FDA concerned about higher doses of investigational sleep agent

May 20, 2013

The proposal of the investigational sleep agent called suvorexant (Merck), is believed to target sleep disturbances and insomnia through a different mechanism compared to the agents that are currently on the market, but FDA has concerns over the higher dosages of the drug and its safety profile.


Currently under consideration by FDA, the proposed sleep agent known as suvorexant (Merck) differs from other agents already on the market, targeting sleep disturbances and insomnia by a novel mechanism that, if approved, would place it first in a new class of drugs known as orexin receptor antagonists. However, FDA has concerns over the higher dosages of the drug and its safety profile.

Suvorexant was studied in more than 2,000 participants and in several trials. One 12-month study evaluated its safety and efficacy, as well as consequences of treatment discontinuation. Two other studies focused on driver functionality the day after taking an evening dose, a significant matter since lingering effects have been shown to disorient patients taking Ambien and similar sleep products.

Studies have examined the effect of doses as low as 10 mg and as high as 80. Merck has proposed 2 starting doses of the product, based on age, as well as 2 higher doses of the drug.

According to Reuters, one medical officer wrote, "suvorexant is effective but not safe at the higher doses mainly studied," citing concerns about next-day driving impairment and daytime sleepiness that "can be severe and worsen suddenly." FDA staff also said the lowest 15-mg doses results in "excessive exposure" in some patient groups such as obese women.

“FDA's evaluation of a lower initial starting dose of 10 mg for suvorexant compared to the current 15 mg may alleviate some of the concerns related to daytime sleepiness or driving impairments,” said Formulary advisor Abimbola Farinde, PharmD, MS, clinical staff pharmacist at Clear Lake Regional Medical Center, Webster, Texas.

“Given previous documented incidences of sleep agents causing abnormal behaviors or impaired functioning in individuals who were later unaware of their actions, this closer examination by FDA is warranted before any consideration is given for possible approval,” Dr Farinde said.

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