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Rare Childhood Epilepsies: Dravet Syndrome and Lennox-Gastaut Syndrome - Episode 7

The Impact of Cannabidiol, Fenfluramine, and Stiripentol/Clobazam for Treating Dravet and Lennox-Gastaut Syndromes

Drs Thiele and Wirrell discuss the benefits of 3 drugs being approved to treat Dravet and Lennox-Gastaut syndromes: cannabidiol, fenfluramine, and the combination of stiripentol and clobazam.

Elizabeth Thiele, MD, PhD: COVID-19 changed things for a lot of us. For a while, if you’ve said, “Here, now we have both of these medications,” I have felt comfortable starting patients on CBD [cannabidiol], even if I couldn’t get blood work done, unless they were on high doses of valproate. But for a period of time, we couldn’t get echocardiograms, and the laboratories were closed, so that made a play…. Also, we should mention stiripentol. We’re lucky going from 0 to 3 FDA-approved medications for Dravet syndrome, and I know you’re working on revisions of the more global treatment recommendations or algorithms for Dravet. How are you viewing the role of these 3 treatment options that we have specifically indicated for Dravet?

Elaine C. Wirrell, MD: As I mentioned, for valproate and clobazam, the efficacy of those was not great, and now we have 3 recently approved therapies. Have I started using these in the first line? Not yet. But I would try; from my standpoint fenfluramine has been a game-changer, and CBD as well, although fenfluramine has more efficacy for Dravet syndrome. Looking at that efficacy and the tolerability, I don’t think we can say it definitely doesn’t cause cardiac adverse effects. But if it does so, it must be infrequent. We still need to follow those echocardiograms. But for a child with Dravet syndrome, I would try and get them on to fenfluramine as quickly as I could. Stiripentol as you mentioned is also effective, and stiripentol needs to be used with clobazam. That’s a mandate from the FDA, you’ve got those 2 medications. Fenfluramine, stiripentol with clobazam, and CBD are all highly effective therapies, and should be considered earlier in the course. I don’t think that we need to put everybody through valproate and everybody through clobazam before we go to something that’s more efficacious.

Elizabeth Thiele, MD, PhD: I agree, and I hope that the payers all agree, because we do have as you said, we have good data for those 3 working in this patient population that we don’t have for others. Clobazam and valproate were the best options we had before these specific trials were done. In reality, I think a lot of my patients with Dravet are going to end up on both, CDB and fenfluramine, and I have a handful of patients on both. Even if I get a 65% reduction in seizures, that child’s not necessarily seizure-free. If you have the opportunity to bring in another drug you know can be effective and is well tolerated, and the children I have on both, they’re doing well. I think they’d benefit from both overall…. It’s great to have all of these.

The one issue we’ve had with fenfluramine that is important for physicians to remember is the contraindicated concomitant medications, because you forget. If a child’s going in for anesthesia for a scan or something then fentanyl should not be given if you’re on fenfluramine. It’s also been a problem for us in some of our children who do have psychiatric comorbidities because it limits the medication options that we have there. But again, it’s not a game-changer in our use of the medication, it’s something that I need to remember to be aware of and to tell families about. We’re heading into cold and flu season again, it’s the dextromethorphan, don‘t take that if you’re on this medication. That’s important to know. Like any medication we have, how do we not only use it to optimize efficacy, but also make sure we’re optimizing safety and tolerability?

This transcript has been edited for clarity.