Objective: It is very difficult to identify the frequency of rare adverse drug reactions (ADRs) precisely.  A study was conducted to estimate the frequency of ADRs that were not observed in clinical studies by referring to the sales volume of the pharmaceuticals until the date when the ADR was first observed after a drug was marketed.
Methods and Subjects: The study was conducted for the 17 pharmaceuticals to estimate the frequency of Hepatopathy.  The date of report of the ADR to the Minister was obtained through information disclosure requests.  The sales volume of the relevant pharmaceuticals was provided by IMS Japan.  On the premise that all the ADRs were detectable, the probability (P) that an ADR was not detected right before drug administration in the first case of the ADR was estimated through Formula 1.
Formula 1 : P=1−{(D₀−S)!÷(D₀−S−D_N)!}/{D₀!÷(D₀−D_N)!} = 1−{(D₀−D₀×F)!÷(D₀−D₀×F−D_N)!}/{D₀!÷(D₀−D_N)!}
  D₀ referred to the estimated person-days for all the patients subject to the drug therapy, S to the number of patients with ADR, D_N to the person-days until the date when the ADR was observed and F to the frequency of the ADR.  F was estimated where the detection P was 0.95 or was close to 0.95.
Results and Discussion: Among the pharmaceuticals investigated, the frequency was highest in product A (0.038%) and was lowest in product X (0.0000088%).  In many cases, the package inserts describe the frequencies of rare ADRs as unknown.  However, the frequency can be estimated relatively precisely through the method stated above using data, which may be kept by pharmaceutical manufacturers.

Objective: Currently, post marketing surveillance (PMS) for prescription-only to over-the-counter (OTC) switched products is conducted based on questionnaires to patients.  These questionnaires appear in the form of postcards and are completed and posted voluntarily by patients.  With such a method, however, it is not possible to select samples randomly and there may be a bias in respondents.  In addition, the response rate of questionnaire postcards tends to be low.  It is not really credible that the efficacy and safety of OTC switches are confirmed by such a method.  An investigation was therefore conducted with the aim of developing an effective method of PMS for OTC switches in order to achieve the intended objective of PMS.
Method and Subjects: Famotidine purchasers were asked to complete a questionnaire form.  The pharmacists asked the subjects to complete the questionnaire form again on their second visit and also checked patient compliance with drug treatment.  The effectiveness of this method was evaluated by reviewing responses to the questionnaire on the first and second visits.
Results and Discussion: It was suggested that the method tested in this investigation may possibly facilitate evaluation of the efficacy of OTC switched products, detection of adverse drug reactions and monitoring of patient compliance with drug treatment.  However, the questionnaire used in the investigation was not suited for detecting symptoms that triggered patients to purchase famotidine.  It was considered necessary to prepare additional questions specifically designed to detect such symptoms.

Objective: If product information provided by pharmaceutical manufactures is not consistent with a product assessment made by the Pharmaceuticals and Medical Devices Agency (PMDA), users may gain false perceptions about the product, which may be detrimental to patients.  An investigation was conducted to compare the contents of product information provided by pharmaceutical manufacturers and product evaluation reports prepared by PMDA to identify any discrepancies between data assessment in the two documents.
Methods: Descriptions in “Product Characteristics” and “Clinical Studies” of product information summaries were compared with product evaluation reports prepared by PMDA.  Inquiries were addressed to manufacturers if any questions arose.
Results: The investigation was conducted on 66 new active ingredients approved in 2009 to 2010.  As 14 questions arose with 12 ingredients, inquiries were addressed to manufacturers, all of whom offered a response.  As a result, four questions were resolved for two ingredients.  However, for the remaining products, it was revealed that the manufacturers described in the product information summaries what they claimed at the time of submission even though their claims were not accepted by PMDA.
Conclusion: It was considered that the pharmaceutical manufacturers possibly did not comprehend the contents of the PMDA’s evaluation reports.  It was suggested that the industry as a whole should examine the issue.  As discrepancies were observed even in product information summaries, which are viewed by a relatively large number of people, it was assumed that more issues may be found in promotional materials provided exclusively to healthcare professionals.

Introduction: A health assessment sheet was developed to establish a new method for post marketing surveillance (PMS) for nonprescription drugs, the status of which has recently been switched from prescription (Rx) to over-the-counter (OTC) to confirm the efficacy and safety of Rx-to-OTC switched drugs.  The assessment sheet was designed to evaluate adverse reactions that may be possibly induced by the drugs and to elicit spontaneous complaints from consumers.  An investigation using the assessment sheet had been conducted earlier for famotidine tablets.  While the earlier investigation suggested the effectiveness of the assessment method, it also revealed some issues.  After making improvements in the assessment sheet, another investigation was conducted for Loxonin®S.
Method: Purchasers of Loxonin®S were asked to tick symptoms that were applicable to them among those listed in the sheet.  They were asked to revisit the pharmacy and complete the sheet for the second time after drug administration.  The possibility of adverse reactions was considered for the symptoms additionally chosen at the second visit and they were then compared with the adverse reactions described in the package insert of Loxonin®S.
Results: Total 284 people completed the health assessment sheet at their first and second visits.  Of them, 44 people (15.5%) reported additional symptoms at the second visit.  Commonly reported symptom was “frequent experience of sleepiness,” “persistent headaches” and “fatigability.”
Conclusion: The study suggested that the health assessment sheet can be an effective tool for PMS for nonprescription drugs immediately after the Rx-to-OTC switch and contributes to detecting adverse reactions of the drugs.

The purpose of the present study was to indicate the relationship between health-related quality of life (HRQOL) measures, the daily rhythm of oral temperature (OT), and lifestyle. Five-hundred young men volunteered to participate in this study. Their OT, measured using a digital thermometer, was recorded every 2h from the time they woke up to the time they went to sleep for 1 week. The daily rhythm of OT was calculated as a quadratic function using the 1-week data. The HRQOL was measured using the Short-Form 36-Item Health Survey version 2 (SF-36v2). The participants were divided into 3 groups: a high-value group (HG) with ≥ 55 points of each summary score and each subscale score, a middle-value group (MG) with score > 45 and < 55 points, and a low-value group (LG) with score ≤ 45 points. Lifestyle was assessed in terms of eating habits, sleeping and exercise, and the presence of unidentified complaints. At the mental component summary, the OT at the time of waking up and the peak OT in the HG were significantly higher than those in the LG. At the physical and mental component summary, lifestyle in the HG was more favorable. These data suggest that the daily rhythms of OT may reflect the mental health status of an individual. The entraining factors in circadian variation might play a role in improving mental health and reducing unidentified complaints. In conclusion, there appears to be an association between mental health status, lifestyle, and daily rhythms of OT.