司替戊醇治疗Dravet综合征是孤儿药吗？

Stipentol is an orphan drug approved for the treatment of epileptic seizures associated with Dravet syndrome (available in Europe since 2007).

Stipentol is a rare drug that is successfully used in combination with valproate and clobazan to treat Dravet syndrome. With the approval of stiripentol in the United States in 2018, treatment options for this rare and severe form of early-onset epilepsy have increased.

Stipentol was granted orphan drug status for the treatment of Dravet syndrome

It is a new anti-epileptic compound produced by Biocodex. Increased in vitro gamma-aminobutyric acidergic transmission was recently demonstrated in an experimental model of immature rats.

Clinical studies are based on the fact that stiripentol can also act as an inhibitor of CYP3A4, CYP1A2 and CYP2C19 in patients with epilepsy. Although studies in adult patients have been disappointing, trials in the pediatric population have demonstrated specific efficacy of stiripentol in severe myoclonic epilepsy in infancy, Dravet syndrome, when used in combination with valproate and clobazan.

Based on these results, stiripentol was granted orphan drug status in the EU for the treatment of Dravet syndrome. French experience with compassionate use suggests that stiripentol may be beneficial in combination with carbamazepine in children with drug-resistant partial epilepsy.

Efficacy of stiripentol in Dravet syndrome

Stipentol is a group of drugs that indirectly enhance GABAergic neurotransmission and exerts protective activity in several experimental epileptic seizure models, including maximal electroshock (MES), pentylenetetrazol, bicuculline, strychnine, and cocaine-induced convulsions. This drug effectively inhibits the metabolism of other antiepileptic drugs and significantly increases their plasma and brain concentrations.

As add-on therapy, stiripentol has been shown to be effective in partial and atypical absence epilepsy. In recognition of its specific efficacy in severe myoclonic seizures in infancy (Dravet syndrome), stiripentol was granted orphan drug status for the adjunctive treatment of this difficult-to-treat disease.

The efficacy of stiripentol in Dravet syndrome (DS) was first discovered in an exploratory study of drug-resistant epilepsy in children. This proof-of-concept efficacy signal led to two independent multicenter randomized, double-blind, placebo-controlled trials in patients with DS.

With the assistance of sodium valproate and clobazan, stiripentol showed significant efficacy. These trials became the basis for the registration of stiripentol as an orphan drug for DS. Although stiripentol has previously shown antiepileptic activity due to its inhibition of cytochrome P450, the increased plasma levels of clobazan (CLB), norclobazan (NCLB), and the NCLB/CLB ratio reported in stiripentol studies have called into question the activity of stiripentol itself.

Precautions for stiripentol

1. Drowsiness: Stipentol can cause drowsiness. Especially when stiripentol is used with other inhibitors or clobazam.

2. Decreased appetite and weight loss: Stipentol can cause decreased appetite and weight loss. The patient's growth and weight should be carefully monitored.

3. Changes in blood cell counts: Stipentol can cause a significant decrease in white blood cell and platelet counts, so blood tests should be performed before starting stiripentol treatment and then every 6 months.

4. Withdrawal symptoms: As with most anti-epileptic drugs, stiripentol should be discontinued gradually to reduce the risk of higher seizure frequency and status epilepticus, which refers to seizures lasting more than five minutes or the inability to fully recover from multiple seizures lasting more than five minutes or longer.

5. Risks for patients with phenylketonuria: Stipentol oral suspension contains phenylalanine, which may be harmful if you have phenylketonuria. Stipentol capsules do not contain phenylalanine.

6. Suicidal behavior and thoughts: Stipentol will increase the risk of suicidal thoughts or behaviors. Your healthcare provider should monitor you for worsening depression, suicidal thoughts or behaviors, or any unusual changes in mood or behavior.

Summary

Stipentol has been granted orphan drug status for the treatment of Dravet syndrome. It has remarkable efficacy. Patients can take the drug under the guidance of a doctor. They are not allowed to stop taking the drug without permission or suddenly reduce the dose, so as not to affect the recovery of the disease.

Recommended hot articles: