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Gastrointestinal (GI) bleeding is any type of bleeding that occurs in the GI tract (also called the digestive tract). The organs of the GI tract include the mouth, esophagus, stomach, small intestine, large intestine (colon), rectum and anus.
GI bleeding is a common cause of hospitalization and in severe cases can result in death.[1] Importantly, many commonly used medications can cause GI bleeding. Some of these drugs can cause such bleeding through direct damage to the inner lining of...
Gastrointestinal (GI) bleeding is any type of bleeding that occurs in the GI tract (also called the digestive tract). The organs of the GI tract include the mouth, esophagus, stomach, small intestine, large intestine (colon), rectum and anus.
GI bleeding is a common cause of hospitalization and in severe cases can result in death.[1] Importantly, many commonly used medications can cause GI bleeding. Some of these drugs can cause such bleeding through direct damage to the inner lining of the GI tract. Other drugs can cause or exacerbate GI bleeding by interfering with the normal blood-clotting process.
Overview of GI bleeding symptoms
Symptoms of upper GI bleeding — bleeding that occurs in the esophagus, stomach or duodenum (the first part of the small intestine that is connected to the stomach) — include vomiting blood or coffee-ground–like material; black, tarry stools; and, in severe cases, passage of bright red or maroon-colored blood in bowel movements.
Symptoms of lower GI bleeding — bleeding that occurs in the small intestine beyond the duodenum, large intestine, rectum or anus — are passage of bright red or maroon-colored blood or blood clots in the stool.
Chronic mild GI bleeding in the upper or lower digestive tract can cause iron-deficiency anemia, which may result in fatigue, weakness, pale skin, shortness of breath and dizziness.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
Aspirin (AGGRENOX, BAYER ASPIRIN, DURLAZA, ECOTRIN, EXCEDRIN [MIGRAINE], FIORINAL, LANORINAL, ORPHENGESIC FORTE, PERCODAN, VAZALORE), ibuprofen (ADVIL, DUEXIS, IBUPROHM COLD AND SINUS, IBU-TAB, MIDOL LIQUID GELS, MOTRIN, REPREXAIN, SINE-AID IB, TAB-PROFEN) and all other prescription and over-the-counter oral NSAIDs (see Table 1, below) can cause serious harm, and even death, from bleeding in the stomach or small intestine.
NSAIDs can cause inflammation, erosions and ulcers in the inner lining of the stomach and duodenum, which can lead to bleeding. These drugs also inhibit the function of platelets, which play a key role in blood clotting.
The product labeling for prescription NSAIDs includes a black-box warning, the strongest warning that the FDA can require, about the risk of GI bleeding.[2],[3] This warning notes that such bleeding can occur at any time during use of these drugs and without warning symptoms. Elderly patients and patients with a prior history of stomach or duodenal ulcers or GI bleeding are at greatest risk of serious adverse GI events with NSAID use. Other factors that increase the risk of GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant (simultaneous) use of oral corticosteroids, anticoagulants (blood thinners) or selective serotonin reuptake inhibitors (SSRIs; for example, fluoxetine [PROZAC, SYMBYAX]); smoking; use of alcohol; and poor general health status.
Table 1: List of Currently Available Oral NSAIDs in the U.S.
| Generic Name | Brand Name(s) |
|---|---|
| aspirin | AGGRENOX†, BAYER ASPIRIN, DURLAZA, ECOTRIN, EXCEDRIN (MIGRAINE)†, FIORINAL†, LANORINAL†, ORPHENGESIC FORTE†, PERCODAN†, VAZALORE |
| celecoxib* | CELEBREX, CONSENSI† |
| diclofenac* | ARTHROTEC†, CAMBIA, CATAFLAM, ZIPSOR, ZORVOLEX |
| diflunisal* | generic only |
| etodolac** | generic only |
| fenoprofen** | NALFON |
| flurbiprofen | generic only |
| ibuprofen | ADVIL, DUEXIS†, IBUPROHM COLD AND SINUS†, IBU-TAB, MIDOL LIQUID GELS, MOTRIN, SINE-AID IB†, TAB-PROFEN |
| indomethacin* | INDOCIN |
| ketoprofen | generic only |
| ketorolac* | generic only |
| mefenamic acid** | PONSTEL |
| meloxicam* | MOBIC |
| nabumetone** | generic only |
| naproxen | ALEVE, ANAPROX DS, NEPRELAN, NAPROSYN, TREXIMET†, VIMOVO† |
| piroxicam* | FELDENE |
| sulindac** | generic only |
| tolmetin** | generic only |
†Combination drug that contains one or more other active ingredients
*Designated as Do Not Use by Worst Pills, Best Pills News
**Designated as Limited Use by Worst Pills, Best Pills News
Corticosteroids
Prednisone (RAYOS) and all other prescription anti-inflammatory, immune-suppressing corticosteroids (also called glucocorticoids or glucocorticosteroids) (see Table 2, below) can cause upper GI bleeding. In particular, these drugs can cause ulcers in the stomach and duodenum, which can lead to perforations (holes through the wall of the stomach or intestine) and bleeding.[4],[5] Corticosteroids also can cause severe inflammation and erosions in the esophagus, which may lead to GI bleeding.
The risk of these adverse events increases with increasing duration of use and concomitant use of other drugs that cause upper GI bleeding.
Table 2: Oral Corticosteroids Available in the U.S.
| Generic Name | Brand Name(s) |
|---|---|
| cortisone | generic only |
| dexamethasone | HEMADY |
| hydrocortisone | ALKINDI SPRINKLE, CORTEF |
| methylprednisolone | MEDROL |
| prednisolone | ORAPRED, PEDIAPRED, PRELONE |
| prednisone | RAYOS |
Other drugs
Table 3, below, provides examples of other drugs that increase the risk of GI bleeding. The list includes anticoagulants, such as warfarin (JANTOVEN); antiplatelet drugs, such as clopidogrel (PLAVIX); bisphosphonates for osteoporosis, such as alendronate (BINOSTO, FOSAMAX); and certain SSRI drugs used to treat depression, among other conditions, which can inhibit platelet function.
Table 3: Examples of Other Drugs That Increase the Risk of GI Bleeding
| Generic Name | Brand Name(s) |
|---|---|
| Anticoagulants (blood thinners) | |
| apixaban* | ELIQUIS |
| dabigatran* | PRADAXA |
| edoxaban* | SAVAYSA |
| rivaroxaban* | XARELTO |
| warfarin | JANTOVEN |
| Antiplatelet drugs | |
| clopidogrel** | PLAVIX |
| prasugrel* | EFFIENT |
| ticagrelor | BRILINTA |
| ticlopidine* | generic only |
| Bisphosphonates for osteoporosis | |
| alendronate** | BINOSTO, FOSAMAX |
| ibandronate** | BONIVA |
| risedronate** | ACTONEL, ATELVIA |
| Selective serotonin reuptake inhibitor antidepressants | |
| citalopram** | CELEXA |
| escitalopram** | LEXAPRO |
| fluoxetine** | PROZAC, SYMBYAX† |
| fluvoxamine** | LUVOX |
| paroxetine** | PAXIL, PEXEVA |
| sertraline** | ZOLOFT |
†Combination drug that contains one or more other active ingredients
*Designated as Do Not Use by Worst Pills, Best Pills News
**Designated as Limited Use by Worst Pills, Best Pills News
What You Can Do
If you are taking any of the drugs discussed in this article, contact your doctor immediately if you develop any symptoms of GI bleeding. Tell your doctor if you previously had GI bleeding or conditions like stomach ulcers that increase your risk of GI bleeding before taking any of these drugs. To minimize your risk of bleeding when taking these drugs, use the lowest dose for the shortest duration necessary to treat your condition.
References
[1] Wuerth BA, Rockey DC. Changing epidemiology of upper gastrointestinal hemorrhage in the last decade: A nationwide analysis. Dig Dis Sci. 2018;63(5):1286-1293.
[2] Pfizer. Label: celecoxib (CELEBREX). April 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/020998s056lbl.pdf. Accessed June 23, 2021.
[3] Horizon Medicines LLC. Label: ibuprofen and famotidine (DUEXIS). April 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/022519s013lbl.pdf. Accessed June 23, 2021.
[4] Horizon Therapeutics USA, Inc. Label: prednisone (RAYOS). December 2019. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202020s012lbl.pdf. Accessed June 23, 2021
[5] Pfizer. Label: methylprednisolone (MEDROL). January 2019. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=39d5270b-d957-4821-93d6-501b7b9f02d4&type=display. Accessed June 23, 2021.
