LINZESS Not Working

LINZESS Stopped Working

LINZESS is prescribed for long-term constipation that does not respond to other drugs.

But sometimes, even LINZESS can fail, which can lead to considerable stress and anxiety in people with chronic constipation.

Many people who take LINZESS complain about its “all-or-none” effect. The drug works initially and causes severe diarrhea but completely stops working after that.

This article will discuss some of the possible reasons behind LINZESS' failure and steps you can take to make it more effective.

In the end, we also discuss an alternative drug to LINZESS.


Let’s begin!

What is LINZESS?

LINZESS is a drug used to treat constipation.

It works by activating guanylate cyclase inside gut cells, which triggers the efflux of chloride and bicarbonate ions.

As chloride and bicarbonate ions enter the gut lumen, they’re followed by water. Increased water content of the gut makes stool softer and triggers gut contractions, both of which are useful in treating constipation.

Why does LINZESS stop working?

We’re not really sure why LINZESS stops working but we do have a few possible explanations. But you should know that LINZESS failure is a real thing and many people have experienced it. You’re not alone!

Here are some possible explanations of why LINZESS has stopped working for you.

You’re taking it for the wrong purpose

It’s important to be clear about the conditions LINZESS treats. It has been approved only for chronic idiopathic constipation and irritable bowel syndrome (constipation-predominant).

Sometimes, it’s also used off label to treat constipation caused by opioids and ulcerative colitis.

If you’re using LINZESS for any reason other than these, it will fail. The most common misconception about LINZESS is that it’s a weight-loss drug.

You should know that the effects of LINZESS on weight are uncertain and both weight gain and weight loss have been reported by users. So make sure you’re using LINZESS for the right purpose.

You’re not taking LINZESS regularly

LINZESS is supposed to be taken once daily for a considerable period of time. If you miss your dose frequently, then there’s a good chance that it will stop working for you.

You’re using it incorrectly

The correct way to use LINZESS is to take it on an empty stomach. This is best achieved by taking the drug 30 minutes before the first meal of the day.

Some people have reported taking LINZESS at night, which can be counterproductive and worsen your symptoms instead of improving them.

That’s because LINZESS normally increases the water content of the gut and when taken on an already full stomach, it can lead to abdominal side effects like bloating, gas, and abdominal pain.

It’s also possible that you’re taking the drug at the right time but using the wrong method. LINZESS is supposed to be taken orally with plain water. If you find it hard to swallow capsules, you can open up the LINZESS capsule and dissolve the powder in applesauce or plain water. Swirl the mixture carefully before swallowing it and do not store it for later use.

Some people also believe that LINZESS becomes ineffective due to improper storage. LINZESS is supposed to be stored at room temperature in the bottle it comes in. It’s also important that you don’t remove the desiccant from the bottle.

Finally, it may be possible that your LINZESS dosage is inadequate. This is something for a doctor to decide and your doctor may adjust your dose once you bring this to his attention.

You just started LINZESS

Another reason why LINZESS might not be working for you is that you just started it.

Remember, LINZESS is not a laxative. It’s not meant to provide immediate relief from constipation. You should wait for at least a week for LINZESS to kick in.

You’re not drinking enough water

It’s recommended to drink about 7-8 glasses of water while taking LINZESS. Although LINZESS is not a laxative, it does require water to work.

If you’re not drinking enough water, try increasing your intake and see if it helps.

Drinking plenty of water while on LINZESS is also important to prevent dehydration because the drug can lead to diarrhea (which can sometimes be severe).

How to make LINZESS effective again?

Determining why LINZESS has stopped working for you and working on the cause is a good way to make it effective again.

For example, if it’s due to inadequate water intake, try drinking more water. If it’s due to improper storage, make sure to follow storage and usage guidelines properly. 

It’s also useful to combine LINZESS with other activities that are known to help with constipation. Examples include regular exercise and dietary modifications. The recommended dietary changes for you will depend on the exact condition you have, so speak to a doctor about it.

However, note that sometimes it’s not really possible to make LINZESS effective again. Gut dysmotility disorders are often unpredictable and may stop responding to a drug for no apparent reason. In that case, trying out an alternative drug may be useful.

Plecanatide — an alternative to LINZESS

Plecanatide is an alternative to LINZESS. It works exactly like LINZESS and goes by the trade name Trulance.

If everything fails, you might want to consider switching to Trulance. But make sure to discuss it with your doctor.

Here are a few important points to keep in mind about Trulance: 

  • It’s as safe and effective as LINZESS, making it a good alternative
  • It has relatively fewer drug interactions than LINZESS
  • It can be taken on a full stomach (unlike LINZESS)


Many people report LINZESS failure. While the exact cause of this is not known, various explanations exist. These include improper usage and storage, using it for the wrong reason, not drinking enough water, and not taking the drug regularly.

Determining the exact cause of LINZESS failure may help you make it more effective again. However, this might not be possible every time because the body can simply stop responding to LINZESS for unknown reasons. In that case, switching to Trulance may be helpful.

Medically Reviewed by Onikepe Adegbola, MD PhD

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