Alternatives to Linzess

LINZESS is used to treat long-term constipation that has not responded to other therapies. It’s often used as a last-resort drug but sometimes, even LINZESS might not be able to relieve your constipation. At other times, it may cause significant side effects that make it impossible to tolerate.

So in this article, we’ll discuss alternative drugs to LINZESS that you can discuss with your healthcare provider. But first, let’s review how LINZESS works, why it might stop working for some people, and what are the side effects that it can cause.

How does LINZESS work?

LINZESS is the brand name for a drug called linaclotide, which binds to the cells lining your gut. After binding to these cells, LINZESS activates a molecule called guanylate cyclase, which leads to the secretion of chloride and bicarbonate ions in the gut.

As the gut lumen fills up with chloride and bicarbonate ions, they pull water inside it. The increased water content of the gut may distend its walls, causing reflex contraction. It also makes your stool soft and both of these mechanisms allow it to treat constipation

LINZESS has very specific uses — it’s been approved to treat constipation due to irritable bowel syndrome (IBS) and chronic idiopathic constipation (CIC). Sometimes, doctors also use it to treat constipation due to opioid use and ulcerative colitis.

Contrary to what some people believe, LINZESS is not a weight loss drug and you should not use it without a doctor’s prescription.

Can LINZESS stop working?

Although we are not sure why, many patients have reported LINZESS failure, where the drug stops working for them. In some patients, LINZESS causes an all-or-none effect, where it causes severe diarrhea at first but then completely stops working.

LINZESS might also stop working if you’re not using it properly. So it’s important to make sure your usage is correct before moving onto an alternative drug. Here are some steps you can take to ensure your LINZESS usage is correct:

  • Take it regularly. LINZESS must be taken consistently in order to work. If you’ve been skipping your doses, it might be one reason why the drug isn’t working for you. If you’ve been taking LINZESS regularly, you should allow at least a week for its effects to show (remember, LINZESS is not a laxative and is not meant to provide immediate relief).
  • Drink plenty of water. It’s recommended to drink plenty of water while taking LINZESS. This not only helps the drug work better but is also important to prevent dehydration (which is a known side effect of the drug).
  • Take it on an empty stomach. Taking LINZESS on a full stomach may cause abdominal pain and bloating. It’s recommended to take LINZESS 30 minutes before breakfast.
  • Take it with plain water only. If you find it difficult to swallow pills, you can open up the LINZESS capsule and dissolve the powder in some plain water. Shake this mixture thoroughly before drinking it and don’t store it for later use.
  • Store it properly. LINZESS must be stored at room temperature. You should also not remove the desiccant that’s found inside the LINZESS bottle. Improper storage may make the drug ineffective.

Can LINZESS cause watery diarrhea?

Yes, LINZESS can sometimes cause severe, watery diarrhea and this might be one reason you’re looking to switch to an alternative. However, severe diarrhea from LINZESS is less common than mild diarrhea.

If your diarrhea becomes severe after taking LINZESS, you must seek immediate medical attention. You should also seek immediate medical attention if you experience difficulty breathing, facial swelling, or skin itchiness, which might be signs of a severe (but rare) allergic reaction that the drug can cause.

LINZESS is also known to interact with a wide range of drugs, which can lead to adverse effects. These include omeprazole (used to treat heartburn), constipation drugs like bisacodyl and psyllium, levothyroxine (used to treat low thyroid hormone levels), and pramlintide (used to treat diabetes mellitus). 

If LINZESS is not working for you or causing significant side effects despite proper usage, switching to an alternative drug might help. Let’s discuss that now.

What is a good substitute for LINZESS?


One substitute for LINZESS is Trulance, which is the trade name for a drug called plecanatide. Trulance works just like LINZESS but it is a newer drug and can be taken with or without food, which is an important advantage of the drug.

Unfortunately, we don’t have a lot of studies to determine whether Trulance is more effective than LINZESS. Current data suggests that both drugs have an equal efficacy, which means you can expect them to have similar effects on your constipation.

If you have CIC, Trulance might be a little more effective for you than LINZESS. But practically speaking, this difference might not be very noticeable.

One major advantage of Trulance over LINZESS is its side effect profile. While Trulance causes almost all side effects that LINZESS has, the frequency is considerably lower with Trulance than with LINZESS (e.g., 5% vs 20% for diarrhea). And unlike LINZESS, Trulance doesn’t cause headaches.

Another major advantage of Trulance is that it has very few drug interactions. Unlike LINZESS, which is known to interact with a wide range of drugs, the only significant drug interaction of Trulance is with idelalisib (a drug used for blood cancer). If Trulance and idelalisib are taken together, you might experience severe, life-threatening diarrhea.


Amitiza is the brand name for a drug called lubiprostone, which works by activating chloride channels in your gut. Since this is similar to how LINZESS works, Amitiza might be considered a substitute for it.

Amitiza is also used to treat long-term constipation due to CIC and IBS and it’s a good idea to discuss it with your healthcare provider.

Just like LINZESS, Amitiza is taken orally as a pill. However, unlike LINZESS, it must be taken twice a day (which may be bothersome for some patients). Important side effects of Amitiza include:




Medically Reviewed by Onikepe Adegbola, MD PhD

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