Objective: To evaluate the validity of dosage adjustment of renally eliminated drugs using Giusti and Hayton method in patients with renal dysfunction by reviewing the pharmacokinetic data of the drugs. Design: A systematic literature review. Methods: Drugs with the following characteristics: ≥70% of the drug excreted in urine is the unchanged form and ≥20% of the drug in plasma is the unbound drug, were retrieved from Goodman and Gilman’s the Pharmacological Basis of Therapeutics, 12th edition. For the drugs identified, the area under the concentration-time curves (AUC) obtained from pharmacokinetic studies in healthy subjects and patients with renal dysfunction were extracted from package inserts, interview forms, summary basis of approval, and by systematic review of the MEDLINE database. Pharmacokinetic studies in children, patients with end-stage renal disease, patients on hemodialysis, and kidney transplanted patients were excluded from this review. The observed AUC ratio (AUCRobserved) of a drug was calculated by dividing mean AUC of patients by that of healthy subjects, and stratified by creatinine clearance (CLcr) into three categories: 50 to 79 mL/min, 30 to 49 mL/min, and 10 to 29 mL/min. Theoretical AUC ratios (AUCRpredicted) of drugs for the respective CLcr categories were calculated using Giusti and Hayton method. Results: Twenty-six drugs met our study criteria, and 43 data sets were obtained from the data sources. The AUCRobserved deviated from the AUCRpredicted by more than ±50% in 3 of 35 (9%) data sets for CLcr 50 to 79 mL/min, 4 of 39 (10%) data sets for CLcr 30 to 49 mL/min, and 7 of 29 (24%) data sets for CLcr 10 to 29 mL/min. Conclusion: Since AUCRpredicted calculated by Giusti and Hayton method erratically over- or under-estimates the maintenance doses in patients with reduced renal function, the use of AUCRobserved is preferred for dose adjustment in these patients.
Objective: Adequate periconceptional folic acid intake decreases the risk of neural tube defects in infants. The present study aimed to investigate the awareness of pharmacy students regarding the importance of folic acid intake for the prevention of neural tube defects. Design: Questionnaire survey. Methods: A self-administered questionnaire regarding the importance of folic acid intake for the prevention of neural tube defects was distributed to 750 pharmacy students at Tohoku and Ohu Universities. Results: Among the 685 respondents (response rate; 91.3%), 74 (10.8%) were aware that folic acid intake decreases the risk of neural tube defects. In multivariate logistic regression analysis, awareness of the importance of folic acid intake was evident among 5th- and 6th-year pharmacy students (odds ratio=3.352, 95% confidence interval=1.797-6.253) and among those who used dietary supplements (2.275, 1.306-3.966). Among the 74 pharmacy students who recognized the importance of folic acid intake, 17 (23.0%) and 3 (4.1%) were aware that women should begin taking a folic acid supplement before conception and should take about 400 μg per day during pregnancy, respectively. Conclusion: Only about 10% of the pharmacy students in this study recognized that folic acid intake decreases the risk of neural tube defects, and many were unaware of the recommended intake amount. Therefore, awareness of the importance of folic acid intake must be more aggressively promoted among pharmacy students.
Objective: Antiplatelet therapy is useful for infraction prevention. But, in elderly patients, adverse events are easily observed, owing to the decrease in metabolism and excretion of drugs. Furthermore, applying guidelines for medical care of each disease does not necessarily result in good conclusions. Therefore, we used Japanese Adverse Drug Event Report database and assessed safety signals with signal detection about adverse events developed by the antiplatelet therapy in the elderly patients. Methods: We analyzed all adverse events reported on ticlopidine hydrochloride that should be carefully administered, and clopidogrel, bisulfate and aspirin that are recommended as the alternative drugs. We used the proportional reporting ratio for a safety index of drugs. Results: While some adverse events were expressed in only ticlopidine hydrochloride, bleeding signal was detected in all the subject agents. In addition, onset risk of ticlopidine hydrochloride was found to be the lowest value. Moreover, adverse events expressed in clopidogrel bisulfate and aspirin were of a wide-variety compared with ticlopidine hydrochloride. Conclusion: It is necessary to carefully administer not only ticlopidine hydrochloride but also the alternative drugs to the elderly patients as indicated, and there is a need to pay careful attention to administration of the alternative drugs.
Objective: The use of generic drugs is promoted for the purpose of reductions of medical costs and patient’s copayment. In general, it is thought that clinical effects of the original brand and the generic drugs are equal if they are bioequivalent. However, it is necessary to inspect their therapeutic equivalence to use the generic drugs securely. We, therefore, assessed the therapeutic equivalence and pharmacoeconomics by substitution of an original drug (Amaryl®) with a generic drug (Glimepiride [Tanabe]). Methods: Therapeutic Equivalence: The total variation was calculated by using the HbA1c levels before it switched from Amaryl® to Glimepiride [Tanabe]. The tolerance limits were set as 1/4 of the total variation. Pharmacoeconomics: The difference of drug prices and the difference of patient’s copayment were calculated. Results: As the variation of HbA1c levels was within tolerance limits before and after switching from Amaryl® to Glimepiride [Tanabe], we evaluated that their therapeutic effect was equivalent. The difference of drug prices after switching from the original to the generic one was 4,582.6 yen/year on average (minimum: 949.0 yen, maximum: 12,045.0 yen); the difference of patient’s copayment was 872.5 yen/year on average (minimum: 0 yen, maximum: 3,613.5 yen). These data show that the use of the generic drugs is effective to reduce medical costs. Conclusion: For further promoting the use of the generic drugs, we consider it essential to compare the therapeutic equivalence and the safety of the original and the generic drugs in clinical practice.
Objective: Currently, Risk Management Plans (RMPs), plan that provide new risk information about drugs, are published on the Pharmaceutical and Medical Devices Agency (PMDA) website. The aim of this study was to compare enumerated risks in RMPs to the product labeling (PL) of the drug package insert. Methods: The risks listed in RMPs on the PMDA website were assessed on February 10, 2014. We investigated the documentation of these risks on the PL. Results: Seven-hundred and eighty-five risks were enumerated in the RMPs of 77 drugs. The enumerated risks were classified as “important identified risks” (66%), “important potential risks” (22%), and “important missing information” (12%). Ninety-four percent of risks listed in RMPs were documented on the PL. A portion of both the “important identified risks” and “important potential risks” groups were not documented on the PL. Conclusion: This study was clearly the relation between risks listed in RMPs and documents on the PL. Because a portion of the risks listed in RMPs was not documented on the PL, RMPs provide more safety information. It is necessary to better understanding their characteristics, considering RMPs are a new source of drug information.
Objective: An external training seminar was held for registered salesclerks of drugs to help them keep and improve their knowledge of drugs. To promote self-medication and to enhance the content of training seminars, we collected data in the form of inquiries the clerks had received from customers and what information the clerks sought from drug companies. Methods: Our survey was conducted with 199 registered salesclerks of drugs at an external training seminar in Tokyo, Japan. Results: The main inquiries from customers to the registered salesclerks were “selection of an analgesic for headache” (83.8%), “selection of an analgesic for cramps” (62.3%), and “selection of an analgesic for toothache” (57.7%). The main information that they sought from drug companies were “side effects,” “interaction between drugs,” “time of onset of action,” and “degree of effect of drugs.” Conclusions: To respond to the inquiries from customers, it was necessary to supply the clerks with knowledge of pharmacokinetics in the external training and to supply them with information on side effects, interaction between drugs, time of onset of action, and degree of effect of drugs on individual products from drug companies. Additionally, this information and knowledge of drugs can be gained from not only the external training and drug companies but also from pharmacists they work with. It was thought that continuing the external training seminars and input of information from drug companies led to levels similar to a pharmacist and the registered salesclerks contributed actively to promoting self-medication.