Esomeprazole is a substrate of CYP2C19 and CYP3A4. It is not likely to inhibit CYP3A4 in vivo. A very large number of reports of carriers of acute porphyria tolerating omeprazole (ATC: A02B C01), the racemate mixture with esomeprazole and R-omeprazole, speaks against porphyrinogenicity. Risk for gastrointestinal adverse events in the form of nausea, vomiting and diarrhoea motivates vigilance against insufficient intake of food, especially of carbohydrate.

Pyridyl sulfinyl-benzamidazole derivative. S-isomeric form of omeprazole.

Esomeprazole is an isomeric form of omeprazole and a proton pump inhibitor used in ventricular hypersecretion. It is indicated for the treatment of gastro-oesophageal reflux, eradication of Helicobacter pylori, continuous NSAID-treatment, prevention against reactivation of bleeding peptic ulcer and Zollinger-Ellison syndrome. 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 nausea, vomiting, abdominal pain, diarrhoea and obstipation.

Esomeprazole is primarily metabolized by CYP2C19 and to some extent by CYP3A4. It is an inhibitor of CYP2C19 (SPC) and in vitro studies have shown that esomeprazole is a weak inhibitor of CYP3A4, 2B6, 2D6, 2C9, 2C8 and 1A2 (Zyvaga 2012), Two in vivo studies have shown that when esomeprazole was co-administered with diazepam, a CYP3A4 and CYP2C19 substrate, the area under the curve and the half-life elimination of diazepam increased (Andersson 2001 and Drewelow 2010). The data indicated that esomeprazole inhibits CYP2C19 competitively (Andersson 2001) and/or CYP3A4. In vitro data indicates that it is a mechanism-based inhibitor of CYP2C19 (Zyvaga 2012), there is however conflicting data indicating that inhibition of CYP3A4 is competitive (Li 2004). In vivo studies with esomeprazole and quinidine and clarithromycin, which are primarily metabolized by CYP3A4, showed that esomeprazole would be less likely to inhibit the metabolism of CYP3A4 substrates (Andersson 2001).

S.Thunell: 1 report of safe use.

Uneventful use reported in 12 patients with acute porphyria. Omeprazole (the racemate mixture with R- and esomeprazole): uneventful use reported in 98 patients with acute porphyria.