Opioids and PPIs, and drug interactions

[Frunobulax]

Hi,

I wrote some time ago that I suspect a connection between my WED and my GERD (reflux) - I do take PPIs to control the GERD. Here are the old threads: http://bb.rls.org/viewtopic.php?f=4&t=8877 and http://bb.rls.org/viewtopic.php?f=5&t=9024.
A short version of my story: My WED started shortly after taking up PPIs. I had severe trouble with impulse control disorders after taking pramipexole for a few years, went through a lot of different drugs until ending up with Oxycodone, which works quite well for me at 30mg a day (10mg in the morning, 20mg in the evening). However, my GERD is not controlled at the moment despite continuing PPIs.

I went to a research center for internal medicine and found a very sympathetic doctor who knew about WED (no surprise since he's married to a neurologist). He put me through a test where stomach acid was measured for 24 hours and said that despite taking PPIs (40mg pantoprazole a day) my ph value is too low (acid levels too high), so my GERD is not effectively treated. He put in some further research, finding that both my opioid medication (I took Tillidin earlier which is a weaker european opioid and switched to Oxycodone some months ago) and the PPIs are metabolized by the same enzyme, CYP3A4 (http://en.wikipedia.org/wiki/CYP3A4). Essentially, it is likely that the effectiveness of one or both of these medications are hampered by this interaction. He suggested switching to Tapentadol, which is an opioid that is metabolized in a different way and shouldn't interact with the PPIs. After conferring with my neurologist, who feels strongly that I shouldn't experiment with my WED medication (and I have to agree, since I went through hell for over a year until the Oxycodone started working about 3 months ago) we decided that I should have a Nissen fundoplication operation in order to treat the GERD and hopefully stop taking PPIs. I will keep you updated how that turns out.

Anyway, there are some interesting details to add.

For a start, I can confirm that my GERD resurfaced when I started taking opioids. When I was still taking dopamine agonists or alpha2delta ligands I didn't have problems with GERD (taking 20mg omeprazole at the time). Also, my WED symptoms seemed to get worse when I increased the PPI dosage, which may be due to an interaction with the opioids.

Possibly related: Oxycodone did not help me right away. I finally started to sleep well about two months after starting Oxycodone when my psychiatrist added Trazodone to the mix, an older antidepressant which is usually considered WED-neutral but metabolized by (you guessed it) CYP3A4.

It is quite interesting to read the list CYP3A4 ligands (http://en.wikipedia.org/wiki/CYP3A4#CYP3A4_ligands), the inducers, inhibitors and substrates of CYP3A4.
The inducers include some anticonvulsants - apparently not Gabapentine and Lyrica, but Carbamazepine (which is well known as a WED medication). Also St. Johns Wort is an inducer, a substance .
The substrates read a bit of who's who of drugs known to affect WED. WED-inducing drugs (tricyclic compounds, SSRIs and other antidepressants) and substances (caffeine) are listed as well as opioids and benzodiazepines.


Basically, here we have a common link between different substances known to affect WED, one that wasn't known to me previously. In fact, it is an intriguing question if the potential to worsen or treat WED is connected to the CYP3A4 metabolism, at least for some patients.

Regards, F.

[pjmccoy1]

This article is well above my pay grade But I am interested. I started my first dose of methadone (very low dose) November 11, 2014. I had a nice long run (9 years) of sinemet and .5mg clonazepam which controlled RLS very nicely until the dreaded augmentation. I had never even heard of this. Anyhow, then added Horizant in addition to the sinemet for 2 years. Then just Horizant alone for about a year until it stopped working. Then upped clonazepam to 1mg at night. That worked ok until depression set in. Major depression, anxiety and insomnia last 1.5 years. Still cannot find an A/D that doesn't exacerbate RLS and I can tolerate. GI physician diagnosed me with GERD and was put on Prilosec (omeprazole) and Pepcid (famotidine) in December (2 weeks after starting low dose of methadone). Started experiencing very dry mouth, dry lips, dry eyes, dry nose and mucus/lump feeling in throat with difficulty swallowing the end of December. Hmmm... After two swallowing tests by GI specialist I was referred to Rheumatologist for possible auto-immune disease. Fortunately all the tests came back negative. Praise God. Rheumatologist thought based on timeline my dryness issues and mucus/lump feeling in my throat might be result of side effects of one of the medications. So now I have stopped methadone to see if it is the culprit. After 2 days still no improvement yet but too soon to have methadone cleared from system. Now I'm wondering if it is the GERD med's.

[Frunobulax]

GI physician diagnosed me with GERD and was put on Prilosec (omeprazole) and Pepcid (famotidine) in December (2 weeks after starting low dose of methadone). Started experiencing very dry mouth, dry lips, dry eyes, dry nose and mucus/lump feeling in throat with difficulty swallowing the end of December. Hmmm... After two swallowing tests by GI specialist I was referred to Rheumatologist for possible auto-immune disease. Fortunately all the tests came back negative. Praise God. Rheumatologist thought based on timeline my dryness issues and mucus/lump feeling in my throat might be result of side effects of one of the medications. So now I have stopped methadone to see if it is the culprit. After 2 days still no improvement yet but too soon to have methadone cleared from system. Now I'm wondering if it is the GERD med's.

Methadone and Omeprazole are both metabolized by CYP 3A4, so it is possible that either of these drugs have reduced efficiency. If your GERD is not too bad so that you can survive a few days without Omeprazole and Famotidine, then you could try to stop the acid blockers for a few days and see if your WED symptoms get better. Alternatively you could up the dosage and see if your WED gets worse (there's a definite yes as far as I am concerned, but every person reacts different to drugs).

Dry mouth and fatigue are possible side effects of famotidine - why do you take two different drugs to control your stomach acid?

The problem with these acid blockers is that low stomach acid is not a good thing as far as food processing and bacteria control in the stomach is concerned - our organisms are designed to work with a pretty high acid level. Lowering stomach acid will reduce GERD, but may cause other problems like helicobacter pylori or bad iron absorption. Also Vitamin B12 deficiency is a known side effect of omeprazole therapy, so is a good idea to take some highly concentrated vitamin B12 (1000mcg per tablet, dissolved under the tongue) every other day or so if you start omeprazole. A vitamin B12 deficiency develops very slowly and it can take years until you see some effect, so this shouldn't be responsible for your new problems though. Unfortunately a lot of doctors don't know either of these facts.

Personally, I think that for all WED patients with reflux/GERD, a fundoplicatio procedure should be considered if opioids are used to control the WED. It is not a good idea to use both opioids and PPIs at the same time.

Regards, F.

[pjmccoy1]

I'm stopping the omeprazole (PPI) to see. Vandy GI had me on aggressive dose. Two pills a day, one before breakfast and one before supper and then add the famotidine at bedtime. I also have osteoporosis and I know these GERD med's are not good for that. I am taking B12 daily but in capsule form so like you have mentioned, probably not being absorbed. I already know my osteoporosis is hereditary and GYN has told my mother and I that we don't absorb calcium well. Interesting. So my WED med's, in combination with PPI's, are working against each other, the PPI's causing absorption issues (especially bad for iron and magnesium absorption - needed for WED) and pain med plus famotidine both cause dry mouth. Anyhow, read shouldn't abruptly stop PPI's due to rebound acid issues. I have the silent GERD with little to no stomach burning mainly throat and mouth issues. The dry mouth is an issue for the burning mouth (tongue) syndrome. I am currently off pain med as recommended by Rheumatologist when they were checking me for Sjögren's Syndrome, auto immune, but don't think I have it based on time table when all the dry issues developed 6 weeks after pain med and 4 weeks after the two GERD med's. Thank you.