Erlotinib-related rhabdomyolysis: the role of pharmacogenetics and drug–drug interaction

but is an uncommon complication of antineoplastic treatment [5–8]. However, cases of rhabdomyolysis have been described in patients treated with imatinib and, up to now, only one case in patient treated with erlotinib alone [9, 10]. Erlotinib is mainly metabolized by cytochrome P450 (CYP) 3A4 isoenzyme and is transported across different barriers by P-glycoprotein (MDR1/ABCB1) and ABCG2 drug transporters; the potential for CYPand transportermediated drug–drug interactions (DDIs) is high, especially with CYP3A4, P-glycoprotein (P-gp), and ABCG2 inhibitors. According to in vitro and in vivo studies, erlotinib is not only the substrate but also a P-gp/ABCG2 inhibitor [11, 12]. Interindividual pharmacokinetic variability of erlotinib is affected not only by the genetic heterogeneity of drug targets, but also by patient’s pharmacogenetic background. Published data show higher erlotinib through concentrations at steady state in patients with the ABCB1 1236TT-2677TT-3435TT genotypes compared with other groups. Patients carrying these genotypes had a higher risk of developing high grade 2 toxicity (moderate to severe skin rash and diarrhea) [13].