Linzess: Another New Drug Resulting from Basic Science Research

Credit Synergy Pharmaceuticals for this diagram. Hopefully it will bring more clarity to my attempts at describing this biochemistry.

Linzess is a new drug that last week received FDA approval by Forrest laboratories for use in irritable bowel syndrome (IBS) with constipation and in chronic idiopathic constipation got my attention more because of its biochemistry than because I think it is going to be a drug I prescribe often.   Learning about the mechanism of action of new drugs like Linzess reminds me how much more is understood about the molecular biological level of physiologic function of the human body than when I was in med school.  Linzess is felt to act as a guanylate cyclase-C agonist. An agonist increases the activity of a process, the opposite of an antagonist. Linzess seems to act locally on the surface of the inside of the intestinal lining cells and by activation of guanylate cyclase-C increases levels of intracellular cGMP (cyclic guanosine monophosphate) which results in increased levels of chloride and bicarbonate in the intestinal lumen and speeds up gastrointestinal transit.  Never having heard of guanylate cyclase-C before I looked and found out that it was initially discovered before I went to med school (just barely), in 1974-5, but as far as I know this is one of the first clinically important results of this study in medicine.  If readers know of others please leave me a comment.

The FDA approved use of Linzess in IBS with constipation is 290 µg orally once daily and in chronic idiopathic constipation the approved dose of Linzess is 145 µg orally daily. In both conditions Linzess is best taken on anti-stomach at least 30 min. prior to first meal of the day. Linzess joins previously FDA approved and Amitiza (lubiprostone) as prescription medications specifically for IBS with constipation and gives us one more option for treatment of this difficult problem. IBS with constipation is among the more common and refractory conditions seen in gastroenterology and in primary care. Chronic laxative use is common in these patients and can lead to laxative dependence and poor colonic function and even toxic megacolon in severe cases. Osmotic laxatives like milk of magnesia and not observable sugars like lactulose are commonly used. MiraLax (polyethylene glycol) has become increasingly popular in recent years but all of these products have limited effectiveness and associated problems.

Linzess has also been shown to reduce intestinal type of nominal pain.  Linzess also has an FDA approval for use in chronic idiopathic constipation at a dose of 145 µg daily.

The efficacy of Linzess in IBS with constipation and in chronic idiopathic constipation is expected to be at best modest. In the to placebo can trial IBS with constipation trials the incidence of an improvement in at least six of the 12 weeks trial duration for improvement in abdominal pain was only 33% for improvement both abdominal pain and constipation versus 21% with placebo or 12.6% benefit over placebo. For abdominal pain response 50% had improvement with Linzess versus 37% with placebo, a 12.7% difference, and in constipation improvement 48% improved with Linzess versus 29% on placebo, a 19% difference. In the two trials looking at improvement in at least nine out of the 12 weeks the numbers were considerably lower but did show significantly more patients improving on Linzess and with placebo.  To look at the data more pacific we can look at the Forest Laboratories prescribing information.

As might be expected diarrhea is the most common side effect of Linzess occurring in up to 20% or patients, and often the diarrhea begins within the first 2 weeks of treatment.  The diarrhea from Linzess  can be severe and the manufacturer recommends that if a person using Linzess  develops diarrhea that should immediately stop the medication and contact their doctor.  Other GI symptoms are common also and include abdominal pain, gas and a feeling of fullness or swelling in the abdomen.  In addition Linzess comes with a strict warning that it is not for use in children. In juvenile rats deaths were noted, and so Linzess is contraindicated for use in persons under age 18.

It is expected that Linzess will be another quite expensive medication, and although Forrest has not yet set a price they have intimated that the drug will be priced to be comparable to Amitiza, or in the $260. / month range.  It remains to be seen if it will be more popular than Amitiza, or whether it will be just a niche drug for refractory cases of IBS with constipation and chronic idiopathic constipation.

8 Responses to Linzess: Another New Drug Resulting from Basic Science Research

  1. I’ve obtained prescriptions for both amitiza and linzess. The linzess has so far been effective about 75% of the time. My constipation is so bad that I take a half doze of exlax at nighttime, then an eith 1/8 of a combo stool softener/laxative at approx. 4am which will wake me up between 5 and 5:30 with a run to the bathroom most of the time. When that is over I take the linzess and go back to bed,usually awakened at 6:30-7am and as I said 75% of the time I’m evacuated.
    What a miserable situation but this is the best it’s been for quite a while. I also take 1.5 percocets a day for chronic long term pain, 24 x 7 now for about 6 years.
    While it’s expensive, to me it’s worth it. With my insurance it costs $180/month

  2. Sherry: Bloating is a common Linzess side effect, but is supposed to often be transient, meaning it goes away or lessens after a while on the med. It is not as likely to cause dryness as the robinol. Good luck. DrP.

  3. I have just taken my 1st dose of Linzess, I have SEVERE BLOATING due to constipation / IBS. I took Robinol for a year and I cannot take it due to it drying ALL my membranes and I already have severe dry eye and this med made it worse. Is Linzess going to INCREASE my bloating? Is it going to make me as dry as the Robinol? TIRED OF BEING MISERABLE!!! WHO can afford this med without prescription coverage? IS there any help?

  4. This is my first try with Linzess. It has given me some diarrhea, but my stomach pain is disappearing. It is too soon to tell. I am a little concerned about some swelling of the abdomen. But I think sodium has played a role in that. If I continue to use it, I may have to limit my sodium intake a little more. What kills me I seldom use my salt shaker at home. The foods I eat must have extra sodium in them. It will be hard to eliminate salt, as I have to eat and I hate drinking plain water. I think Linzess works like a strong laxative, which I am not sure I want to take everyday. It is hard to take everyday if you have to go out during the day, as I have to run fast to the bathroom. If I decide to stay on it to clean out my system, I may have to stay at home alot until my body gets used to it which is easier said than done. The reason why I started taking it was I just wasn’t going well enough and was suffering from it. I want to take it but I don’t want to swell from it as medicines that causes diarrhea also raises your sodium levels. Can’t decide. I have fatty liver disease probably from taking my prescription medicines. It seems all doctors recommend is taking more. I don’t think they know how to help people without giving people medication for all their problems. If I continue to take it, it will help relieve my stomach pain at a cost. Like I said – can’t decide. By the way instead of having severe constipation all the time, try to wean yourself from relying on pain medication. Not only does it require greater doses of it to relieve the pain, it plays havoc with your health. I don’t know the answer to pain, except not to keep doing things that cause it to hurt more. I know a person who kept hurting his shoulder by doing odd jobs relying more and more on pain meds. The doctors don’t care if you get hooked. That is why they prescribe it so readily. If you are up in years I say yes. If you are young, I say it will be a downward spiral. I know someone who got cortisone shots for her bad hip to take the pain away. Meanwhile her hip is getting worse and more damaged. She can’t feel the pain with the shot. Now they told her it probably won’t help her anymore. What is that all about? I don’t know the answer. If your job caused your severe pain, surgery is an option, but sometimes it just doesn’t work. I’m not sure I want to pay the cost. Might give it a week.

  5. I’ve been on Linzess 290 for several months, taking with one dose of Miralax. When it works, I have 6 bouts of diarhhea-like BMs which mean I can’t leave the house before 10 a.m. When it doesn’t do the trick, I’m in agonizing pain for a day or two until the dam breaks (so to speak). :/

  6. My Dr. recently gave me an 8 day sample of linzess. I have IBS. It gave me some relief, but my prescription drug company wants me to try amatiza. They told me what to do if the amatiza doesn’t work. I’m thankful I got a little relief from the linzess 290 mcg.

  7. I have suffered with Ibsen and serious constipation issues for approx 15years.i started using linzess about 2months ago,the results for me were a blessing.my issues were primarily due to pain medication which bound me to agonizing attempts to move my bowels.after two weeks I started to see significant improvement.aftr using linzess for four weeks ,my bowel movement have become regular and pain or pressure free.i have found this medication to be life changing for me.i am a 74year old male and would recommend this product to anyone suffering with severe constipation.thank you linzess

  8. Hello there – it seems to me that this drug could be another disaster like Zelnorm.
    What is the point of taking Linzess when the side effects are EXACTLY the same as IBS anyway.
    I have suffered ever since I was given a penicillin injection which had a bad effect on the gut – that was 50 years ago – I am 82 and still suffering.

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