Ambien Manufacturing, Supply & Shortage History

What the FDA approval records show

Ambien immediate-release tablets were approved under NDA 019908 on 16 December 1992, and the strengths listed on that application are 5 mg and 10 mg tablets [1][2]. The company on the application is Cosette [2], which is also the contact named in the current Ambien label [3].

Ambien CR, the extended-release tablet, is a separate application, NDA 021774, approved on 2 September 2005 [1]. Edluar, the sublingual tablet (Viatris), was approved under NDA 021997 on 13 March 2009 [1]. Generic zolpidem is FDA-approved as immediate-release tablets, extended-release tablets and sublingual tablets [1].

Two branded products are discontinued

Drugs@FDA lists two other branded zolpidem products as discontinued: Intermezzo, a low-dose sublingual tablet approved under NDA 022328 on 23 November 2011, and Zolpimist, an oral spray approved under NDA 022196 on 19 December 2008 [1]. Intermezzo was the product approved for use after a middle-of-the-night awakening followed by difficulty returning to sleep [4]. The current Ambien label directs a single dose immediately before bedtime with at least 7 to 8 hours remaining before planned awakening, and says it should not be readministered the same night [3].

What the label says about how it works

The Ambien label describes zolpidem as a gamma-aminobutyric acid (GABA) A receptor positive modulator [3].

Schedule IV status

The Ambien label states that zolpidem is "classified as a Schedule IV controlled substance by federal regulation" [3].

Differences between the forms

The label says the recommended initial Ambien dose is 5 mg for women and 5 or 10 mg for men. The Ambien CR label says 6.25 mg for women and 6.25 or 12.5 mg for men [3][6]. The Ambien CR label says to swallow the tablet whole rather than crush, divide or chew it [6]. Edluar is a sublingual tablet placed under the tongue; it is not swallowed or taken with water [7].

Why the recommended doses changed in 2013

On 10 January 2013 the FDA announced it was requiring lower recommended doses because blood levels in some patients may be high enough the next morning to impair activities that require alertness, including driving. The recommended dose for women was lowered from 10 mg to 5 mg for immediate-release products (Ambien, Edluar, Zolpimist) and from 12.5 mg to 6.25 mg for extended-release products (Ambien CR). For men, labeling was to recommend that prescribers consider the lower dose [4].