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By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD
The fda approved wyeth ayerst’s zaleplon (Sonata) for the short-term treatment of insomnia in adults. Zaleplon represents the first in a new class of nonbenzodiazepine hypnotics, the pyrazolopyrimidines. The drug is characterized by rapid absorption, rapid elimination, rapid onset, and short duration of action.
Zaleplon is indicated for the short-term treatment of insomnia. As with other hypnotics, zaleplon should generally be limited to 7-10 days of therapy.1
The recommended dose of zaleplon is 10 mg, although a 20-mg dose may benefit certain patients. For the elderly, patients with low body weights, or patients with mild to moderate hepatic impairment, the dose should be reduced to 5 mg. No dose adjustment is necessary in patients with mild to moderate renal impairment. The drug should be taken immediately before bedtime or after the patient has gone to bed but failed to fall asleep, but it should not be taken if there are less than four hours left before the patient needs to be active. Zaleplon should not be taken with a heavy, high-fat meal as the absorption of the drug is significantly delayed.1
Zaleplon is supplied as 5 mg and 10 mg capsules. The FDA has given the drug a schedule IV classification similar to the benzodiazepines.
Zaleplon has a short half-life of elimination (0.9-1 hour); therefore, there is generally no next-day hangover or grogginess. The drug may be taken late into the night without risk of daytime sleepiness, as long as the patient has at least four hours left in bed. The metabolites of zaleplon do not appear to be active.
Due to its short duration of action, zaleplon is effective in inducing sleep rapidly, but may not be effective in sleep maintenance. Even though zaleplon is not a benzodiazepine, its behavior pharmacologic profile has been reported to be similar to that of triazolam when administered to subjects with a history of drug abuse.3 Same-day and next-day subject-rated measures suggesting abuse potential were similar for the two drugs.3
Cytochrome P450 inducers such as rifampin decrease the zaleplon plasma concentration by 80%. Coadministration of zaleplon with rifampin and other inducers such as phenytoin, carbamazepine, and phenobarbital should be avoided. Cimetidine increases the bioavailability by 85% due to the inhibition of the major (aldehyde oxidase) and minor (cytochrome P450 isoenzyme 3A4) pathways. A 5-mg dose should be used if zaleplon is coadministered with cimetidine.1
Zaleplon is a pyrazolopyrimidine that binds selectively to the BZ1 (omega 1) subtype of the GABA benzodiazepine-receptor complex.2 In animal studies, zaleplon demonstrated a similar pharmacologic profile to zolpidem.2 Its pharmacokinetics properties suggest that the drug may be most useful for insomnia characterized by difficulty falling sleep. Zaleplon does not appear to benefit patients with frequent awakenings or waking too early in the morning. Zaleplon does not appear to affect sleep duration. Clinical trials indicated that zaleplon reduced sleep latency by 10-20 minutes (15-30%) less than placebo.1 Daytime anxiety was not observed in the clinical trials and rebound insomnia was reported to resolve by the second night following withdrawal.1
The cost of zaleplon is $1.72 and $2.12 per day for the 5 mg and 10 mg, respectively. It costs the same as 5 mg and 10 mg of zolpidem.
Insomia is the most common sleep disorder characterized by one or more of the following: difficulty falling asleep, difficulty maintaining sleep, and early awakening. The daytime consequences of insomnia include tiredness, difficulty concentrating, lack of energy, and irritability.4 About 30-40% of adults have some form of insomnia per year and 10-15% consider the problem serious.4 Insomnia is more prevalent in women and increases with age and socioeconomic class.5 There are many causes of insomnia including environmental or situational factors, medication side effect, substance abuse, or medical and/or psychiatric conditions.
Insomnia can be categorized as transient and intermittent or chronic. Treatment should be directed toward correcting any underlying conditions and improving sleep hygiene. Short-term pharmacologic management has included benzodiazepines (e.g., temazepam, triazolam) as well as nonbenzodiazepine (zolpidem). Due to its short elimination half-life compared to other drugs, zaleplon is probably most useful for the short-term treatment of patients whose primary complaint is difficulty in falling asleep.
1. Sonata Product Information. Wyeth Ayerst. August 1999.
2. Sanger DJ, et al. Eur J Pharmacol 1996;10:313(1-2): 35-42.
3. Rush CR, et al. Psychopharmacology (Berl) 1999; 145(1):39-51.
4. National Heart, Lung, and Blood Institute Working Group on Insomnia. September 1998.
5. Gillin JC, et al. N Engl J Med 1990;322:239-248.
a. It is not affected by cytochrome P450 inducers.
b. It has a short duration of action.
c. It is not a benzodiazepine.
d. It is most effective for inducing rapid onset of sleep.