Epilepsy Talk

Epilepsy Medication Conflicts… | May 1, 2018

But for many of us, monotherapy just doesn’t work.

However adjunct therapy has its dangers.

And both treatments carry their own interactive risks – even with things as innocent as aspirin.

For example, some seizure medicines can lower or raise the levels of other types of medicines in your blood.

Some combinations cause the levels of both medications to fall.

Some cause one level to fall and one level to rise.

And some cause unpredictable side-effects.

So I hunkered down to discover the unhappy marriages between anti-seizure meds.

I’m sure there are many more, but it’s a start.

And more than I knew before embarking on this research.

Here’s what I discovered…

Depakote (valproic acid) can cause serum Phenobarbital to increase by as much as 40%. A reduction of Phenobarbital by up to 80% may be necessary to avoid side-effects.

Aspirin, Persantine, or Warfarin taken together with Depakote can be lessened in efficacy.

The serum concentration of Lamictal is increased by 211%, causing possible toxicity.

Dilantin (phenytoin) efficacy will decrease with alcohol intake, increases metabolism of corticosteroids and oral contraceptives, lessening oral contraceptives effectiveness and other anticonvulsants.

In addition, Cordarone, Prilosec and Chloromycetin increase Dilantin levels.

Klonopin (clonazepam) increases Dilantin levels.

But it’s useful in treating myoclonic seizures in children and absence seizures.

It may also be used (sometimes in combination with other drugs) to treat: akinetic seizures, Lennox-Gastaut syndrome, absence seizures, infantile spasms and restless legs.

May cause drowsiness.

Phenobarbital increases metabolism of oral anticoagulants, steroid hormones, oral contraceptives, anti-epilepticus (other anti-epilepsy drugs), and heart medications, which means they are LESS effective.

It is also an immuno-suppressant. Serum Phenobarbital concentrations may increase considerably after adding Depakote.

Tegretol (carbamazepine) increases estrogen metabolism, thus decreasing effectiveness of oral contraception.

Serum levels of other anticonvulsants may decrease due to increased metabolic activity.

It may also decrease effectiveness of anti-depressant and anti-psychotics, plus it decreases Dilantin, Zarontin, Depakote, Lamictal and Gabitril levels.

Valium (diazepam) by injection can cause shock, coma and acute alcohol intoxication in infants less than 30 days old.

By tablet, it can cause glaucoma in children less than 6 months. Safe use in pregnancy is not established.

Zarontin (ethosuximide) levels of Zarontin in the blood is reduced if it is taken along with Tegretol, Dilantin, Mysoline or Phenobarbital.

Why are there so few drugs listed?

Because most of the negative interactions come from the earliest anti-convulsives.

Modern AEDs have measurably fewer negative interactions.

Which is a GOOD thing!

Now, if they could just get rid of those nasty side-effects!


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  1. Thank you for that hard work Phylis – it is a big help to all of us. Can I just ask about the comment on the serum concentration in Lamictal – I’m sorry but I wasn’t sure what that particular aspect of the information was referring to. Sorry to be a pest!

    Liked by 1 person

    Comment by Margaret Hay — May 1, 2018 @ 10:43 AM

    • Serum blood level describes the amount of a given medication present in your blood at the time of testing.

      Many medications have what is known as a small “therapeutic window” meaning the difference between a therapeutic level and toxic level can be small in some individuals.


      Comment by Phylis Feiner Johnson — May 1, 2018 @ 12:24 PM

  2. Onfi is so expensive. Side effects are not like the keppra rage! That was awful. Now my friends and other relationships are different. Can’t drive, can’t deal with the stress of difficult conversations, start having breakthrough issues and need a prn. 3 meds. But I am a Christian and trust in the Lord.
    Can you get onfi from Canada for less money?
    Thanks for your help.

    Liked by 1 person

    Comment by Nancy — May 1, 2018 @ 10:48 AM

    • Many drugs are less expensive in Canada.

      Prescription drug prices are lower in Canada (and elsewhere) because the government limits the amount pharmaceutical manufacturers can charge for brand name drugs.

      Drug companies selling into Canada are not allowed to advertise their products.

      In Canada, generics become available 5 years earlier than in the United States and must be at least 25% less than name brands.



      Comment by Phylis Feiner Johnson — May 1, 2018 @ 12:30 PM

    • Nancy,
      Thank you for your precise & candid information about the side effects of Keppra.
      When I was reading your comments, I felt as if you were writing my own experience with Epilepsy & the side effects of Keppra, after years of wondering where the stress, anger & rage over simple conversations with good old friends & family members are coming from, to the point of avoiding socializing with family members & good old friends.
      Mixing Dilantin with Keppra is most likely making the side effects more complicated than I’ve been able to figure it out, even though the combination seem to have better control of my seizures.
      But as if the embarrassment & humiliation of having seizures in the middle of social events with friends & family members is not disturbing enough, the side-effects of the medications makes it more harder to confidently attend & enjoy the social events once I use to be part of.
      As you pointed out, driving has been lost privilege for the inconvenience of public transportation, arranging & rearranging to attend or not attend, the very social events that use to be available for grant.
      Thank you for sharing your experience, I feel a whole lot better knowing that some people understand what I’ve been going through all these time.
      Prayers & best wishes,

      Liked by 1 person

      Comment by BahreNegash Eritrea — May 2, 2018 @ 6:31 AM

    • Nancy I know what you mean about the Onfi being expensive cause I myself have to take it and I think the price is too high for being a seizure medicine, At least I have insurances that do help me out with it.

      Liked by 1 person

      Comment by Corina — May 2, 2018 @ 10:45 AM

  3. I would like to know the real list of the true AED’s / ASD’s as people / doctors call them as to WHAT is the actuall AED / ASD for controlling seizures. A few weeks ago I learned that LAMICTAL is not really any ASD / AED, but it’s an AAD & ADD for Anxiety & Depression, and they use it for Epilepsy ? Is there any wonder as to WHY the drugs have a BIG FAILURE list for stopping seizures, when they really are not made to stop seizures. LYRICA is suppose to be for FIBROMYAGIA PAIN, and it is used for people with seizures. I know there are many newer drugs that don’t have the side affects like DILANTIN, PHENOBARBITAL & others that are barbituates, so what are the really true epilepsy drugs that were made for epilepsy only ? When Dilantin or any other of these drugs gets combined with a drug like Dilantin, or other AED’s/ASD’s and those drugs were not made for Epilepsy, then you have to wonder WHY the game of RU$$IAN ROULETTE is played on our brains and it’s okay to have side affects daily because drugs never work together to stop seizures.

    Liked by 1 person

    Comment by C D — May 1, 2018 @ 1:15 PM

  4. C D, I can’t you exactly which drugs are primarily epilepsy drugs, because as you know, many of the drugs used for epilepsy have that effectiveness as an ancillary “benefit”.

    As you say, at its lowest dose, Lamictal is an antidepressant, next dose up is for seizures and finally the largest dose is used for bipolar disorders.


    Comment by Phylis Feiner Johnson — May 1, 2018 @ 1:57 PM

  5. Thanks so lot for the information you give much appreciate. I need to now I’m on epitec, teratol,urbanol for 4 yrs know and it did decrease my seizures but know the neurologist at keppra but I’m so scared to use the keppra I’m still working and its hard for me to stay awake the whole day cause all this meds make me drowsy. Do you have advice for it .I do have complex partial epilypsy I be so thankfull for your support

    Liked by 1 person

    Comment by leone — May 1, 2018 @ 3:38 PM

    • People report that supplementing Keppra with a Vitamin B Complex helps abate the side-effects of Keppra.

      Does that help any?


      Comment by Phylis Feiner Johnson — May 1, 2018 @ 4:05 PM

  6. I take a lot of vitamins because I believe anti-seizure meds take vitamins out of system. Do you know if they interact with toperimate. Right now my doctor has me on 400 mg. a day and since I still have seizures 2 a month) he wants to add on another drug and I want to stay on monotherapy at all costs. He does want me to take a lot of vitamins but I don’t think he knows a lot about them. If anyone knows, e-mail me mjlevell@yahoo.com

    Liked by 1 person

    Comment by Mary Jane Levell — May 1, 2018 @ 4:10 PM

  7. I noticed it doesn’t say anything about the newer meds that are out there now these days for seizures cause none of the ones I take where listed.

    Liked by 1 person

    Comment by Corina — May 1, 2018 @ 10:28 PM

    • Hi Corina,

      That’s because most of the negative interactions come from the earliest anti-convulsives.

      Modern AEDs have measurably fewer negative interactions.


      Comment by Phylis Feiner Johnson — May 2, 2018 @ 7:34 AM

      • Okay and thanks for telling me.

        Liked by 1 person

        Comment by Corina — May 2, 2018 @ 10:40 AM

  8. Serum concentration of lamictal is increased by 211% by what????

    Liked by 1 person

    Comment by Kathy — May 3, 2018 @ 12:55 PM

    • Other drugs contribute to the serum level of your blood. A conflict between these can cause the amount of a given medication to amplify the drug and turn toxic for some individuals.

      That’s why blood work is so important to have regularly. To make sure the meds are at their therapeutic level — doing their job — and not causing toxicity.

      Example: I took Dilantin in the 60s and didn’t have blood work. The dose was not properly measured for my age, height and weight. So, it turned toxic and I went into a brief coma.


      Comment by Phylis Feiner Johnson — May 3, 2018 @ 3:26 PM

  9. Thanks for the the information, Phylis. With my case, it’s seemed as though every anticonvulsant clashes with the others that I’m taking. Or have overwhelming side effects. Right now, I’m on Felbamate and Phenobarbital, the two that I can’t be taken off of, along with Klonopin and Onfi. They work and control my seizures about 50%, but make me constantly tired during the day, and wide awake at night, messing up my sleep hours. My Epilepsy Specialist is slowly working with Johns Hopkins, on the issue of tests for a second operation.

    Liked by 1 person

    Comment by David Jensen — December 8, 2018 @ 2:56 PM

    • One quick fix, David.

      I find that 10 MG of Melatonin helps me when I can’t sleep at night.

      And it’s an herb, so it shouldn’t interfere with your meds.

      Ask your doc.


      Comment by Phylis Feiner Johnson — December 8, 2018 @ 3:48 PM

  10. Thanks for all of your research. I know that in the new med age range
    Onfi and Epidiolex have a strong reaction when used together. Sometimes you need to be taken off Onfi altogether if using Epidiolex and others may just need to use them together. if you do that you need to find the exact perfect balance so they help each other not mix things up.

    Liked by 1 person

    Comment by Cindy Fiser — August 11, 2020 @ 10:41 AM

  11. Cindy, thanks for the heads-up. Much appreciated.


    Comment by Phylis Feiner Johnson — August 11, 2020 @ 11:00 AM

  12. When 5 years old I was on Zarontin 250 mg 3 x a day, Dilantin 100 mg 4 x a day and Mysoline 250 mg 3 x a day. Age 19 neurologist took me off of the Zarontin, then at around 2006 another neurologist took me off of my Dilantin and put me on the “Generic” of Keppra. My husband has told me he notices how alert I am and I remember things a lot better. I am 61 and I currently take Keppra 500 mg 2 x a day and my Mysoline 250 mg 3 x a day. No seizures no mood swings of any kind.

    Liked by 1 person

    Comment by Janet M Harris — November 5, 2020 @ 9:15 PM

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    About the author

    Phylis Feiner Johnson

    Phylis Feiner Johnson

    I've been a professional copywriter for over 35 years. I also had epilepsy for decades. My mission is advocacy; to increase education, awareness and funding for epilepsy research. Together, we can make a huge difference. If not changing the world, at least helping each other, with wisdom, compassion and sharing.

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