Sunday, November 11, 2018

Clobazam oral film

The US Food and Drug Administration (FDA) has approved an oral film formulation of clobazam (Sympazan, Aquestive Therapeutics) for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients aged 2 years and older, the manufacturer has announced.

Sympazan is the first oral film formulation of clobazam approved by the FDA to treat seizures associated with LGS.

"Many LGS patients have a hard time swallowing pills and suspensions. This can make administering medication hard for caregivers. We believe Sympazan will be welcomed by patients and caregivers impacted by LGS and searching for treatment solutions," Christina SanInocencio, executive director of the LGS Foundation, said in a news release from the manufacturer.

The FDA approved clobazam tablets and oral suspension as adjunctive treatment for LGS in 2011. Sympazan oral film has been shown to be bioequivalent to clobazam tablets and to have a comparable safety profile, the company said.

Sympazan oral film is berry flavored and comes in three strengths, 5 mg, 10 mg, and 20 mg. The manufacturer said it plans to make Sympazan available this month.

Adverse reactions with Sympazan (≥10% and more frequently than placebo) included constipation, somnolence or sedation, pyrexia, lethargy, and drooling.

Sympazan contains a boxed warning noting that the concomitant use of benzodiazepines and opioids may lead to profound sedation, respiratory depression, coma, and death.

Concomitant prescribing of these drugs should be reserved for patients for whom alternative treatment options are inadequate. Patients should be monitored for signs and symptoms of respiratory depression and sedation. Sympazan is contraindicated in patients with a history of hypersensitivity to the drug or its ingredients.

1 comment:

  1. A new oral-film formulation of clobazam (Sympazan; Aquestive, Warren, NJ) was recently approved by the Food and Drug Administration (FDA) for adjunctive treatment of people with seizures associated with Lennox-Gastaut syndrome (LGS). At the American Epilepsy Society Annual Meeting in New Orleans, LA, data on pharmacokinetics of clobazam and its active metabolite N-desmethylclobazam that led to that approval were presented.

    For a drug formulation to be considered of average bioequivalence to a previously approved drug by the FDA, there must be a 90% CI that pharmacokinetic measures fall within 80% to 125% of the same measures for the dose originally approved. As shown in the Table, the oral formulation meets a more rigorous standard with all measures falling between 90 and 110%. This strongly supports for physicians, patients, and caregivers that they can feel confident that the oral film formulation is providing a dose that is consistent with other formulations they may have already used. In addition, the oral film may be easier and more consistent for caregivers to administer as it requires rapid placement on the tongue with no crushing tablets, swallowing pills with water, or leaving residue of the medication in a cup.

    In this study, 51 healthy adults received 10 mg or 20 mg of clobazam as a tablet or an oral film on an open-label basis. Participants were randomly assigned to groups that received the 4 different doses and formulations in 4 different sequences for 4 different time periods after an overnight fast of at least 10 hours. Subjects also fasted for 4 hours after receiving the medication. Levels of clobazam and N-desmethylclobazam were measured before dosing and at regular intervals for 21 days after dosing and there was a 28-day washout period between doses. No significant differences in adverse effects between formulations was observed.