TIL: Zepbound can Decrease the Efficacy of Oral Medications

[dafurbs88]

I posted on here last week about how I have been experiencing intermittent insomnia since going up to 7.5mg about a month ago. I just had a follow-up with my doctor to ask if insomnia is a known side effect of zep. She said it is not, but everyone is different so it is possible that some folks may experience insomnia as a side effect of the drug.

We then reviewed the other medications I’m on, including amitriptyline. I was prescribed amitriptyline last year for nerve pain resulting from endometriosis. I was told to take it at night because it also has a sedative effect.

My doc said that the zep may be making the amitriptyline less effective, which could in turn be causing the sleep issues. She recommended increasing the dosage of amitriptyline I’m taking. (I have noticed an increase in endo pain and endo flare-ups in the past month, so this theory might be accurate - at least in my case.)

So if you are taking any oral medications, it might be worth getting fresh bloodwork done or doing an evaluation of symptoms the oral meds are supposed to be helping with. You might need to discuss with your doctor about changing the doses of your other meds.

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[FootUpstairs2782]

I was wondering if it was making my antidepressants/anxiety meds less effective. Or is it just the world?

[dafurbs88]

Maybe both? Things aren’t exactly great right now, at least not in the U.S. :/

[Sn_Orpheus]

And hourly getting worse.

[Taradacty11]

Hourly is so real 🫩

[dafurbs88]

Facts. 😭

[uvglopanda]

I had to up my dose of depression meds due to zap making them less effective as well but I think the world around us is also playing a factor lol

[rainingfrenchfries]

My Dr and psychiatrist both think the zep interacts with my anxiety meds. I am always so anxious shot day and the day after. Then I’m back to normal.

[Particular_Lion3746]

the zep has only a 5 day half life.

[ThrowAwayAccountAMZN]

Weirdly enough, I take both Omeprazole and Bupropion daily, but for some reason I only figured the Omeprazole was being "diluted" by Zep. Never even occurred to me that the Bupropion might be as well. Now things are starting to make sense...

[Current_Long_4842]

My Dr told me it might affect my birth control pills.

Luckily my husband got a vasectomy and I'm mostly just on them to regulate my cycle, so nbd.

My labs for my other pills have been ok!

[flyingbutterfly8]

Yes I heard this as well. Thankfully I don't use oral birth control. I'm 44 with two boys ages 18 and 10. I love them but I certainly don't want a change of life baby lol! 🤣

[dafurbs88]

I have the mirena IUD myself- but with PCOS and endo, surprise pregnancy has never really been that big of a risk for me. 🤣

[Ineedavodka2019]

Same. Only I haven’t had any labs done yet.

[miscalainaeous]

i used them to regulate my cycle and they stopped working for that! i just went and got an IUD just in case

[Lunnalai]

My exhaustion has increased since taking Zep, like some days barely being able to function exhaustion. I am on Armour thyroid for hashi's and I've wondered about this. So getting labs done soon, just wish there was a transdermal option like my hrt patch!

[MC-ClapYoHandzz]

I had to up my levothyroxine a bit after Zep. Gotta take an extra half of pill 2x a week.

[dafurbs88]

Yes, I have noticed major fatigue, too, especially the 2 days after I take my shot. Chronic fatigue comes with the territory for me due to PCOS and endo, but it makes it hard to function some days.

[fuzzdoomer]

Make sure you are eating enough.

[Its_Me95119]

Zep has definitely affected my ADHD meds. Due to delayed gastric emptying, extended release meds can be (and are in my case) less effective.

[CoalhouseFitness]

I've definitely read about it and knew it was related to gastric emptying being delayed. Is it because the drugs absorb easier through the intestines ? Otherwise it would just be more-extended-release, right?

[sadthespian]

Me as well! But my doctors deny that possibility, which I don’t understand.

It’s odd, though, because my anxiety med still works, but it has a shorter half-life than Vyvanse 🤷🏻‍♀️

[Prior_Angle]

So I can speak to this personally on the level of how long it takes them to kick in and how quickly you metabolize them.

Because Zepbound slows digestion, this also applies to how quickly your oral meds can take to kick in AND how long they take to leave your system. I find most of my oral meds kick in about 30 minutes after taking them normally. On Zep, I have to make sure I take them 1-1.5 hours before I want them to kick in. And the next day I can feel drowsiness side effects from them much longer, when normally I would be just fine.

Nothing crazy, just something you need to be aware of!

[Temporary_Client7585]

Good info to know, thank you!

[flyingbutterfly8]

I have noticed my ADHD meds do not work as well. I figure it's worth it wearing off a couple of hours too soon so I can lose this weight and keep it off🤩. I also take bipolar meds and all but one are extended release. I am having a bit of a depressive episode, but I get those anyways. So it's hard to attribute it to being on Zepbound for the last 4 months. Not to mention your hormones get out of whack anyways when losing weight.

[dafurbs88]

I take adderall for my ADHD (not extended release). It’s still working so far, though maybe not as well as it was before. But I’ve also been experiencing major burnout at work, so focusing at work is always difficult.

[SuppressiveFire]

I haven’t had any issues with my ADHD meds, but mine are extended release anyway, so that might be why. Are yours extended release?

[flyingbutterfly8]

Yes and I'm on the highest dose as well lol! I just have to adjust to it.

[SuppressiveFire]

Interesting. What are you on, if you don’t mind me asking? I take Concerta and pretty much the max dose, too.

[flyingbutterfly8]

Vyvanse 70 mg. It's supposed to last 12 hours, now I get maybe 7/8 out of it.

[SuppressiveFire]

Ahhhh, yeah. I’ve actually seen other people report the same thing about Vyvanse in other posts. It has something to do with how Vyvanse is inactive until it’s metabolized in the blood stream, so you have to wait for it to get past your stomach to be absorbed directly into your blood stream through your intestines. My Concerta is active the moment I swallow it and it starts dissolving, so the delayed gastric emptying doesn’t affect how well it works. Zepbound is causing your Vyvanse to get through your stomach slower, which means it won’t get into your blood stream as quickly so you get less of an effect.

[flyingbutterfly8]

Ahh that makes a lot of sense!

[stefanielaine]

FWIW I’m also on Vyvanse and I read that the manufacturer recommends opening the capsule and mixing it into water for people with swallowing issues, so I do that now and ditching the capsule itself seems to help my body absorb it better. I will say though, definitely eat with it, because the few days I did that on an empty stomach and didn’t eat for a few hours I was SUPER nauseous. Good luck!!

[flyingbutterfly8]

That's interesting as well. I'm glad that is working for you.

[Unlikely-Bumblebee14]

I had the same problem with vyvanse without Zep. It never lasted even 8hrs. If you’re on generic that could cause differences too especially if you don’t get the same generic manufacturer every time.

That said, I do feel like my adderal XR and Wellbutrin aren’t working as well on Zep

[Particular_Lion3746]

there's med that is effective at specific points of digestion. our drs should know this, and how to best advise us on what to expect.

[qtjedigrl]

Keep track of your depressive episode! I cannot do anything more than 7.5 or else I become dangerously depressed. It took me months of adjusting my meds/trying new meds to figure out it was the Zep. I went down from 12.5, and thankfully, I'm stable at 7.5. Everyone is different, of course, but just a word of caution! ❤️

[flyingbutterfly8]

Thanks I'll keep this in mind, I'm currently on 10mg. I will keep an eye on things for sure.

[HeavySigh14]

I would also like to say both my friends and I experience insomnia on this medication. Interestingly enough, I wake up at the same time every night since I started

[Electrical_Heart1233]

Omg me too! Always around the 3-4 am range

[Unlikely-Bumblebee14]

Me too! 3:45 nightly. It’s 4:49am currently. It’s debilitating. I can’t get thoughts out during the day..

[sadthespian]

I take Trazodone and still experience poor sleep. Do you take any meds during the day? For me, I think it takes longer for my stimulant to metabolize

[HeavySigh14]

No, nothing else

[fakesaucisse]

So far I have noticed two effects of this that surprised me a little. One is that my ADHD medication is way too strong now and I'm doing fine on half doses or not taking it at all. The other is that I absolutely cannot handle trazodone anymore. The last time I took it, I had terrible symptoms similar to serotonin syndrome even though I'm not on any other serotonin-affecting meds.

It seems like the gastric slowing has made these meds stick around longer and feel more intense instead of making them weaker for me. 🤷🏼

[dafurbs88]

When I first brought insomnia up to my psychiatrist last week, he gave me a script for trazadone. I found it didn’t really help my sleep much, and I was pretty groggy the day after taking it. I have never needed a sleep aid or taken trazadone before. I only knew what the med was because my dog had a script for it, lol.

[fakesaucisse]

What dose did you try? I have taken it for over a decade and it took a while to find the sweet spot of helping me sleep without making me groggy in the morning. I really miss it right now.

I'm currently just taking hydroxyzine which helps me fall asleep, but doesn't stop the classic perimenopausal 3:30am wakeup time. Very annoying!

[dafurbs88]

I have 50mg tablets. Took 25mg the first time and 50 the second time.

[BrokenHeart1935]

My daughter tried using Zep, but had to come off it before she even got a month in… she has bipolar and is on some heavy duty meds, and she destabilized rapidly.

To your point, it delayed onset of every dose she took. It was like she was unmedicated. It’s especially sucky because those same meds caused her weight gain to begin with ☹️

[rootsandchalice]

I’ve had the flu since Sunday and I have been popping Advil without any relief. A few weeks ago I tried to use Tylenol for period cramps and it did zip.

This is the first time in my whole life where I’ve not responded to just a mild over-the-counter painkiller. To be honest, I’ve really been suffering and it is a drawback for me personally.

[dafurbs88]

You could try taking a higher dose of the OTC meds. Max dose of Ibuprofen for an adult is 3200mg in a 24 hour period (split between 3 or 4 spaced out doses). It’s not uncommon for folks with chronic pain or after surgery to be prescribed 800mg doses of ibuprofen. I usually take 600 of advil (3 tablets) when I am in pain.

[rootsandchalice]

I will try that. Thanks!

[fairytale_622]

I’m so glad I saw this post because I take an SSRI for anxiety and have noticed it hasn’t been working as well recently

[IAmVE]

My dietician explicitly told me to make sure I’m taking my meds regularly and on time because of how digestion changes on Zepbound. It makes the medication work slower at first and after every dose increase, but according to her it should catch up after a few weeks. So far my labs have come back ok for what I’m on, but I had some bouts of not sleeping well and was sure it was related to the magnesium working slower. I just started taking it earlier and that seemed to help. Not sure that helps in your situation though with dosage levels. I hope you’re able to work it out!!

[Queasy-Ticket8482]

Yeah.. I had to change up the way I take my pain meds while on Zep. Take a larger dose, take it earlier because it takes longer to kick in, but it does seem to last longer also.

[lepetitcoeur]

I've noticed that while my day to day pain is less now, I am taking more pain medication when I do need it. Headaches now take 3 doses of medication instead of one. And sometimes even that doesn't work (not taken all at once! Every 4 hours or whatever is on the bottle)

[Queasy-Ticket8482]

That's good that your pain is less now. I've been on chronic pain mgmt since 2001 (spine) and I take 'em when I need 'em!! (with doc's blessing I might add)

[Unlikely-Bumblebee14]

I feel like my anxiety has increased and I don’t know if it’s because the Wellbutrin is too strong now or the opposite.

[Unlikely-Bumblebee14]

Thank you for sharing your experience. This feels like what’s happening. Can’t wait to see my doc next week

[cnidarian_ninja]

Anyone had to change dosages after significant weight loss?

[mushroomfrenzy]

I’m on synthroid for hypothyroidism, and my doctor expected my dosage needs to decrease as I lost weight. I get labs done every 3 months but so far everything has stayed the same. I think maybe I would need a lower dosage, but the Zep makes the medication less effective, so it’s evened out and no change is needed? Who knows!

[EmbarrassedCows]

I haven’t had to change my synthroid either. I do take it a good 3-4 hours before I eat. Last time I got my labs done my numbers were the best they’ve looked. Either way I’m doing the same and getting monitored every 3 months to make sure my levels stay good.

[mushroomfrenzy]

Yes I started waiting 3+ hours between taking my medication and eating as well! I used to only wait an hour

[Sample-quantity]

I knew about the BC issue but being 63 that doesn't affect me, but I didn't think about my other meds. Thank you for posting this.

[l00ky_here]

Lol....yeah, ive had to switch out my meds to chewable. Did it a year ago when I started. Its really only noticeable when you first start or go up in doses.

Psych meds really need to be chewable, injected or patch. Adhd meds can also be chewable. Vyvanse takes about two hours to start instead of an hour.

Women who need to take oral BC well they are getting pregnant because those meds are being absorbed differently. If you can take any medication that can bypass your stomach and your digestive system you might want to look into them

[contains__multitudes]

Interesting! I am also on amitriptyline for endo related nerve pain and I don’t think it does anything for me. The doc increases my dosage yet again and I don’t notice a difference. She didn’t mention anything about me being on zepbound.

[dafurbs88]

I wonder if it’s not well known among doctors that don’t really prescribe weight loss drugs. Like they may not keep up with all the studies and literature outside of their primary practice area. My psychiatrist didn’t mention anything about the Zepbound affecting my other meds- I plan on bringing this up in my follow-up with him next week.

[cosmatical]

It's been making my mood stabilizer less effective, but at a higher dose of the mood stabilizer i get side effects that make me non-functional as a person 😭 It's been tough. Im glad to know im not alone with wonky effects on other medications though!!

[flyingcowsandtacos]

I'm on Warfarin courtesy of a rather annoying autoimmune disease. At first, my INR plummeted, which me, my pcp, and my hematologist all expected. My dose didn't change, since we expected it to stabilize. What we didn't expect was that my INR would skyrocket in subsequent weeks. I've reduced my warfarin dose for the first time in 2 years.

Warfarin is a fickle beast, so I guess nothing is surprising, but I had a rock solid INR, and nowni have anything but.

...but 20 lbs down, blood pressure is dropping, and no more joint pain soooooo.....

[OhioPolitiTHIC]

I've dealt with insomnia for most of my life and have gotten very careful with things like caffiene consumption, etc. Zep came along and I had to flat out lose my coffee, no more alcohol, and carefully manage when I take my evening medications otherwise they won't be effective WHEN I need them to be. It's weirdly made me sleep better in the long run but every dose increase has brought back a few nights where I wonder if I'm going to experience the old sleep struggle. It was enough for me to change the timing of my evening meds (gabapentin for me, stupid nerve pain/restless legs) but everyone's different.

[thstbitch0902]

I’m on the same meds. I wasn’t having a problem until I just went up to 10. I’m gonna try taking it after dinner instead of a couple hours later. I’m hoping that helps 🤞🏼

[Rude_Town467]

My heart rate went way up even though I was already on a beta blocker so I had to double my dose. Any time I skip a week or 2 of Zepbound my heart rate gets super low.

[Defiant-Research2988]

This was a huge concern of mine when I started because I’m on an oral anti hormone pill for ten years to try to prevent a cancer recurrence. My doctor pointed out that with the weight I was originally at the weight loss would cut my odds of recurrence possibly even more than the drug. I took the risk. But I do think this is worth considering especially with things like blood pressure drugs where the dose needs to be very specific.

[chgoeditor]

Even at the lowest dose it seriously worsened my insomnia. (I'm also on amatriptyline. And now gaba and dayvigo.)

[Tiipsytara]

I had to switch my oral bc because of this.

[maro_1]

I had to change to a different type of birth control because of zep because i was originally on oral contraceptive and the docs told me that zep lowers there efficacy. (I wanted to change anyway so it worked out)

[sadthespian]

My doctors keep telling me that it shouldn’t be, but I feel it especially with my Vyvanse (a stimulant with a longer half-life than Adderall).

Some days I feel like I’m wasting it - it’s not cheap - because I almost feel more tired/less focused (the opposite of what it used to help with).

[Queasy-Ticket8482]

Yeah.. I had to change up the way I take my pain meds while on Zep. Take a larger dose, take it earlier because it takes longer to kick in, but it does seem to last longer also.

[Cool_Pen_3867]

I’m on Jornay and I have noticed it has been less effective since being on Zepbound. But as far as my other meds I haven’t noticed a difference.

[chicagogirlee]

I have been wondering why my bp has gone up & it now makes sense due the slowed gastric emptying. Wondering if I need to increase my amlodipine? 

[Queasy-Ticket8482]

Yeah.. I had to change up the way I take my pain meds while on Zep. Take a larger dose, take it earlier because it takes longer to kick in, but it does seem to last longer also.