Zaleplon adverse effects

More recently, non-BZD anxiolytics, such as buspirone, and nonbarbiturate, non-BZD hypnotics, such as zolpidem and zaleplon, have been developed. The more recent anxiolytics and hypnotics offer equal efficacy, fewer serious adverse effects, and less risk of a fatal consequence due to accidental or intentional overdose. Unfortunately, these compounds have not entirely eliminated the hazards of tolerance, dependency, and withdrawal syndromes, although they do have a lower abuse potential than their predecessors. 

Zaleplon and zolpidem - stated to have little adverse effect on sleep profile. There is evidence that the therapeutic efficacy is maintained even after several months of treatment. 

Zaleplon is a non-benzodiazepine that induces sleep comparable to other hypnotics but with significantly fewer residual effects (1), related at least in part to its short half-life. It is a pyrazolopyrimidine hypnotic that binds selectively to the GABAa1a receptor, previously known as the benzodiazepine type 1 (BDZi) receptor. Whereas such agonist selectivity was hoped to confer advantages in terms of the risk of adverse effects, in practice zaleplon is similar to the older non-selective benzodiazepines in terms of both efficacy and safety (2-4). The so-called Z drugs, including zaleplon, are significantly more expensive than benzodiazepines and are therefore likely to be less cost-effective (5). 

After oral administration zaleplon is well absorbed (71%) and peak concentrations are reached in about 60 minutes. However, it undergoes presystemic elimination and has a systemic availability of about 30%. Its adverse effects include anterograde amnesia, depression, paradoxical reactions (for example restlessness, agitation), dependence, and withdrawal symptoms (related to the dose and duration of treatment). Although the data are limited, it is thought to be relatively safe in overdose, unless it is combined with other CNS depressants. 

Three doses of zaleplon have been compared with placebo in outpatients with insomnia in a 4-week study (11). During week 1, sleep latency was significantly shorter with zaleplon 5, 10, and 20 mg than with placebo. The significant reduction in sleep latency persisted to week 3 with zaleplon 10 mg and to week 4 with zaleplon 20 mg. Compared with placebo, zaleplon 10 mg and 20 mg also had significant positive effects on sleep duration, number of awakenings, and sleep quality. Pharmacological tolerance did not develop with zaleplon and there were no indications of rebound insomnia or withdrawal symptoms after discontinuation. There was no significant difference in the frequency of adverse events with zaleplon compared with placebo. The authors concluded that zaleplon provides effective treatment of insomnia with a favorable safety profile. 

The interaction of zaleplon with digoxin has been investigated in 20 subjects (22). There were one or more adverse effects in 18% of those who took digoxin alone and 35% of those who took digoxin plus zaleplon, but these were all mild and resolved quickly. Zaleplon had no significant effects on selected pharmacokinetic and pharmacodynamic properties of digoxin. 

The interaction of zaleplon with ibuprofen has been investigated in 17 subjects (23). Healthy adult volunteers were given zaleplon 10 mg alone, ibuprofen 600 mg alone, or zaleplon 10 mg plus ibuprofen 600 mg in an open, randomized, crossover study. The adverse effects were mild and resolved without intervention. The authors concluded that there was no evidence of a significant interaction between zaleplon and ibuprofen. 

The most common adverse effects with zaleplon are dizziness, headache, and somnolence. There is some concern about the possible occurrence of dependence, but insufficient data exist to determine whether this will be an issue with this agent. Development of tolerance does not appear to be significant. There are two drug interactions of note zaleplon plasma levels are increased when combined with cimetidine and decreased with rifampin. ... 

Other adverse effects Barbiturates and carbamates (but not benzodiazepines, buspirone, zolpidem, or zaleplon) induce the formation of the liver microsomal enzymes that metabolize dmgs. This enzyme induction may lead to multiple drug interactions. Barbiturates may also precipitate acute intermittent porphyria in susceptible patients. Chloral hydrate may displace coumarins from plasma protein binding sites and increase anticoagulant effects. 

Zaleplon (Sonata) [C IV] [Sedotive/Hypnotic] Uses Insomnia Action A nonbenzodiazepine sedative/hypnotic, a pyrazolopyrimidine Dose 5-20 mg hs PRN -1- w/ renal/hepatic insuff, elderly Caution [C, /-] w/ mental/ psychological conditions Contra Component allergy Disp Caps SE HA, edema, amnesia, somnolence, photosens Interactions t CNS depression W/ CNS d es-sants, imipramine, thioridazine, EtOH X effects W/ carbamazepine, phenobarbital, phenytoin, rifampin EMS Concurrent EtOH can t adverse CNS effects OD May cause profound CNS depression symptomatic and supportive Zanamivir (Relenza) [Antiviral/Neuramidase Inhibitor] Uses Influenza A (including HlNl swine flu) B Action X Viral neuraminidase Dose Adults Feds > 7 y.2 inhal (10 mg) bid for 5 d initiate w/in 48 h of Sxs Caution [C, M] Contra Pulm Dz Disp Powder for inhal SE Bron-chospasm, HA, GI upset EMS Does not reduce risk of transmitting virus monitor for bronchospasm or other severe resp events OD May cause resp problems s5rmptomatic and supportive... 

Zaleplon and zolpidem have been compared in two concurrent multicenter, randomized, double-blind, placebo-controlled crossover studies in chronic insomniacs (12). In study 1, zaleplon 10 mg, zolpidem 10 mg, or placebo were given double-bhnd to 36 healthy subjects under standardized conditions in a six-period, incomplete-block, crossover study (13). The subjects were gently awakened and given the medication at predetermined times, 5, 4, 3, or 2 hours before morning awakening, which occurred 8 hours after bedtime. When they awoke in the morning, subjective and objective assessments of residual effects of hypnotics were administered. There were no serious adverse experiences during the study all adverse events were mild to moderate. The most commonly reported adverse events associated with zaleplon were weakness and somnolence. Weakness, depersonalization, dizziness, and somnolence were the most frequent nervous system adverse events associated with zolpidem. 

Diclofenac reduces the dose of midazolam needed to produce sedation and hypnosis. Diazepam has a small effect on the pharmacokinetics of diclofenac, ibuprofen and naproxen. Diazepam and indometacin appear not to interact adversely, although feelings of dizziness may be increased. Zaleplon and ibuprofen appear not to interact... 

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