FDA Warning: Commonly Used Diarrhea Drug Can Cause Life-Threatening Heart Problems

In June 2016, the Food and Drug Administration (FDA) warned health care professionals and consumers that taking higher-than-recommended doses of loperamide (IMODIUM A-D, IMODIUM MULTI-SYMPTOM RELIEF) — an opioid-like drug — may cause serious, sometimes fatal, heart problems.[1]

Loperamide is approved by the FDA for, among other things, treating acute (sudden) diarrhea, including traveler’s diarrhea, in adults and children.[2],[3] Initially approved by the FDA in 1976 as a prescription medication, the drug is now available in several over-the-counter (OTC) forms — including oral tablets and capsules that are swallowed whole, chewable tablets, and liquid solutions and suspensions.

The FDA announced in November that the agency had required the addition of a black-box warning about the risk of serious heart problems to the labels of prescription loperamide products.[4],[5] But, disturbingly, a warning about this danger is absent from the labels of many OTC loperamide products.[6]

Loperamide overview

Loperamide acts on opioid receptors in the gut to slow down movement of the intestines and colon and to decrease the amounts of water and electrolytes in the stool.[7] It also increases the contraction of the anal sphincter muscle, which reduces stool incontinence and the urge to defecate. Together, these effects decrease the number of bowel movements and make stools less watery.

The standard initial dose of loperamide for an adult is two 2-milligram (mg) tablets after the first loose stool, followed by another 2-mg dose after each unformed stool, up to a maximum total dosage of 8 mg in 24 hours.

Common side effects of loperamide are similar to those seen with opioid pain medications and include dizziness and constipation. Overdoses of loperamide, as with opioids, may depress breathing. In severe cases, this can lead to loss of consciousness, brain injury and even death. Overdoses also can lead to low blood pressure and an inability to urinate.

Heart toxicity

The FDA’s 2016 warning about loperamide was prompted by a review of adverse event reports submitted to the agency: From December 1976 to December 2015, the FDA had received reports of 48 cases of serious cardiac events associated with use of the drug.[8] These events included the following:

• Syncope (sudden loss of consciousness) in 24 patients
• Cardiac arrest in 13 patients
• QT prolongation (a change in the electrical activity of the heart that can lead to a fatal heart rhythm disturbance called “torsades de pointes,” resulting in sudden death) in 13 patients
• Ventricular tachycardia (another life-threatening abnormal heart rhythm with a very fast heart rate) in 10 patients
• Torsades de pointes in seven patients

Some patients experienced more than one of these events. Ten of the patients died. Nine deaths were linked to ingestion of large amounts of loperamide, and in one case of sudden cardiac death, the amount ingested was unknown.

The FDA noted that 22 of the 48 cases involved people who were abusing high doses of loperamide, whereas 17 cases involved patients using the drug to treat diarrhea. Among those taking loperamide for diarrhea, 11 reported taking recommended doses of the drug and five reported ingesting higher-than-recommended doses. Thus, serious cardiac adverse events can occur on rare occasion even when patients adhere to the recommended dose. Among all cases, the reported dosage taken ranged from 1 mg per day to an extraordinary 1,600 mg per day, and the duration of use ranged from less than one day to 18 months.

The FDA also reviewed medical journals and identified nine additional cases of serious heart problems that were associated with loperamide and had not been reported to the agency. In three of these cases, the patients died.

Finally, data from U.S. poison control call centers showed that since 2006, there has been an increase in calls related to intentional loperamide ingestion — including intentional abuse or misuse and suspected suicide attempts.
 

Examples of Drugs That May Interact with Loperamide

*Brand-name product contains additional active ingredients.
**Quinine and quinidine also are present in tonic water.

Dangerous drug interactions

Loperamide can interact with multiple other drugs, including some commonly used antibiotics and heartburn drugs (see table above for examples; this is not a complete list, and the extent of the effects of each drug’s interaction with loperamide is unknown).[9] Combining loperamide with one or more of these drugs may increase blood loperamide levels and heighten the risk of serious cardiac and other adverse events.

What You Can Do

Most cases of acute diarrhea last only a few days and will typically resolve without the use of any medication. The primary treatment is to drink plenty of fluids to avoid dehydration. For severe acute diarrhea, you should drink oral rehydration solution (see box for a simple recipe).[10]

If nondrug treatments do not control your diarrhea, ask your doctor if loperamide is appropriate for you and make sure you are not taking any drugs that may interact dangerously with it (see table for examples). If you use loperamide, never take more than four 2-mg tablets or capsules per day (a total of 8 mgs per day). If you still have diarrhea after using loperamide for two days, or if you develop a fever, stop taking the drug and call your doctor.

Do not use loperamide to treat diarrhea in children, especially those younger than two. Never take loperamide if you have any of the following:

• Abdominal pain in the absence of diarrhea
• Bloody stools and a high fever
• Acute ulcerative colitis (a type of inflammatory bowel disease)
• Diarrhea caused by invasive bacteria, including Salmonella, Shigella and Campylobacter (these can only be identified by a stool culture ordered by your doctor)
• Antibiotic-associated Clostridium difficile diarrhea

For more guidance, see our review of diarrhea at WorstPills.org.

References
[1]Food and Drug Administration. FDA drug safety communication: FDA warns about serious heart problems with high doses of the antidiarrheal medicine loperamide (Imodium), including from abuse and misuse. http://www.fda.gov/Drugs/DrugSafety/ucm504617.htm. Accessed February 15, 2017.
[2]Johnson & Johnson Consumer. Label: loperamide (IMODIUM). October 2016. http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/017690s005lbl.pdf. Accessed February 15, 2017.
[3]Johnson & Johnson Consumer. Label: loperamide (IMODIUM A-D). November 2016. https://dailymed.nlm.nih.gov/dailymed/getFile.cfm?setid=01da76d0-1979-4c45-9d39-c72ae4e4ffe2&type=pdf&name=01da76d0-1979-4c45-9d39-c72ae4e4ffe2. Accessed February 15, 2017.
[4]Food and Drug Administration. FDA drug safety communication: FDA warns about serious heart problems with high doses of the antidiarrheal medicine loperamide (Imodium), including from abuse and misuse. http://www.fda.gov/Drugs/DrugSafety/ucm504617.htm. Accessed February 15, 2017.
[5]Mylan Pharmaceuticals. Label: loperamide. November 2016. https://dailymed.nlm.nih.gov/dailymed/getFile.cfm?setid=01da76d0-1979-4c45-9d39-c72ae4e4ffe2&type=pdf&name=01da76d0-1979-4c45-9d39-c72ae4e4ffe2. Accessed March 8, 2017.
[6]Johnson & Johnson Consumer. Label: loperamide and simethicone (IMODIUM MULTI-SYMPTOM RELIEF). December 2016. https://dailymed.nlm.nih.gov/dailymed/getFile.cfm?setid=ecb91e47-2b0c-47c8-9256-4623d8bc825e&type=pdf&name=ecb91e47-2b0c-47c8-9256-4623d8bc825e. Accessed February 15, 2017.
[7]Johnson & Johnson Consumer. Label: loperamide (IMODIUM). October 2016. http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/017690s005lbl.pdf. Accessed February 15, 2017.
[8]Food and Drug Administration. FDA drug safety communication: FDA warns about serious heart problems with high doses of the antidiarrheal medicine loperamide (Imodium), including from abuse and misuse. http://www.fda.gov/Drugs/DrugSafety/ucm504617.htm. Accessed February 15, 2017.
[9]Ibid.
[10]Worst Pills, Best Pills. Diarrhea. /chapters/view/31. Accessed February 16, 2017.