Erlotinib Hydrochloride (2 brand names, 1 dosage form, 1 route)
Available dosage forms: TABLET.
Routes of administration: ORAL.
Brand Names
- ERLOTINIB HYDROCHLORIDE
- TARCEVA
Contraindications
None.
Adverse Reactions
The following serious adverse reactions, which may include fatalities, are discussed in greater detail in other sections of the labeling: Interstitial Lung Disease (ILD) [see Warnings and Precautions (5.1)] Renal Failure [see Warnings and Precautions (5.2)] Hepatotoxicity with or without Hepatic Impairment [see Warnings and Precautions (5.3)] Gastrointestinal Perforation [see Warnings and Precautions (5.4)] Bullous and Exfoliative Skin Disorders [see Warnings and Precautions (5.5)] Cerebrovascular Accident [see Warnings and Precautions (5.6)] Microangiopathic Hemolytic Anemia with Thrombocytopenia [see Warnings and Precautions (5.7)] Ocular Disorders [see Warnings and Precautions (5.8)] Hemorrhage in Patients Taking Warfarin [see Warnings and Precautions (5.9)]
Drug Interactions
CYP3A4 Inhibitors Co-administration of erlotinib with a strong CYP3A4 inhibitor or a combined CYP3A4 and CYP1A2 inhibitor increased erlotinib exposure. Erlotinib is metabolized primarily by CYP3A4 and to a lesser extent by CYP1A2. Increased erlotinib exposure may increase the risk of exposure-related toxicity [see Clinical Pharmacology (12.3)]. Avoid co-administering erlotinib with strong CYP3A4 inhibitors (e.g., boceprevir, clarithromycin, conivaptan, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telithromycin, voriconazole, grapefruit or grapefruit juice) or a combined CYP3A4 and CYP1A2 inhibitor (e.g., ciprofloxacin). Reduce the erlotinib dosage when co-administering with a strong CYP3A4 inhibitor or a combined CYP3A4 and CYP1A2 inhibitor if co-administration is unavoidable [see Dosage and Administration (2.4)]. CYP3A4 Inducers Pre-treatment with a CYP3A4 inducer prior to erlotinib decreased erlotinib exposure [see Clinical Pharmacology (12.3)]. Increase the erlotinib dosage if co-administration with CYP3A4 inducers (e.g., carbamazepine, phenytoin, rifampin, rifabutin, rifapentine, phenobarbital and St. John’s wort) is unavoidable [see Dosage and Administration (2.4)]. CYP1A2 Inducers and Cigarette Smoking Cigarette smoking decreased erlotinib exposure. Avoid smoking tobacco (CYP1A2 inducer) and avoid concomitant use of erlotinib with moderate CYP1A2 inducers (e.g., teriflunomide, rifampin, or phenytoin). Increase the erlotinib dosage in patients that smoke tobacco or when co-administration with moderate CYP1A2 inducers is unavoidable [see Dosage and Administration (2.4) and Clinical Pharmacology (12.3)]. Drugs the Increase Gastric pH Co-administration of erlotinib with proton pump inhibitors (e.g., omeprazole) and H-2 receptor antagonists (e.g., ranitidine) decreased erlotinib exposure [see Clinical Pharmacology (12.3)]. For proton pump inhibitors, avoid concomitant use if possible. For H
Mechanism of Action
Epidermal growth factor receptor (EGFR) is expressed on the cell surface of both normal and cancer cells. In some tumor cells signaling through this receptor plays a role in tumor cell survival and proliferation irrespective of EGFR mutation status. Erlotinib reversibly inhibits the kinase activity of EGFR, preventing autophosphorylation of tyrosine residues associated with the receptor and thereby inhibiting further downstream signaling. Erlotinib binding affinity for EGFR exon 19 deletion or exon 21 (L858R) mutations is higher than its affinity for the wild type receptor. Erlotinib inhibition of other tyrosine kinase receptors has not been fully characterized.
Overdosage
Withhold erlotinib in patients with an overdose or suspected overdose and institute symptomatic treatment.