What are the best off-label medications for treating diarrhea?

From the Guidelines

Loperamide (Imodium) at 2-4mg initially followed by 2mg after each loose stool (maximum 16mg daily) is the most effective off-label medication for treating diarrhea, but for more persistent cases, tricyclic antidepressants like amitriptyline (10-50mg at bedtime) or nortriptyline (10-25mg at bedtime) can be effective. When considering off-label treatments for diarrhea, it's essential to weigh the benefits and risks of each medication.

• Loperamide is generally well-tolerated but should be avoided in children under 18 years of age with acute diarrhea and in cases of suspected or proven toxic megacolon, inflammatory diarrhea, or diarrhea with fever 1.
• Tricyclic antidepressants, such as amitriptyline, can be effective for global symptoms and abdominal pain in irritable bowel syndrome (IBS) and may be used off-label for diarrhea, starting at a low dose of 10mg once a day and titrating slowly to a maximum of 30-50mg once a day 1.
• Other off-label options for diarrhea include atropine-diphenoxylate (Lomotil), selective serotonin reuptake inhibitors (SSRIs) like paroxetine, clonidine, and cholestyramine, which should be used cautiously and under medical supervision.
• Eluxadoline, a mixed opioid receptor drug, and 5-Hydroxytryptamine 3 receptor antagonists like ondansetron may also be effective for IBS with diarrhea, but their use is limited by availability and potential side effects 1.
• Patients should always prioritize staying hydrated and seeking medical attention if diarrhea is severe, contains blood, or is accompanied by fever.

From the FDA Drug Label

XIFAXAN is indicated for the treatment of travelers’ diarrhea (TD) caused by noninvasive strains of Escherichia coli in adults and pediatric patients 12 years of age and older XIFAXAN is indicated for the treatment of irritable bowel syndrome with diarrhea (IBS-D) in adults.

The best off-label medications for diarrhea are not explicitly stated in the provided drug label. However, rifaximin (XIFAXAN) is indicated for the treatment of:

• Travelers’ diarrhea caused by noninvasive strains of Escherichia coli
• Irritable bowel syndrome with diarrhea (IBS-D) in adults It is essential to note that XIFAXAN should not be used in patients with diarrhea complicated by fever or blood in the stool or diarrhea due to pathogens other than Escherichia coli 2.

From the Research

Off-Label Medications for Diarrhea

• The most frequently used therapies for diarrhea are opiate antidiarrheal drugs, which are effective for a wide variety of diarrheal conditions and can be used safely if monitored closely 3.
• Other agents that may be used to treat diarrhea include octreotide, which has been shown to be more effective than loperamide in controlling diarrhea and eliminating the need for replenishment of fluids and electrolytes 4.
• For acute infectious diarrhea, symptomatic therapy is still the most important component of treatment, but empirical antibiotic therapy may be considered for severely ill patients with a high frequency of stools, fever, bloody diarrhea, underlying immune deficiency, advanced age, or significant comorbidities 5.
• For travelers' diarrhea, antibiotics such as azithromycin, fluoroquinolones, and rifaximin may be used for treatment, while bismuth subsalicylate and loperamide may be used as standalone treatments or in conjunction with antibiotics 6.
• Over-the-counter antidiarrheal medications that are safe and effective for the self-treatment of acute nonspecific diarrhea include attapulgite, polycarbophil, and loperamide 7.

Specific Medications

• Loperamide is a commonly used medication for diarrhea, but it may not be as effective as octreotide in controlling diarrhea and eliminating the need for replenishment of fluids and electrolytes 4.
• Azithromycin is the drug of choice for treating travelers' diarrhea, especially in Asia where Campylobacter is common 6.
• Rifaximin is a current option for preventing travelers' diarrhea, while doxycycline, trimethoprim-sulfamethoxazole, and fluoroquinolones may have limited use due to increasing resistance 6.
• Bismuth subsalicylate is an option for prophylaxis and treatment of travelers' diarrhea, and may be used alone or in conjunction with antibiotics 6.