Abstract and Introduction
Abstract
Purpose. The case of a patient who developed elevated International Normalized Ratio (INR) values after concomitant administration of warfarin and erlotinib is reported.
Summary. A 47-year-old Caucasian man with a history of atrial fibrillation, anxiety, and a 40-pack-year smoking history was diagnosed with advanced, moderately differentiated adenocarcinoma of the lung. Soon after being diagnosed with non-small-cell lung cancer, warfarin was initiated for the treatment of a venous thromboembolism. The patient's warfarin dosage was adjusted to reach a target INR of 2–3. His INR was relatively stable (2.1–3.2) for at least eight weeks before erlotinib was added to the chemotherapy regimen. The patient developed a well-disseminated rash and diarrhea soon after starting erlotinib. Seven days after the initiation of erlotinib therapy, the patient's INR value increased from 2.8 to 5.3, with no concurrent changes in warfarin dosage, other medications, or diet. After withholding two doses of warfarin, the patient's INR value increased to 9.1, and the patient developed an elbow hematoma. His anticoagulation was rapidly reversed with the administration of subcutaneous phytonadione. The patient elected to discontinue erlotinib nine days after its initiation. The next day, his INR value was 2.4. The patient returned to the hematology–oncology clinic for follow-up two days later, where his INR was found to be 0.9.
Conclusion. Concomitant administration of erlotinib and warfarin resulted in an increase in INR values in a 47-year-old man with advanced lung cancer.
Introduction
Lung cancer is the leading cause of cancer-related death among men and women in the United States. An estimated 219,440 new cases of lung and bronchus cancer and 159,390 deaths from these cancers were projected to occur in 2009 in the United States. Non-small-cell lung cancer (NSCLC) is the most common, accounting for 85–90% of all lung cancer cases.
Erlotinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. Erlotinib specifically inhibits human EGFR-1, which blocks the downstream signal trans-duction that is critical to cellular processes. Overexpression of EGFR has been reported in patients with NSCLC. Although two Phase III clinical trials found that erlotinib did not improve overall survival in previously untreated patients with advanced NSCLC, erlotinib was approved for the treatment of refractory advanced or metastatic NSCLC. Common adverse effects of erlotinib include skin rash, diarrhea, and elevated liver enzyme values.
Cancer and cancer therapy are risk factors for venous thromboembolism (VTE). Treatment of VTE in this patient population has historically included anticoagulation with warfarin. Updated treatment guidelines recommend the use of a low-molecular-weight heparin (LMWH) for the first three to six months and then warfarin or an LMWH indefinitely or until the cancer is resolved. The prescribing information for erlotinib includes a precaution for patients receiving concomitant warfarin therapy due to reports of elevated International Normalized Ratio (INR) values and bleeding events. The mechanism of action for this interaction is unknown. A literature search in MEDLINE and International Pharmaceutical Abstracts revealed no case reports or discussions of the mechanism of action for this drug interaction. We report the case of a patient with lung cancer who experienced an increase in INR values after concomitant administration of erlotinib and warfarin.