GUIDE: Why Linzess Fails, And How To Make It Work Again - Inspire

Hey everyone,

I have been on the STC/CI/PFD journey for a few years now and I want to make a few posts that address major points of interest for the dysmotility community. I hope you find these helpful. I'm also publishing this here because Inspire.com has good Search Engine Optimization, so hopefully anybody seeking answers on Google will land on this guide. This one is for Linzess / linaclotide.

THE PROBLEM WITH LINZESS

So many people report the same problem with Linzess: it gives them insane diarrhea the first few times they use it, and then it stops working altogether.

WHY IT STOPS WORKING

There are a few reasons that are not well-understood. One is that people are often put on Linzess at the outset of their motility symptoms. As the disorder progresses, the body's response to and the efficacy of Linzess change over time. Also, the patient can cause the drug to fail. Lastly, the drug is regularly improperly stored.

HOW TO MAKE LINZESS WORK TO ITS MAXIMUM POTENTIAL

1. Motility disorders, and digestive disorders in general, usually change over time. Sometimes they disappear for no reason, and sometimes they worsen without any obvious catalyst. Sometimes Linzess will stop working on you simply because your condition is worsening or changing. If this is the case for you, there isn't much you can do. But try the other ideas anyway.

2. There is a pet theory circulating the internet, unconfirmed by pharmacists and doctors, that Linzess is deactivated when exposed to even modest heat for long periods of time. I personally refrigerate my Linzess bottles in a tupperware container, and they appear to retain potency much longer than when I leave the bottles on the counter or in the cupboard. As soon as you pick up your prescription, get it in the refrigerator. Measure the effectiveness of this month's course against the previous one to see if this works for you.

3. Linzess is not really an osmotic laxative (it's a guanylate cyclase 2C agonist) but it behaves exactly like one. This means Linzess doesn't do anything if you aren't properly hydrated. When you take it, pound a huge glass of water. I drink 2, and I'm talking BIG ASS glasses. You want to create a waterfall in your intestines to move everything along, not just a little stream.

4. Nobody ever talks about this, but Linzess works a thousand times better on an empty stomach. I take it right when I wake up in the morning with a ton of water, and I do not eat any food until the drug has started working. For me, on an empty stomach, Linzess takes effect in 2 hours (results will vary depending on your weight and metabolism), and it will continue working for about an hour or two after that. During this "active" period, I continuously hydrate with lots of water. I'm talking LOTS.

If I ever take Linzess with a meal, it does absolutely nothing. It's a wasted pill. So I've kissed breakfast goodbye and I just keep nuts and fruit at my desk at work so that around 10AM, when the drug is starting to wear off, I can eat.

5. When you take Linzess, ideally your guts are full of water. Shaking that water around helps it wash through the digestion. Each time I take it, I drink water as mentioned above, and then I go on a morning walk or run (depending on my energy level). I run for 30 minutes, and by the time I get back to my house, I can already feel it working. On days when I do not exercise, the Linzess doesn't work as well, and sometimes it doesn't work at all. Some of you are debilitated physically so this might not be a good idea for you. But if you can, get out and move. Walking and running stimulates the vagus nerve, which is something you want to do for motility problems.

6. Some foods are extremely difficult to digest when you have a motility disorder. For me, it's bread. Bread turns into cement in my guts, and even Linzess can't do much about it. Once I switched my diet over to tons of watery fruits, nuts, and bread substitutes, the drug started working much much better. I still enjoy pizza but with cauliflower crust, and I still enjoy burgers with lettuce wraps or sometimes a gluten-free bun. Gluten, by the way, is Latin for GLUE.

ON DEHYDRATION AND OSMOTICS

Linzess can easily cause dehydration. I personally get a lot of light-headedness, headaches, and sometimes even dizziness if it works too well. I combat this by chugging water mixed with mineral supplements, and I always make sure to take vitamin and mineral supplements. I'm not sure which mineral deficiency causes my specific reaction to Linzess, so I try to ensure I get replacement sodium and potassium since those are the likely culprits. If I'm feeling particularly bad from Linzess whooping my ass, I'll grab some PediaLyte from a drug store and chug that. It's salty and gross though.

If Linzess makes you empty out so much you're pooping yellow water, congratulations, you're cleared out. This isn't really optimal, so you can control it by eating a little bit earlier or by reducing your dosage.

OTHER USEFUL INFO

1. Doctors will typically prescribe Linzess once per day, but for me personally, it works much more effectively if I take it every other day. I think the extra day between doses allows my small intestine to recover some degree of sensitivity to the drug.

2. Linzess is safe to combine with some other drugs, but not all. I combine it with Motegrity (prucalopride), AKA Resolor / Resotran. I take both pills at the same time on my "Linzess days." On my "no Linzess days", I take just the Motegrity. They are quite effective for my STC when combined. I also take 400mg magnesium citrate the night before my "Linzess day", but since both magnesium citrate and Linzess act through osmosis, it's probably not the safest thing to do. Talk to your doctor.

3. Linzess has a mild prokinetic action on the lower GI tract, in addition to its osmotic effect. This is why it is stronger than Amitiza (lubiprostone). It also has a different mechanism of action than Amitiza that results in a lower incidence of nausea / intestinal pain. Overall, I strongly prefer it to Amitiza.

Let me know if you've got any questions, I'd be glad to try to help.