The main drug-drug interactions associated with erlotinib include
CYP3A4 Inhibitors/ inducers
Potent CYP3A4 inhibitors increase erlotinib plasma concentrations and may lead to increased toxicity.1,2 Co-administration of ketoconazole increased erlotinib Cmax by 69% and AUC by 86%.2
CYP3A4 inducers decrease erlotinib plasma concentrations and may reduce efficacy.1,2 Pre-treatment with rifampicin for 7-11 days prior to erlotinib decreased erlotinib AUC by 58-80%.1 Concomitant erlotinib and rifampicin (600 mg once daily for 7 days) decreased the erlotinib AUC by 69%.2
Other Drug-drug Interactions
Medicines that Alter Gastric pH
As the solubility of erlotinib decreases above pH 5, drugs affecting gastric pH can lower erlotinib plasma concentrations.1,2 Co-administration of erlotinib with omeprazole, a proton pump inhibitor, decreased the erlotinib Cmax and AUC by 61% and 46%, respectively.1,2 Co-administration of erlotinib with 300 mg ranitidine, an H2-receptor antagonist, decreased erlotinib Cmax and AUC by 54% and 33%, respectively; this effect was substantially reduced when erlotinib was dosed in a staggered manner 2 hours before or 10 hours after ranitidine 150 mg bid.1,2
Cigarette smoking decreases erlotinib plasma concentrations and dose modifications are recommended.1 A pharmacokinetic interaction study identified a significant 2.8-, 1.5- and 9-fold reduction in AUCinf, Cmax and plasma concentration at 24 hours, respectively, after erlotinib administration in smokers vs. non-smokers; this is likely to represent a clinically significant effect.2 Smokers had a 24% higher rate of erlotinib clearance.1,2
Interaction between erlotinib and coumarin-derived anticoagulants (including warfarin) can lead to increased INR and bleeding; severe and fatal haemorrhage has been reported.1,2
Ciprofloxacin: co-administration of ciprofloxacin (a moderate CYP1A2 inhibitor) increased the erlotinib AUC by 39% and that of the active metabolite by 60%; the clinical relevance of this increase is unknown.2
Statins: erlotinib may increase the potential for statin-induced myopathy (rare).2 As this is likely due to competition for CYP3A4, pravastatin (eliminated by the kidneys) may be considered.3
P-glycoprotein inhibitors: as erlotinib is a P-gp substrate, co-administration of P-gp inhibitors may lead to altered distribution and/or elimination of erlotinib.2
Capecitabine: capecitabine may increase erlotinib concentrations.2
Proteasome inhibitors: studies have shown EGFR degradation through the proteasome, indicating a potential for interaction.2
- Food and Drug Administration. Erlotinib (TARCEVA) Prescribing information. 2015.
- European Medicines Agency. Erlotinib (TARCEVA). Summary of Product Characteristics. 2015.
- Pajares B, Torres E, Trigo JM et al. Tyrosine kinase inhibitors and drug interactions: a review with practical recommendations. Clin Transl Oncol 2012; 14: 94-101.