Rabeprazole is mainly metabolized non-enzymatically with minor contributions by CYP2C19 and CYP3A4. Clinical data indicates that rabeprazole is a weak inhibitor of CYP2C19, but no data indicates mechanism-based inhibition. It is not an inhibitor or inducer of CYP1A2 in vivo. Risk for gastrointestinal adverse events in the form of nausea, vomiting and diarrhoea motivates vigilance against insufficient intake of food, especially of carbohydrate.

Pyridylbenzamidazole derivative, with secondary as well as tertiary amine functions.

Rabeprazole is a proton pump inhibitor used in the treatment of active duodenal ulcer, active benign gastric ulcer, symptomatic erosive or ulcerative gastro-oesophageal reflux disease, gastro-oesophageal reflux disease long-term management, symptomatic treatment of moderate to very severe gastro-oesophageal reflux disease, Zollinger-Ellison syndrome, therapeutic or preventive in NSAID-treatment and in combination with appropriate antibacterial therapeutic regimens for the eradication of Helicobacter pylori in patients with peptic ulcer disease. 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, vomiting and nausea. Other common side effects are abdominal pain, constipation, back pain, non-specific musculoskeletal pain, asthenia, influenza like illness, flatulence, cough, pharyngitis, rhinitis, headache, dizziness and infections.

Probably not significant

The metabolism of rabeprazole is mainly and almost complete non-enzymatic (Horn 2004 and Shi 2008), with minor contribution by CYP2C19 and CYP3A4 (Ishizaki 1999, Itagaki 2004 and Shi 2008). In vitro data indicates that it is then stereoselectively re-oxidized by CYP3A4 mainly to (R)-rabeprazole (Miura 2006). In vitro studies have shown that rabeprazole is a weak inhibitor of CYP3A4, 2B6, 2D6, 2C9, 2C8 and 1A2. (Zhou 2007 and Zyvaga 2012). In vitro studies indicates that it is a competitive inhibitor of CYP3A4, CYP2C19 (Ishizaki 1999) and CYP2C9 (Li 2004). A clinical study showed that rabeprazole increased the AUC of lansoprazole, a CYP2C19 substrate, by 15% (Itagaki 2004) which indicates that it is a weak inhibitor of CYP2C19. In vitro data indicates that rabeprazole has low potential to induce hPXR (Sinz 2006). Rabeprazole has been shown in vitro to induce CYP1A1 and CYP1A2 (Krusekopf 2003) and at expected human plasma concentrations it does not induce or inhibit CYP3A4 (SPC). Rabeprazole does not interact with theophylline, a CYP1A2 substrate, which indicates that it does not inhibit or induce CYP1A2 in vivo (Stedman 2000). Rabeprazole has low potential for drug interactions involving CYP enzymes (Horn 2004 and Shi 2008) and is also listed as an unlikely major perpetrator of CYP2C19 (Polsaek 2011).

Two reports of attacks of acute porphyria in AIP patients following the use of rabeprazole (Kumar, 2010). The reports are however, of low quality with very limited data which makes it problematic to evaluate the causality.

Uneventful use reported in 3 patients with acute porphyria.