Zolpidem

Zolpidem is a drug that is used in sleeping pills. The substance is structurally an imidazopyridine derivative with a spectrum of activity similar to that of benzodiazepines and, along with zopiclone and zaleplon, is one of the Z-drugs. Zolpidem usually has a very short half-life (2-3 hours) and no pharmacologically active metabolites. In isolated cases, however, much longer half-lives are observed (up to 10 hours). It is currently the most prescribed sleep aid in the US and Europe. Zolpidem is quickly and easily absorbed by the body, the maximum plasma level is reached after about two hours. In Germany, for example, the prescription of drugs containing zolpidem is legally restricted, primarily because of the risk of addiction.

Use

Zolpidem is approved in Germany for the short-term treatment of sleep disorders and is used as tartrate salt (zolpidem tartrate) in the form of film-coated tablets of 5 mg or 10 mg.

Due to the high doses required for an anticonvulsant and muscle-relaxing effect and the associated side effects, zolpidem is not used for these indications.

Contraindications

Zolpidem must not be used with pathological muscle weakness (myasthenia gravis), with severe breathing problems, with repeated interruption of breathing during sleep (sleep apnea syndrome), with severe liver damage and also not in children and adolescents under 18 years of age.

Side effects and restrictions on use

The spectrum of side effects is similar to that of the benzodiazepines. As with these, in addition to fatigue, dullness, headaches and visual disturbances, temporary memory gaps (anterograde amnesias), “paradoxical reactions” (restlessness, irritability, aggressiveness) and other behavioral disorders as well as hallucinations and delusions can occur; the risk of the latter occurring is increased, especially at higher doses and in elderly patients.

As expected from the relationship with the benzodiazepine group, rebound phenomena, tolerance development, physical and psychological dependencies, and withdrawal symptoms upon termination of therapy are possible despite the short plasma half-life. For this reason, it should not be prescribed for more than a few days. The risk of addiction is increased in patients with pre-existing addiction disorders. In combination with alcohol or other sedative substances (especially benzodiazepines), an increase in the effect is to be expected, which is why the maximum daily dose of 10 mg (adults) and 5 mg (elderly and debilitated patients) should not be exceeded. Women in particular are affected due to gender-specific differences in the breakdown of zolpidem via the cytochrome P450 system of the liver, since relevant blood levels may still exist in the morning after ingestion. The American Food and Drug Administration (FDA) recommends not driving or engaging in other activities that also require full mental alertness in the morning after taking zolpidem, even in low doses (6.25 mg), because of the risk of delayed reactions. These recommendations were confirmed by the MHRA in 2014.

Legal status

According to Annex III to the Narcotics Act (BtMG), zolpidem is a prescription drug in Germany. This does not apply to preparations for oral use which, without another substance in Annexes I to III BtMG, contain only up to 8.5 mg of zolpidem (calculated as base) per divided form and can therefore be prescribed on a non-official prescription form.

In Austria and Switzerland, zolpidem requires a prescription.

Trade names

Monopreparations: Ambien (USA), Bikalm (D), Ivadal (A), Mondeal (A), Stilnox (D, CH, I, F, E, GB, CZ), Zoldem (D, A), Zoldorm (CH) , numerous generics (D, A, CH)

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Zolpidem