Acute acalculous cholecystitis: A new safety risk for patients with MS treated with alemtuzumab.

OBJECTIVE: To evaluate acute acalculous cholecystitis (AAC) as a potential safety risk for patients treated with alemtuzumab. METHODS: The Food and Drug Administration Adverse Event Reporting System and the medical literature were searched for cases of AAC in conjunction with alemtuzumab for all clinical indications. RESULTS: Eight spontaneously reported cases meeting the case definition of AAC in close temporal association with alemtuzumab use were identified. Based on established criteria within the Food and Drug Administration Division of Pharmacovigilance for causality assessment, 4 cases were assessed as probable while 4 were possible. All cases occurred in patients with relapsing-remitting multiple sclerosis. Seven of the 8 cases presented with AAC during or shortly after alemtuzumab treatment, thereby suggesting an acute cytokine release syndrome as a putative pathogenic mechanism. The cases identified in this review differ from the typical AAC cases described in the medical literature based on female preponderance, lack of concurrent critical illnesses, inconsistent presence of other risk factors, and resolution with conservative treatment in the majority of cases. CONCLUSIONS: AAC represents a new and potentially life-threatening adverse event associated with alemtuzumab use in relapsing-remitting multiple sclerosis. In cases seen to date, early and conservative treatment resulted in good clinical outcome, although the natural history of AAC in this population without critical illness is not well defined. Awareness of this safety risk by general and specialty neurologists is important for prompt recognition and optimal management.

Clinical profile of oxcarbazepine-related angioneurotic edema: case report and review.

Oxcarbazepine, a carbamazepine analog, was approved for use as an antiepileptic agent in the United States in 2000. A search of the United States Food and Drug Administration's Adverse Event Reporting System identified nine cases of oxcarbazepine-associated angioedema in pediatric patients aged 16 years and younger. We describe in detail the first U.S. case report, of a 4(1/2)-year-old boy who experienced angioedema during treatment with oxcarbazepine. The reporting rate for angioedema was calculated to be 9.8 cases per 1,000,000 pediatric patients. Oxcarbazepine-associated angioedema manifested by swelling of the face, eyes, lips, or tongue or difficulty swallowing or breathing (or both) is a rare but potentially life-threatening reaction for which early recognition and management are vital.

Improving the quality of adverse drug reaction reporting by 4th-year medical students.

PURPOSE: Evaluate whether a 15-minute lecture intervention will improve adverse drug reaction reporting quality on standard MedWatch forms. METHODS: Seventy-eight 4th-year medical students were randomized to intervention 'Group-A' or non-intervention 'Group-B' on the first day of a required five-day clinical pharmacology rotation. Group-A participants attended a 15-minute lecture on completing a MedWatch form with quality information considered by the Food and Drug Administration as critical to adequate adverse drug reaction reporting. Group-B participants did not attend this lecture. Both groups then watched a standardized patient interview of a recognizable adverse drug reaction and completed MedWatch forms. Four Safety Evaluators from the Food and Drug Administration (FDA) rated student responses in a blinded fashion for the primary efficacy variable of Overall Impression and six informational domins using a standardized data quality analysis form that was developed within the Office of Postmarketing Drug Risk Assessment of the FDA. RESULTS: Seventy-eight MedWatch forms were evaluated (Group-A = 40, Group B = 38). Overall MedWatch information quality scores for the intervention group were significantly higher than the non-intervention group (p < 0.004). CONCLUSIONS: As little as a 15-minute intervention can significantly improve the quality of adverse drug reaction reporting by 4th-year medical students. Academic medical centers should consider incorporating adverse drug reaction reporting curriculum into the clinical training of medical students.