Safety profile and clinical course of patients with insomnia administered suvorexant by initial treatment status in a post-marketing survey.

Objectives: Suvorexant is a dual orexin receptor antagonist used for treating insomnia. The authors elucidated the safety profiles and clinical course of insomnia therapy with suvorexant under different initial treatment status seen in daily routine practice. Methods: Subgroup analysis of a post-marketing survey (PMS; 2015-2017) divided patients based on their initial treatment status with suvorexant into 'hypnotic-naïve (Group N)', 'switching from a prior sleep medication (Group S),' 'add-on therapy (Group A),' and 'others (Group O).' Results: Among 3248 patients analyzed in the PMS, the number of patients in Groups N, S, A, and O was 1946 (59.9%), 703 (21.6%), 536 (16.5%), and 63 (1.9%), respectively. The incidence of insomnia-related adverse drug reactions (ADRs) in Group S (5.3%) tended to be higher than that in Groups N (0.46%) and A (1.5%). Discontinuation rate due to an inadequate effect at 6 months in Group S (14.9%) tended to be higher than that in Groups N (9.6%) and A (10.4%). Conclusion: The results suggest that initiating suvorexant treatment after switching from other insomnia medication must require careful monitoring of insomnia-related ADRs, which might be due to abrupt discontinuation of the prior insomnia medication use.

Long-term tolerability and effectiveness of raltegravir in Japanese patients: Results from post-marketing surveillance.

Antiretroviral agents are approved in Japan based on non-clinical and clinical data reported from overseas. Neither the long-term tolerability nor the effectiveness of raltegravir or other integrase strand transfer inhibitors in Japan is known. This study reports on the long-term tolerability and effectiveness of raltegravir in Japanese clinical practice using data collected through approximately 9 years of post-marketing surveillance. This observational survey used data on human immunodeficiency virus (HIV) infected patients initiated treatment with raltegravir between 2008 and 2017 in the HIV-related drug (HRD) cooperative survey to assess the safety and effectiveness of raltegravir in real world clinical practice. There were totally 1,303 patients prescribed raltegravir across 30 institutions; 1,293 patients and 1,178 patients were included for the safety and effectiveness analyses, respectively. The overall risk of adverse drug reaction was 17.25%, with abnormal hepatic function and hyperlipidaemia (<1.5%) having the highest proportion. Median HIV-1 RNA viral loads rapidly decreased below 40 copies/mL after 3 months of raltegravir use in treatment-naïve patients, and consistently sustained below 40 copies/mL after the start of raltegravir use in treatment-experienced patients. Among the patients who were treated for 7 years, 92.00% (95% CI: 73.97-99.02) maintained HIV-1 RNA viral load below 50 copies/mL. Additionally, CD4+ cell counts exceeded >500 cells/µL in treatment-naïve and treatment-experienced patients after 3 years and 4 years of treatment, respectively. In Japanese HIV patients, long-term treatment with raltegravir is well-tolerated and effective at viral suppression as measured by HIV-1 RNA levels and subsequent change in CD4+ cell counts. Such benefits can be expected for not only treatment-naïve but also treatment-experienced patients.

Suvorexant (Belsomra® Tablets 10, 15, and 20 mg): Japanese Drug-Use Results Survey.

BACKGROUND: We report on the results of a Japanese postmarketing drug-use survey of suvorexant (Belsomra®) tablets. METHODS: A survey with a ≤ 6-month observation period after the start of administration was conducted, targeting insomnia patients who were treated with suvorexant for the first time in Japan. Information on the safety and efficacy of the drug product was collected. The evaluation period was July 21, 2015-August 12, 2017, and the target number of patients was 3428. RESULTS: The mean administration period for the safety analysis population of 3248 patients was 113 days. At 6 months after the start of treatment, 48.6% (1577/3248) of the patients had been continually receiving treatment, and 51.4% (1671/3248) of the patients discontinued/dropped out of treatment before 6 months. Among the patients who discontinued/dropped out of the treatment, more than 30% discontinued due to improvement. The mean treatment duration for those who had discontinued treatment for this reason was 62 days. The incidence rate of adverse drug reactions among those in the safety analysis population was 9.7%, and the common adverse drug reactions were somnolence (3.6%), insomnia (1.2%), dizziness (1.1%), and nightmare (0.8%), all of which are described in the product label. No additional noteworthy events were observed. In 2439 patients with a final overall global assessment of sleep judged by physicians, the 'improved' rate was 74.0%. Among 2424 patients who provided a final overall global assessment, the improvement rate was 73.2%, which was comparable with the improvement rate judged by physicians. Regarding clinical effects (based on patient diary data or physician's assessment), reduction in median sleep latency and increase in median total sleep time (reduction from 60 to 50 min and increase from 300 to 360 min compared with baseline, respectively) were observed at 1 week after the start of treatment and onwards, and the effect was maintained after the start of treatment for 6 months. A similar effect was observed irrespective of age groups or reasons for using suvorexant. CONCLUSION: This survey was an exploratory observational study without a control group; the interpretation of results may require the consideration of factors that may have caused bias in the results, such as demographic characteristics and effects of other drugs. However, the results suggest that suvorexant can be a useful drug in daily clinical practice for treating insomnia.

Safety and effectiveness, including intelligence prognosis, of diazoxide in pediatric patients with hyperinsulinemic hypoglycemia: special survey in Japan (long-term, all-case survey).

To evaluate the safety and effectiveness of the long-term administration of diazoxide in patients with hyperinsulinemic hypoglycemia, a post-marketing surveillance study was conducted. Between 2008 and 2015, with a maximum observation period of 7 yr, 384 patients were monitored; 117 (30.5%) experienced at least one adverse drug reaction (ADR). The most commonly observed ADR was hypertrichosis (8.6%). The incidence of water retention-related ADRs and cardiac failure-related ADRs was 8.3% and 3.4%, respectively, and many of these occurred within the first 2 mo of treatment. The mean fasting blood glucose level was 44.9 mg/dL at baseline and was maintained at > 70 mg/dL, the control target, for 4 yr. A total of 113 infants < 1 yr of age were evaluated for the prognosis for intelligence, and a majority (77.9%) were assessed as "normal" at the final evaluation. Most ADRs occurred at an early stage of treatment and blood glucose levels were well controlled during long-term administration. The proportion of "normal" patients tended to be higher in those who started treatment at a younger age. However, because of the exploratory nature of this analysis, potential effects of coexisting or underlying diseases and the age of onset or diagnosis should not be ignored.