Real-world safety and efficacy of amenamevir in patients with herpes zoster in Japan: A postmarketing observational study (REWARD).

The helicase-primase inhibitor amenamevir (AMNV) was approved for herpes zoster in Japan in 2017. The authors conducted a 1-month postmarketing observational study to evaluate the real-world safety and efficacy (cutaneous improvement and pain resolution) of AMNV in patients with herpes zoster. Of the 3453 patients registered between March 2018 and December 2020, 3110 were included in the safety analyses. The mean age (±standard deviation) was 63.7 ± 17.5 years, with 57.9% of patients aged ≥65 years. Most patients had mild (53.3%) or moderate (41.0%) cutaneous lesions. Regarding pain, 43.9%, 25.6%, and 12.5% of patients had pain at the levels of 1-3, 4-6, and 7-10 on the numerical rating scale. In total, 30.0%, 27.2%, and 16.1% of patients were concomitantly treated with analgesics: acetaminophen, nonsteroidal anti-inflammatory drugs, and Ca2+ channel α 2δ ligands, respectively, and 10.6% were treated with topical antiherpetic drugs. Adverse drug reactions occurred in 0.77% of patients, including four serious adverse drug reactions in four patients (hyponatremia, thrombocytopenia, rash, and rhabdomyolysis). Regarding important potential risks, renal disorder, cardiovascular events, and decreased platelets were observed in one, one, and two patients, respectively. Concerning efficacy, the cutaneous improvement rate (significantly improved or improved) was 95.5%, with significantly higher improvement rates in patients treated with AMNV for 7 days and in patients with less severe cutaneous lesions or less pain. Factors affecting the time to pain resolution were the severity of cutaneous lesions and pain at the start of AMNV treatment and older age. This study demonstrated that the AMNV is safe and effective in patients with herpes zoster in a real-world clinical setting.

Safety and Effectiveness of Micafungin in Japanese Pediatric Patients: Results of a Postmarketing Surveillance Study.

Limited data are available about the safety and efficacy of micafungin in children. A postmarketing surveillance study was conducted to assess the safety and effectiveness of micafungin, an echinocandin antifungal, in pediatric patients. A prospective multicenter postmarketing observational study was carried out between October 2006 and September 2008 in Japan. Pediatric patients under 16 years received an intravenous infusion of micafungin at a dose of 1 mg/kg for candidiasis and 1 to 3 mg/kg for aspergillosis, with the option of increasing the dose if required to 6 mg/kg once daily. All adverse events were recorded. A total of 201 pediatric patients were enrolled. There were 55 adverse drug reactions reported among 42 of 190 patients evaluated for safety (22.1%); the most frequently reported adverse drug reaction was hepatobiliary disorders. No adverse drug reactions were reported in 18 neonates (aged below 4 wk). The overall clinical response rate in 91 patients evaluated for efficacy was 86.8%. The response rate in neonates was 90.0%, and there were no differences in the response rate by age. Micafungin was found to have sufficient safety and effectiveness for the treatment of fungal infections in pediatric patients with various backgrounds.

Safety and efficacy of micafungin for prophylaxis against invasive fungal infections in Japanese patients undergoing hematopoietic stem cell transplantation: Results of a post-marketing surveillance study.

Invasive fungal infections are a major cause of morbidity and mortality in patients with hematopoietic stem cell transplantation. A prospective multicenter post-marketing observational surveillance study was conducted from July 2007 to June 2010 to assess the safety and efficacy of micafungin, an echinocandin antifungal, for prophylaxis against invasive fungal infections in Japanese patients undergoing hematopoietic stem cell transplantation. Among 241 patients evaluated for safety, 143 adverse drug reactions were reported in 86 patients (35.7%), with hepatobiliary disorders the most frequently reported adverse drug reactions. The success rate for prophylaxis at the end of observation was 72.8% (131/180 patients), and the incidence of breakthrough infections was only 4.4% (8/180 patients). In conclusion, micafungin had sufficient safety and efficacy for prophylaxis against invasive fungal infections in Japanese patients with various backgrounds undergoing hematopoietic stem cell transplantation.

Evaluation of the safety and efficacy of micafungin in Japanese patients with deep mycosis: a post-marketing survey report.

The safety and efficacy of micafungin were evaluated in a Japanese post-marketing survey involving 1,142 patients with deep mycosis caused by Candida or Aspergillus. The overall clinical response was 83.0%, and the respective responses for patients with candidiasis or aspergillosis were 86.3 and 70.8%. With regard to drug reactions, 562 adverse reactions were observed in 28.5% of patients. Among the 83 serious adverse drug reactions reported by 53 patients, a causal relationship with micafungin was assessed as definite or probable for 6 reactions in 5 patients. Age and baseline hepatic and renal function status did not affect the incidence of adverse reactions, although incidence increased significantly in proportion to the severity of mycosis and daily dose (p < 0.01). In multiple logistic regression analysis, neither baseline hepatic impairment nor increased daily dose of micafungin affected the incidence of hepatobiliary disorders, however, the severity of mycosis was found to correlate significantly with hepatobiliary disorders (p = 0.031). Taken together, our post-marketing findings show that micafungin is effective against deep mycosis caused by Candida or Aspergillus in patients across a range of backgrounds.