PHILADELPHIA, May 8, 2012 /PRNewswire/ -- The new prescription sleep aid Intermezzo (zolpidem tartrate) sublingual tablet CIV is the first and only prescription sleep aid approved by the U.S. Food and Drug Administration (FDA) for the treatment of insomnia when a middle-of-the-night awakening is followed by difficulty returning to sleep, and the patient has at least four hours of bedtime remaining before the planned time of waking. Intermezzo has gender-specific dosing (1.75 mg for adult women and 3.5 mg for adult men) taken only once per night as needed if a middle-of-the-night awakening is followed by difficulty returning to sleep. Intermezzo 1.75 mg is also the recommended dose for men and women over 65 years of age, patients with hepatic impairment, or patients taking concomitant CNS depressants.
In the double-blind, placebo-controlled, cross-over pharmacokinetic study in healthy volunteers, Intermezzo doses of 1.0 mg, 1.75 mg, and 3.5 mg were administered on two consecutive days to 11 women and 13 men. At the same dose, the plasma levels of zolpidem tartrate in women were approximately 45 percent higher than in men. The study found that women taking a 3.5 mg dose cleared the drug at a slower rate than men taking 3.5 mg (2.7 ml/min/kg vs. 4.00 ml/min/kg, respectively).
"Given that women clear the active ingredient in Intermezzo at a lower rate than men, the results of the study support a recommended lower dosage of Intermezzo for women and a higher dosage for men," said study co-author Thomas Roth, Ph.D., Director of Sleep Medicine at Henry Ford Hospital in Detroit.
Intermezzo was approved by the FDA in November 2011 and is available nationwide in spearmint-flavored sublingual tablets that are placed under the tongue and allowed to disintegrate completely before swallowing. Intermezzo contains a bicarbonate-carbonate buffer. On average, Intermezzo is rapidly absorbed in both genders, achieving peak mean plasma levels of zolpidem in about 35 to 75 minutes. For optimal effect, Intermezzo should not be administered with or immediately after a meal.
Important Safety Information
Intermezzo 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 four hours of bedtime remaining; if a 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 four hours after the 1.75 mg dose in women, and after the 3.5 mg dose in men, such that a potential negative effect on driving cannot be completely excluded.
Additional Important Safety Information is presented below.
About Intermezzo Clinical Studies
The safety and efficacy of Intermezzo was evaluated in two randomized, double-blind, placebo-controlled studies in patients with insomnia characterized by difficulty returning to sleep after a middle-of-the-night awakening. Patients met the diagnosis for primary insomnia as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) and had at least 3 prolonged middle-of-the-night awakenings per week of at least 30 minutes in duration.
In a four-week outpatient study in 295 adult patients aged 18 to 64 years (201 females, 94 males), Intermezzo 3.5 mg or placebo was taken on an as-needed basis following spontaneous awakenings when patients had difficulty returning to sleep after waking in the middle of the night, provided they had at least four hours remaining in bed. Subjective time to fall back to sleep after a middle-of-the-night awakening was significantly shorter for Intermezzo 3.5 mg (38 minutes) compared to placebo (56 minutes).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%).(1)
In a sleep laboratory study, 82 adult patients aged 19 to 64 years (58 females, 24 males) were evaluated in a 3-period, 2-consecutive-night treatment period cross-over design. Patients were awakened four hours after bedtime, administered Intermezzo 3.5 mg, 1.75 mg, or placebo, were kept awake for 30 minutes before lights-out, and then allowed to return to sleep for four hours. As compared to placebo, patients taking Intermezzo had significantly shorter objective mean time to fall back asleep after the middle-of-the-night awakening (women taking 1.75 mg: 16 min vs. placebo: 28 min; men taking 3.5 mg: 13 min vs. placebo: 29 min).(1)
Use of Intermezzo in Elderly, in Hepatic Impairment, or with Concomitant CNS Depressants
Geriatric patients may be especially sensitive to the effects of zolpidem. The recommended dose for elderly men and women over 65 years old is 1.75 mg taken only once per night if needed. The recommended dose for men and women with hepatic impairment or those taking concomitant CNS depressants is 1.75 mg. Dose adjustment of concomitant CNS depressants may be necessary when co-administered with Intermezzo because of potentially additive effects. The use of Intermezzo with other sedative-hypnotics (including other zolpidem products) at bedtime or the middle of the night is not recommended.
How to Take Intermezzo
Intermezzo is to be taken in bed when a patient wakes in the middle of the night and has difficulty returning to sleep. Intermezzo should only be taken if the patient has at least four hours of bedtime remaining before the planned time of waking.
Intermezzo should be placed under the tongue and allowed to disintegrate completely before swallowing. The tablet should not be swallowed whole. For optimal effect, Intermezzo should not be administered with or immediately after a meal. The blister should be removed from the pouch just prior to dosing.
Each sublingual tablet is individually packaged in a foil blister inside a unit-dose pouch. Before going to bed, a single pouch should be placed by the bedside with a clock or watch nearby. All other unopened Intermezzo pouches should be stored with other medicines away from the bedside. Patients should open the Intermezzo pouch only when they are ready to use it.
Patients can either use the Dosing Time Chart or the Dosing Time Tool that comes with Intermezzo to find the latest time during the night they can take Intermezzo.
Dosing Time Tool: Patients turn a wheel to find the earliest time they must be awake, which corresponds with instructions to take Intermezzo before a specified time.
Dosing Time Chart: The chart helps patients locate the earliest time they need to be awake and match it to the latest time they can take Intermezzo.
When patients wake in the morning, they should make sure that at least four hours have passed since they took Intermezzo and they feel fully awake before driving or engaging in other activities requiring full mental alertness. Patients should not do dangerous activities until they know how Intermezzo affects them.
Additional Important Safety Information
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 be fatal. Patients who develop angioedema or anaphylaxis should not be re-challenged.
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. Prescribe the least amount of Intermezzo that is feasible in these patients.
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.
For additional information, please read the Intermezzo Full Prescribing Information available at http://app.purduepharma.com/xmlpublishing/pi.aspx?id=i
About Purdue Pharma L.P.
Purdue Pharma and its associated U.S. companies are privately-held pharmaceutical companies known for pioneering research on persistent pain. Headquartered in Stamford, Conn., Purdue Pharma is engaged in the research, development, production, and distribution of both prescription and over-the-counter medicines and hospital products. Additional information about Purdue Pharma can be found at www.purduepharma.com.
(1) Data on File, Purdue Pharma LP.
SOURCE Purdue Pharma L.P.