Drug Interaction Report

GENERALLY AVOID: Coadministration with irinotecan-based chemotherapy increases the toxicity of panitumumab, especially severe diarrhea. The mechanism has not been described. In a study of 19 patients receiving panitumumab in combination with the IFL regimen consisting of irinotecan (125 mg/m2), bolus 5-fluorouracil (500 mg/m2) and leucovorin (20 mg/m2), the incidence of National Cancer Institute-Common Toxicity Criteria (NCI-CTC) grade 3 to 4 diarrhea was 58% and fatal in one patient. In a study of 24 patients receiving panitumumab plus the FOLFIRI regimen consisting of infusional 5-fluorouracil, leucovorin, and irinotecan for the second-line treatment of patients who have received first-line fluoropyrimidine-based chemotherapy (excluding irinotecan), the incidence of NCI-CTC grade 3 diarrhea was 25%. Acute renal failure has been observed in patients who develop severe diarrhea and dehydration during panitumumab therapy, with or without concomitant chemotherapy. In elderly patients, an increased number of serious adverse events were reported for panitumumab in combination with FOLFIRI compared to chemotherapy alone (45% vs 37%). The most increased serious adverse events were diarrhea, dehydration, and pulmonary embolism. No evidence of pharmacokinetic interaction has been seen in clinical studies in which panitumumab was administered concurrently with irinotecan-containing chemotherapy regimens.

MANAGEMENT: Due to a high incidence of severe diarrhea, which may lead to electrolyte depletion and acute renal failure, the use of panitumumab in combination with the IFL regimen should generally be avoided. Patients treated with panitumumab should be monitored for signs and symptoms of severe diarrhea and dehydration such as decreased urine output, dizziness, low blood pressure, and rapid heartbeat. Appropriate medical therapy should be rendered promptly as necessary for the treatment of these complications, and panitumumab withheld until the patient recovers.