Esomeprazole Diazepam

While generally not of major concern, omeprazole may inhibit the metabolism of warfarin, diazepam, and phenytoin lansoprazole may decrease theophylline concentrations. Drug interactions with omeprazole are of particular concern in patients who are considered slow metabolizers, as are approximately 3% of the Caucasian population. Unfortunately, it is unclear which patients have the polymorphic gene variation that makes them slow metabolizers.17 The metabolism of esomeprazole may also be altered in patients with this polymorphic gene variation. Patients on potentially interacting drugs should be monitored for development of drug-related problems. 

Gait disturbances (attributed to benzodiazepine toxicity) occurred in two patients given triazoiam and lorazepam or flu-razepam with omeprazoie, and another patient taking diazepam and omeprazole became wobbly and sedated. Lansoprazole, pan-toprazole, or rabeprazole appear not to interact to a clinically relevant extent with diazepam. Diazepam serum levels are increased by esomeprazole but the clinical relevance of this is unknown. 

Esomeprazole inhibits the cytochrome P450 isoenzyme CYP2C19 so the plasma levels of drugs that are metabolised by this isoenzyme might be expected to be increased by concurrent use. This is true for diazepam, whieh showed a 45% decrease in clearance (whieh would be expeeted to result in some increase in its levels) when given with esomeprazole 40 mg. ... 

Information is limited, but what is eurrentiy known suggests that patients given omeprazole, and possibly esomeprazole, with diazepam may expe-rienee inereased benzodiazepine effeets (sedation, unstable gait ete). If this oeeurs the benzodiazepine dosage should be reduced. Lansoprazole, pantoprazole and rabeprazole do not appear to interaet with diazepam. 

Omeprazole and esomeprazole are also inhibitors of CYP2C19, and therefore they may increase the levels of drugs that are metabolised by CYP2C19, such as diazepam. Other CYP2C19 substrates are listed in Table 1.3 , (p.6).h Particular care may be required when giving drugs that... 

---