Zaleplon cimetidine

Cimetidine Cimetidine inhibits aldehyde oxidase and CYP3A4, the primary and secondary enzymes, respectively, responsible for zaleplon metabolism. Use an initial... 

A 10 mg bedtime dose of zaleplon is usually effective. A few patients may require a 20 mg dose. A 5 mg dose is safer and effective for elderly and debilitated patients or for those with hepatic impairment. A 5 mg dose is also preferable and safer for patients taking cimetidine, which increases zaleplon s serum concentration by almost 85%. 

Zaleplon is primarily metabolized by aldehyde oxidase and use with inhibitors of this enzyme, such as cimetidine, may result in increased plasma concentrations of zaleplon. Zaleplon is also partly metabolized by the cytochrome P450 isoenzyme CYP3A4 and, consequently, caution is advised when zaleplon is given with drugs that are substrates for, or potent inhibitors of, this isoenzyme. Cimetidine is also an inhibitor of CYP3A4 and thus inhibits both the primary and secondary metabolic pathways of zaleplon. Use with rifampicin or other potent enzyme-inducing drugs may accelerate the metabolism of zaleplon and reduce its plasma concentrations [40]. 

Renwick AB, Ball SE, Tredger JM, et al. Inhibition of zaleplon metabolism by cimetidine in the human liver in vitro studies with subcellular fractions and precision-cut liver slices. Xenobiotica 2002 32 849-862. 

Cimetidine may increase plasma concentrations of zaleplon, requiring a lower initial dose of zaleplon (5 mg/day)... 

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. ... 

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. 

Cimetidine increases plasma levels of zaleplon and slightly increases sleep duration with zolpidem. Cimetidine reduces the clearance of clomethiazole and increases sleep duration from a range of 30 to 60 minutes up to at least 2 hours. ... 

Cimetidine inhibits the liver enzymes concerned with the metabolism of diazepam, alprazolam, chlordiazepoxide, clomethiazole, clorazepate, flu-razepam, nitrazepam, triazolam, and zaleplon. As a result their clearance from the body is reduced and their serum levels rise. 

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