Table 2.

Overview of Medications Commonly Used in the Management of IBS-C or CIC

	MoA	Indication	Dose and Administration	Efficacy and Safety	Other Considerations	ACG Recommendation26,27a
OTC medications
Peppermint oil	Smooth muscle relaxant	IBS-C	1–2 capsules TID orally, 15–30 min before food for 1 month37	Improves abdominal pain, discomfort, and bloating38 Impact on motility is more limited38 Most common AE is heartburn	Formulations using novel coating have been developed in an attempt to overcome AEs38	Weak recommendation for overall symptom improvement in IBS based on low-quality evidence
Polyethylene glycol	Osmotic laxative	IBS-C CIC	17 g/day, dissolved in 8 oz of water23,39	Improves stool consistency and frequency in IBS-C26,38 No evidence of improvement in abdominal pain or global symptoms compared with PBO26,32,38 Common AEs include abdominal pain and headache11	Not approved for chronic use	Weak recommendation for overall symptom improvement in IBS based on low-quality evidence Strongly recommended for improving CIC symptoms based on high-quality evidence
FDA-approved medications
Linaclotide	GC-C agonist	IBS-C CIC	IBS-C: 290 µg QD CIC: 72 or 145 µg QD To be taken on an empty stomach at least 30 minutes prior to the first meal of the day40	In IBS-C, significantly more pts receiving linaclotide met the primary efficacy endpoints: ≥30% improvement in WAP and an increase of ≥1 CSBM from baseline within the same wk (≥6/12 wks of treatment FDA endpoint); or ≥3 CSBMs/wk with an increase of ≥1 CSBM from baseline (and component responses) for ≥9/12 wks vs PBO41,42 In CIC, significantly more pts receiving either dose of linaclotide achieved the primary endpoint compared with PBO (≥3 CSBMs/wk and increase of ≥1 CSBM from baseline for ≥9/12 wks)43 The most common AEs (reported in ≥2% of pts with IBS-C or CIC) are diarrhea, abdominal pain, flatulence, and abdominal distension40	Contraindicated in pts <6 years of age and pts with known or suspected mechanical GI obstruction Recommended to avoid linaclotide in pts 6 to <18 years of age40	Strongly recommended for overall symptom improvement in IBS-C based on high-quality evidence Strongly recommended for treatment of CIC based on high-quality evidence
Lubiprostone	Chloride channel activator	IBS-C (females), CIC	IBS-C: 8 µg BID CIC: 24 µg BID To be taken with food and water44	Significantly more pts receiving lubiprostone were considered overall responders (reported moderate relief 4 wks/month or significant relief ≥2 wks/month [with no reports of moderate or severely worse relief] for ≥2/3 months) compared with PBO in pts with IBS-C45 Studies in pts with CIC demonstrated higher frequency of SBMs across 4 wks of treatment in lubiprostone-treated pts compared with PBO-treated pts44 The most common AEs (reported in >4% of pts): nausea, diarrhea and abdominal pain for IBS-C pts and nausea, headache, abdominal pain, abdominal distension and flatulence for CIC pts44	Contraindicated in pts with known or suspected mechanical GI obstruction Approved for use in female adult pts with IBS-C; not determined if men with IBS-C respond differently44	Strongly recommended for overall symptom improvement in IBS-C pts based on moderate-quality evidence Strongly recommended for treatment of CIC based on high-quality evidence
Plecanatide	GC-C agonist	IBS-C CIC	3 mg QD To be taken with or without food46	In IBS-C, a significantly greater proportion of pts receiving plecanatide were overall responders compared with pts receiving PBO (≥30% improvement in WAP and increase in ≥1 CSBM/wk from baseline for ≥6/12 wks)47 A significantly greater percentage of durable overall CSBM responders was observed with plecanatide vs PBO in pts with CIC (≥3 CSBMs/wk with an increase of ≥1 CSBM/wk from baseline for ≥9/12 wks including ≥3 of the last 4 wks)48,49 Diarrhea is the most common AE (occurring in ≥2% of pts)46–49	Contraindicated in pts <6 years of age and pts with known or suspected mechanical GI obstruction Recommended to avoid plecanatide in pts 6 to <18 years of age46	Recommended for overall symptom improvement in IBS-C based on moderate-quality evidenceb
Prucalopride	5-HT4 receptor agonist	CIC	2 mg QD 1 mg QD for pts with severe renal impairment50	A significantly greater proportion of pts receiving prucalopride were responders vs pts receiving PBO (responder defined as ≥3 CSBMs/wk over 12 wks)51,52 The most common AEs (occurring in ≥2% of pts): headache, abdominal pain, nausea, diarrhea, abdominal distension, dizziness, vomiting, flatulence, and fatigue50	Contraindicated in pts with hypersensitivity to prucalopride or in pts with intestinal perforation or obstruction Pts should be monitored for suicidal ideation and behavior as suicides, suicide attempts, and suicidal ideation have been reported50	Strongly recommended and determined to be more effective than PBO in improving symptoms of CIC based on moderate-quality evidencec
Tegaserod	5-HT4 receptor agonist	IBS-C, female pts aged <65 yearsd	6 mg BID ≥30 min before meals53	Significantly greater proportions of pts receiving tegaserod were responders vs pts receiving PBO (responders defined as pts reporting considerable or complete relief of IBS symptoms 2/4 wks or somewhat relieved 4/4 wks)53 Headache, abdominal pain, nausea, flatulence, dyspepsia, and dizziness are the most common AEs (occurring in ≥2% of pts)	Contraindicated in pts with a history of MI, stroke, intestinal ischemia, severe renal impairment, moderate or severe hepatic impairment, bowel obstruction, symptomatic gallbladder disease, suspected SOD, abdominal adhesions, or hypersensitivity to tegaserod53 Pts should be monitored for clinical worsening of depression and emergence of suicidal thoughts and behaviors53	–
Tenapanore	NHE3 inhibitor	IBS-C	50 mg, BID To be taken immediately prior to the first and last meals of the day54	A significantly greater proportion of pts receiving tenapanor were primary responders (defined as simultaneous ≥30% improvement in WAP and increase of ≥1 CSBM/wk from baseline for 6/12 wks)54 The most common AEs (occurring in ≥2% of pts) are diarrhea, abdominal distension, flatulence, and dizziness54	Tenapanor is contraindicated in pts <6 years of age and pts with known or suspected mechanical GI obstruction Recommended to avoid tenapanor in pts 6 to <12 years of age54	–
Non-FDA-approved prescription medications
Antispasmodics	Smooth muscle relaxant	Not approved for use in IBS or CIC	Hyoscyamine, up to 15 mg/day Dicyclomine 20–40 mg QD37	Can provide short-term symptom relief Effective as a category in IBS, although evidence supporting individual agents is limited26 Blurred vision, dizziness, and dry mouth are common AEs	–	Weak recommendation for certain antispasmodics (otilonium, pinaverium, hyoscine, cimetropium, drotaverine, and dicyclomine) for overall symptom improvement in IBS based on low-quality evidence
SSRIs: fluoxetine, paroxetine, citalopram	Serotonin reuptake inhibitor	Not approved for use in IBS or CIC	Fluoxetine: 20 mg QD Paroxetine: 10–50 mg QD Citalopram: 20–40 mg QD37	Effective in providing global symptom relief and improving pain26,55 Nausea, insomnia, diarrhea or constipation, decreased libido, ejaculatory dysfunction, and weight gain are common AEs37 Use may be limited by AEs and healthcare provider acceptance27	Cost of SSRIs may be a concern for some pts27	Weak recommendation for overall symptom improvement in IBS based on low-quality evidence

Notes: ^aIBS-C recommendations based on the 2018 monograph and CIC recommendations based on the 2014 monograph; ^bplecanatide was approved for treatment of CIC subsequent to the publication of the 2014 monograph for CIC; ^cprucalopride was not available in the US at the time of the 2014 ACG monograph for CIC, but was available in Canada and the European Union; ^dtegaserod was withdrawn from the US market in 2007 owing to concerns about cardiovascular AEs and was approved for this specific patient population in March 2019, subsequent to publication of the monograph; ^etenapanor was approved for treatment of IBS-C in September 2019.

Abbreviations: 5-HT₄, serotonin-4; ACG, American College of Gastroenterology; AE, adverse event; BID, twice daily; CIC, chronic idiopathic constipation; CSBM, complete spontaneous bowel movement; FDA, US Food and Drug Administration; GC-C, guanylate cyclase-C; GI, gastrointestinal; IBS, irritable bowel syndrome; IBS-C, irritable bowel syndrome with constipation; MI, myocardial infarction; mo, month; MoA, mechanism of action; NHE3, sodium/hydrogen exchanger 3; OTC, over-the-counter; PBO, placebo; pts, patients; QD, once daily; SBM, spontaneous bowel movement; SOD, sphincter of Oddi dysfunction; SSRI, selective serotonin reuptake inhibitor; TID, three times daily; WAP, worst abdominal pain; wk, week.