Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to reduce inflammation, with notable benefits in increasing survival and reducing risk of several types of cancer; however expert consensus is that the risks of harm from using these drugs long-term are greater than the benefits for prevention against cancer for many people.

Safety and precautions

NSAIDs can have serious, even life-threatening side effects. Some NSAIDs have more frequent or more serious side effects than others. Use them only under medical supervision.

Cancer mortality or risk

Some use of NSAIDs is linked to a few instances of higher cancer mortalitydeath, or the death rate in a population; cancer studies often report all-cause mortality (death from any cause) and cancer-specific mortality (death due to the cancer under investigation) or risk of cancer.

  • Higher cancer-specific mortality among people with a non-serous ovarian tumor with non-aspirin NSAID use after diagnosis in a large observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods study1Verdoodt F, Dehlendorff C, Friis S, Kjaer SK. Non-aspirin NSAID use and ovarian cancer mortality. Gynecologic Oncology. 2018 Aug;150(2):331-337.
  • Higher risk of ER+/PR+, HER2−, and p53− breast cancers, as well as luminal A or B breast cancers, among people with recent use of ibuprofen compared to no use in a large observational study2Brasky TM, Bonner MR et al. Non-steroidal anti-inflammatory drugs (NSAIDs) and breast cancer risk: differences by molecular subtype. Cancer Causes and Control. 2011 Jul;22(7):965-75.  

Cancer-specific side effects and symptoms

A few side effects and symptoms of cancer are worsened by some uses of NSAIDs.

Cardiovascular side effects 

Celecoxib (Celebrex): strong evidenceconsistent, significant effects in several large (or at least one very large) well designed clinical studies or at least two meta-analyses of clinical studies of moderate or better quality (or one large meta-analysis) finding similar results (this is the CancerChoices definition; other researchers and studies may define this differently) of higher risk of hypertension of any grade during FOLFOX treatment and increased risk of a grade 2 or higher elevation in creatinine levels after completion of FOLFOX among people with stage III colon cancer using celecoxib

  • Higher risk of hypertension of any grade during FOLFOX treatment and increased risk of a grade 2 or higher elevation in creatinine levels after completion of FOLFOX among people with stage III colon cancer using celecoxib in a very large RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects3Meyerhardt JA, Shi Q. Effect of celecoxib vs placebo added to standard adjuvant therapy on disease-free survival among patients with stage III colon cancer: the CALGB/SWOG 80702 (Alliance) randomized clinical trial. JAMA. 2021 Apr 6;325(13):1277-1286.

Pain

Celcoxib: preliminary evidencesignificant effects in small or poorly designed clinical studies OR conflicting results in adequate studies but a preponderance of evidence of an effect (this is the CancerChoices definition; other researchers and studies may define this differently) of worse pain during chemotherapy among people with metastatic or postoperative recurrent stomach (gastric) cancer treated with celecoxib

Indomethacin: good evidencesignificant effects in one large or several mid-sized and well-designed clinical studies (randomized controlled trials (RCTs) with an appropriate placebo or other strong comparison control or observational studies that control for confounds) (this is the CancerChoices definition; other researchers and studies may define this differently) of worse chronic cancer pain among people treated with indomethacin

  • Worse chronic cancer pain among people treated with indomethacin compared to placebo in a large meta-analysisa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 18 RCTs5Huang R, Jiang L et al. Comparative efficacy of therapeutics for chronic cancer pain: a Bayesian network meta-analysis. Journal of Clinical Oncology. 2019 Jul 10;37(20):1742-1752.

Other side effects or adverse events

The US Food and Drug Administration warns that ibuprofen (Advil, Motrin and other brands), naproxen (Aleve and other brands), diclofenac, celecoxib (Celebrex) and other NSAIDs increase the risk of heart attack or stroke, even after just a few weeks of use. Medical supervision is strongly advised with all NSAIDs.6US Food and Drug Administration. FDA Drug Safety Communication: FDA strengthens warning that non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) can cause heart attacks or strokes. US Department of Health and Human Services. February 26, 2018. Viewed January 11, 2021.

Because of these risks, many researchers investigating use of NSAIDs other than aspirin for reducing cancer risk have concluded that risks of serious cardiovascular events outweigh the cancer-preventive benefits of long-term use;7Veettil SK, Lim KG et al. Effects of aspirin and non-aspirin nonsteroidal anti-inflammatory drugs on the incidence of recurrent colorectal adenomas: a systematic review with meta-analysis and trial sequential analysis of randomized clinical trials. BMC Cancer. 2017 Nov 14;17(1):763; Wakeman C, Keenan J et al. Chemoprevention of colorectal neoplasia. ANZ Journal of Surgery. 2017 Dec;87(12):E228-E232; Arber N, Eagle CJ et al. Celecoxib for the prevention of colorectal adenomatous polyps. New England Journal of Medicine. 2006 Aug 31;355(9):885-95; Bertagnolli MM, Eagle CJ et al. Celecoxib for the prevention of sporadic colorectal adenomas. New England Journal of Medicine. 2006 Aug 31;355(9):873-84; Mohammed A, Yarla NS, Madka V, Rao CV. Clinically relevant anti-inflammatory agents for chemoprevention of colorectal cancer: new perspectives. International Journal of Molecular Sciences. 2018 Aug 8;19(8). pii: E2332; Kerr DJ, Dunn JA et al; VICTOR Trial Group. Rofecoxib and cardiovascular adverse events in adjuvant treatment of colorectal cancer. New England Journal of Medicine. 2007 Jul 26;357(4):360-9; Tomić T, Domínguez-López S, Barrios-Rodríguez R. Non-aspirin non-steroidal anti-inflammatory drugs in prevention of colorectal cancer in people aged 40 or older: a systematic review and meta-analysis. Cancer Epidemiology. 2019;58:52–62; Fajardo AM, Piazza GA. Chemoprevention in gastrointestinal physiology and disease. Anti-inflammatory approaches for colorectal cancer chemoprevention. American Journal of Physiology. Gastrointestinal and Liver Physiology. 2015 Jul 15;309(2):G59-70. several studies were halted before completion because of safety concerns.8Bertagnolli MM, Eagle CJ et al; Adenoma Prevention with Celecoxib Study Investigators. Five-year efficacy and safety analysis of the Adenoma Prevention with Celecoxib Trial. Cancer Prevention Research (Phila). 2009 Apr;2(4):310-21. 

All NSAIDs, including those available over-the-counter, can have these common side effects:9Ogbru A, Marks JW. COX-2 Inhibitor Medications. Rx List. Viewed February 8, 2021; Pantziarka P, Sukhatme V, Bouche G, Meheus L, Sukhatme VP. Repurposing Drugs in Oncology (ReDO)-diclofenac as an anti-cancer agent. Ecancermedicalscience. 2016;10:610.

  • Abdominal pain
  • Allergic reactions, including potentially serious reactions (anaphylaxis)
  • Bleeding, including bleeding of the stomach or intestines or within the skull
  • Constipation
  • Diarrhea
  • Drowsiness
  • Excess stomach acid secretion
  • Flatulence
  • Gastrointestinal upset, nausea or ulcers (risk of ulcers is increased with alcohol use)
  • Headache 
  • Heartburn
  • Indigestion
  • Insomnia
  • Nausea
  • Worsening asthma symptoms

Rare side effects:10Ogbru A, Marks JW. COX-2 Inhibitor Medications. Rx List. Viewed February 8, 2021; Pantziarka P, Sukhatme V, Bouche G, Meheus L, Sukhatme VP. Repurposing Drugs in Oncology (ReDO)-diclofenac as an anti-cancer agent. Ecancermedicalscience. 2016;10:610.

  • Anxiety
  • Blurred vision
  • Bloating
  • Cardiovascular events, including stroke or heart attack
  • Dizziness
  • Fainting
  • Inflammation of the pancreas (pancreatitis) (ask your doctor about signs and symptoms)
  • Kidney failure (ask your doctor about signs and symptoms)
  • Liver failure (ask your doctor about signs and symptoms)
  • Pneumonia
  • Ringing in the ears
  • Sensitivity to light
  • Swelling (edema)
  • Water retention
  • Weakness
  • Weight gain
  • Worsening of high blood pressure

Do not use (contraindications)

If you’re receiving treatments—for cancer or other conditions—that cause low platelet counts or thin your blood, you should check with your doctor before use.

Caution is advised if you have hypertension or risk factors for gastrointestinal bleeding. Avoiding or discontinuing NSAID use in cancer patients is not advised in one review, but careful monitoring for side effects such as cardiovascular events (with COX-2 inhibitors) or gastrointestinal bleeding is recommended if used.11Solheim TS, Fearon KC, Blum D, Kaasa S. Non-steroidal anti-inflammatory treatment in cancer cachexia: a systematic literature review. Acta Oncologica 2013 Jan;52(1):6-17.

Drug Interactions

Celecoxib (Celebrex) may interact with these drugs:12Ogbru A, Marks JW. COX-2 Inhibitor Medications. Rx List. Viewed February 8, 2021.

  • Increases the concentration of lithium in the blood and may increase the blood-thinning effect of warfarin (Coumadin)
  • Fluconazole (Diflucan) impairs metabolism of celecoxib (Celebrex), increasing its level in the body.

Further drug interactions are listed on these sites:

Resources

Keep reading about non-aspirin NSAIDs

Author

Nancy Hepp, MS

Lead Researcher and Program Manager
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Ms. Hepp is a researcher and communicator who has been writing and editing educational content on varied health topics for more than 20 years. She serves as lead researcher, program manager, and writer for CancerChoices. Her graduate work in research and cognitive psychology, her master’s degree in instructional design, and her certificate in web design have all guided her in writing and presenting information for a wide variety of audiences and uses. Nancy’s service as faculty development coordinator in the Department of Family Medicine at Wright State University also provided experience in medical research, plus insights into medical education and medical care from the professional’s perspective.

Nancy Hepp, MS Lead Researcher and Program Manager

Reviewers

Laura Pole, RN, MSN, OCNS

Senior Clinical Consultant
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Laura Pole is senior clinical consultant for CancerChoices. Laura is an oncology clinical nurse specialist who has been providing integrative oncology clinical care, navigation, consultation, and education services for over 40 years. She is the co-creator and co-coordinator of the Integrative Oncology Navigation Training at Smith Center for Healing and the Arts in Washington, DC. Laura also manages the “Media Watch Cancer News That You Can Use” listserv for Smith Center/Commonweal. In her role as a palliative care educator and consultant, Laura has served as statewide Respecting Choices Faculty for the Virginia POST (Physician Orders for Scope of Treatment) Collaborative as well as provided statewide professional education on palliative and end-of-life care for the Virginia Association for Hospices and Palliative Care.

For CancerChoices, Laura curates content and research, networks with clinical and organizational partners, brings awareness and education of integrative oncology at professional and patient conferences and programs, and translates research into information relevant to the patient experience as well as clinical practice.

Laura sees her work with CancerChoices as a perfect alignment of all her passions, knowledge and skills in integrative oncology care. She is honored to serve you.

Laura Pole, RN, MSN, OCNS Senior Clinical Consultant

Barry D. Elson, MD

Integrative physician and CancerChoices advisor
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Barry D. Elson, MD, has been practicing and teaching integrative medicine for over 40 years. He has been the medical director of Northampton Wellness Associates, adjunct faculty for Touro University College of Medicine, medical director at Commonweal, and professor of medicine at the Pacific College of Naturopathic Medicine. He recently retired from clinical practice and has been providing freelance medical consulting. He is an avid biker, cross country skier, and sailor. He currently resides in the rolling hills of western Massachusetts.

Barry D. Elson, MD Integrative physician and CancerChoices advisor

Andrew Jackson, ND

Research Associate
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Andrew Jackson, ND, serves as a CancerChoices research associate. As a naturopathic physician practicing in Kirkland, Washington, he teaches critical evaluation of the medical literture at Bastyr University in Kenmore, Washington. His great appreciation of scientific inquiry and the scientific process has led him to view research with a critical eye.

Andrew Jackson, ND Research Associate

Last update: May 17, 2022

CancerChoices provides information about integrative in cancer care, a patient-centered approach combining the best of conventional care, self care and evidence-informed complementary care in an integrated plan cancer care. We review complementaryin cancer care, complementary care involves the use of therapies intended to enhance or add to standard conventional treatments; examples include supplements, mind-body approaches such as yoga or psychosocial therapy, and acupuncture therapies and self-care lifestyle actions and behaviors that may impact cancer outcomes; examples include eating health-promoting foods, limiting alcohol, increasing physical activity, and managing stress practices to help patients and professionals explore and integrate the best combination of conventionalthe cancer care offered by conventionally trained physicians and most hospitals; examples are chemotherapy, surgery, and radiotherapy and complementary therapies and practices for each person.

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