Should the concomitant use of erlotinib and acid-reducing agents be avoided? The drug interaction between erlotinib and acid-reducing agents

Abstract

Context. Erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor, exhibits a drug interaction with proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs). The manufacturer recommends avoidance of the combination however, the extent of the drug interaction is not clearly understood. Evidence acquisition. A literature search was performed and the pharmacokinetics and pharmacology of acid-reducing agents were reviewed. Results. Acid-reducing agents reduce the solubility, and subsequent absorption, of erlotinib by raising gastric pH. Our literature search was unable to identify any published studies or case reports that address this issue. Until more information is available, the clinical relevance of this interaction, and whether it actually leads to failure of therapy, is unknown. PPIs would all be expected to exhibit a similar effect on erlotinib. Of the H2RAs, co-administration appears to have a greater impact than administering them separately. Ranitidine, famotidine, and nizatidine should likely have similar effects on erlotinib absorption. Cimetidine has a shorter duration of action, but should be used with caution because of its effects on cytochrome P450 3A4, a pathway also utilized by erlotinib. Antacids are not expected to have a significant effect. Conclusions. The clinical relevance of this drug interaction is unknown. Until more information is available, decision making regarding this interaction should be on a patient-by-patient basis. The indication for acid-reducing therapy should be reevaluated and stopping therapy or changing therapy can be considered. However, there may be occasions where any benefit of such actions will be exceeded by its risks.