Somaxon Pharmaceuticals' Silenor (doxepin HCl) has been FDA approved to treat long- or short-term insomnia in patients who have difficulty maintaining sleep.
A Closer Look at New FDA Actions
SOMAXON PHARMACEUTICALS’ SILENOR
On March 18, 2010, the FDA approved Silenor (doxepin HCl) to treat longor short-term insomnia in patients who have difficulty maintaining sleep.1
The new drug application approval was based on clinical trials in adults and elderly individuals diagnosed with chronic and transient insomnia. Although doxepin has been approved for depression, anxiety, and dermatologic treatment, these indications are not approved for Silenor. Doxepin exerts sedation by blocking histamine 1 receptors.2,3
It also possesses pharmacologic properties similar to tricyclic antidepressants.3
The efficacy and safety of Silenor for sleep maintenance was evaluated in several randomized clinical trials enrolling men and women aged 18 to 93 years old.2
The efficacy and safety of Silenor was evaluated in adults aged 18 to 64 years diagnosed with chronic insomnia (≥3 months), who were experiencing ≥60 minutes of wake-after-sleep-onset (WASO) and ≥20 minutes of latency to sleep onset, as confirmed by polysomnography. Subjects were randomized to receive nightly doses for 35 days: doxepin 3 mg (n=75), 6 mg (n=73), or matching placebo (n=72). The 3- and 6-mg arms demonstrated improved WASO on night 1 (P <.0001) and at night 29 (both, P = .0299 and P = .0012, respectively). Both doses also showed improvement in various end points.4
Another randomized, double- blind, placebo-controlled study enrolled elderly subjects diagnosed with chronic insomnia using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text revision scale. This study evaluated the efficacy of doxepin 1 mg (n=77), 3 mg (n=82), and placebo (n=81) taken nightly for 3 months. The doxepin arms were superior in onset of sleep and maintenance of sleep and reduced the incidence of early awakenings.5
A 6-mg doxepin dose was also evaluated in a 4-week treatment trial, which also included elderly subjects diagnosed with chronic insomnia. The subjects were randomized to receive once-nightly 6-mg doxepin (n=130) or matching placebo (n=125).6
The double-blind study resulted in improvement in sleep maintenance and sleep duration. The time to sleep onset was improved but not superior to the placebo group.
Silenor is available in 3- and 6-mg tablets. Silenor 6 mg in adults and 3 mg in the elderly is the recommended starting dose. A washout period of 2 weeks from monoamine oxidase inhibitors is recommended before treatment with Silenor begins. It had no effect on QT prolongation. Silenor is taken 30 minutes before bedtime without food.
The most common adverse events reported in the clinical studies were headache, sedation, nausea, and vomiting.2
Doxepin is metabolized mainly by the enzymes cytochrome P450 2C19 (CYP2C19) and CYP2D6, and to a lesser extent, by CYP1A2 and CYP2C9. Therefore, patients who are poor metabolizers of these enzymes will have higher doxepin concentrations.2
Doxepin carries the FDA warning of an increase in suicidal risk and is contraindicated in patients with glaucoma and urinary retention. Silenor is a pregnancy category C drug and is excreted in human milk. Patients should be counseled on complex behaviors associated with taking hypnotics, as outlined in the Silenor package insert.
Both Ms. Belisle and Dr. Patel are pharmacists at Brigham and Women’s Hospital, Boston, Massachusetts.
Silenor Web site. www.silenor.com. Accessed May 21, 2010.
Silenor [package insert]. San Diego, CA: Somaxon 3/2010
www.thomsonhc.com/hcs/librarian/ND_T/HCS/ND_CPR/ProductList/ND_PR/Drugs/CS/BFC038/DUPLICATIONSHIELDSYNC/A2A6CF/ND_PG/PRIH/ND_B/HCS/SBK/1/ND_P/Drugs/PFActionId/hcs.common.RetrieveDocumentCommon/DocId/2570/ContentSetId/31#secN13F6A. Accessed June 15, 2010.
Lankford A, Hull S, et al. Poster presentation: Efficacy and Safety of Doxepin 3 and 6 mg in Adults with Primary Insomnia.
Roth T, Gotfried M, et al. Poster presentation: Long-term Efficacy and Safety of Doxepin 1 and 3 mg in Elderly Subjects with Chronic Primary Insomnia.
Segal S, Lankford A, et al. Poster presentation: Efficacy and Safety of Doxepin 6 mg in a 4-Week Outpatient Trial of Elderly Subjects with Primary Insomnia.