Zolpidem is not an inhibitor or an inducer of CYP1A2 or CYP3A4 in vivo. Risk for gastrointestinal adverse events in the form of diarrhoea, nausea, vomiting, abdominal pain and fatigue motivates vigilance against insufficient intake of food, especially of carbohydrate.

Zolpidem is indicated for the short-term treatment of insomnia. Common side effects that can be potentially porphyrinogenic through reduction in carbohydrate intake and that also can be confused with an acute porphyria attack are diarrhoea, nausea, vomiting, abdominal pain and fatigue. Other common side effects are headache, dizziness and somnolence.

Zolpidem is metabolised mainly by CYP3A4 with contribution by CYP2C9, CYP1A2 and to a minor degree by CYP2D6 (Cysneiros 2007 and SPC). All the metabolites are pharmacologically inactive (SPC). The mean half-life elimination is 2.4 hours. Zolpidem produced in an in vitro study a negligible or weak inhibition of human CYP1A2, 2B6, 2C9, 2D6 and 3A. The inhibition was observed at 100 µM concentrations which correspond to 200 times maximum therapeutic concentrations (von Moltke 2002). Two in vitro studies indicates that zolpidem is a weak mechanism-based inhibitor of CYP3A (Bomsien 2006, 2007 and Polasek 2010). Zolpidem did not significantly affect the pharmacokinetics of caffeine (CYP1A2 substrate) or its metabolites when co-administered (single-dose) (Cysneiros 2007) which indicates that zolpidem is not an inhibitor or an inducer of CYP1A2 in vivo. In vivo studies have also shown that zolpidem have minimal impact on the pharmacokinetics of sertraline (Allard 1999 and Polasek 2010), a CYP3A4 substrate (Norsk legemiddelhåndbok). Only a small decrease in the AUC of sertraline (6%) was observed which, according to the FDA, is too low for zolpidem to be considered as an inducer. This result also indicates that zolpidem is not an inhibitor of CYP3A4 in vivo.

Uneventful use reported in 9 patients with acute porphyria.