Zolpidem tartrate (Intermezzo): First insomnia therapy for middle-of-the-night waking followed by difficulty returning to sleep

February 1, 2012

New indication: FDA approved Zolpidem tartrate sublingual tablets or the treatment of insomnia characterized by middle-of-the-night (MOTN) wakening followed by difficulty returning to sleep.

On November 23, 2011, FDA approved zolpidem tartrate sublingual tablets for the treatment of insomnia characterized by middle-of-the-night (MOTN) wakening followed by difficulty returning to sleep. Zolpidem is a GABAA agonist that acts as a hypnotic agent by selectively binding to BZ1 receptors.

Efficacy. Sublingual zolpidem's efficacy was established in 2 randomized, double-blind, placebo-controlled trials in patients characterized with difficulty returning to sleep after MOTN wakening. In an 82-adult participant (aged 18 to 64 years) sleep-laboratory study using 1.75- and 3.5-mg scheduled doses of sublingual zolpidem or placebo, participants assigned to zolpidem realized significantly shortened sleep latency as measured by objective (polysomnography) and subjective (patient-estimated) measures compared to placebo. Of note, sublingual zolpidem's effect on sleep latency was similar for females receiving the 1.75-mg and males receiving the 3.5-mg dose. In a second 4-week study of 295 patients in a similar population but using as needed (PRN) dosing, sublingual zolpidem 3.5 mg again significantly shortened the patient-estimated time to fall back to sleep after MOTN wakening compared to placebo.

Safety. The safety of sublingual zolpidem was evaluated during the same 2 double-blind, placebo-controlled trials of adult patients. Combined, these trials included 230 and 82 patients treated with 3.5 mg and 1.75 mg of sublingual zolpidem, respectively. The most common adverse events (occurring in >1%) during clinical trials included headache, nausea, and fatigue. Zolpidem is a central nervous system (CNS) depressant and may impair alertness, motor function, and respiratory function. Consequently, driving and other complex motor functions may be impaired due to zolpidem. "Sleep-driving" and other complex behaviors while not fully awake may occur, and this risk increases with higher doses and/or coadministration with other CNS depressants (eg, alcohol). Zolpidem use may worsen depression or result in suicidal thinking. Patients should be re-evaluated within 7 to 10 days to determine any comorbid diagnosis to insomnia and any adverse reactions that may have occurred because of zolpidem administration.