Understanding middle-of-the-night insomnia

The term insomnia literally means “no sleep.” It originates from the Latin in (no) and somnus (sleep). Insomnia is often defined by a patient who reports difficulty with sleep.1,2 Because there are different manifestations of insomnia, it’s important to recognize each type to effectively diagnose and provide appropriate treatment.

Types of insomnia

Intermezzo is the first and only prescription sleep aid approved for use as needed for the treatment of insomnia when a middle-of-the-night awakening is followed by difficulty returning to sleep with at least 4 hours left for sleep.

In adults, a middle-of-the-night awakening followed by difficulty returning to sleep has been consistently identified as a common type of insomnia8

Important Safety Information

Intermezzo® (zolpidem tartrate) is contraindicated in patients with known hypersensitivity to zolpidem. Observed reactions with zolpidem include anaphylaxis and angioedema.

Co-administration with Intermezzo and other CNS depressants increases the risk of CNS depression. Intermezzo should not be taken with alcohol. The use of Intermezzo with other sedative-hypnotics (including other zolpidem products) at bedtime or the middle of the night is not recommended.

The risk of next-day driving impairment (and psychomotor impairment) is increased if Intermezzo is taken with less than 4 hours of bedtime remaining; if higher than recommended dose is taken; if co-administered with other CNS depressants; or co-administered with other drugs that increase the blood levels of zolpidem. A small negative effect on SDLP (standard deviation of lateral position, a measure of driving impairment) may remain in some patients 4 hours after taking Intermezzo, such that a potential negative effect on driving cannot be completely excluded.

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.

Cases of angioedema involving the tongue, glottis, or larynx have been reported in patients after taking the first or subsequent doses of zolpidem. Some patients have had additional symptoms such as dyspnea, throat closing, or nausea and vomiting that suggest anaphylaxis. Some patients have required medical therapy in the emergency department. Angioedema, and additional symptoms suggesting anaphylaxis, may occur in patients taking zolpidem and may be fatal. Patients who develop angioedema or anaphylaxis should not be rechallenged.

Abnormal thinking and behavior changes have been reported in patients treated with a sedative-hypnotic including zolpidem. Complex behaviors, including driving or eating while not fully awake, with amnesia for the event, as well as visual and auditory hallucinations and abnormal behaviors such as decreased inhibition, bizarre behavior, agitation, and depersonalization may occur. Although behaviors such as “sleep-driving” have occurred with zolpidem alone at therapeutic doses, the co-administration of zolpidem with alcohol and other CNS depressants increases the risk of such behaviors, as does the use of zolpidem at doses exceeding the maximum recommended dose. Discontinuation of Intermezzo should be strongly considered for patients reporting a “sleep-driving” episode.

In primarily depressed patients, worsening of depression, including suicidal thoughts and actions (including completed suicides) have been reported with the use of sedative-hypnotics. Intentional overdosage is more common in this group of patients; therefore, protective measures may be required and prescribe the least amount of Intermezzo that is feasible.

Because persons with a history of addiction to or abuse of drugs or alcohol are at increased risk for misuse, abuse, and addiction of zolpidem, they should be monitored carefully when receiving Intermezzo. Zolpidem tartrate is a Schedule IV controlled substance. Post-marketing reports of abuse, dependence, and withdrawal resulting from use of oral zolpidem tartrate have been received. Zolpidem has produced withdrawal signs and symptoms following a rapid dose decrease or abrupt discontinuation.

The most commonly observed adverse reactions (>1%) were headache (Intermezzo 3%, placebo 1%), nausea (1% for both patient groups), and fatigue (Intermezzo 1%, placebo 0%).

Please read the Full Prescribing Information.

To report SUSPECTED ADVERSE REACTIONS, contact Purdue Pharma L.P. at 1-888-726-7535 or FDA at 1-800-FDA-1088 or www.fda.gov/Safety/MedWatch.

References: 1. Estivill E, Bové A, García-Borreguero D, et al. Consensus on drug treatment, definition and diagnosis for insomnia. Clin Drug Invest. 2003;23:351-385. 2. Roth T. Insomnia: Definition, prevalence, etiology, and consequences. J Clin Sleep Med. 2007;3:S7-S10. 3. Morin AK, Jarvis CI, Lynch AM. Therapeutic options for sleep-maintenance and sleep-onset insomnia. Pharmacotherapy. 2007;27:89-110. 4. American Academy of Sleep Medicine website. Insomnia. http://yoursleep.aasmnet.org/disorder.aspx?id=6. Accessed June 20, 2012. 5. US Food and Drug Administration website. Sleep disorders. http://www.fda.gov/ForConsumers/ByAudience/ForWomen/ucm118563.htm. Accessed June 20, 2012. 6. Ohayon MM, Krystal A, Roehrs TA, Roth T, Vitiello MV. Using difficulty resuming sleep to define nocturnal awakenings. Sleep Med. 2010;11:236-241. 7. Edinger JD, Means MK. Overview of insomnia: definitions, epidemiology, differential diagnosis, and assessment. In: Kryger MH, Roth T, Dement WC, eds. Principles and Practice of Sleep Medicine. Philadelphia, PA: Elsevier Saunders; 2005:702-711. 8. Roth T, Hull SG, Lankford DA, et al; for the Intermezzo Study Group. Low-dose sublingual zolpidem tartrate is associated with dose-related improvement in sleep onset and duration in insomnia characterized by middle-of-the-night (MOTN) awakenings. Sleep. 2008;31:1277-1284.

Intended for healthcare professionals of the United States of America only. ©2014 Purdue Pharma L.P., Stamford, CT 06901-3431

Important Safety Informationclick to expand

Intermezzo® (zolpidem tartrate) is contraindicated in patients with known hypersensitivity to zolpidem. Observed reactions with zolpidem include anaphylaxis and angioedema.

Co-administration with Intermezzo and other CNS depressants increases the risk of CNS depression. Intermezzo should not be taken with alcohol. The use of Intermezzo with other sedative-hypnotics (including other zolpidem products) at bedtime or the middle of the night is not recommended.

The risk of next-day driving impairment (and psychomotor impairment) is increased if Intermezzo is taken with less than 4 hours of bedtime remaining; if higher than recommended dose is taken; if co-administered with other CNS depressants; or co-administered with other drugs that increase the blood levels of zolpidem. A small negative effect on SDLP (standard deviation of lateral position, a measure of driving impairment) may remain in some patients 4 hours after taking Intermezzo, such that a potential negative effect on driving cannot be completely excluded.

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.

Cases of angioedema involving the tongue, glottis, or larynx have been reported in patients after taking the first or subsequent doses of zolpidem. Some patients have had additional symptoms such as dyspnea, throat closing, or nausea and vomiting that suggest anaphylaxis. Some patients have required medical therapy in the emergency department. Angioedema, and additional symptoms suggesting anaphylaxis, may occur in patients taking zolpidem and may be fatal. Patients who develop angioedema or anaphylaxis should not be rechallenged.

Abnormal thinking and behavior changes have been reported in patients treated with a sedative-hypnotic including zolpidem. Complex behaviors, including driving or eating while not fully awake, with amnesia for the event, as well as visual and auditory hallucinations and abnormal behaviors such as decreased inhibition, bizarre behavior, agitation, and depersonalization may occur. Although behaviors such as “sleep-driving” have occurred with zolpidem alone at therapeutic doses, the co-administration of zolpidem with alcohol and other CNS depressants increases the risk of such behaviors, as does the use of zolpidem at doses exceeding the maximum recommended dose. Discontinuation of Intermezzo should be strongly considered for patients reporting a “sleep-driving” episode.

In primarily depressed patients, worsening of depression, including suicidal thoughts and actions (including completed suicides) have been reported with the use of sedative-hypnotics. Intentional overdosage is more common in this group of patients; therefore, protective measures may be required and prescribe the least amount of Intermezzo that is feasible.

Because persons with a history of addiction to or abuse of drugs or alcohol are at increased risk for misuse, abuse, and addiction of zolpidem, they should be monitored carefully when receiving Intermezzo. Zolpidem tartrate is a Schedule IV controlled substance. Post-marketing reports of abuse, dependence, and withdrawal resulting from use of oral zolpidem tartrate have been received. Zolpidem has produced withdrawal signs and symptoms following a rapid dose decrease or abrupt discontinuation.

The most commonly observed adverse reactions (>1%) were headache (Intermezzo 3%, placebo 1%), nausea (1% for both patient groups), and fatigue (Intermezzo 1%, placebo 0%).

Please read the Full Prescribing Information.

To report SUSPECTED ADVERSE REACTIONS, contact Purdue Pharma L.P. at 1-888-726-7535 or FDA at 1-800-FDA-1088 or www.fda.gov/Safety/MedWatch.

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