Fatal neutropenic enterocolitis associated with docetaxel use: A review of cases reported to the United States Food and Drug Administration Adverse Event Reporting System.

Docetaxel is a microtubule inhibitor indicated for the treatment of multiple cancers as a single agent or in combination with other antineoplastics. The U.S. Food and Drug Administration (FDA) conducted a postmarketing review of fatal neutropenic enterocolitis cases reported with docetaxel using the FDA Adverse Event Reporting System (FAERS) and literature to determine whether the drug was a potential cause. We searched FAERS and the literature for reports of fatal neutropenic enterocolitis with docetaxel-based treatment reported between 14 May 1996 and 13 March 2017. We characterized the clinical course and severity of neutropenic enterocolitis and utilized the World Health Organization-Uppsala Monitoring Centre rubric to assess drug causality. We identified 41 fatal cases of neutropenic enterocolitis with docetaxel from FAERS and the literature. The median time to onset of neutropenic enterocolitis from last docetaxel dose was seven days (range 2-13 days), and median time to death was nine days (range 3-23 days). The cause of death in 83% (34/41) of patients was neutropenic enterocolitis. We determined the drug-event association as probable in seven cases. Neutropenic enterocolitis with docetaxel monotherapy occurred in six cases; however, in 85% (35/41) of cases, neutropenic enterocolitis occurred when docetaxel was used in combination with other cytotoxic chemotherapy. In some cases, neutropenic enterocolitis occurred despite use of granulocyte colony-stimulating factors. Neutropenic enterocolitis is a severe and potentially fatal complication of docetaxel-based treatment, especially when combined with other antineoplastic treatments known to cause neutropenia. Practitioners should be aware of this safety risk to promptly recognize and manage patients.

Wound healing complications with lenvatinib identified in a pharmacovigilance database.

The U.S. Food and Drug Administration (FDA) has approved several vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors, including lenvatinib, for thyroid and renal malignancies. Inhibition of the VEGFR signaling pathway impairs angiogenesis and can disrupt wound healing. The objective of this work was to evaluate wound healing complications as a potential safety risk for patients treated with lenvatinib. We searched the FDA Adverse Event Reporting System (FAERS) database for postmarketing reports of wound healing complications with lenvatinib between 13 February 2015 (FDA approval date) and 15 February 2017. The search identified nine FAERS cases of lenvatinib-associated wound healing complications that were not previously reported in the medical literature. Seven cases involved postoperative wound healing complications, such as impaired healing or wound dehiscence. In our case series, the reported time to identification of delayed wound healing from tissue injury or surgery varied over a wide range (4-58 days). The time of initial lenvatinib exposure relative to the tissue injury was also highly varied in our series, which may have influenced the development and detection of impaired healing. FAERS case-level evidence suggests that lenvatinib may have contributed to wound healing complications based on temporality and biologic plausibility. Healthcare professionals should be aware of this safety risk to facilitate prompt recognition and risk mitigation.