What is a Good Substitute for Linzess?

October 12, 2025 •

4 min read

According to a 2018 report from the National Institute of Diabetes and Digestive and Kidney Diseases, chronic constipation affects a significant portion of the adult population. For many, Linzess (linaclotide) is a cornerstone of treatment, but exploring what is a good substitute for Linzess can be necessary due to side effects, cost, or a lack of effectiveness.

Quick Summary

Medication alternatives for Linzess include prescription drugs like Trulance and Amitiza, along with several over-the-counter options and natural remedies. The right alternative depends on the patient's specific condition and response to treatment.

Key Points

Prescription Alternatives: Trulance, Amitiza, Motegrity, and Ibsrela are FDA-approved prescription alternatives to Linzess for chronic constipation and IBS-C.
Differing Mechanisms: While Trulance is a similar GC-C agonist, Amitiza is a chloride channel activator, and Motegrity is a 5-HT4 agonist, offering different pharmacological approaches.
Side Effect Variation: Trulance may cause less diarrhea than Linzess, while Amitiza can cause more nausea, and Motegrity requires monitoring for mood changes.
OTC Options: Over-the-counter laxatives like MiraLAX and bulk-forming agents like psyllium are accessible alternatives for milder or occasional constipation.
Lifestyle Changes: Simple remedies like increasing dietary fiber, staying hydrated, and regular exercise can significantly impact bowel regularity.
Personalized Medical Advice: Consulting a healthcare provider is essential for determining the most suitable and safe substitute based on individual medical needs and tolerance.
Cost Considerations: Because Linzess and Trulance are brand-name-only, cheaper generic options like Amitiza and Motegrity might be preferred depending on insurance coverage.

Understanding Linzess and the Need for Alternatives

Linzess (linaclotide) is a brand-name prescription medication used to treat chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C) in adults. It works as a guanylate cyclase-C (GC-C) agonist, increasing fluid secretion into the intestines to help stimulate bowel movements.

While effective for many, reasons for seeking a substitute for Linzess can include:

Intolerable side effects, particularly diarrhea, which is a common complaint.
High cost, as Linzess is only available as a brand-name drug with no generic equivalent yet.
Lack of sufficient symptom improvement despite adherence to the medication.
Interaction with other medications or specific contraindications.

Prescription Alternatives to Linzess

For patients who find Linzess unsuitable, several other prescription options exist, each with a different mechanism of action or side effect profile.

Trulance (plecanatide)

Drug Class: Another guanylate cyclase-C (GC-C) agonist, similar to Linzess.
How it Works: Increases intestinal fluid and accelerates stool transit.
Key Differences: Trulance is taken as a tablet, unlike Linzess capsules. A key advantage is that it can be taken with or without food, whereas Linzess requires an empty stomach 30 minutes before a meal. Some studies suggest it may cause less diarrhea than Linzess.
Approved for: IBS-C and CIC in adults.

Amitiza (lubiprostone)

Drug Class: Chloride channel activator.
How it Works: Boosts fluid in the intestines by activating chloride channels, helping to soften stool and promote bowel movements.
Key Differences: Amitiza is typically taken twice daily, compared to once-daily Linzess. It is available in a generic version (lubiprostone), which can be more affordable. Common side effects include nausea and headache.
Approved for: CIC in adults, IBS-C in women over 18, and opioid-induced constipation.

Motegrity (prucalopride)

Drug Class: Serotonin-4 (5-HT4) receptor agonist.
How it Works: Increases muscle contractions in the large intestine to improve motility.
Key Differences: Motegrity has a different mechanism of action and is approved only for CIC in adults. Patients taking it must be monitored for suicidal thoughts and behavior or worsening depression. A generic version is available.
Approved for: CIC in adults.

Ibsrela (tenapanor)

Drug Class: Sodium/hydrogen exchanger 3 (NHE3) inhibitor.
How it Works: Reduces sodium absorption in the gut, which increases water in the intestines and softens stool. It also helps with pain sensation.
Key Differences: It is taken twice daily before meals and is specifically for IBS-C.
Approved for: IBS-C in adults.

Over-the-Counter and Natural Options

Before turning to a prescription alternative, many patients have tried over-the-counter (OTC) products or lifestyle adjustments.

Over-the-counter options

Osmotic Laxatives: MiraLAX (polyethylene glycol) works by drawing water into the colon to soften stools.
Fiber Supplements: Bulk-forming agents like Metamucil (psyllium) add bulk to the stool, promoting more regular bowel movements.
Stool Softeners: Docusate (Colace) makes stools softer and easier to pass.
Stimulant Laxatives: Medications like Dulcolax (bisacodyl) cause the intestinal muscles to contract more frequently.

Natural and lifestyle remedies

Dietary Fiber: Increasing the intake of fiber-rich foods, such as fruits, vegetables, and whole grains, can significantly improve bowel regularity.
Hydration: Drinking plenty of water helps soften stool and prevent dehydration, a side effect of some medications.
Regular Exercise: Physical activity can stimulate the digestive system and promote more consistent bowel movements.

Comparison of Linzess and Key Alternatives


Feature	Linzess (linaclotide)	Trulance (plecanatide)	Amitiza (lubiprostone)	Motegrity (prucalopride)
Drug Class	Guanylate Cyclase-C Agonist	Guanylate Cyclase-C Agonist	Chloride Channel Activator	Serotonin-4 (5-HT4) Agonist
Indications	IBS-C, CIC, FC (pediatric)	IBS-C, CIC	IBS-C (women), CIC, OIC	CIC
Dosage	Once daily, empty stomach	Once daily, with or without food	Twice daily	Once daily
Common Side Effects	Diarrhea, abdominal pain, gas, bloating	Diarrhea	Nausea, headache, diarrhea	Headache, abdominal pain, nausea
Availability	Brand-name only	Brand-name only	Brand-name and generic	Brand-name and generic
Form	Capsule	Tablet	Capsule	Tablet

Making the Switch from Linzess

Deciding on a substitute for Linzess is a decision that must be made in consultation with a healthcare provider. The process involves several key steps:

Discuss with Your Doctor: Always speak with your doctor or a gastroenterologist before discontinuing or switching medications. They can help determine the underlying cause of your symptoms and recommend the most appropriate alternative based on your medical history.
Identify Goals: Consider what your primary goal is—is it reducing side effects, finding a more affordable option, or seeking a different mechanism of action? This will help guide the decision-making process.
Trial Period: Your doctor may recommend a trial period for a new medication to assess its effectiveness and tolerance. They will monitor your progress and make any necessary adjustments.
Consider Costs and Insurance: Factors like cost and insurance coverage can significantly influence which medication is viable for you. Check with your insurance provider to understand your coverage for different brand-name and generic alternatives.

Conclusion

While Linzess is an effective treatment for many, a range of alternative options is available for those who need a substitute. Prescription alternatives like Trulance, Amitiza, and Motegrity offer different pharmacological approaches to treating chronic constipation and IBS-C. Over-the-counter products and simple lifestyle adjustments can also provide relief. The best course of action is to have an open conversation with your healthcare provider to find a treatment plan that aligns with your specific needs, side effect tolerance, and lifestyle.

Frequently Asked Questions

Linzess is a guanylate cyclase-C agonist that increases intestinal fluid, while Amitiza is a chloride channel activator that also increases intestinal fluid but works through a different pathway.

Clinical trials suggest that Trulance and Linzess have similar effectiveness for treating CIC and IBS-C. However, Trulance may be associated with a lower risk of diarrhea for some patients.

Yes, unlike Linzess and Trulance which are currently brand-name only, generic versions are available for Amitiza (lubiprostone) and Motegrity (prucalopride).

No, you should not switch medications without consulting your doctor. A healthcare provider can assess your individual situation and guide you through the process safely to ensure uninterrupted treatment.

Over-the-counter options include osmotic laxatives like MiraLAX, bulk-forming agents like psyllium (Metamucil), and stool softeners like docusate (Colace).

Increasing dietary fiber from fruits, vegetables, and whole grains, along with maintaining adequate hydration and regular exercise, can naturally help promote bowel regularity and may reduce the need for medication.

Motegrity is specifically approved for chronic idiopathic constipation (CIC) in adults. While Linzess treats both CIC and IBS-C, Motegrity's indication is more limited.

Neither Trulance nor Linzess provides instant relief. Most patients begin to see symptom improvement within about one week of consistent daily use.