What are the alternatives to Linzess (linaclotide) for treating chronic idiopathic constipation and IBS-C (Irritable Bowel Syndrome with Constipation)?

Alternatives to Linzess for Chronic Constipation and IBS-C

For chronic idiopathic constipation (CIC), start with over-the-counter polyethylene glycol (PEG) 17g daily as the most cost-effective first-line alternative, and if prescription therapy is needed after OTC failure, consider plecanatide or prucalopride as equally effective alternatives to linaclotide, or lubiprostone as a more affordable option. 1, 2

First-Line OTC Alternatives (Try These First)

Polyethylene Glycol (PEG) is the preferred initial alternative, costing only $10-45/month compared to linaclotide's $523/month. 2 The AGA-ACG 2023 guidelines recommend PEG 17g daily with proven efficacy and durable response over 6 months. 1, 2 This should be your starting point for cost-conscious management.

Magnesium oxide 400-500mg daily is another viable first-line option at less than $50/month, though it must be avoided in patients with renal insufficiency. 2

Lactulose 15g daily (less than $50/month) represents the only osmotic agent studied in pregnancy, making it the preferred choice in this population. 2

Short-Term or Rescue Therapy

Bisacodyl 5-10mg daily (maximum 10mg) costs less than $50/month and works well for occasional use or rescue therapy in combination with other agents. 1, 2 The guidelines define short-term use as daily use for 4 weeks or less, though longer-term use is probably appropriate. 1

Senna 8.6-17.2mg daily is conditionally recommended by the AGA-ACG guidelines, though the dose evaluated in trials is higher than commonly used in practice. 1, 2 Start at a lower dose and increase if there's no response, as abdominal pain and cramping may occur with higher doses. 1

Prescription Alternatives When OTC Agents Fail

Equally Effective Alternatives to Linaclotide

Plecanatide 3mg once daily receives a strong recommendation with moderate certainty evidence from the 2023 AGA-ACG guidelines—the same strength of recommendation as linaclotide. 1 It's a guanylate cyclase-C agonist like linaclotide but binds in a pH-dependent manner, confining most activity to the proximal small bowel. 1 The drug is contraindicated in patients under 6 years due to dehydration risk and in those with mechanical GI obstruction. 3 Diarrhea is the main side effect leading to discontinuation. 1

Prucalopride also receives a strong recommendation with moderate certainty evidence from the AGA-ACG guidelines. 1 This 5-HT4 agonist has prokinetic effects and accelerates transit. 1 Duration of treatment in trials was 4-24 weeks, and it may cause headache, abdominal pain, nausea, and diarrhea. 1

More Affordable Prescription Alternative

Lubiprostone 24μg twice daily costs $374/month—significantly less than linaclotide's $523/month—making it the most cost-effective prescription secretagogue. 2 The AGA-ACG guidelines give it a conditional recommendation with low certainty evidence (lower than linaclotide's moderate certainty). 1 This prostaglandin E1 derivative activates chloride type 2 channels, improving stool frequency, consistency, abdominal discomfort, and bloating within 2 days among responders. 2 Nausea is the most common side effect but is typically mild to moderate and can be mitigated by taking with food and water. 1, 2 For IBS-C specifically, lubiprostone 8μg twice daily was superior to placebo for the FDA composite endpoint. 1

For IBS-C Specifically

The British Society of Gastroenterology 2021 guidelines note that linaclotide 290μg once daily is particularly effective for IBS-C, improving both the FDA composite endpoint (abdominal pain plus bowel movements) and abdominal bloating. 1

If seeking alternatives for IBS-C:

• Lubiprostone 8μg twice daily is effective for both abdominal pain and bowel symptoms in IBS-C 1
• Plecanatide 3μg or 6μg once daily improves the FDA composite endpoint and abdominal pain 1

Practical Treatment Algorithm

1. Start with PEG 17g daily, titrating up to response 2
2. If inadequate response, add or switch to magnesium oxide 400-500mg daily (if no renal insufficiency) 2
3. Use bisacodyl 5-10mg as needed for short-term relief 2
4. If OTC agents fail, choose based on priorities:
   • For cost-effectiveness: Lubiprostone 24μg twice daily 2
   • For highest efficacy: Plecanatide 3mg daily or prucalopride 1
   • For IBS-C with significant pain: Consider lubiprostone or plecanatide for dual benefit 1

Important Caveats

Certainty of evidence matters: Linaclotide, plecanatide, and prucalopride all have moderate certainty evidence with strong recommendations, while lubiprostone has lower certainty evidence despite being more affordable. 1

Combination therapy is reasonable: OTC agents can be combined with prescription secretagogues at any stage. 2

Adequate hydration is essential if adding fiber supplementation, which can be incorporated at any stage. 2

Diarrhea is the limiting side effect for all secretagogues and prokinetics—this may lead to discontinuation in approximately 4.7% of patients. 4