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nausea with flagyl/cipro and/or methotrexate

Thank you for this great forum, it has been very helpful so far with lots of information. Here is some background with 16 year kid with Crohn’s disease, any advice or opinions very much appreciated.

- Remicade April 2016 to July 2019. Started with 5mg-8weeks. had to increase 7.5mg then 10mg while duration from 8 weeks to 6 to 4. worked intially but loss of response over time, not fully effective
- Humira - August 2019 to Feb 2020 - Did not work even with increase dosage frequency from 2 weeks to each week. Tried Prednisone three times during this time. First time short course of one week of 40mg/day. No tapering. Second time started with 40 mg and tapered over 3 months. Third time low maintenance dose 15 mg with tapering over a month.
- Tried Methotrexate+Remicade again in March-April 2020. Did not see any improvement and oral Methotrexate may be giving pain in the lower abdomen.
- May 2020- Switched to Methotrexate + Stelara. MTX by injection. Still was having loss of appetite and pain in lower-right abdomen. So far 5 weeks into the treatment plan with weekly MTX and 2 weeks ago today Stelara induction infusion.
- Two dosage of Injectfer for Iron infusion over the period of two weeks, two weeks ago.
- Last week, checked with for severe pain in TI area. Resulted into the hospitalization to do MRE for suspicion of abscess and to determine any nutritional supplement needs for weight loss. MRE came same as what was in the March MRE. No significant abscess or any drainage of fluid needed. inflammation with some narrowing and some small fluid in TI area, No blocking of walls. There was one area with soft tissue in the glute. Hence it was determined to start Antibiotics as there could be possibility of infection.
- Antibiotics - Flagyl (400mg/8hrs) by IV and Cipro (400mg/12 hrs) orally started on Friday(06/18). scheduled Methotrexate was given by injection (taking that every week from the last 5 weeks.
- Saturday afternoon was discharge from the hospital resulting into Flagyl switch to orally. was okay on Saturday
- Sunday morning vomiting 3 times and super nausea resulting into no intake of food and low fever with mild dehydration
- Monday severe nausea continued resulting into Hospitalization again. Since oral antibiotics are not tolerated, IV antibiotics are started

Current problems are extreme nausea with antibiotics and crohns issues are inflammation in the TI area with some fluid build up and soft tissue in the gluteal area.

What can be done to reduce nausea for short term and any other opinions suggestions for short term and long term. Thank you for reading.
 

my little penguin

Moderator
Staff member
When you switched to mtx plus Stelara did they leave him on any oral steroids ???
Stelara requires “bridge” therapy of steroids in most cases For 6-8 months
Stelara takes on average 8 months to start working
Ds required pred for the first six months with sterlara before he started to slowly wean off during the next two months
At 8 months scopes showed mild inflammation in ti
So Stelara was increased to 90 mg every 4 weeks
He had been on Stelara at 90 mg every 8 weeks with mtx

Mtx by shot can cause nausea
For ds this was fixed by switching to pills and adding 2 mg of folic acid a day.


The antibiotics always made him sick though
Zofran can sometimes help ...maybe
But he even hated the taste of water on the abx

Is he on een (formula only ) ?
That can also help calm inflammation while you wait for Stelara to kick in
And it is a very long wait
I was ready to toss it out the window when Ds started
Now almost 3 years later I am glad that we didn’t
 
Sorry that you are all dealing with so much right now. I don't have any great advice, except to say that the current extreme nausea seems like it's due to the antibiotics more than the mtx, since it came on so suddenly after starting those.

My daughter gets mild nausea from her mtx injections; she takes 2mg of folic acid a day and a zofran 2 hours before the injection to help with it.
 
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Thank you for the replies. We are feeling that lot of his issues started after MTX was added and the nausea got severe after adding antibiotics . How do we determine if MTX is helping or adding more issues? Skip couple of doses until abx dose is done and watch if there is any improvement? Or drop MTX and add steroids until he starts improving and then add MTX if needed?

Currently he is not on any steroid, steroid was stopped in March. Possible options are either add solumedrol or entocort. They have reservations on starting prednisone because of covid-19
 
Thank you for the replies. We are feeling that lot of his issues started after MTX was added and the nausea got severe after adding antibiotics . How do we determine if MTX is helping or adding more issues? Skip couple of doses until abx dose is done and watch if there is any improvement? Or drop MTX and add steroids until he starts improving and then add MTX if needed?

Currently he is not on any steroid, steroid was stopped in March. Possible options are either add solumedrol or entocort. They have reservations on starting prednisone because of covid-19
And is it usual practice to have MTX with Stelara? Can it be added later if needed?
 

my little penguin

Moderator
Staff member
Stelara won’t be working until he has been taking it for close to 8 months
During that time inflammation goes up if your not on steriods

As far as mtx they might be using that since it starts to work after 12 weeks to help with the inflammation some but wouldn’t be enough by itself depending mtx dose and form

Some kids just don’t tolerate the mtx injection
Ds is one of those -he gets sicker than sick
No matter what the dose

Pills he only tolerated up to 20 mg
After that he gets sicker than sick

As far as Stelara with or without mtx
Depends on his level of disease

Ds has to have Stelara plus mtx for his arthritis (worse than his crohns )
Just depends on the kid and disease burden

Given Stelara takes so long to work
You probably want to talk to the Gi about what bridge therapy options you have
Solumedrol is only by iv and doesn’t last long (2 -3 days ) -I thought
Entocort only helps in part of the intestine but not the whole intestine
That’s why it really depends on the kid /disease

Talk things over with your child’s Gi on what is the best option
 

crohnsinct

Well-known member
There is a lot to unpack here. Just my thoughts as a parent of two Cronies not an MD.

- seems they gave up on Remicade super fast. Three months? My daughter was not even responding in the least to Remicade until about 6 months but water under the bridge. The point I wanted to make was that she was steroid dependent also but we had to get her off steroids. GI suggested max to boost the Remicade and help slow down the metabolism of it. We opted for an 8 week course of EEN. EEN worked better than the steroids and helped her up nicely. The Remicade couldn't heal the massive inflammation but it was able to take a healed bowel and maintain it for another year. At that point in time inflammation snuck back and we added MTX to help.

- MTX made my daughter super nauseous. Is your child taking folic acid. MTX is a folate antagonist so you have to take folic acid. The folic acid also helps with the nausea. As others have said, Zofran also helps. Taking the max at night before bed helps them sleep through the worst affects. I will also add that at the beginning my daughter had a lot of problems with max but over time they subsided or maybe she just got used to them.

- the nausea could be due to anything you listed really. The max, the antibiotics, Crohn's inflammation in the TI, dehydration from the vomitted or if they have diarrhea that or from lack of eating, malnourishment can make a child even more sick. We went through all of this last summer and it is very hard to tease out what is causing what. Antibiotics made my daughter feel awful.

- the weight loss is going to only contribute to the inflammatory cascade and that cascade will make the disease worse and nausea etc. It is a house of cards. So I would see if he/she could tolerate any formulas. They may have to put in an NG tube and feed that way for awhile. Last resort a PICC line (assuming you are still inpatient.

- I second and third that these drugs take a while to work and it seems the GI is jumping around a bit without the use of bridge therapy. Stelara is notorious for taking forever to work and you need a bridge therapy. Your options would be EEN, steroids, Entocort or Tacrolimus. True they are trying to stay away from steroids as much as possible with Covid but flaring Crohn's leaves you just as susceptible to Covid and complications so the first rule is to get the inflammation under control. After a year or two of prednisone my daughter was put on Tacro because it doesn't cause the issues that prednisone does but I think it is equally as immune suppressing so the Covid concern would be there also. Entocort could help and doesn't have the risk or side effects of prednisone but it isn't as successful as EEN or prednisone in getting the inflammation under control.

- yes I have seen max be used in addition to Stelara but max takes at least 12 weeks to become effective so even with that you would need some sort of bridge therapy.

- at this point I might seek out a second opinion as well because you are burning through these drugs pretty quickly and a second set of eyes might be helpful.

Sorry you are having such a tough go of it. I hope you get a handle on it quickly.
 

Maya142

Moderator
Staff member
We are feeling that lot of his issues started after MTX was added and the nausea got severe after adding antibiotics . How do we determine if MTX is helping or adding more issues? Skip couple of doses until abx dose is done and watch if there is any improvement? Or drop MTX and add steroids until he starts improving and then add MTX if needed?
You could stop MTX - we're actually doing just that, to see if my daughter's nausea was related to MTX. Unlike when she had been on MTX before, this nausea was at any random time during the week, generally after eating. When she had MTX side effects in the past, she'd have nausea the day after the shot and it would last 2-3 days. We used to give her a higher dose of folic acid (2 mg daily vs. 1 mg daily) and Zofran before the injection and the days after, as needed.

We think her current nausea is NOT related to MTX because she has been off it for 4 weeks and it hasn't gotten better. So I suspect we will re-start it.

I would look at your son's symptoms very carefully (maybe keep a symptom log) and see if they tend to worsen after the shot or if they're mostly constant and the shot doesn't seem to worsen nausea. Some kids tolerate the pill form better but generally most GIs and rheumatologists will say that the injection is easier to tolerate and you know what you're getting - when it's given orally, it's harder to know how much is really absorbed. So for that reason, in our experience, most of the rheumatologists/GIs we've seen have preferred the injection.

That said, every kid is different and there are some that truly do a lot better on MTX pills.

The other thing you can try for MTX related nausea is Leucovorin. It's folinic acid and helps with the side effects of MTX. In our experience, rheumatologists seem to prescribe it more than GIs - I have no idea why (perhaps because they have been using MTX for much longer than GIs?). But it's something you can ask about.

I agree that weight loss and being malnourished can cause severe nausea - my daughter has dealt with that more than once. We were told that your stomach is a muscle and then less you use it, the more unused to food it gets, and then all food can cause nausea. If he cannot eat, then drinking shakes or using an NG tube for formula might help. I know it sounds intimidating - my daughter was SO against a tube. But once she got one, she realized how much easier it was to do tube feeds vs. drinking and that she felt a whole lot better when she was getting proper nutrition. It was like night and day - she went from being exhausted all the time to being a pretty normal teenager in a couple months!

She inserted the tube at night every day and pulled it out in the morning. The first few days were rough - her nose and throat were sore - but by day 7 she was inserting it in 10 seconds or less.

Of course, antibiotics are likely what's causing much of the nausea but unfortunately, there's not much you can do except give him anti-nausea meds. If you're still in the hospital, they can give IV Zofran which might help more than oral Zofran.

Hang in there - I know this is a lot and very overwhelming. Take it one day at a time, one step at a time.
 
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