According to our number one neuro-Lyme doc, Flagyl for sure and possibly other standard Lyme meds can change how our bodies process Provigil.
What happens is that the uptake of provigil is slowed down- temporarily--then released with a larger than typical smack into the brain.
That smack can cause acute, severe MANIA.
This bad med interaction can occur for each day you are taking the meds concurrently(and until the non-provigil med has cleared your body).
From personal experience I can tell you it is a singularly hellish and scary ride.
Since little is known about how provigil works, I'm guessing llmds probably are unfamiliar with this possible med interaction.
All of us who are on provigil- time to educate our docs..
Posted by Erica741 (Member # 15186) on :
Sometimesdilly: What you wrote about the interaction of Provigil with lyme meds makes sense based on my experiences.
Since starting Lyme treatment in May, I've noticed that Provigil does not work as well for me. I thought I had either built up a tolerance after having previously taken it daily for 2 months, or that my herxing was making me so exhausted that the Provigil couldn't make a dent in my fatigue.
But if our lyme meds slow down the aborption and effect of Provigil, that explains a lot.
From your knowledge, would the Provigil work better if we were to take it when we wake up and then wait an hour or 2 to take our first round of abx? I've been taking my Provigil with the abx (omnicef and zithromax) and olive leaf extract I take as soon as I wake.
Thanks for sharing that info with us! Is there a website where we can read that LLMD's explanation of Provigil's interaction with Lyme meds? I'd like to share with my LLMD.
Thanks, Erica
Posted by lymednva (Member # 9098) on :
Dilly, I'm glad you found a reason for the ups and downs you have been going through. Hope it has leveled off for you by now. Posted by cactus (Member # 7347) on :
Thanks for posting this very important info!
Another one that's an important caution regarding provigil, and often forgotten: it shouldn't be taken if one has Mitral Valve Prolapse Syndrome.
I think it's okay if one has Mitral Valve Prolapse, but not if one is symptomatic. I'm not sure exactly where the line is drawn between MVP and MVPS.
Posted by lymeHerx001 (Member # 6215) on :
SAME gave me severe dysphoric mania that I think poisoned my brain.
Posted by lymednva (Member # 9098) on :
MVPS is another name for orthostatic intolerance. When you stand your BP drops and you can begin to feel faint and even nauseous.
I hadn't heard that before. Thanks for mentioning it.
Posted by Lymetoo (Member # 743) on :
quote:Originally posted by lymeHerx001: SAME gave me severe dysphoric mania that I think poisoned my brain.
Are you referring to SAM-e??
Posted by sometimesdilly (Member # 9982) on :
Erica- I'm not aware of any articles to read about this, sorry.
I think the Lyme neuro doc I saw based his information on his specialized knowledge of the chemistry of various meds and on patterns he has seen in his patients over many years.
Also, i couldn't begin to advise you about how to time taking provigil with other meds.
I can only tell you from my own experience - and have no idea how applicable this is to anyone else--that flagyl has been the only med i've taken while on provigil that caused this transparently bad interaction.
Before flagyl i would have said that provigil has been a 100% positive for me, the difference between being able to function at all or sleeping literally all day.
(((Diva))) thank you. yes, all is explained and my relief knows no bounds. Posted by sometimesdilly (Member # 9982) on :
toots- i think she meant same here, not sam-E.. Posted by scared08 (Member # 14695) on :
Thank you for posting this!!!!! I've been on Provigil off and on for a few years. I also noticed that when I started tx, the Provigil just didn't work. Or even on really bad days on no tx, the Provigil doesn't work.
But lately if I don't take it for a month or two, then start back; it does okay for about a week. Then I REALLY get moody and even more spacey!!!! It's such a double-edge sword! We want so desparatly to have some energy, and then that causes problems or backfires!!! Frustrating!
Posted by Tracy9 (Member # 7521) on :
Dilly said:
"thank you. yes, all is explained and my relief knows no bounds."
Oh, I am SO happy for you! Woo hoo!!!
I take Adderall and have no problems with it, for anyone who might be looking for an alternative.
Posted by AliG (Member # 9734) on :
Dilly-
Thanks for sharing your findings. I'm so sorry that you had to find this out the hard way.
I'm really glad that you finally got a helpful answer!
Ali
Posted by sometimesdilly (Member # 9982) on :
(((tx, Tracy and Ali!))
Adding one more thing I'm remembering the doc said.
Sounds like the DOSE of provigil is another variable here too.
I'm taking 400mg a day, at one time(that's a high dose), which he seemed to think accounted in part for what kind of whammy was delayed then delivered.
From what you'all are posting, the other possibility seems to be (possibly because of lower doses??) a delayed provigil may simply get absorbed or diluted or some such, so it never gets delivered at all, as opposed to packing a delayed whallop.
Hmm.
Posted by AmyInMI (Member # 9506) on :
Dilly, thanks for posting this info!! I also have been taking Provigil for quite some time now. I first started taking it daily about a year ago but was not taking any abx with it. After about 2 or so months, I noticed it was not working as well for me, which I contribute to my body building up a tolerance to it because I was not on any abx.
Once I started to notice the decrease in effectiveness for me, my doc prescribed Vyvanse, which is in the same class as Adderal. The Vyvanse has been GREAT for me but has one side effect that is beginning to really take a toll on me, it decreases your appetite tremendously. Since starting it in December/January, I have dropped from 143lbs to 119.5lbs, which is technically "under-weight" for a 5'9" tall smaller built woman.
I now have been taking the Provigil on most days and the Vyvanse only when I know I am going to have a really busy day. I am taking 300mg of Provigil and am also taking Bicillin injections, as well as other supplements. If you find out any more info on this, please post it!! I am very curious to find out more info!! I will try to find more info myself and will post if I find anything!!
Thanks again! Amy
Posted by MariaA (Member # 9128) on :
By the way, it is normal for provigil to stop working as well. I used to cut my pills into quarters and halves to get the smallest effective dose, though I don't know for sure that this would slow down the resistance effect.
Maria "I am not a doctor" A.
Posted by sometimesdilly (Member # 9982) on :
hi Amy and Maria-
Building tolerance to Provigil over time is a real issue-- maybe... I think.
The info provided by P's manufacturer says not- that no study has demonstrated greater efficacy with increased doses.
Looking back to when I first began taking it, 2 1/2 years or so ago, I remember feeling downright exhilarated for the first several weeks.
I had energy for the first time in years, and i definitely felt an enormous improvement in my ability to concentrate/focus.
That first phase passed pretty quickly, and within several months I thought the dose of 100mg must be too low.
Perhaps the provigil was losing efficacy because of the other meds i was on then- i think mino and malarone.
It is also possible, though (or in addition to?) that the initial huge improvement simply wasn't followed by any other improvement?
So that it was a false impression that the provigil wasn't working as well as it had been?
So, perhaps not a problem of building tolerance?
Posted by AmyInMI (Member # 9506) on :
Dilly,
I think it is a matter of building up tolerance to the med, it happens a lot with various medications. My GP stated that she has seen patients on 400+ mg/day because of sleep disturbances associate with shift work.
I know for me, I noticed a great decrease in the effectiveness after 2-3 months of frequent use. I then switched to the Vyvanse and just recently started the Provigil back up. It seemed to work well for a few weeks but now I am not seeing much effect and I do not want to have my docs up the dose... who knows!
Posted by sometimesdilly (Member # 9982) on :
hi Amy-
Who knows indeed?
I'm hoping to drop Provigil altogether, actually. The specialist I saw prescribed 2 meds towards that end-
Lunesta, to achieve deep, replenishing sleep every night so that i am less tired and less in need of Provigilled energy (that's working),
and Namenda, to help with the brain fog/concentration Provigil works on too.
the jury is still out on Namenda, but i can how this game plan might work.
course, whether Namenda is any safer or more desirable than Provigil is a while 'nuther question.
take care- dilly
Posted by Mo (Member # 2863) on :
hey dill,
we're still in crisis in my home.
you know the deal, no brain injury programming forthcoming, accepted clinically but not funded by insurance or school as of yet.
in the meantime, top ll psych specialist has presribed both provigil and namenda for my ds - i found this post informative and am looking for more feedback, updates from anyone.
he has a history of extreme reactions to many meds, that we will watch. just looking for feedback on how to best avoid this kick-back situation. sounds like a concern to me.
his med list as of now is as follows:
mino rifampin ammox
lexapro lithium ambien CR
had highly significant neuropsych testing results, and severe auditory processing disorder (diagnosed via eval at nyu) so, now to try provigil and namenda.
was described by doc that each of these meds can help with different aspects of the processing disorder.
provigil - focus, concentration, initiative namenda - information processing, ability to streamline focus.
i am struggling with the idea of this many meds, and so is he. but, we have to do something to attempt to get relief from these god-awful symptoms so he can function at a basic level.
i'm also concerned that the provigil may worsen his already horrible insomnia.
m
Posted by Curiouser (Member # 14128) on :
Interesting.
My neuro rx'd Provigil and I took it for a couple of weeks and then stopped.
Low dose, 100mg. Didn't do diddly. It also seemed to trigger microtremors in my jaw and right arm - the same places that tremor when I get simple partial seizures.
Wasn't on any other meds during that 2 week test run of Provigil either.
Posted by minoucat (Member # 5175) on :
very interesting. I've been taking a loading dose of Provigil in the morning (200 mg for me; haven't tried more than that), then a half pill (100mg) that afternoon, then half pill morning and night for the 2 following days; then a 2-3 day break.
This keeps me from getting nuts but helps me be alert.
I've noticed since I switched to cephtil and zith the provigil seems to have less effect.
I've just added 2.5 cortef am and afternoon into this to see if I can be more lively.
Something better than basically comatose would be delightful. That's my main problem now -- I'm so incredibly tired and slow-thinking all the time. Otherwise, not much body pain or problems.
Mo, good to hear from you; sorry the news isn't better. You've been in my thoughts.
Dilly, thanks for the thread and let us know how you do on Nemanda.
Posted by jam338 (Member # 14002) on :
Thanks for this thread! I was trying to get an RX authorization for Provigil, but didn't realize there is a MVP contraindication. I have MVP. My doctor is aware of it, but apparently didn't know or think of it.
Posted by Erica741 (Member # 15186) on :
quote:Originally posted by minoucat: Something better than basically comatose would be delightful. That's my main problem now -- I'm so incredibly tired and slow-thinking all the time.
Ditto Minoucat! Feeling half-dead is not fun.
Provigil and other stimulants seem to only work if you have at least a base-line of energy. During herxes and stages of severe exhaustion, taking Provigil is like taking a placebo.
Vyvanse helped me for a few months, but I've either built up a tolerance or am so exhausted from herxing that it doesn't help anymore either.
Does anyone know what a typical dose of Vyvanse or Adderall is? Are these meds less likely to result in tolerance than Provigil?
What is Namenda? Does it help with energy?
Posted by Tracy9 (Member # 7521) on :
Agree with everything in the post above. I've taken Adderall for years, and don't even bother with it if I'm herxing or really bad off.
However it can turn a so so day into a functional day. I think everyone has to play with their own dose. I am prescribed 30 mg of short acting twice a day.
I take a half a pill. Sometimes in an hour, I take the other half. Sometimes one half is enough. Sometimes a couple hours later I take the other half. I go based on how I am feeling and how my energy level is, and it does change day to day.
I will say Adderall has given me a much improved quality of life on days when I can get up and move.
Posted by charlie (Member # 25) on :
bump^
Posted by Kreynolds (Member # 15117) on :
Hey does anyone know if taking Tindamax will cause same reactions???
I know that Tindamax is only one molecule off from Flagyl.....
Just Curious...
Posted by eagle (Member # 19278) on :
quote:Originally posted by Kreynolds: Hey does anyone know if taking Tindamax will cause same reactions???
I know that Tindamax is only one molecule off from Flagyl.....
Just Curious...
Anyone know????
Posted by Kreynolds (Member # 15117) on :
eagle,
I had taken the Provigil and I had a bad reaction to it.
Could it have been the Tindamax being somewhat related to the Flagyl, I don't know......
Could it have been just the way my brain is with these meds, again I don't know.
I don't think the Tindamax helped, I can tell you that!
Posted by AliG (Member # 9734) on :
I believe that it is very likely that it interacts with Tinidazole, as well.
Simultaneous administration of tinidazole with drugs that induce liver microsomal enzymes, i.e., CYP3A4 inducers such as phenobarbital, rifampin, phenytoin, and fosphenytoin (a pro-drug of phenytoin), may accelerate the elimination of tinidazole, decreasing the plasma level of tinidazole.
Simultaneous administration of drugs that inhibit the activity of liver microsomal enzymes, i.e., CYP3A4 inhibitors such as cimetidine and ketoconazole, may prolong the half-life and decrease the plasma clearance of tinidazole, increasing the plasma concentrations of tinidazole.
The major route of elimination is metabolism (~90%), primarily by the liver, with subsequent renal elimination of the metabolites. Urine alkalinization has no effect on the elimination of modafinil.
Metabolism occurs through hydrolytic deamidation, S-oxidation, aromatic ring hydroxylation, and glucuronide conjugation. Less than 10% of an administered dose is excreted as the parent compound.
In a clinical study using radiolabeled modafinil, a total of 81% of the administered radioactivity was recovered in 11 days post-dose, predominantly in the urine (80% vs. 1.0% in the feces).
The largest fraction of the drug in urine was modafinil acid, but at least six other metabolites were present in lower concentrations.
Only two metabolites reach appreciable concentrations in plasma, i.e., modafinil acid and modafinil sulfone. In preclinical models, modafinil acid, modafinil sulfone, 2-[(diphenylmethyl)sulfonyl]acetic acid and 4-hydroxy modafinil, were inactive or did not appear to mediate the arousal effects of modafinil.
In adults, decreases in trough levels of modafinil have sometimes been observed after multiple weeks of dosing, suggesting auto-induction, but the magnitude of the decreases and the inconsistency of their occurrence suggest that their clinical significance is minimal.
Significant accumulation of modafinil sulfone has been observed after multiple doses due to its long elimination half-life of 40 hours.
Induction of metabolizing enzymes, most importantly cytochrome P-450 (CYP) 3A4, has also been observed in vitro after incubation of primary cultures of human hepatocytes with modafinil and in vivo after extended administration of modafinil at 400 mg/day. (For further discussion of the effects of modafinil on CYP enzyme activities, see PRECAUTIONS, Drug Interactions.)
Drug-Drug Interactions: Based on in vitro data, modafinil is metabolized partially by the 3A isoform subfamily of hepatic cytochrome P450 (CYP3A4).
In addition, modafinil has the potential to inhibit CYP2C19, suppress CYP2C9, and induce CYP3A4, CYP2B6, and CYP1A2.
Because modafinil and modafinil sulfone are reversible inhibitors of the drug-metabolizing enzyme CYP2C19, co-administration of modafinil with drugs such as diazepam, phenytoin and propranolol, which are largely eliminated via that pathway, may increase the circulating levels of those compounds.
In addition, in individuals deficient in the enzyme CYP2D6 (i.e., 7-10% of the Caucasian population; similar or lower in other populations), the levels of CYP2D6 substrates such as tricyclic antidepressants and selective serotonin reuptake inhibitors, which have ancillary routes of elimination through CYP2C19, may be increased by co-administration of modafinil.
Dose adjustments may be necessary for patients being treated with these and similar medications (See PRECAUTIONS, Drug Interactions).
An in vitro study demonstrated that armodafinil (one of the enantiomers of modafinil) is a substrate of P-glycoprotein.
Coadministration of modafinil with other CNS active drugs such as methylphenidate and dextroamphetamine did not significantly alter the pharmacokinetics of either drug.
Chronic administration of modafinil 400 mg was found to decrease the systemic exposure to two CYP3A4 substrates, ethinyl estradiol and triazolam, after oral administration suggesting that CYP3A4 had been induced.
Chronic administration of modafinil can increase the elimination of substrates of CYP3A4.
Dose adjustments may be necessary for patients being treated with these and similar medications (See PRECAUTIONS, Drug Interactions).
An apparent concentration-related suppression of CYP2C9 activity was observed in human hepatocytes after exposure to modafinil in vitro suggesting that there is a potential for a metabolic interaction between modafinil and the substrates of this enzyme (e.g., S-warfarin, phenytoin).
However, in an interaction study in healthy volunteers, chronic modafinil treatment did not show a significant effect on the pharmacokinetics of warfarin when compared to placebo. (See PRECAUTIONS, Drug Interactions, Other Drugs, Warfarin).
Posted by Kreynolds (Member # 15117) on :
AliG:
Thanks for the find! I wish I would have seen that 3 days ago! Posted by AliG (Member # 9734) on :
Sorry K,
I've been a little distracted lately. Posted by Kreynolds (Member # 15117) on :
It's ok, sometimes you gotta learn the hard way right?
Thanks for all that info!
Posted by BugBarb (Member # 210) on :
I started namenda about six weeks ago. I noticed an improvement after two doses!
Now, I feel happy! I can think. I can use complex words. I have an interest in sex! I get along with my husband.
I am doing so good, I am freaking out a bit. I'm not feeling high or weird. It's just that I don't ever remember feeling happy and being so functional psychologically. All my psych meds have got me to a point where I'm stable and i thought I was doing great. Man, all of them combined (inc. provigil) don't hold a candle to what namenda is doing for me.
I daresay I think I feel normal? I don't know what normal is, but I think there are people who feel like I do on namenda, but naturally. They are the people who light up the room when they walk in. The people everybody wants to be friends with because they are so positive. You could strap them down and torture them and they would still whistle a happy tune. Ok, so I exaggerate a bit...... You get the idea.
I still get my monthly herx....but it doesn't seem to hit me as bad....but it hasn't been very long I've been on the stuff. Only time will tell how my herx's are going to be on namenda. Even when I was physically down with a herx this week, I was still happy. The misery didn't get me down. I'm too happy?
![[Eek!]](eek.gif)
![[hi]](graemlins/hi.gif)
![[kiss]](graemlins/kissing.gif)
![[Big Grin]](biggrin.gif)
![[woohoo]](graemlins/woohoo.gif)
![[Frown]](frown.gif)
![[group hug]](graemlins/grouphug.gif)
![[Smile]](smile.gif)
![[Roll Eyes]](rolleyes.gif)
![[sleepy]](graemlins/sleepy.gif)
![[bonk]](graemlins/bonk.gif)
![[spinning smile]](graemlins/spinsmile.gif)
![[bow]](graemlins/bow.gif)
namenda about six weeks ago.