Among the AAPs used in Japan, only olanzapine was found to have an elevated risk of hyperlipidemia. In contrast, risperidone, perospirone hydrochloride hydrate, blonanserin, quetiapine fumarate, and aripiprazole had relatively low risks.

Purpose We evaluated the cardiovascular risk associated with dipeptidyl peptidase‐4 inhibitors (DPP‐4Is) as monotherapy compared with other antidiabetic drugs in Japan. Methods We conducted a nationwide cohort study involving 2 716 000 diabetes patients in Japan. New users of any antidiabetic drug as monotherapy between 1 April 2010 and 31 October 2014 were identified. Occurrences of myocardial infarction (MI), heart failure (HF), and stroke requiring hospitalization associated with DPP‐4Is were compared with those associated with biguanides (BGs), sulfonylureas (SUs), or α‐glucosidase inhibitors (α‐GIs). Adjusted hazard ratios (aHRs) for these outcomes were estimated by Cox proportional hazards model. Propensity score standardization was used to control for confounding. Results We identified 1 105 103 patients using DPP‐4Is, 278 280 patients using BGs, 273 449 patients using SUs, and 217 026 patients using α‐GIs. The risks of MI and HF for DPP‐4I users were significantly higher than those for BG users (MI: aHR, 1.48 [95%CI, 1.20‐1.82], HF: aHR, 1.46 [95%CI, 1.31‐1.62]), while significantly lower than those for SU users (MI: aHR, 0.84 [95%CI, 0.72‐0.98], HF: aHR, 0.86 [95%CI, 0.81‐0.92]). The risk of MI for DPP‐4I users was similar to that for α‐GI users, while the risk of HF for DPP‐4I users was slightly higher than for α‐GI users (MI: aHR, 0.98 [95%CI, 0.82‐1.17], HF: aHR, 1.12[95%CI, 1.04‐1.21]). Conclusions Risk of MI and HF requiring hospitalization associated with DPP‐4Is as monotherapy was significantly higher than BGs, significantly lower than SUs, and similar to α‐GIs.

In the present study, we aimed to investigate the association between uratelowering drugs and cardiovascular events, primarily focusing on the risk of febuxostat and topiroxostat when compared with allopurinol in Japan. We conducted an observational study with a cohort design using the National Database

Although several spontaneous case reports on the occurrence of thrombocytopenia in patients treated with human granulocyte colony-stimulating factor (G-CSF) preparations have been accumulated, its actual causality is still unclear. To investigate the association between G-CSF preparations (filgrastim, nartograstim, lenograstim, and pegfilgrastim) available in Japan and thrombocytopenia in patients treated with antineoplastic agents, a nested case-control study was conducted using the Medical Information Database NETwork (MID-NET®) with the cohort of the Japanese population taking antineoplastic agents between 2009 and 2018. A case of thrombocytopenia was defined as a patient who had decreased platelet counts (< 50,000/mm 3 ). We identified a maximum of 10 controls for each case matched on the index date. Adjusted odds ratios (aORs) and their 95% confidence intervals (CIs) of thrombocytopenia for the use of G-CSF preparations compared with nonuse were estimated using conditional logistic regression. From the cohort in which 33,124 patients were included, 733 cases and 5,592 controls were identified. Compared with the nonuse of G-CSF preparations, the use of any G-CSF preparations increased the risk of thrombocytopenia (aOR: 5.7, 95% CI: 4.3-7.5). More detailed analysis showed that a distinctive increased risk was observed when pegfilgrastim was prescribed at 2-7 days before the index date (aOR: 7.4 95% CI: 2.0-28.1). Associations of the other G-CSF preparations with thrombocytopenia were unclear due to the inconsistent results among different analyses. A significantly increased risk of thrombocytopenia associated with pegfilgrastim was identified, leading to a revision of precautions in the package inserts of pegfilgrastim as a regulatory safety action.

Despite the requirement of routine blood tests during thiamazole treatment in Japan, granulocytopenia among patients treated with thiamazole has been occasionally reported to the Pharmaceuticals and Medical Devices Agency (PMDA). To characterize granulocytopenia in patients with thiamazole in Japan, the effects of routine blood tests were examined in a cohort of new users of thiamazole or propylthiouracil utilizing the MID‐NET. The occurrence of granulocytopenia (neutrophil count ≤ 1,500/μL) in a given period was compared between patients with and without blood test results prior to the period. The trend in neutrophil count during thiamazole treatment was also compared between patients with and without granulocytopenia. A nested case–control study based on the cohort was conducted to identify potential risk factors for granulocytopenia during thiamazole treatment. In the new user cohort including 4,371 patients treated with thiamazole, the occurrence of granulocytopenia in patients who had undergone blood tests at all previous periods was similar or higher than that among those who had not undergone blood test in all previous periods (e.g., adjusted odds ratio in period 2 was 1.63). The neutrophil count was relatively lower in the group of patients with granulocytopenia even before the occurrence of granulocytopenia. In a nested case–control study, an upward tendency of the risk was observed when a patient was co‐prescribed anti‐arrhythmic drugs or antiulcer drugs with thiamazole. The characteristics of granulocytopenia during thiamazole treatment elucidated in this study should be recognized in clinical practice for the proper use of thiamazole.