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LINZESS
Generic Name and Formulations:
Linaclotide 145mcg, 290mcg; capsules.
Company:
Forest Laboratories
Indications for LINZESS:
Irritable bowel syndrome with constipation (IBS-C).

Adult Dose for LINZESS:
Swallow whole. Take on empty stomach, at least 30 minutes before first meal of the day. 290mcg once daily.

Children's Dose for LINZESS:
<6yrs: contraindicated. 6–17yrs: avoid.

Pharmacological Class:
Guanylate cyclase-C agonist.

Contraindications:
Children up to 6 years old. Known or suspected mechanical GI obstruction.

Warnings/Precautions:
Hold or stop if severe diarrhea occurs. Pregnancy (Cat. C). Nursing mothers.

Adverse Reactions:
Diarrhea, abdominal pain, flatulence, abdominal distention.

Metabolism:
GI.

Elimination:
Fecal.

Generic Availability:
NO

How Supplied:
Caps—30

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Linzess for the treatment of Constipation Predominant IBS | A Patient’s Guide
I just returned from a weekend meeting to learn about the new medication for constipation predominant IBS (IBS-C) and chronic idiopathic constipation (CIC) called Linzess ™ ( linaclotide).
My initial impressions are that this will be a very safe treatment option for those who suffer from one of these conditions. Like any medication, it doesn’t work for everyone but most people had significant improvement in their symptoms while on the medication and it appears to be very safe for adults with either IBS-C or CIC. Keep in mind, though, that it should not be used by anyone 17 years of age or younger.
The design of the medication is rather unique. Original investigators identified a receptor in the gastrointestinal tract that when stimulated, increases water secretion into the bowel lumen. In addition, it does seem to have an effect on the nerves in the GI tract by decreasing abdominal pain associated with IBS-C.
In this article, we will review what I have learned so far about this new medication and how it should be used for the treatment of IBS-C and CIC.
Indications for Linzess
Linzess has been approved by the US Food and Drug administration for adults with IBS-C and adults with CIC. It is not recommended for anyone 17 years of age or younger.
Mechanism of Action:
This may get a bit technical so I will first explain it in simple terms and then go into a bit more detail. Feel free to skip the more technical portion.
Simplified Mechanism of Action:
Within the lining of the large and small intestine are several receptors called guanylate cyclase-C (GC-C). The medication, Linzess ™, once ingested, will stay within the bowel and will bind to these GC-C receptors. This triggers a response in the intestinal cell to secrete water into the bowel improving constipation. And for those who take the higher dose of medication for IBS-C, there is a second reaction within the cell. The second reaction is that the intestinal cell decreases the sensitivity of the nerves in the small and large intestine, and as a result, improves abdominal pain.
Scientific Mechanism of Action:
The mucosal cells of the large and small intestine contain receptors for guanylate cyclase-C (GC-C). Linzess ™ is a GC-C agonist and binds to the GC-C receptor on the cell. Linzess is a GC-C agonist. This increases the intracellular and extracellular concentration of cyclic guanine monophosphate (cGMP) which in turn stimulates the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel to secrete bicarbonate and chloride into the bowel lumen. This increases intestinal fluid and increases intestinal transit in the intestines. As a result, constipation improves as well as abdominal pain associated with IBS-C. In animal models, there appears to be an increase in the extracellular cGMP and it is felt that this is what decreases the sensitivity of the visceral nerves and improves the abdominal pain and cramping symptoms.
Dosage and Administration
Linzess ™ comes in two strengths. Those who have IBS-C should take the 290 mcg capsule once daily. For those with CIC the dose is 145 mcg once daily. The medicine should be taken about 30 minutes before the first meal of the day on an empty stomach. Once ingested, the medication remains within the bowel and binds to the GC-C  receptor as we discussed above. Very little if any of it is absorbed. In fact, when they tried to measure it in the blood stream, it wasn’t detected. This is great, because it also means that there are no known systemic side effects or drug to drug interactions.
How fast does the medicine work?
There appear to be two things to consider here. If you are taking the medication for constipation, then most people will see improvement right away and the maximum improvement in constipation is seen within the first 1 to 2 weeks. Exactly how fast it works, nobody knows. However, I would recommend that when you first start taking the medication that you plan ahead. Pick a time that you will be at home and have easy access to a restroom. This is not a medication you want to start taking while on holiday or your honeymoon. As we will discuss later, some people will actually get diarrhea but only 2% of people had diarrhea that was severe enough to stop the medication.
If you have IBS-C and are taking the medication to help improve the pain associated with IBS-C then you will see gradual improvement starting in the first few days and then maximum improvement in pain at after taking the medication for about 6 weeks.
What if I am taking a stool softner or Fiber? Do I need to stop these first?
Some of the people in the studies were taking stool softeners and fiber during the study. If they had been on a stable dose for 30 days before entering the trial, then they were allowed to continue these medications. However, they were not allowed to increase their dose or change the dose of fiber or stool softeners.
So, the take home message here is that it is ok to continue on a stool softener or fiber if you are taking one. However, I wouldn’t start a stool softener or new fiber supplement at the same time you begin taking Linzess ™. I would also recommend that you discuss this with your prescribing doctor as well.
Side Effects and Risks
This medication is only to be used in adults age 18 and over. You should not take this medication if you are pregnant as it is considered Category Class C. No studies have been conducted on the safety of this medication in pregnant humans. You should not use it if you are breastfeeding either because this has not been studied. The most common side effect of the medication was diarrhea. For most patients who suffer IBS-C or CIC, diarrhea would be a welcome change. So, it depends on how you look at it. Only 2% of the people who took the medication had to stop it because the diarrhea was considered severe.
Other side effects that were present were minimal.
Storage Considerations
It is important to note that this medication does require some special handling. It should only be kept in the original bottle with the desiccant in the bottle. It must be kept in a cool dry place as moisture can affect the capsules and ruin them.
So, if you put your pills in a pill box, remember, you CAN NOT do that with this medication. It has to remain in the original bottle given to you by your pharmacist.
Summary
In summary, this is an exciting new medication to help those patients whose symptoms don’t respond to dietary and lifestyle changes. I still recommend avoiding medications when possible when treating IBS and first line of therapy should be dietary and life style changes as outlined in my Low FODMaP IBS Diet plan. However, if you are doing these things and IBS-C and CIC remain symptomatic, Linzess may be a good option for you. As always, talk with your doctor as this medication does require a prescription. Only you and your doctor can make the right decision for your health.