M. Scott Perry, MD, reviews how cannabidiol and fenfluramine are chosen for patients with Dravet syndrome based on concomitant medications and associated adverse events.
M. Scott Perry, MD: Are there any populations where a cannabidiol might be preferable over fenfluramine? I think in general both medications have good seizure response, so I think it comes down to maybe concomitant medications that the child is on and the adverse effects associated with it. If you’ve got a child who maybe is already on clobazam or valproic, you may have a little more risk of somnolence or elevated liver enzymes; maybe you would choose fenfluramine instead.
If you’ve got a kid who already has issues with feeding, weight has already been a problem, maybe they have preexisting cardiac conditions, maybe you would choose cannabidiol. In my own population, I’ll tell you, the majority of them have probably been on both medications at some point. It’s almost always a matter of trying to find which one, or maybe both together, gives you the best seizure control, but the adverse effects may play a role in which one you choose first when you’re trying to figure that out.
Dosing for the both these medications is fairly simple. The cannabidiol is generally titrated up to about 10 mg/kg per day as a starting target dose. I usually start the first week with around 5 mg/kg per day, divided twice a day, and then up to 10 mg/kg. Then if it’s tolerated, if they’re still having seizures, you can try to go higher, working your way up to 20 mg/kg per day. I generally tell people as I titrate up that as we go up, if we’re not seeing seizure control get any better, there’s probably no need to stay at the higher dose.
We can just come right back down to where we were. If we get some additional efficacy, as long as it’s tolerated, that’s fine. We’ll work our way on up to the higher dose. Same with fenfluramine. The indication and titration schedule for fenfluramine is up 0.7 mg/kg per day. No higher—this is important—no higher than 26 mg per day. There is a limit on how much fenfluramine you give based on weight, and that is if the patient is not on stiripentol.
If the patient is taking stiripentol, the dose of fenfluramine should be titrated up to 0.4 mg/kg per day, not to exceed a daily dose of 17 mg. The reason for that is there is a higher viability of fenfluramine in the setting of stiripentol, and so the dosing needs to be adjusted. Personally, the way I have had done it, my experience with fenfluramine, is I generally start the dosing at about 0.2 mg/kg per day and work up to around 0.4 to 0.5 mg/kg, see how the child is doing, and then go the rest of the way to 0.7 mg/kg per day if it is necessary.
I’ve seen a lot of kids who tend to do well in that middle area, and so I don’t need to go all the way up. Fenfluramine is a drug whose concentration is 2.2 mg/mL, so from a mathematic standpoint and ease of use for parents, I try to find doses that are at nice, even, or at 0.5 increments, to make the dose simple for them. I think that’s something people should always think about.