• Efficacy in Adults
• Efficacy in the Elderly
• Safety and Tolerability Profile
• Clinical Trials
• Dosing Recommendations

Efficacy demonstrated in adults with chronic sleep maintenance insomnia

Silenor is indicated for the treatment of insomnia characterized by difficulty with sleep maintenance.¹

In a 35-night sleep laboratory study, Silenor delivered immediate and sustained improvement in objective wake after sleep onset (WASO).

Objective WASO following treatment with Silenor 3 mg
and 6 mg doses in adults with chronic insomnia^2,a

Data from a double-blind, randomized, placebo-controlled, multicenter, parallel-group study of Silenor 3 mg and 6 mg administered to adult patients (N=221) aged 18 to 64 years. Patients with sleep maintenance difficulties were enrolled from 22 centers in the United States between June and December 2005. Study medication was administered for 35 nights, and objective WASO was the primary efficacy endpoint.²

^a WASO is the total amount of time awake after onset of persistent sleep.²

Other important results of this study in adults showed:

• Silenor supports up to 7 hours of sleep²
  • The mean total sleep time (TST) in this phase 3 trial in adults on night 1 was 415 minutes for the 3 mg and 420 minutes for the 6 mg²
• Silenor 3 mg was superior to placebo on subjective WASO (sWASO) at night 1 only¹
• Silenor 6 mg was superior to placebo on sWASO at night 1 and nominally superior at some later time points out to day 30¹
• No anticholinergic side effects were reported²
  • Anticholinergic side effects, such as constipation and urinary retention, have been associated with doxepin at doses higher than 6 mg¹
• No suppression of REM sleep with Silenor 3 mg or 6 mg in this trial²
  • REM sleep was not suppressed significantly in any of the 3 phase 3 studies; small but significant reductions in REM sleep were seen with Silenor 3 mg and 6 mg in 1 of the 2 phase 2 studies
  REM = rapid eye movement

Silenor is approved for use at 3 mg and 6 mg. Do not substitute: There is no generic Silenor.

Silenor helps adults with chronic insomnia stay asleep during the night

In a 35-night chronic insomnia study, on night 1, significant improvements in sleep efficiency, a secondary endpoint, were achieved at all study hours, except for Silenor 3 mg at hour 7 and for Silenor 6 mg at hour 1²

Sleep efficiency (% per hour) on night 1²

NS = not significant; P value > 0.05

Study Design: Data from a double-blind, randomized, placebo-controlled, multicenter, parallel-group study of Silenor 3 mg and 6 mg administered to adult patients (N=221) aged 18 to 64 years. Patients with sleep maintenance difficulties were enrolled from 22 centers in the United States between June and December 2005. Study medication was administered for 35 nights, and objective WASO was the primary efficacy endpoint.²

In this 35-night chronic sleep maintenance insomnia study in adults, assessment of next-day residual effects was evaluated

Small decreases in the DSST and SCT occurred in the 6 mg group.^1,2

• No statistically significant differences were seen in next-day residual effects between the placebo group and the Silenor 3 mg or Silenor 6 mg group²

Effect of Silenor on psychomotor function
in adults with chronic insomnia^2,a

Note: Plotting of visual analog scale (VAS) scores is inverted for consistency with digit symbol substitution test (DSST) and symbol copying test (SCT) scores.

^a Standard measures of next day residual effects, including the DSST, SCT, and VAS for sleepiness scores. These assessments were conducted in the evening (predose) and in the morning approximately 1 hour after the end of each nightly polysomnography (PSG) recording. ²

Data from a phase 3, randomized, double-blind, placebo-controlled, parallel-group, multicenter, 35-day study designed to assess the efficacy and safety of Silenor 3 mg and 6 mg in adults with primary insomnia and sleep maintenance difficulties. Seventy-three patients received placebo, 75 received Silenor 3 mg, and 73 received Silenor 6 mg.²

Efficacy demonstrated in adults with transient sleep maintenance insomnia

In a 6 mg single-dose study, Silenor demonstrated sleep maintenance benefits on the first night of treatment.²

• Patients with transient insomnia experienced significant decreases in objective and subjective WASO following a single 6 mg dose²

Objective WASO at night 1 following treatment with Silenor 6 mg
in a single-dose study²

Study Design: Data from a double-blind, randomized, placebo-controlled, multicenter, parallel-group study of a single 6 mg dose of Silenor administered to healthy adults (N=565) aged 25 to 55 years. Patients were enrolled from 6 centers in the United States between February and June 2006. Objective WASO was a key efficacy endpoint, and subjective WASO was an additional efficacy endpoint.²

Subjective WASO at night 1 following treatment with Silenor 6 mg
in a single-dose study²

Study Design: Data from a double-blind, randomized, placebo-controlled, multicenter, parallel-group study of a single 6 mg dose of Silenor administered to healthy adults (N=565) aged 25 to 55 years. Patients were enrolled from 6 centers in the United States between February and June 2006. Objective WASO was a key efficacy endpoint, and subjective WASO was an additional efficacy endpoint.²

In this 1-night single 6 mg dose study of adults with transient insomnia, next-day residual effects were evaluated

In this study, Silenor 6 mg showed modest negative changes in SCT and VAS.^1,2

• No statistically significant differences were seen between the treatment groups in the mean change in DSST score from night 1 to day 2²
• Changes in SCT and VAS for sleepiness were statistically significant but modest (mean difference <5)

Effect of Silenor 6 mg on psychomotor function in adults with transient insomnia^2,a

Note: Plotting of VAS scores is inverted for consistency with DSST and SCT scores.

^a Standard measures of next day residual effects, including the DSST, SCT, and VAS for sleepiness scores. These assessments were conducted in the evening (predose) and in the morning approximately 1 hour after the end of the night 1 PSG recording.²

Data from a phase 3, randomized, double-blind, placebo-controlled, parallel-group, multicenter, 1 night study to assess the efficacy and safety of Silenor 6 mg in adult patients with transient insomnia and sleep maintenance difficulties. Two-hundred and eighty-two patients received placebo and 283 received Silenor 6 mg.²

Next: Efficacy in the elderly

Silenor is indicated for the treatment of insomnia characterized by difficulty with sleep maintenance.

IMPORTANT SAFETY INFORMATION

Silenor is contraindicated in individuals who have shown hypersensitivity to doxepin HCl, any of its inactive ingredients, or other dibenzoxepines. Serious side effects and even death have been reported following the concomitant use of certain drugs with MAO inhibitors (MAOIs). Do not administer Silenor if patient is currently on MAOIs or has used MAOIs within the past two weeks. The exact length of time may vary depending on the particular MAOI dosage and duration of treatment.

Silenor is contraindicated in individuals with untreated narrow angle glaucoma or severe urinary retention.

The failure of insomnia to remit after 7 to 10 days of treatment may indicate the presence of a primary psychiatric and/or medical illness that should be evaluated.

Complex behaviors such as "sleep-driving" (i.e., driving while not fully awake after ingestion of a hypnotic, with amnesia for the event) have been reported with hypnotics. These events can occur in hypnotic-naive as well as in hypnotic-experienced persons. Although behaviors such as "sleep-driving" may occur with hypnotics alone at therapeutic doses, the use of alcohol or other central nervous system depressants with hypnotics appears to increase the risk of such behaviors, as does the use of hypnotics at doses exceeding the maximum recommended dose. Due to the risk to the patient and the community, discontinuation of Silenor should be strongly considered for patients who report a "sleep-driving" episode. Other complex behaviors (i.e., preparing and eating food, making phone calls, or having sex) have been reported in patients who are not fully awake after taking a hypnotic. As with "sleep-driving", patients usually do not remember these events. Amnesia, anxiety and other neuro-psychiatric symptoms may occur unpredictably.

Patients should not consume alcohol with Silenor. Patients should be cautioned about potential additive effects of Silenor used in combination with CNS depressants or sedating antihistamines.

In primarily depressed patients, worsening of depression, including suicidal thoughts and actions (including completed suicides), has been reported in association with the use of hypnotics. Doxepin, the active ingredient in Silenor, is an antidepressant at doses 10- to 100-fold higher than in Silenor. Antidepressants increased the risk compared to placebo of suicidal thinking and behavior in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Risk from the lower dose of doxepin in Silenor can not be excluded.

Patients should not take Silenor unless they are prepared to get a full night’s sleep. After taking Silenor, patients should confine their activities to those necessary to prepare for bed. Patients should avoid engaging in hazardous activities, such as operating a motor vehicle or heavy machinery, at night after taking Silenor, and should be cautioned about potential impairment in the performance of such activities that may occur the day following ingestion.

For faster onset and to minimize the potential for next day effects, Silenor should not be taken within 3 hours of a meal.

In clinical trials, the most common treatment-emergent adverse reaction was somnolence/sedation.

Silenor has not been studied in pregnant women. Silenor is excreted in human milk after oral administration. Silenor is not approved for use in children.

Please see complete Prescribing Information before prescribing Silenor.