Pharmacological Management of Irritable Bowel Syndrome With Diarrhea (IBS-D)

In patients with IBS-D, the AGA suggests using eluxadoline. Note that eluxadoline is contraindicated in patients without a gallbladder or those who drink more than 3 alcoholic beverages per day.

In patients with IBS-D, the AGA suggests using rifaximin.

In patients with IBS-D with initial response to rifaximin who develop recurrent symptoms, the AGA suggests retreatment with rifaximin.

In patients with IBS-D, the AGA suggests using alosetron.

In patients with IBS-D, the AGA suggests using loperamide.

In patients with IBS, the AGA suggests using TCAs.

In patients with IBS, the AGA suggests against using SSRIs.

In patients with IBS, the AGA suggests using antispasmodics.

100mg BID is the recommended dose of eluxadoline. 75mg BID can be used in hepatic impairment or in those who cannot tolerate the higher dose.

550mg PO TID for 14 days is the recommended dose for rifaximin.

0.5mg PO BID is the recommended starting dose for alosetron. This can be increased to 1mg BID if symptoms are not controlled after a 4-week trial of 0.5mg BID

A range of 2-16mg daily in divided doses is recommended for loperamide.

Different tricyclic antidepressants (TCAs) can be used including amitriptyline, nortriptyline, and desipramine. 10-25 mg at bedtime is the recommended starting dose which can gradually be increased up to 100 mg at bedtime if needed.

Commonly used antispasmodic medications include dicyclomine and hyoscyamine. Dosing may vary.

SSRI dosing can range from 10-40 mg daily. Recommended dosing for escitalopram is 5-20 mg daily. Recommended dosing for sertraline and fluvoxamine is 50-150 mg daily.

Eluxadoline is a mixed µ-and κ-opioid receptor agonist and δ-opioid receptor antagonist.

Rifaxamin is a nonabsorbable antibiotic with broad spectrum activity against both gram positive and negative as well as aerobic and anaerobic bacteria.

Alosetron is a selective 5-HT3 antagonist with central and peripheral activity which can reduce intestinal transit time and reduce visceral sensitivity.

Loperamide is a synthetic peripheral opioid receptor agonist, inhibiting peristalsis and antisecretory activity, prolonging intestinal transit time.

TCAs are serotonin and norepinephrine reuptake inhibitors and antagonize cholinergic and histamine-1 receptors. Peripheral and central actions which can affect motility, secretion and sensation.

Antispasmodics can be cholinergic, muscarinic or calcium channel blockers which relaxes smooth muscle in the gut.

Selective serotonin reuptake inhibitors work at receptors in the brain and gut.

When prescribing eluxadoline, patients should be counseled on the potential for constipation, nausea, and abdominal pain.

When prescribing rifaximin, patients should be counseled on the potential for nausea.

When prescribing alosetron, patients should be counseled on the potential for ischemic colitis and constipation.

When prescribing loperamide, patients should be counseled on the potential for constipation and abdominal cramping.

When prescribing TCAs, patients should be counseled on the potential for dry mouth, sedation, and constipation.

When prescribing antispasmodics, patients should be counseled on the potential for constipation, xerostomia, and visual disturbance.

When prescribing SSRIs, patients should be counseled on the potential for nausea, dry mouth, and diaphoresis.

Eluxadoline is contraindicated in patients without a gall bladder, who drink >3 alcoholic beverages per day, or with a history of bile duct obstruction, Sphincter of Oddi disease, pancreatitis, or severe hepatic impairment.

In patients with initial response to rifaximin who develop recurrent symptoms, the AGA suggests retreatment up to 2 times with the same dosage regimen.

Alosetron is indicated in women with severe IBS-D who have failed conventional therapy. Initially withdrawn in 2000 due to ischemic colitis (1:750-1000) and serious complications of constipation, but it was reintroduced in 2002 with restrictive use in women under 65 years of age. In 2023, the FDA determined that the risk mitigation program is no longer needed.

When using loperamide, there was a lack of beneficial effect on global improvement of symptoms of IBS, but there was improvement in abdominal pain and stool consistency although certainty of evidence was very low.

When prescribing TCAs, secondary amines (desipramine, nortriptyline) may be preferred over tertiary amines (amitriptyline) in patients to minimize sedation and constipation.

Antispasmodics are commonly used in clinical practice to reduce abdominal pain associated with IBS.

The AGA suggests against using SSRIs for primary treatment of IBS. Consider using in patients with coexistent anxiety or depression.