Already in January 2013 the U.S. FDA issued a Safety Warning for the hypnotic zolpidem. According to the statement, overhang effects are possible in the morning after intake of zolpidem, which can lead to impaired performance of activities that require full attention and alertness (eg, driving). Particularly vulnerable are women, because they metabolize the substance slowly.The FDA has therefore required the manufacturers of zolpidem to change their dosage recommendation. In women, the recommended dose of 10 mg has to be reduced to 5 mg. For men, the FDA also requests that in the future the product information has to contain the recommendation to consider a reduced dose of 5 mg.
Zolpidem is actually characterized because of its short half-life of only 2-3 hours by the lack of overhang effects. It is particularly suitable, for example, for people who must drive a vehicle in the morning. The new data, which were submitted to the FDA show that plasma concentrations are occasionally measured – especially in women – in the morning after the dose that are associated with an impaired driving ability. 50 ng/mL are being considered as a threshold plasma concentration. In a group of 250 women and 250 men 15% of women and 3% of men had a plasma concentration above 50 ng/mL in the morning after ingestion of 10 mg zolpidem. In three women and one man, the plasma concentration was even above 90 ng/mL eight hours after drug administration. After intake of an extended release preparation (12.5 mg zolpidem, not available in Germany and Austria, but in Switzerland), eight hours after ingestion of the drug plasma concentrations above 50 ng/mL were measured in 33% of women and 25% of men.
The Task Force „Therapeutic Drug Monitoring“ (TDM) of the German Working Group for Neuropsychopharmacology and Pharmacopsychiatry (AGNP) in its recent Consensus Paper recommends a therapeutic reference range of 80-150 ng/ml for zolpidem.
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