hi my name is Dr. Joe Sirven editor in chief of epilepsy dot com and I want to
welcome you all to the Epilepsy Foundation video on cannabidiol for
epilepsy I have two guests and I'm gonna let them introduce themselves Barry
hi I'm Dr. Barry Gidal University Wisconsin-Madison and I'm the co-editor
of the medication section of epilepsy dot com hi I'm Anup Patel section chief of
neurology at Nationwide Children's Hospital in Columbus Ohio and I'm also
the medical cannabis editor for epilepsy dot com so Anup what is the indication for cannabidiol
yeah so based on the clinical studies the FDA approved this
for anybody two years and older who have seizures that are secondary to Dravet
syndrome or Lennox-Gastaut syndrome what's important about that label is
that even though many of the studies were done in children there were adults
in that study and therefore it's greater than 2 and greater but there's no age
limit so this is both for children and adults who have seizures because of
Lennox-Gastaut syndrome or Dravet syndrome is there any one we need to
worry about in terms of a contraindication that this is not the
medication for you just off the bat you know Epidiolex is also in sesame oil so
if you've had an allergic reaction or a reaction to sesame oil it's not all
peanuts or nuts allergies it's just sesame oil then that medicine is
contraindicated also for whatever reason if you've had exposures to CBD or
cannabidiol and had an adverse reaction then again this product would not be for you
how effective is this what we saw in the pivotal studies for Dravet Syndrome
and Lennox-Gastaut syndrome that led to the FDA approval was very similar
results you know you saw around 39 to 45 percent what we call median seizure
reduction what that means is that those seizures had reduced by that percentage
compared to when they were started a responder rate refers to how many
patients in the studies had at least a 50% or more reduction of their seizures
and again with through the platform of studies you saw about a 40 to
45% of patients having at least 50% or more reduction of their seizures
interestingly in one of the studies that we ran showed efficacy at a lower dose
range so the other ones that I mentioned are usually at a 20 milligrams of
medicine per kilogram of the individual in one of our Lennox-Gastaut syndrome
studies we also looked at a lower dose to see if that was effective and we
did see that at 10 milligrams of medicine per kilogram of patient we saw
efficacy and we saw a 39% median seizure reduction and again when you compare
those all to placebo the rates there were statistical significance or
differences between that so that's the gold standard way of knowing something is effective
how similar are those numbers to what is already approved for
medications that isn't cannabidiol well I think I'll start and I'll defer to Anup
but I think you know we do need to keep in mind that there have not been
head-to-head trials in similar populations of patients so I think that
is we need to understand that having said that when you look at all the
studies that have been done in Lennox-Gastaut or Dravet and all the other
therapies are available the response rate is about the same
this is a medicine work similarly to a lot of other medicines can be very
effective for some and is another option which is always helpful for our patients
who do not respond to the therapies that we've tried and so it's encouraging to
have this but by no means is this a magic bullet or a fix-all for everyone
who has seizures let's talk about dosing I know you brought up the 10 milligram
per kilogram 20 milligram per kilogram what's the the dose that we're looking
at from a practical standpoint how often does one take it and how much are we
talking about yeah and I think the important point here is it's all going
to be weight based and so you're going to take the amount of medicine that you
need and if you want to start low and go slow that's how
we would recommend it so you could start at five milligram per kilogram per day
but let me explain what that means it means that you're gonna take five
milligrams multiplied by how many kilograms that person weighs to know
how many milligrams that person will take so in some cases you may be on as
little as 10 milligrams to 100 milligrams
where in other cases for adults specifically obviously weigh more than our
little or smaller children you know they might have to take 1500
milligrams twice a day the medication should be dosed twice a day that's how
the trials were done that's what the data suggests Barry you know one of the
things that people already asking is well I can get a version of cannabidiol
in a dispensary or other location that may provide this is the dosing that was
seen in the trial translate to the dosing you go and use in these other
products that say it's cannabidiol the short answer is no I think we need to
understand that Epidiolex is a purified form of cannabidiol so we know
exactly what we're getting in every dosage form from dose to dose so I think
it would be a mistake to try to translate what we know from the clinical
studies over to these other preparations the question I've been asked is well are
these other formulations can we consider them a generic no there is
no generic version of this molecule we really don't know how to dose these
vernacular or artisanal products because we don't know what's in them we don't
know the consistency how much CBD and etc and they're not tested so it is very
important for everyone to know that the results from the trials cannot be
extrapolated to any other product that results in the trial and the dosing
that's recommended from the trial only pertain to Epidiolex the purified
plant-based formulation of CBD what kind of side effects were seen in the trials
at least we'll start off there and then we'll talk a little bit more about side effects
yeah I think the more common side effects were sedation or tiredness
some nausea diarrhea some stomach GI upsets the other side effect that was
seen was increase in liver function test transaminases we know that cannabidiol
can inhibit one of the cytochrome p450 isozymes p450 to C19 why is that
important that enzyme metabolizes the active metabolite of clobazam which
is going to be as well you know commonly used drug in this population what was
seen fairly consistently was that levels of the endasmethyl clobazam were
significantly increased and it's reasonable to assume that that may have
been contributing to a lot of the sedation I think it's an important point
and one of the things that we could do or what we did do was either lower the
dose of the clobazam or in some cases the Epidiolex and that sometimes made
this sedation go away and you were able to keep that seizure control at the same
level as you did before but not have that sedation of a significant way and
it's really a balancing act and what you can do with that is really going to be
working with your family your patient to be sure they understand what to look for
and then how you can handle it does the other side also come into play that is
lowering the dose of the other AED if they happen to be on a joint combination
therapy or something you know that's one of the recommendations I make too many
patients regardless of its you know Epidiolex or other medications you know
when you add a new medication it is sometimes the original medicine that
needs to be lowered because that's what's causing the effect I think we're
quick to blame the new guy on the block and one example of that might be with
the interaction with valproic acid there may not be a pharmacokinetic one it may
be a pharmacodynamic interaction we know from the clinical trials that
transaminase levels could go up now fortunately there was no cases of liver
failure there was Hy's law was not violated so that's a good thing
but nonetheless we're going to have to monitor for transaminases but that did
tend to occur at higher doses of cannabidiol and especially in
conjunction without valproic acid again we don't know what the mechanism is for
that particular interaction so I think in terms of how we handle that we should
be monitoring periodically both before we start CBD and
and periodically at least for the first few months and when you see that or if
you were to see that again one of the things you'd want to consider is
lowering the valproic acid dosing or again that the Epidiolex dosing you have
two options as it relates to that during the trials when we were able to do that
in all cases either lowering the cannabidiol or the valproic acid we're
actually able to get those liver enzymes back to the normal range
kind of what's your take home main message in point for our viewers listeners out there with
regards to the prescribing of this medication and what they need to be concerned with
sure I I think what the clinical trials have informed us is that
this has the potential to be a very efficacious medicine and generally well
tolerated there are some side effects that we've talked about that maybe more
than troublesome and there is the potential for drug interaction so I
think that needs to be on everybody's radar when they're prescribing this is
think about this there is guidance in the package insert about
potential interactions Anup - yeah I think that what we learned from the
trials is that both at 10 milligrams per kilogram per day and 20 milligrams per
kilogram per day that Epidiolex can be effective for a certain part of the
population who have seizures from Dravet and Lennox-Gastaut syndrome in the case
of Dravet syndrome this is now the first FDA-approved medication for Dravet
syndrome so we're very excited about that
there are obviously other FDA-approved medications for Lennox-Gastaut syndrome
however you know Lennox-Gastaut syndrome patients are very difficult to control
so having other options is very exciting and so we're really pleased with the
results and we're really pleased with the methodology that was taken to make
sure that these results are sound and follow the scientific method
well I want to take this opportunity to thank our fantastic guests Barry and Anup and I
want to also thank you all the viewers for joining us today for the Epilepsy
Foundation video discussion on cannabidiol for epilepsy my name is
Dr. Joe Sirven and I am editor in chief of epilepsy dot com
thanks so much for joining us today