J Neurogastroenterol Motil 2024; 30(1): 4-6  https://doi.org/10.5056/jnm23183
Mind the Gap: The Realities of Novel Irritable Bowel Syndrome Drug Access in Asian Clinical Practice
Yong Sung Kim,1,2 Tadayuki Oshima,3,4 Kewin T H Siah,5,6 and Suck Chei Choi1,7*
1Wonkwang Digestive Disease Research Institute, Iksan, Jeonlabuk-do, Korea; 2Good Breath Clinic, Gunpo, Gyeonggi-do, Korea; 3Department of Gastroenterology, Okazaki City Medical Association Public Health Center, Okazaki, Japan; 4Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Science, Nagoya, Japan; 5Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 6Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore; and 7Department of Gastroenterology, School of Medicine, Wonkwang University, Iksan, Jeonlabuk-do, Korea
Correspondence to: *Suck Chei Choi, MD, PhD
Department of Gastroenterology, Wonkwang University Hospital, 895 Muwang-ro, Iksan, Jeollabuk-do 54538, Korea
Tel: +82-63-859-2670, E-mail: medcsc@wonkwang.ac.kr
Received: December 1, 2023; Accepted: December 16, 2023; Published online: January 30, 2024
© The Korean Society of Neurogastroenterology and Motility. All rights reserved.

cc This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Irritable bowel syndrome (IBS) is a widespread gastrointestinal disorder with a global prevalence estimated at 8.8% (8.7-8.9%) in adults, as indicated by literature reviews.1 Regional heterogeneity is notable, ranging from 5.8% in the Middle East and Africa to 17.5% in Latin America, with a higher prevalence in females.1 The overall prevalence of IBS in a recent study in East Asia, including Japan, China, and South Korea, using Rome III criteria was slightly higher than the global prevalence, and male patients comprised 54.9% of the cases.2 IBS is associated with a significant financial burden on healthcare and adversely affects patients’ quality of life.3 With these challenges, there is an urgent need to develop and implement novel IBS drugs. The application of these treatments should consider the unique characteristics of each region.

Diagnosis and management primarily depend on whether patients have diarrhea or constipation as their predominant symptom. However, the multifactorial pathogenesis and complex symptoms of IBS present challenges for physicians in selecting appropriate drugs. Recognizing these therapeutic difficulties, major academic societies, including the American Gastroenterological Association (AGA), have published authoritative guidelines4,5 to assist general physicians in providing standard treatment. The AGA clinical guidelines for IBS with constipation (IBS-C)4 and IBS with diarrhea (IBS-D)5 published in 2022 include novel drugs targeting various aspects of IBS pathogenesis (Table 1). Unlike traditional drugs, these novel drugs have shown efficacy in clinical trials with the United States Food and Drug Administration responder endpoint.6

Table 1 . Characteristics of the Novel Drugs Recommended in the American Gastroenterological Association Guidelines for Irritable Bowel Syndrome With Constipation and Irritable Bowel Syndrome With Diarrhea

DrugMechanismDaily doseFDA approvalComments
LinaclotideGC-C agonists

290 μg qd

72 or 145 μg qd

IBS-C (2012)

CC (2017)

Antinociceptive effects

3 mg qd

3 mg qd

IBS-C (2016)

CC (2017)

Antinociceptive effects
TenapanorNHE3 inhibitor50 mg bidIBS-C (2019)Antinociceptive effects
LubiprostoneClC-2 activator

8 μg bid

24 μg bid

24 μg bid

IBS-C (2008, female only)

CC (2006)

OIC (2013)

TegaserodPartial 5-HT4 agonist6 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
PrucaloprideFull 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
EluxadolineMixed MOR and KOR agonist and DOR antagonist100 mg bidIBS-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

RifaximinAntibiotics550 mg 3 tid for 14 daysIBS-D (2015)
Alosetron5-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)
Ramosetron5-HT3 antagonist

5 μg, max 10 μg, qd for male

2.5 μg, max 5 μg, qd for female

No FDA approval for IBS-DApproved 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.

Professor Yong Sung Kim presented a lecture on novel drugs on IBS at the 7th Biennial Congress of the Asian Neurogastroenterology and Motility Association (ANMA) in Taipei, Taiwan, on November 10-11, 2023. He noted that a substantial number of AGA guidelines-recommended IBS drugs were not prescribed in Korea. This led to a systematic survey via email and social network services to experts across Asia, uncovering an unexpected and widespread limitation in the availability of novel IBS drugs across the majority of Asian nations (Table 2). With this lecture, the audience in ANMA 2023 was rather relieved to know that there are shared concerns in all Asian countries, and they questioned the practicality of major society guidelines, highlighting a noticeable gap between recommendations and actual clinical drug use. Such a gap was also found in related Asian guidelines.7 Prucalopride, a 5-hydroxytryptamine receptor 4 agonist similar to tegaserod, is not included in the AGA IBS-C guidelines due to a lack of studies evaluating its efficacy in IBS-C.4 However, experts expect it may also be efficacious for reducing symptoms in patients with IBS-C.8 Thus, if prucalopride is included in the table of novel drugs for IBS, the availability seems to be slightly increased (Table 2).

Table 2 . Availability of the Novel Drugs Recommended in the Guidelines for Irritable Bowel Syndrome With Constipation and Irritable Bowel Syndrome With Diarrhea in Each Asian Country (as of the Lecture of Professor Yong Sung Kim in 7th Biennial Congress of the Asian Neurogastroenterology and Motility Association, 11 November 2023)

Hong Kong

IBS-C, irritable bowel syndrome with constipation; IBS-D, irritable bowel syndrome with diarrhea; ○, available; ✕, not available; ○→✕, previously available, but not currently available.

After the ANMA 2023, we discussed the reason for this issue and found 2 major problems. First, high prices of novel drugs create a significant challenge for medical insurance in Asia, limiting inclusive coverage and patient access. The financial burden placed on patients due to these costly medications further discourages pharmaceutical companies from introducing their novel drugs in Asian markets. Second, even when novel drugs are available, they may lack specific indications for IBS, requiring off-label use. For example, in Korea, the indication of rifaximin is limited to infectious diarrhea, prevention of perioperative gastrointestinal surgery, and hyperammonemia. In Japan, rifaximin is specifically indicated for improving hyperammonemia in hepatic encephalopathy. In addition, only a 200 mg formulation is available. The approved dose for the above indications in Korea and Japan is 800-1200 mg daily, which is lower than the recommended dose for IBS-D.5 Similarly, linaclotide is available in Japan, and lubiprostone is available in Korea and Japan. Still, the indication of these drugs in both countries is only for chronic constipation and not for IBS-C.

Our editorial urges practical measures for better IBS management. Calling for collaboration with pharmaceutical entities and policy adjustments, we stress the pivotal roles of patient advocacy groups, policymakers, and pharmaceutical companies. The ANMA and Journal of Neurogastroenterology and Motility play crucial roles in steering collaborative efforts and ensuring region-specific solutions. There is a need for a united IBS landscape where novel drugs align with Asian healthcare needs.


Thank you to the following experts for informing us of each country’s data

Financial support

This work was supported by Wonkwang University 2023 (CSC).

Conflicts of interest


Author contributions

Yong Sung Kim: conceptualization, data acquisition, data analysis, and writing of original draft; Tadayuki Oshima: data acquisition and data analysis; Kewin T H Siah: data acquisition and data analysis; and Suck Chei Choi: conceptualization and final approval.

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