Characteristics of the Novel Drugs Recommended in the American Gastroenterological Association Guidelines for Irritable Bowel Syndrome With Constipation and Irritable Bowel Syndrome With Diarrhea
| Drug | Mechanism | Daily dose | FDA approval | Comments |
|---|---|---|---|---|
| Linaclotide | GC-C agonists |
290 μg qd 72 or 145 μg qd |
IBS-C (2012) CC (2017) |
Antinociceptive effects |
| Plecanatide |
3 mg qd 3 mg qd |
IBS-C (2016) CC (2017) |
Antinociceptive effects | |
| Tenapanor | NHE3 inhibitor | 50 mg bid | IBS-C (2019) | Antinociceptive effects |
| Lubiprostone | ClC-2 activator |
8 μg bid 24 μg bid 24 μg bid |
IBS-C (2008, female only) CC (2006) OIC (2013) |
|
| Tegaserod | Partial 5-HT4 agonist | 6 mg bid |
IBS-C (Approved for female IBS-C in 2002, for male and female CC in 2004 < 65 years of age → Withdrawn in 2007 due to CV ischemic events → Reapproved in 2019 for female IBS-C < 65 years of age and without a history of MI, stroke, TIA, or angina) |
The manufacturer withdrew tegaserod from the market for a second time in 2022 due to business-related, not safety, issues |
| Prucalopride | Full 5-HT4 agonist |
2 mg qd If CrCL < 30 mL/min, 1 mg qd |
CC (2018) No FDA approval for IBS-C |
Prucalopride was not included in the AGA IBS-C guideline because of the lack of RCT for IBS |
| Eluxadoline | Mixed MOR and KOR agonist and DOR antagonist | 100 mg bid | IBS-D (2015) |
5 pancreatitis and 8 SOS events in clinical trial Contraindicated in patients without a GB or those who drink > 3 alcoholic beverages/day |
| Rifaximin | Antibiotics | 550 mg 3 tid for 14 days | IBS-D (2015) | |
| Alosetron | 5-HT3 antagonist |
0.5 mg bid If constipation occurs, stop and restart 0.5 mg qd If the symptom is not controlled, 1 mg bid |
IBS-D (Approved 9 Feb 2000 → Withdrawn 28 Nov 2000 → Reapproved in 2002 for female only) | |
| Ramosetron | 5-HT3 antagonist |
5 μg, max 10 μg, qd for male 2.5 μg, max 5 μg, qd for female |
No FDA approval for IBS-D | Approved in 2008 in Japan for IBS-D |
FDA, Food and Drug Administration; GC-C, Guanylate cyclase-C; IBS-C, irritable bowel syndrome with constipation; CC, chronic idiopathic constipation; NHE3, sodium/hydrogen exchanger isoform-3; ClC-2, type-2 chloride channel; OIC, opioid-induced constipation; 5-HT4, 5-hydroxytryptamine receptor 4; CV, cardiovascular; MI, myocardial infarction; TIA, transient ischemic attack; CrCL, creatinine clearance; AGA, American Gastroenterological Association; RCT, randomized clinical trial; MOR, μ-opioid receptor; KOR, κ-opioid receptor; DOR, δ-opioid receptor; IBS-D, irritable bowel syndrome with diarrhea; SOS, Sphincter of Oddi spasm; GB, gallbladder; qd, once a day; bid, twice a day; tid, three times a day.