Zaleplon drug interactions

Research on drug interactions with zolpidem and zaleplon is limited, but any drug with CNS depressant effects could potentially enhance the CNS depressant effects of zolpidem and zaleplon through pharmacodynamic interactions. In addition, zolpidem is primarily metabolized by CYP 3A3/4, and zaleplon is partially metabolized by CYP 3A3/4. Thus, inhibitors of these enzymes may increase blood levels and the toxicity of zolpidem. 

Hesse LM et al Clinically important drug interactions with zopiclone, zolpidem and zaleplon. CNS Drugs 2003 17 513. [PMID 12751920]... 

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. 

Darwin M Overview of drug interaction studies with zaleplon Poster presented at 13" Annual Meetup of Associated ofessiaial Sleep Studies (APSS), Orlando, Florida, June 23 ", 1999. 

DarwidiM. Analysis of potential drug interactions with zaleplon. J Am Geriatr Soc 47, S62. 

Drug/Food interactions The effects of zaleplon on sleep onset may be reduced if it is taken with or immediately after a high-fat/heavy meal. 

Other drugs The anxiolytic ding buspirone interacts with the S-HT, subclass of brain serotonin receptors as a partial agonist, but the precise mechanism of its anxiolytic effect is unknown. The hypnotics zolpidem and zaleplon are not benzodiazepines but appear to exert their CNS effects via interaction with certain benzodiazepine receptors, classified as BZ, or omega, subtypes their CNS depressant effects are antagonized by flumazenil. 

The serum levels of many of the benzodiazepines and related drugs are raised by cimetidine, but normally this appears to be of little or no clinical importance and only the occasional patient may experience an increase in the effects (sedation). The interactions with midazolam, zaleplon, and Zolpidem may be more significant, but this is not established. Famotidine, nizatidine and ranitidine do not normally appear to interact with most benzodiazepines. Increased sedation appears to occur with clomethiazole and cimetidine. 

---