patients, naproxen may be the best choice.

Patients at risk for kidney disease

People at significant risk for, or who have kidney disease, are in a difficult position when it comes to chronic pain relief. Nonselective NSAIDs negatively affect the kidneys in several ways. They increase the risk of acute renal failure and other forms of acute kidney injury, can increase blood pressure, interfere with electrolytes and fluid balance, and even increase the risk of renal cell cancer.10,11 COX-2 selective NSAIDs seem to be similarly destructive to the kidneys as nonselective NSAIDs12 and are generally avoided in people with chronic renal insufficiency.13 That said, short-term and intermediate-term use of low-dose, COX-2 selective NSAIDs may not pose a significant risk to people with moderate or even severe chronic kidney disease.14 Australia's best online pharmacy


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  2. Howard RL, Avery AJ, Slavenburg S, et al. Which drugs cause preventable admissions to hospital? A systematic review. Br J Clin Pharmacol. Feb 2007;63(2):136-147. doi:10.1111/j.1365-2125.2006.02698.x
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  7. Gislason GH, Jacobsen S, Rasmussen JN, et al. Risk of death or reinfarction associated with the use of selective cyclooxygenase-2 inhibitors and nonselective nonsteroidal antiinflammatory drugs after acute myocardial infarction. Circulation. Jun 27 2006;113(25):2906-2913. doi:10.1161/circulationaha.106.616219
  8. Catella-Lawson F, Reilly MP, Kapoor SC, et al. Cyclooxygenase inhibitors and the antiplatelet effects of aspirin. N Engl J Med. Dec 20 2001;345(25):1809-1817. doi:10.1056/NEJMoa003199
  9. US Food and Drug Administration. Concomitant use of ibuprofen and aspirin: potential for attenuation of the anti-platelet effect of aspirin. September 8, 2006. 2008.
  10. Whelton A. Nephrotoxicity of nonsteroidal anti-inflammatory drugs: physiologic foundations and clinical implications. Am J Med. May 31 1999;106(5B):13S-24S.
  11. Cho E, Curhan G, Hankinson SE, et al. Prospective evaluation of analgesic use and risk of renal cell cancer. Arch Intern Med. Sep 12 2011;171(16):1487-1493. doi:10.1001/archinternmed.2011.356
  12. Perazella MA, Tray K. Selective cyclooxygenase-2 inhibitors: a pattern of nephrotoxicity similar to traditional nonsteroidal anti-inflammatory drugs. Am J Med. Jul 2001;111(1):64-67.
  13. Dunn MJ. Are COX-2 selective inhibitors nephrotoxic? Am J Kidney Dis. May 2000;35(5):976-977.
  14. Nderitu P, Doos L, Jones PW, Davies SJ, Kadam UT. Non-steroidal anti-inflammatory drugs and chronic kidney disease progression: a systematic review. Fam Pract. Jun 2013;30(3):247-255. doi:10.1093/fampra/cms086
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