indication

For the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen. Also for use, in combination with gemcitabine, as the first-line treatment of patients with locally advanced, unresectable or metastatic pancreatic cancer.

pharmacology

Erlotinib is a Human Epidermal Growth Factor Receptor Type 1/Epidermal Growth Factor Receptor (HER1/EGFR) tyrosine kinase inhibitor.

mechanism of action

The mechanism of clinical antitumor action of erlotinib is not fully characterized. Erlotinib inhibits the intracellular phosphorylation of tyrosine kinase associated with the epidermal growth factor receptor (EGFR). Specificity of inhibition with regard to other tyrosine kinase receptors has not been fully characterized. EGFR is expressed on the cell surface of normal cells and cancer cells.

toxicity

Symptoms of overdose include diarrhea, rash, and liver transaminase elevation.

biotransformation

In vitro assays of cytochrome P450 metabolism showed that erlotinib is metabolized primarily by CYP3A4 and to a lesser extent by CYP1A2, and the extrahepatic isoform CYP1A1.

absorption

Erlotinib is about 60% absorbed after oral administration and its bioavailability is substantially increased by food to almost 100%.

half life

Median half-life of 36.2 hours.

drug interactions

Atazanavir: This CYP3A4 inhibitor increases levels/toxicity of erlotinib

Clarithromycin: This CYP3A4 inhibitor increases levels/toxicity of erlotinib

Erythromycin: This CYP3A4 inhibitor increases levels/toxicity of erlotinib

Indinavir: This CYP3A4 inhibitor increases levels/toxicity of erlotinib

Itraconazole: Itraconazole may decrease the metabolism of erlotinib. Monitor for changes in the therapeutic and adverse effects of erlotinib if itraconazole is initiated, discontinued or dose changed.

Ketoconazole: This CYP3A4 inhibitor increases levels/toxicity of erlotinib

Nefazodone: This CYP3A4 inhibitor increases levels/toxicity of erlotinib

Nelfinavir: This CYP3A4 inhibitor increases levels/toxicity of erlotinib

Rifabutin: Decreased levels/effect of erlotinib

Rifampin: Decreased levels/effect of erlotinib

Rifapentine: Decreased levels/effect of erlotinib

Ritonavir: This CYP3A4 inhibitor increases levels/toxicity of erlotinib

Saquinavir: This CYP3A4 inhibitor increases levels/toxicity of erlotinib

St. John's Wort: Decreased levels/effect of erlotinib

Telithromycin: Telithromycin may reduce clearance of Erlotinib. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Erlotinib if Telithromycin is initiated, discontinued or dose changed.

Trastuzumab: Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.

Troleandomycin: This CYP3A4 inhibitor increases levels/toxicity of erlotinib

Voriconazole: Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of erlotinib by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of erlotinib if voriconazole is initiated, discontinued or dose changed.