Omeprazole markedly raised levels of a single dose of carbamazepine, but had no significant effect on carbamazepine taken long-term. Some anecdotal reports suggest that carbamazepine serum levels may possibly be reduced by lansoprazole. Pantoprazole did not affect pharmacokinetics of carbamazepine in one study.
In 2001 manufacturers of lansoprazole had on record 5 undetailed case reports of apparent interactions between lansoprazole and carbamazepine. One of them describes development of carbamazepine toxicity when lansoprazole was added, but there is some doubt about this case because it is thought that patient may have started to take higher doses of carbamazepine.
The other 4 cases are consistent, in that carbamazepine levels fell shortly after lansoprazole was added, and/or control of seizures suddenly worsened. One patient had a fall in carbamazepine serum levels from 11.5 to 7.7 mg/L. The carbamazepine levels of another patient returned to normal when lansoprazole was stopped (See reference number 1).
Omeprazole 20mg daily for 14 days was found to increase AUC of a single 400mg dose of carbamazepine in 7 patients by 75%. The clearance was reduced by 40 % and elimination half-life was more than doubled (from 17.2 to 37.3 hours) (See reference number 2). However, a retrospective study of records of 10 patients who had been taking omeprazole 20mg daily with long-term carbamazepine (rather than a single dose) found a non-significant reduction in carbamazepine serum levels (See reference number 3).
Pantoprazole 40mg daily for 5 days had no effect on AUC of carbamazepine or carbamazepine-10,11-epoxide after a single 400mg dose of carbamazepine in healthy subjects (See reference number 4)
Omeprazole may inhibit oxidative metabolism of single doses of carbamazepine. However, when carbamazepine is taken continuously it induces its own metabolism by cytochrome P450 isoenzyme CYP3A4, thereby possibly opposing effects of this interaction (See reference number 3).
It seems that in practice no clinically relevant interaction is likely to occur between omeprazole and carbamazepine. For lansoprazole,information seems to be limited to this handful of reports from which no broad general conclusions can be drawn, but they do suggest that this interaction should be considered if lansoprazole is added to established treatment with carbamazepine. Pantoprazole appears not to affect pharmacokinetics of carbamazepine.
Wyeth (UK). Personal communication,September 2001.
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