Objective: Clinical trials are designed to clarify the dose-dependency of drugs.  However, the dose-dependency of adverse drug reactions (ADR), especially in the subtherapeutic range, often remains unclear.  Whether decreasing a drug’s dose would reduce the risk of ADR is of interest to both clinicians and regulators.  This study aimed to clarify the dose-dependency of ADR during subtherapeutic exposure to non-steroidal anti-inflammatory drugs, immunosuppressants, β-adrenoceptor antagonists, or corticosteroids.
Methods: Data about the ADR risk profiles and the area under the concentration curve (AUC) values of the examined drugs during their subtherapeutic administration, e.g., after their topical or low-dose oral administration, were collected from the literature and compared with data obtained during the therapeutic administration of the drugs; i.e., at the standard oral dosage.
Results: The drugs that exhibited AUC of ≥20% during their therapeutic administration continued to cause significant systemic ADR during their subtherapeutic administration.  Whilst the drugs that demonstrated AUC of 3-20% during their therapeutic administration continued to cause systemic ADR during their subtherapeutic administration, the ADR tended to be less frequent.
Conclusion: The dose-dependency of ADR can be estimated by comparing the AUC and ADR risk profile data for a drug obtained during its topical, parenteral, or low-dose oral administration with that obtained during its oral administration at the standard dose.  However, some studies have detected high ADR frequencies even during reduced systemic exposure, suggesting that factors affecting the risk of ADR, e.g., patients’ background data, should be carefully matched between the datasets being compared.

Objective : To determine how much label information on over-the-counter (OTC) medicines is contained on packaging, we investigated the items, description methods, and area of label information on packages.
Methods : We selected 75 common cold remedy products for investigation and classified the items into 3 categories (“items for use”, “items with a regulation requirement”, “items related to product image”) and measured the space given to each item in the total package area.
Results : All 75 products had “items with a regulation requirement (total 13 items),” but 8 products (only 2 manufacturers) had “consult a physician or pharmacist before use,” which was not a regulation requirement.  There were differences in description methods, especially in “caution” and “product name.”  Sixty percent of the OTC products used non-red characters with no box-frame, and 11% used red characters and box-frames.  The description order was not standardized, but “caution” was located in the lowest space on 80% of products.  Many item descriptions appeared in one place, but “product name” generally appeared in more than 4 places. While 4.5 to 8.0 points were commonly given for “items for use,” 16 to 100 points were given for “product name,” and the difference in number of points was greater than 6-fold among products.  The percentage of average area for “items related to product image” (6.1%) was 2-fold greater than for “items for use” (3.1%) and “items with a regulation requirement” (2.9%).  Almost half of the total package area was blank space.
Conclusion : Current descriptions in label information vary among items, products, and pharmaceutical companies.  Rules on describing information on OTC medicine packaging are thus necessary.

Objective: Over-the-counter (OTC) drugs play an important role in medical treatment.  Triage and counseling by pharmacists are important to ensure that self-medication with OTC drugs is effective.
Methods: We conducted a questionnaire survey to evaluate the education about OTC drugs offered by 79 Japanese pharmaceutical universities, from August to September 2009.  The questionnaire asked whether or not lectures and practical training concerning OTC drugs are given to students, and if so, the number of hours and the school year in which they are given.  Questions about future plans were also included.
Results: The response rate was 70 %.  Eighty percent of respondent universities gave lectures on OTC drugs, and 98 % expected to do so in the future.  Lectures on OTC drugs were most commonly given in the fourth year.  Fifty percent of universities offered practical training about OTC drugs, and 75 % expected to do so in the future.
Conclusion: Compared with our 2005 survey, the number of universities offering lectures had increased more than twofold.  Although education about OTC drugs in pharmaceutical universities has improved, it remains insufficient.

Objective: It is unclear whether the importance of the healthcare professional’s role and the relationship between healthcare users and providers are well understood in self-medication (SM) practices.  We conducted a self-report survey to examine how the role of healthcare professionals in SM is interpreted and how the reciprocal relationship between consumers and pharmacists in SM is recognized.
Design: Questionnaire survey.
Methods: The sample comprised 493 medical professionals (283 pharmacists at hospitals, community pharmacies, and drug stores; 74 instructors at colleges of pharmacy; and 136 personnel of SM-related academic societies).  We mailed questionnaires with informed consent forms from September to November, 2014; those who agreed to participate mailed completed questionnaires back.  We examined how individuals define and interpret SM, clarified each role of pharmacists and consumers regarding several aspects of SM, and collected respondents’ demographic information.
Results: Of the 493 questionnaires mailed, 125 (25%) were returned.  Over 65% of respondents reported familiarity with the preexisting definitions of SM that include the healthcare professional’s role.  However, when asked to define SM in their own words, only 30% included the role of healthcare professionals.  Among respondents who were not engaged in SM-related research, education or promotion, only 24% included the healthcare professionals’ role.  Also, when asked to describe the concrete roles of both pharmacists and consumers, respondents wrote fewer comments on improving living habits, consulting about health concerns, and implementing self-checks than on serving consumers with over-the-counter drugs and health foods.
Conclusion: The importance of reciprocal relationships in SM was not well recognized in our sample.  Our results suggest that it is imperative to disseminate information to raise healthcare professional’s recognition on the importance and clarification of some or all roles of theirs in SM.

Objective:The aim of this study was to measure the value of over-the-counter (OTC) pravastatin as a healthcare-related item by investigating the public's willingness to pay(WTP)in self-medication for the primary prevention of myocardial infarction (MI)if pravastatin were switched to OTC status.
Methods:A questionnaire survey was distributed among those receiving health checkups at Kitasato Institute Hospital. For the WTP question format, the double-bound dichotomous choice approach was employed. Participants were randomly assigned to three groups. Group A was provided with a starting price per month of \5,000, group B with \8,000, and group C with \12,000. To investigate factors affecting WTP, Weibull regression analysis was used.
Results:The questionnaire survey was completed by 242 individuals(150 men, age range 30-82 years), and the mean WTP was \9,583 per month. Weibull regression analysis showed that age significantly affected WTP. The monthly cost for a physician consultation to receive prescribed pravastatin is \3,540 to \6,590 in the Japanese health insurance system.
Conclusion:The WTP was about \10,000 per month, and the WTP based on the questionnaire responses was more than two-fold higher than the present cost for a physician visit. This study clarified the WTP if pravastatin for the primary prevention of MI were switched to OTC status. Further studies are necessary to elucidate whether this would contribute to the promotion of self-medication among Japanese.

Objective: To investigate quantitatively the risk factors of hyperkalaemia or increased blood potassium associated with ACE-inhibitor therapy
Design: Nested case-control study
Methods: We used the antihypertensive drug database(72,379 subjects)developed by the RAD-AR Council, Japan and the Institute of Statistical Mathematics based on the post-marketing surveillance(PMS) data of pharmaceutical companies. Of 37,372 subjects taking ACE-inhibitors, the case group was composed of 64 patients who experienced hyperkalaemia or blood potassium increase while taking ACE-inhibitors, and the control group was composed of 1,280 patients(20 patients per case)randomly selected from patients who did not experience hyperkalaemia or blood potassium increase while taking ACE-inhibitors. The relevant factors that can be extracted from the database were the followings: age, WHO classification of hypertension, complications, antihypertensive drugs used before the PMS survey, and concomitant drugs.
Results: Among the subjects taking antihypertensive agents, 65 patients experienced hyperkalaemia orincreased blood potassium, 64(98.5%)of whom were taking ACE-inhibitors. The factors that were significantly different between two groups(p<0.05)by univariate analysis were WHO classification of hypertension(p=0.005), complications of nephritis/nephrosis(p<0.001), other disorder of urinary system(p<0.001), unclear symptom or diagnosis(p=0.005), taking diuretics as antihypertensive drugs before study(p=0.032), and concomitant treatment with diuretics(p=0.004), vasodilators(p<0.001), and antigout agents(p=0.001). Conditional multivariate logistic analysis of these factors yielded adjusted odds ratio of 21.31 for complications of nephritis/nephrosis(p<0.001), 6.83 for other disorder of urinary system(p<0.001), and 2.30 for concomitant therapy with diuretics(p=0.049).
Conclusion: The risk factors of hyperkalaemia or blood potassium increase associated with taking ACE-inhibitors were nephritis/nephrosis, other disorder of urinary system and concomitant therapy with diuretics.

Objective : The Pharmacy and Therapeutic Committee generally selects formulary drugs by evaluating the comparative data from non-clinical and clinical studies of pharmacologically similar type drugs. Usually there are few data from directly comparative studies among all similar type drugs, and there are only two types of studies, standard drug or placebo-control study. In this situation, it is very difficult to select the superior drug.
Therefore, we conducted a retrospective cohort study to compare the efficiency among three 5-HT₃ antagonists and to investigate the possibility of data from this study, as a reference for decision making.
Design : Retrospective cohort study.
Methods : A retrospective cohort was assembled comprising in-patients of to Surgery, Obstetrics and Gynecology, Ophthalmology, Orthopedics, Dermatology, Psychiatry, or Thoracic Surgery Departments, who received chemotherapy and a 5-HT₃ receptor antagonist from January to June in 1996. We compared the side effects of nausea and vomiting among patients receiving various 5-HT₃ receptor antagonists. Physicians could freely prescribe three 5-HT₃ antagonists that were adopted in our hospital during the period. Pharmacists collected information regarding the efficacy of 5-HT₃ receptor antagonists on the first prescribed day by reviewing medical charts, nurses' reports and interviews with the nurses.
Statistical Analysis : ANOVA was used for testing the age differences among patients receiving 5-HT₃ receptor antagonists. Chi-square was used for testing difference of sex, administration route, number of chemotherapy treatment. Kruskal-Wallis rank test was used for testing the difference of efficacy. Probabilities less than 5% (P<0.05) were considered significant.
Results : Out of 68 patients, 35% received cisplatin and 65% received non-cisplatin anti-tumor drugs. The average age was 53.1±17.4 (49% male, 51% female). A total of 82% received intravenous drip injection.
Percentage of non-changed cases in ingestion ratio was 32% of ramosetron, 50% of ondansetron and 53% of azasetron. There was no significant difference in the ingestion ratio (p = 0.026).
Percentage of non-changed cases with regard to vomiting (complete control) was 80% of ramosetron, 50% of ondansetron, 79% of azasetron. There was a significant difference in vomiting (completecontrol) (p = 0.044). Ondansetron was less effective as an antiemetic function.
Discussion : When no data from a directly comparative study are available to determine the adoption of a new medicine from among numerous candidate drugs, an observational study such as this appears useful.

Objective: To develop a label comprehension study (LCS) of package inserts for over-the-counter medications in Japan, we evaluated whether it would be possible to detect differences in the level of understanding due to layout, and font size of different types of package insert using the interview method for LCS we developed previously.
Design: A face-to-face questionnaire investigation.
Methods: Two different types of package insert (including layout, and font size) for H₂-antagonists (package insert groups A and B) were used.  Study participants (≥18 years old) comprised consumers who visited a drugstore with a dispensing service in Saitama Prefecture.  They were randomly assigned to group A or B and divided by age range (young, 18-39 years; middle-aged, 40-59 years; eldely, ≥60 years).  First, the volunteers read the package insert with no time limitation and then answered 14 scenario-type questions during an interview to determine the level of understanding of the insert.  When both the correct answer and correct reason were given, the response was judged as correct.  The level of understanding of the package insert was calculated as the number of persons giving correct responses divided by all respondents.
Results: Questionnaire responses from 86 consumers (43 in each group) were obtained.  The mean age in groups A and B was 46.5 years and 47.0 years, respectively.  The mean level of understanding of the package insert (14 questions) in groups A and B was 50.2 and 38.1%, respectively.  By age range, the mean level of understanding of the package insert in groups A and B in the young group was 60.6 and 56.9%, respectively, and there was no statistically significant difference between the two groups.  However, the mean level of understanding in groups A and B was 56.9 and 35.0% in the middle-aged group and 26.3 and 14.5% in the elderly group, respectively.  The mean understanding in group A was therefore higher than that in group B in both age ranges.  The association between understanding and age within groups indicated that with increasing age, understanding was lower in both groups (group A, p=0.001; group B, p<0.001).  There was no difference in the level of understanding between the young and middle-aged in group A, but the difference in group B was greater than 20%.
Conclusion: By comparing two package inserts of products in a similar pharmacological category using our LCS method, it suggested that font size and layout influenced consumers’ understanding of package inserts.  It might be able to evaluate the difference in the understanding of the package insert by using our LCS method.

Objective: In pharmacy school, most faculty members use generic names when discussing medicine; however, in clinical clerkships, most staff members use brand names. This sometimes leads to poor communication and understanding between the students and medical staff.  The purpose of this study was to clarify the need for a tool to improve communication and understanding in relation to drug information.  Based on the findings of this survey, our secondary aim was to develop and subsequently evaluate such a tool.
Methods: To clarify the need for a self-learning tool, we conducted a questionnaire survey on 58 faculty members who teach courses on drug informatics.  Based on their responses, we then developed a self-learning tool that was subsequently evaluated by a total of 78 undergraduate students.
Results: Most of the faculty agreed concerning the necessity of a self-learning tool for drug information, particularly in regard to the establishment of a more user-friendly system and reduced user fees for students.  The faculty also believed that students should be able to associate the generic drug name with various kinds of information, including its safety, efficacy, and brand name.  All students agreed that the tool was helpful, very easy to use, and could be learned during their commute to school.
Conclusion: Our results suggest that most faculty members support the idea of having a tool capable of promoting a better understanding and grasp of drug information.  Therefore, our self-learning tool should be helpful in promoting increased knowledge concerning drug information for students in clinical clerkships.