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More than 700 medications have been implicated in inducing diarrhea, accounting for nearly 7% of all adverse drug events.[1] Depending on the causative drug, diarrhea can be acute or chronic and can develop soon after drug initiation or even after years of continued use.[2] Therefore, it is important not to overlook the role of drugs early in any assessment of diarrhea before adding a new treatment for what may actually be a drug-induced condition.
In this article, we discuss three main...
More than 700 medications have been implicated in inducing diarrhea, accounting for nearly 7% of all adverse drug events.[1] Depending on the causative drug, diarrhea can be acute or chronic and can develop soon after drug initiation or even after years of continued use.[2] Therefore, it is important not to overlook the role of drugs early in any assessment of diarrhea before adding a new treatment for what may actually be a drug-induced condition.
In this article, we discuss three main types of drug-induced diarrhea and some of the common drugs that cause them (see Table, below, for a list of examples).
Inflammatory diarrhea
Drug-induced inflammatory diarrhea involves inflammation and, sometimes, destruction of the absorptive epithelial cells that line the intestines.[3],[4]
Antibiotics, especially when used for a long time, are a common culprit of inflammatory diarrhea, which tends to be mild and reversible without treatment when these antibiotics are stopped. However, some antibiotics (such as clindamycin [CLEOCIN]) and stomach-acid–reducing proton pump inhibitors (such as omeprazole [PRILOSEC]) can cause overgrowth of Clostridium difficile. These notorious bacteria can infect the colon, leading to release of toxins that cause severe diarrhea with mucus or blood in the stool and usually abdominal pain or fever.
The blood-pressure–lowering medication olmesartan (BENICAR), which belongs to the angiotensin II receptor blocker (ARB) drug class, causes an unusual, severe enteropathy (inflammation in the intestines) that is similar to gluten-induced celiac disease, resulting in severe diarrhea, weight loss, nausea, vomiting and abdominal pain. As a result, Public Citizen’s Health Research Group petitioned the Food and Drug Administration to ban olmesartan in 2017 and subsequently designated the drug as Do Not Use.[5] This adverse event has been much less frequently reported with other ARBs,[6] such as valsartan (DIOVAN).[7]
Inflammatory diarrhea commonly occurs with immunosuppressants, including mycophenolate mofetil (CELLCEPT).[8]
Nonsteroidal anti-inflammatory drugs (for example, ibuprofen [ADVIL, IBU-TAB, MIDOL LIQUID GELS, MOTRIN IB, TAB-PROFEN]) and many other medications, including the acne drug isotretinoin (ABSORICA, AMNESTEEM, CLARAVIS, MYORISAN, ZENATANE), can cause inflammatory diarrhea.[9]
Watery diarrhea
For this type of diarrhea, the causative drugs induce diarrhea by pulling fluid into the intestinal cavity, increasing the secretion of fluids from the colon or decreasing the absorption of fluids.[10] Laxatives such as polyethylene glycol 3350 (MIRALAX) are common causes of this type of diarrhea.
The diabetes drug metformin (FORTAMET, GLUMETZA, RIOMET) causes watery diarrhea in up to 20% of users.[11] Additionally, the diabetes drugs acarbose (available in generic only) and miglitol (GLYSET) cause watery diarrhea in some patients.[12]
Digoxin (LANOXIN), which is used to treat heart failure and atrial fibrillation, can cause diarrhea, most frequently with dosages that result in blood levels above the therapeutic range, especially in elderly patients.[13]
Other drugs that cause watery diarrhea include the gout drug colchicine (COLCRYS, GLOPERBA, MITIGARE) and the rheumatoid arthritis drug auranofin (RIDAURA), which causes diarrhea in up to three-quarters of patients.[14]
Fatty diarrhea
This type of diarrhea occurs with certain drugs that interfere with the digestion or absorption of fat, leading to frequent steatorrhea (fat-laden bowel movements).[15] It commonly occurs with the weight-loss drug orlistat (ALLI, XENICAL), the diabetes drug exenatide (BYDUREON, BYETTA) and the antibiotic tetracycline (ACHROMYCIN V).[16],[17] We have designated orlistat and exenatide as Do Not Use drugs.
In addition, the gout drug allopurinol (LOPURIN, ZYLOPRIM) is among several other drugs that cause steatorrhea.[18]
Examples of Drugs That Can Cause Diarrhea[19],[20]
| Drug Category | Generic Drug Name (Brand Name[s]†) |
|---|---|
| Antibiotics |
|
| Cardiovascular drugs |
|
| Diabetes drugs |
|
| Diet drug |
|
| Gastrointestinal drugs |
|
| Gout drugs |
|
| Immunosuppressants |
|
| Laxatives |
|
| Nonsteroidal anti-inflammatory drugs |
|
| Other drugs |
|
†Combination brand-name drug products excluded
*Designated as Limited Use by Worst Pills, Best Pills News
**Designated as Do Not Use by Worst Pills, Best Pills News
What You Can Do
Before starting any new drugs, ask your doctor whether diarrhea is a possible adverse effect. If you develop diarrhea, do not delay seeking medical care, especially if there is blood in the stool or you have a fever. Tell your doctor about the drugs that you took over the last six to eight weeks to consider whether any of them may be causing your symptoms.
If drug-induced diarrhea is suspected, your doctor may lower the dose of the possible causative drug or suggest an alternative one. This usually can resolve your symptoms within a few days. Occasionally, your doctor may ask you to continue to take a certain causative drug, such as metformin, because it usually will stop causing diarrhea over time as your body adjusts to it. Do not stop any medication you are taking before consulting your doctor.
References
[1] Chassany O, Michaux A, Bergmann JF. Drug-induced diarrhoea. Drug Saf. 2000;22(1):53-72.
[2] Drug-induced diarrhoea. Prescrire Int. 2017;26(180):67-71.
[3] Abraham BP, Sellin JH. Drug-induced diarrhea. In: McDonald JWD, Feagan BG, Jalan R, Kahrilas PJ, eds. Evidence-Based Gastroenterology and Hepatology. Hoboken, NJ; 2019:208-224.
[4] Philip NA, Ahmed N, Pitchumoni CS. Spectrum of drug-induced chronic diarrhea. J Clin Gastroenterol. 2017;51(2):111-117.
[5] Do not use olmesartan for high blood pressure. Worst Pills, Best Pills News. January 2018. https://www.worstpills.org/newsletters/view/1170. Accessed January 6, 2022.
[6] Kamal A, Fain C, Park A, et al. Angiotensin II receptor blockers and gastrointestinal adverse events of resembling sprue-like enteropathy: a systematic review. Gastroenterol Rep. 2019;7(3):162-167.
[7] Philip NA, Ahmed N, Pitchumoni CS. Spectrum of drug-induced chronic diarrhea. J Clin Gastroenterol. 2017;51(2):111-117.
[8] Ibid.
[9] Ibid.
[10] Abraham BP, Sellin JH. Drug-induced diarrhea. In: McDonald JWD, Feagan BG, Jalan R, Kahrilas PJ, eds. Evidence-Based Gastroenterology and Hepatology. Hoboken, NJ; 2019:208-224.
[11] Sharma A, Walsh D. An old friend turned foe: Metformin-induced diarrhea with resultant symptomatic hypokalemia, hypomagnesemia, hypocalcemia, and hypophosphatemia. Clin Case Rep. 2021;9(8):e04621.
[12] Abraham BP, Sellin JH. Drug-induced diarrhea. In: McDonald JWD, Feagan BG, Jalan R, Kahrilas PJ, eds. Evidence-Based Gastroenterology and Hepatology. Hoboken, NJ; 2019:208-224.
[13] Ibid.
[14] Ibid.
[15] Ibid.
[16] Ibid.
[17] Philip NA, Ahmed N, Pitchumoni CS. Spectrum of drug-induced chronic diarrhea. J Clin Gastroenterol. 2017;51(2):111-117.
[18] Abraham BP, Sellin JH. Drug-induced diarrhea. In: McDonald JWD, Feagan BG, Jalan R, Kahrilas PJ, eds. Evidence-Based Gastroenterology and Hepatology. Hoboken, NJ; 2019:208-224.
[19] Philip NA, Ahmed N, Pitchumoni CS. Spectrum of drug-induced chronic diarrhea. J Clin Gastroenterol. 2017;51(2):111-117.
[20] Abraham BP, Sellin JH. Drug-induced diarrhea. In: McDonald JWD, Feagan BG, Jalan R, Kahrilas PJ, eds. Evidence-Based Gastroenterology and Hepatology. Hoboken, NJ; 2019:208-224.
