The multikinase inhibitor, regorafenib, is known to exert its antitumor effects by targeting several kinases, inhibiting interstitial intracellular signaling and suppressing tumor cell proliferation. Regorafenib causes gastrointestinal perforation and gastrointestinal fistula as adverse events, and discontinuation is recommended if these adverse events occur during administration. However, there are no prescribed standards for re-administration after discontinuation and for administration in patients with a history of gastrointestinal perforation. Herein, we report a case of gastrointestinal perforation in a patient, with a history of gastrointestinal microperforation, undergoing bevacizumab therapy, within a few days of starting regorafenib; this had a significant effect on the prognosis. The site of gastrointestinal perforation was consistent with previously reported sites around the tumor and at the anastomotic site. Based on a review of literature and our experience with the case presented here, we recommend that administration of regorafenib to patients with a history of gastrointestinal perforation should be avoided to the extent possible. Moreover, in case of prior administration of a drug reported to cause gastrointestinal perforation, such as an anti-VEGFR drug, the risk of gastrointestinal perforation should be considered during the administration of regorafenib. In the event of complaints, such as abdominal pain, gastrointestinal perforation should be considered as a differential diagnosis and appropriate tests and treatments should be initiated at an early stage.
Low-dose benzodiazepine receptor agonists may be completely replaced by lemborexant at about the same dose AIM Because of problems such as tolerance, addiction, abuse, and falls, many attempts have been made to reduce the prescription dose of benzodiazepine receptor agonists (BZD-RAs). 1 However, BZD-RAs remain the first-line hypnotic drug in Japanese clinical practice. 2 The US Food and Drug Administration issued a warning about the risks of BZD-RAs in 2020. 3 A phase III clinical study on lemborexant, a recently developed orexin receptor blocker, stated that lemborexant therapy showed better efficacy than BZD-RAs for objectively measured sleep onset and maintenance. 4 Moreover, another report stated that lemborexant significantly improved subjective sleep latency in the first week of administration compared to suvorexant, an existing orexin receptor blocker. 5 Therefore, lemborexant was regarded as a candidate drug for switchover from BZD-RAs. Recently, it was reported that the dose of BZD-RAs used could be reduced using lemborexant in clinical practice. 6,7 Hence, this study aimed to characterize patients in whom BZD-RAs could be completely or not completely replaced by lemborexant at our facility.
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