Increased post-marketing reports of interstitial lung disease in Japan have been recognized. An understanding of its regional groundings can be important for the global pharmacovigilance community. The objective of this study was to explore the correlation between high rates of interstitial lung disease reporting and regulatory actions in Japan. Post-marketing interstitial lung disease-related label changes and interstitial lung disease reports were classified by the anatomical therapeutic chemical classification groups of the suspected drugs. Regulatory actions for the top interstitial lung disease-reporting drugs were compared. The interstitial lung disease reporting patterns of protein kinase inhibitors were compared to those of methotrexate. Interstitial lung disease-related label changes predominantly occurred for drugs in the anatomical therapeutic chemical classification groups L, J, C, and herbal medicines. Interstitial lung disease was reported most frequently for L group, especially for the protein kinase inhibitors. The regulatory actions for those drugs with the highest number of interstitial lung disease reports (methotrexate, protease kinase inhibitors, gemcitabine, docetaxel) plus monoclonal antibodies were analyzed. The ratio of interstitial lung disease reports to all reports over time was initially high in the re-examination period, while it was constantly low after the period expired. The increase in interstitial lung disease reporting was observed for the drugs for which interstitial lung disease was designated as a priority item in the use-results survey. Methotrexate had more interstitial lung disease reports with multiple suspected drugs and fewer reports with high completeness than the protease kinase inhibitors. The high rates of interstitial lung disease reporting derived from mainly the anatomical therapeutic chemical classification group L drugs. Interstitial lung disease is the targeted adverse drug reaction in the use-results survey mandated in the re-examination of those drugs. This system provides at least one explanation for the high reporting of interstitial lung disease in Japan.
We have seen 9 moderately to severely mentally-retarded autistic children and adolescents who waited for small-step instructions to perform previously acquired daily life activities (called "waiting-for-instruction" behavior). None of these patients were capable of expressing their depressive mood. All cases were considered to meet the criteria for major depressive episode described in DSM-IN. The "waiting-for-instruction" behavior was suggested to be a diagnostic key for depressive state in mentally retarded children and adolescents. GAF scales for depressive symptoms including the "waiting-for-instruction" behavior improved in 7 of these 9 cases with fluvoxamine. Risperidone and valproate sodium were useful for these symptoms in patients who were not responsive to fluvoxamine. Therefore, there is a possibility that they met the criteria for bipolar II disorder in DSM-IV.
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.
We have experienced a case of bipolor I disorder complicated by mental retardation and autistic disorder. Acquired daily life activities such as eating, clothing and toileting without assistance were gradually lost during depressive periods, which was consistent with the previous reports. Before losing daily life skills, the patient could no longer perform daily life activities without consecutive instructions. This "waiting-for-instruction" behavior may be an early diagnostic key for major depressive episode in mentally-retarded children and adolescents.
