General Information

Intermezzo is a sublingual tablet formulation of zolpidem tartrate, a non-benzodiazepine hypnotic of the imidazopyridine class.

Intermezzo is specifically indicated for for use as needed for the treatment of insomnia when a middle-of-the-night awakening is followed by difficulty returning to sleep. Intermezzo should only be taken if the patient has at least four hours of bedtime remaining before the planned time of waking.

Intermezzo is supplied as a tablet for sublingual administation. Intermezzo should be placed under the tongue and allowed to disintegrate completely before swallowing. The tablet should not be swallowed whole. The recommended and maximum dose of Intermezzo is 1.75 mg for women and 3.5 mg for men, taken only once per night as needed if a middle-of-the-night awakening is followed by difficulty returning to sleep.

Clinical Results

FDA Approval
The FDA approval of Intermezzo was based on two randomized, double-blind, placebo-controlled studies (Studies 1 and 2). All subjects met the diagnosis for primary insomnia as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) and had at least three prolonged middle of the night awakenings per week that were at least 30 minutes in duration.
Sleep Laboratory Study (Scheduled Dosing)
This double-blind, placebo-controlled, 3-period cross-over sleep laboratory study enrolled 82 subjects with a history of difficulty returning to sleep after middle-of-the-night awakenings. The primary outcome measure was latency to persistent sleep. Doses of 3.5 mg and 1.75 mg of Intermezzo significantly decreased both objective (by polysomnography) and subjective (patient-estimated) sleep latency after a scheduled middle-of-the-night awakening as compared to placebo. The effect on sleep latency was similar for females receiving 1.75 mg of Intermezzo and males receiving 3.5 mg of Intermezzo.
Outpatient Study (As-needed Dosing)
This double-blind, placebo-controlled four-week outpatient study 295 subjects with difficulty returning to sleep after middle-of-the-night awakenings. The subjects took Intermezzo (3.5 mg) or placebo on an as needed (prn) basis, when they had difficulty returning to sleep after waking in the middle of the night, provided they had at least four hours time remaining in bed. Subjective (patient-estimated) time to fall back to sleep after middle-of- the-night awakening was significantly shorter for Intermezzo 3.5 mg compared to placebo.

Mechanism of Action

Intermezzo is a sublingual tablet formulation of zolpidem tartrate, a non-benzodiazepine hypnotic of the imidazopyridine class. Zolpidem tartrate interacts with a GABA-BZ complex and shares some of the pharmacological properties of the benzodiazepines. In contrast to the benzodiazepines, which nonselectively bind to and activate all BZ receptor subtypes, zolpidem in vitro binds the BZ1 receptor preferentially with a high affinity ratio of the alpha1/alpha5 subunits. This selective binding of zolpidem on the BZ1 receptor is not absolute, but it may explain the relative absence of myorelaxant and anticonvulsant effects in animal studies as well as the preservation of deep sleep (stages 3 and 4) in human studies of zolpidem at hypnotic doses.