Safety evaluation of laninamivir octanoate hydrate through analysis of adverse events reported during early post-marketing phase vigilance.

BACKGROUND: Abnormal behavior and delirium are common in children with influenza. While abnormal behavior and delirium are considered to be associated with influenza encephalopathy, an increased risk of such neuropsychiatric symptoms in patients receiving neuraminidase inhibitor treatment is suspected. Laninamivir octanoate hydrate, recently approved in Japan, is a long-acting neuraminidase inhibitor. It is important to establish a safety profile for laninamivir early, based on post-marketing experiences. METHODS: Spontaneous safety reports collected in the early post-marketing phase vigilance were analyzed. Adverse events of interest such as abnormal behavior/delirium, dizziness/vertigo, respiratory disorders, shock/syncope, and any other serious events were intensively reviewed by the Safety Evaluation Committee. RESULTS: Abnormal behavior/delirium was a frequently reported event. Almost all the reported cases were considered to be due to influenza and not laninamivir. There were 32 cases of abnormal behavior/delirium that could lead to dangerous accidents, and these were observed more frequently in males and teenagers. Syncope probably related to the act of inhalation per se of laninamivir was reported during this survey. CONCLUSIONS: This safety review revealed that the safety profile of laninamivir for abnormal behavior/delirium and syncope was similar to that of other neuraminidase inhibitors. As stated in the labeling, teenage patients inhaling laninamivir should remain under constant parental supervision for at least 2 days and should be closely monitored for behavioral changes to prevent serious accidents associated with abnormal behavior/delirium. Furthermore, to avoid syncope because of inhalation, patients should be instructed to inhale in a relaxed sitting position.

[Efficacy and safety of sitafloxacin in patients with urinary tract infections].

Sitafloxacin (STFX, Gracevit 50mg, fine granules 10%), a new quinolone antibacterial agent, was approved in January 2008, and the use-results survey was carried out over the 2 years between December 2008 and November 2010. We studied the efficacy and safety of STFX in 1,452 patients with urinary tract infections (cystitis, pyelonephritis, urethritis). The total efficacy rate for urinary tract infections was 91.4% (1,235/1,351 patients). Efficacy rates, classified by the type of infection, were: uncomplicated cystitis 95.9% (466/486 patients), complicated cystitis 87.2% (511/586 patients), uncomplicated pyelonephritis 96.1% (49/51 patients), complicated pyelonephritis 93.5% (145/155 patients), and urethritis 87.7% (64/73 patients). Efficacy rates were 86.0% (49/57 patients) for non-responders to cephems and 77.4% (48/62 patients) for non-responders to quinolones. The eradication rate of indicated strains was 90.5% (545/602 strains). The eradication rates of major causative bacteria were; Escherichia coli 92.7% (294/317 isolates), Enterococcus faecalis 86.0% (43/50 isolates), Pseudomonas aeruginosa 66.7% (16/24 isolates), Klebsiella pneumoniae 95.2% (20/21 isolates), and Chlamydia trachomatis 88.9% (8/9 isolates). The incidence of adverse drug reactions (ADRs) was 2.71% (37/1,365 cases). Major ADRs were diarrhoea (0.88%, 12 cases) and hepatic function disorders (0.51%, 7 cases). A serious ADR (hepatic function abnormality) was observed in 1 case, and the hepatic function in this patient returned to normal after treatment with STFX was discontinued. In conclusion, these results suggest that STFX is a useful antibacterial agent with an efficacy rate of 91.4% against urinary tract infections, with a minimum efficacy rate of 87.2% (against complicated cystitis), and has no serious problems in its safety profile.

[Study on the safety and efficacy of sitafloxacin--results of the use-results survey].

Sitafloxacin (STFX, Gracevit 50 mg, fine granules 10%), a new quinolone antibacterial agent, was approved in January 2008, and the use-results survey was performed for 2 years from December 2008 to November 2010. In total, 3558 case cards were collected from 287 medical institutions and 3331 cases were subjected to a safety evaluation and 3225 were subjected to an efficacy evaluation. Incidence of adverse drug reactions (ADRs) was 4.44% (148/3331 cases). Major ADRs were diarrhea (55 cases) and hepatic function disorders (39 cases), and the incidences were 1.65% and 1.17%, respectively. Serious ADRs were observed in 5 cases (7 episodes); gastrointestinal haemorrhage, hepatic function abnormal, white blood cell count decreased, drug eruption, hypoglycemia, pneumonia, and superinfection in one case each. Efficacy rate was 92.9% (2997/3225 patients) in total with a range of 91.4 to 97.8% by type of infection such as respiratory tract and urinary tract. Eradication rate of indicated strains was 91.5% (808/883 strains) including Gram-positive bacteria at 92.3% (310/336 strains), Gram-negative bacteria at 90.7% (458/505 strains), anaerobes at 100.0% (28/28 strains) and atypical bacteria at 85.7% (12/14 strains). In conclusion, this use-results survey confirmed that STFX is a useful antibacterial agent with no serious problems in its safety profile and efficacy rates of over 90% against all infections.