Analysis of Time-to-Onset and Onset-Pattern of Drug-Induced Blood Disorders with Monoclonal Antibody Agents / 医薬品情報学

Objectives: The aim of this study was to investigate both the time‐to‐onset and the onset‐pattern of drug‐induced blood disorders (DIBD) following the administration of monoclonal antibody agents through the use of the spontaneous adverse reaction reporting system of the Japanese Adverse Drug Event Report （JADER) database.Methods: Data in the JADER database from April 2004 to October 2017 were downloaded from the Pharmaceuticals and Medical Devices Agency website.　The DIBD dataset for monoclonal antibody agents was constructed based on the data for the drug information and adverse drug reactions.　The information for the adverse drug reactions was categorized in accordance with the preferred terms of the Medical Dictionary for Regulatory Activities and included thrombocytopenia, platelet count decreased, neutropenia, neutrophil count decreased, leukopenia, white blood cell count decreased, pancytopenia, anaemia, agranulocytosis, granulocyte count decreased, granulocytopenia, and bone marrow failure.　This dataset was then used to calculate the median onset times for the DIBD and the Weibull distribution parameters.Results: The median onset times of the DIBD for gemtuzumab ozogamicin, cetuximab, ramucirumab, trastuzumab, panitumumab, bevacizumab, infliximab, rituximab, trastuzumab, and ibritumomab tiuxetan (90Y) were 4, 10, 13, 14, 14, 14, 16, 16, 27, and 28 days, respectively.　The Weibull distributions for cetuximab, trastuzumab, bevacizumab, infliximab, and tocilizumab were estimated to fit the early failure type profile, while those for gemtuzumab ozogamicin, ramucirumab, rituximab, and ibritumomab tiuxetan (90Y) were estimated to fit the wear out failure type profile.　The Weibull distributions for panitumumab were estimated to fit the random failure type profile.Conclusions: The results of the present study clarified both the most likely time period and the onset‐pattern of DIBD that can occur in patients after the administration of monoclonal antibody agents.

Surveillance to Determine Adverse Reactions to Carbamazepine and Lamotrigine: / 医薬品情報学

<b>Objective: </b>We previously showed that interstitial lung disease, pneumonia, abnormal liver function, and anaphylactic reactions were frequent adverse events, and we analyzed outcomes, suspected causative drugs, and the onset of adverse events using information derived from the “Japanese Adverse Drug Event Report” (JADER) database.  Here, we aimed to determine the status of actual adverse reactions to carbamazepine (CBZ) and lamotrigine (LTG) using national public databases.<br><b>Methods: </b>Data from the “Information on Decision on Payment/non-payment of Adverse Reaction Relief Benefits” (IARRB; April 2012-March 2016) and JADER (April 2012-March 2016) databases were downloaded from the website of the Pharmaceuticals and Medical Devices Agency.  Information from the national database of the “Health Insurance Claims and Specific Health Checkups of Japan” (NDB) (April 2014-March 2015) was downloaded from the website of the Ministry of Health, Labour and Welfare.<br><b>Results: </b>The numbers of females and males in the IARRB were 169 and 229, respectively, for CBZ and 135 and 56, respectively, for LTG.  Those in JADER were 1,152 and 1,352, respectively, for CBZ and 1,358 and 806, respectively, for LTG.  The respective ratios of males and females prescribed CBZ and LTG in the NDB were 46.2 and 53.8%, and 56.3 and 43.7%, respectively.  Both CBZ and LTG were identified as very high-risk drugs associated with extreme skin reactions such as drug-induced hypersensitivity syndrome (DIHS), toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), erythema multiforme type drug eruption (EM), and disseminated papuloerythematous drug eruption (DPE).  CBZ induced DIHS, EM, and DPE more frequently among elderly men (over 60 years old), whereas LTG induced these reactions in women of reproductive age.<br><b>Conclusions: </b>Elderly men prescribed CBZ and women of reproductive age prescribed LTG should be advised about extreme adverse skin reactions.

The Surveillance for Contents of Pharmacogenomics Information in Package Inserts and Interview Forms / 医薬品情報学

<b>Objective: </b>Pharmacogenomics (PGx) is the study of the relationship between the efficacy and/or safety of drugs and the genetic polymorphism.  Since PGx information can be used to personalize medical treatments, there has been a recent increase in the development of drug and companion diagnostic devices based on genome-wide analyses.  Therefore, we surveyed the contents of PGx information in package inserts and interview forms (IF) of Japanese pharmaceuticals, and investigated potential problems with the PGx information supplied by Japanese pharmaceuticals.<br><b>Methods: </b>PGx information content in package inserts and the IF used by Japanese pharmaceuticals was compared with that listed in the U.S. pharmaceuticals “Table of Pharmacogenomic Biomarkers in Drug Labeling.”<br><b>Results: </b>There were 166 PGx information content listings for 137 drugs described in the “Table of Pharmacogenomic Biomarkers in Drug Labeling.”  However, there were 31 PGx information content listings for 20 biomarkers of 24 drugs that were described in the U.S. but not the Japanese package inserts.  In addition, there was no PGx information for 17 biomarkers of 20 drugs in both the Japanese package inserts and the IF.  We additionally found that 57.7% of the biomarkers with PGx information listed in the package inserts were for drugs that are normally covered by <i>in vitro </i>diagnostic medical insurance.  These biomarkers were mainly the gene mutations and expression of the target molecules.<br><b>Conclusions: </b>The Japanese PGx information associated with gene mutations and expression of the target molecules was similar to the U.S. PGx information.  However, the contents of the PGx information for drug-metabolizing enzymes differed widely among each of the drugs.  In order to more effectively use PGx information, a more careful inspection of the information regarding efficacies and side effects will need to be undertaken to ensure better evaluations of patient therapies.

Creating a List of Oral Anticancer Drugs using the Simple Suspension Method for Appropriate Therapy / 社会薬学

In cancer chemotherapy, it is very important to take into account the patient’s background. In recent years, a simple suspension method has attracted increased attention as a method that prevents changes in the stability and safety of various drugs. However, of 135 oral anticancer drugs, only 28 have been examined using this method, as of April 2013. In this study, we carefully investigated whether 53 oral anticancer drugs could be adapted to the simple suspension method, except for the 28 drugs that had already been previously reported. The results showed that most of these oral anticancer drugs could be adapted to the simple suspension method. Of seven drugs that were not adapted, six were generic drugs. In addition, it was clear that the evaluation of bicalutamide tablets was significantly different from our expected results. In conclusion, we were able to qualitatively assess all 53 oral anticancer drugs. This is equivalent to half of 107 untested drugs. These results provide useful information to cancer patients using oral anticancer drugs prepared using the simple suspension method.

Analysis of Research Trends in Drug Informatics Based on Articles in the Japanese Journal of Drug Informatics / 医薬品情報学

<b>Objective: </b>We analyzed articles in the Japanese Journal of Drug Informatics with the goal of identifying recent research trends in drug informatics.<br><b>Method: </b>The appearance frequencies of keywords in the Japanese Journal of Drug Informatics (2001: vol. 3 (1) to 2009: vol. 11 (4)) and Japanese Journal of Pharmaceutical Health Care and Sciences (2009: vol. 35 (1) to (6)), and words in abstracts in Japanese Journal of Drug Informatics (2009: vol. 11 (1) to 2010: vol. 12 (4)) were analyzed. <br><b>Results: </b>To investigate keywords in the Japanese Journal of Drug Informatics, appearance frequencies of information, drug, drugs and pharmacist in 2001: vol. 3 (1) to 2003: vol. 5 (4), those of information, drug, drugs, medical, medication and questionnaire in 2004: vol. 6 (1) to 2006: vol. 8 (4), and those of information, drug, questionnaire, survey, pharmacist, adverse and generic in 2007: vol. 9 (1) to 2009: vol. 11 (4) were higher than those of other keywords.  In the Japanese Journal of Pharmaceutical Health Care and Sciences, appearance frequencies of drug, pharmacy, care, patient, pharmaceutical, cancer, education, training, analysis and drugs were higher than those of other keywords.  Information, drug(s), patients, pharmacists, hospital, use, questionnaire, medical, adverse, survey, agents, generic and pharmaceutical were high frequency words used in abstracts published in the Japanese Journal of Drug Informatics.  These words in abstracts indicate a Zipf’s law-like rank distribution.  Co-occurrence network graphs using abstracts showed that the first cluster consisted of medical, drug, adverse, drugs, pharmaceutical, hospital, doctors, contents and drug around information and pharmacists as hubs, and the second cluster consisted of 3 words (agents, woman and pregnant).  Furthermore, co-occurrence network graphs indicated that care, medical, pharmaceutical, information, adverse, pharmacists, hospital, doctors, questionnaire, woman, pregnant, package and side were matters of important arguments and/or phenomena.<br><b>Conclusion: </b>These data suggest that the scope of themes in articles published in the Japanese Journal of Drug Informatics is establishing definitive categories.  The recent themes and contents of the Japanese Journal of Drug Informatics were closely and mutually related.

A Survey of the relationships between outcomes from therapy and patients background in the therapy of smoking cessation / 医薬品情報学

<b>Purpose</b>: With the aim of improving the efficiency of smoking cessation treatment, we analyzed and classified various factors to identify the relationships between the background of patients and effects of treatment, and examine their characteristics.<br><b>Methods</b>: We conducted a questionnaire survey to collect information on the situation of patients, and obtained their treatment data from medical records.  Decision tree analysis, a data mining method, was employed to examine these data.<br><b>Results</b>: According to the results of the survey, the smoking cessation rate was 80.4%.  The rate was associated with CO concentrations in the breath at the initial examination, nicotine content in cigarettes smoked by patients, and the daily and total number of cigarettes smoked.  The smoking cessation rate among patients under emotional stress was 76.2%; the rate was higher when patients were able to reduce their mental stress levels.<br><b>Conclusion</b>: We identified characteristic relationships between the background of patients and the effects of treatment, and they proved to be useful for the improvement of the smoking cessation rate.