Objective: The aim of this study was to analyze the factors influencing the addition of clinically significant adverse reactions (CSDR) section in drug package inserts in Japan.
Methods: The summaries of investigation results from August 2011 to July 2014 were evaluated.  The revisions were classified into revisions based only on case reports from Japan ([Revision Y]) and revisions based on other information and/or case reports from Japan ([Revision X]).  The revisions were classified into MedDRA system organ class (SOC).  As index of amount of information from domestic case reports, the number of accumulated cases ([Case A]), cases for which a causal relationship to the product could not be ruled out ([Case B]), and fatal cases ([Case C]) were used.  In each SOC, as index of causal relationship to the product, [Index B/A] ([Case B]/[Case A]) was calculated.  Relationship of [Index B/A] to [Revision X]/all revisions, or to the number of [Case A] in [Revision Y] were evaluated.  Deference of drug lag between [Revision X] and [Revision Y] was evaluated.
Results: Three hundreds twenty-three revisions with respect to the addition of CSDR section were identified.  [Revision Y] was 203 revisions (63%).  The number of [Case A], ([Case B], and ([Case C]) that were required for [Revision X] (120 revisions) were significantly lower than that were required for [Revision Y] (p<0.0001 for all comparisons).  [Index B/A] tended to inversely correlate with [Revision X]/all revisions (r=−0.52, p=0.066), and the number of [Case A] in [Revision Y] (r=−0.61, p=0.025).  Drug lag of [Revision X] was significantly longer than that of [Revision Y] (p<0.001).
Conclusions: In future, it would especially needed to pay attention to adverse reactions with a low [Index B/A] of which revisions relatively depend on other information.

This study describes the successful use of modified dorsolumbar epidural anesthesia with a fixed volume of anesthetic in a bovine referral center. Among the 130 Holstein cattle scheduled for flank surgery, 90 cattle received a mixed anesthetic consisting of 1 ml of xylazine hydrochloride and 3 ml of lidocaine hydrochloride by modified dorsolumbar epidural anesthesia. Eighteen cattle with dehydration and/or lameness received a mixed anesthetic containing 0.5 ml of xylazine and 3 ml of lidocaine. Infiltration anesthesia was performed in 22 cattle whose epidural space could not be reached in order to perform the flank surgery. The surgeries began about 12 min after the administration of the anesthetic and lasted for about 36 min. The modified method using a fixed volume of anesthetic was successfully introduced and effectively used in a bovine referral center. This modified method will allow veterinarians to save time and effort, thus lowering the cost of each surgery.
Anesthesia, Epidural/methods/*veterinary ; Anesthetics, Local/*administration & dosage ; Animals ; Cattle/*surgery ; Epidural Space ; Female ; Lidocaine/*administration & dosage ; Lumbar Vertebrae ; Xylazine/*administration & dosage