Drug-drug interaction (DDI) is defined as a change in effect or safety of a drug by another co-administered drug. The fact that more than half of the market withdrawal cases for the past ten years was caused by potentially fatal DDI's demonstrates its clinical importance. The mechanism of DDI can be categorized into pharmacokinetic and pharmacodynamic interactions. Most of the clinically important drug interactions are caused by inhibition or induction of oxidative metabolism by cytochrome P450 (CYP) isozymes. Recent researches are also focusing on drug transporter interactions as another significant factor underlying DDI's. It is hard to prevent unexpected or rare DDI's. However, most of the cases of DDI occur from an erroneous prescription of drugs that are already known to result in deleterious interactions. To avoid such well-established DDI's, physicians are first recommended to utilize hands-on summary tables for CYP substrates before prescribing. It should also be remembered that old age, polypharmacy and damaged hepatic or renal function are risk factors of DDI as well as adverse drug reactions. Moreover, patients treated with drugs with a narrow therapeutic index (immunosuppressants, antiarrhythmics, anticoagulants, digoxin, theophylline etc) deserve a special consideration when their prescriptions are changed. In Korea, the clinical significance of DDI has been underemphasized. The fundamental prescription to this old prescription habit is to teach medical students and physicians clinical pharmacology and therapeutics, which have long been neglected in Korea.
Anticoagulants ; Cytochrome P-450 Enzyme System ; Digoxin ; Drug Interactions ; Drug-Related Side Effects and Adverse Reactions ; Humans ; Isoenzymes ; Korea ; Metabolism ; Pharmacology, Clinical ; Polypharmacy ; Prescriptions ; Product Recalls and Withdrawals ; Risk Factors ; Students, Medical ; Theophylline

Cases of drug-induced QT prolongation and sudden cardiac deaths resulted in market withdrawal of many drugs and world-wide regulatory changes through accepting the ICH guidelines E14 and S7B. However, because the guidelines were not comprehensive enough to cover the electrophysiological changes by drug-induced cardiac ion channel blocking, CiPA was initiated by experts in governments and academia in the USA, Europe, and Japan in 2013. Five years have passed since the launch of the CiPA initiative that aimed to improve the current ICH guidelines. This report reviews the current achievements of the CiPA initiative and explores unresolved issues.
Computer Simulation ; Death, Sudden, Cardiac ; Europe ; Ion Channels ; Japan ; Myocytes, Cardiac ; Product Recalls and Withdrawals

OBJECTIVESTo analyze medical device recall information of FDA U.S. and to address the safety issue of medical device.

METHODFor each report, the recall class, product name, product class and recall reason were recorded and classified for analysis.

RESULTS3093 reports were identified; the recalling reasons of the three classes were significantly different. It is found that the main recall reason for medical material is package problems (39%) and design defectiveness (19%), for medical tools are design defectiveness (27%) and package problems (26%), and for medical equipment are design defectiveness (45%) and system failures (39%). The number of software recalled is 109. The main recall reason for high risk equipment is design defectiveness, and the I class level of high risk equipment recalled was decline in 2006 compared to that in 2005.

CONCLUSIONMonitoring and application of medical device recall information should be strengthened, and the objective law of medical device safety issue should be summed up, in order to provide reference for supervision of medical device.

A medical device recall event tracking system was designed, which can enable the users to obtain the recall, early warning and other information related to medical devices in time. The tracking system can timely obtain and release the recall information of medical devices, effectively improve the quality control of hospital medical devices, reduce the use risk of medical devices, and ensure the life safety of patients.
Humans ; Medical Device Recalls ; Product Surveillance, Postmarketing

Adolescent ; Adult ; Anti-HIV Agents ; adverse effects ; Child ; Guideline Adherence ; HIV Infections ; drug therapy ; Humans ; Medical Audit ; Middle Aged ; Practice Guidelines as Topic ; Retrospective Studies ; Safety-Based Drug Withdrawals ; Singapore ; Stavudine ; adverse effects ; World Health Organization ; Young Adult

The relationship between the number of withdrawn/restricted drugs and socioeconomic, health, and welfare indicators were investigated in a comprehensive review of drug regulation information in the United Nations (UN) countries. A total of of 362 drugs were withdrawn and 248 were restricted during 1950-2010, corresponding to rates of 12.02+/-13.07 and 5.77+/-8.69 (mean+/-SD), respectively, among 94 UN countries. A socioeconomic, health, and welfare analysis was performed for 33 OECD countries for which data were available regarding withdrawn/restricted drugs. The gross domestic product (GDP) per capita, GDP per hour worked, health expenditure per GDP, and elderly population rate were positively correlated with the numbers of withdrawn and restricted drugs (P<0.05), while the out-of-pocket health expenditure payment rate was negatively correlated. The number of restricted drugs was also correlated with the rate of drug-related deaths (P<0.05). The World Bank data cross-validated the findings of 33 OECD countries. The lists of withdrawn/restricted drugs showed markedly poor international agreement between them (Fleiss's kappa=-0.114). Twenty-seven drugs that had been withdrawn internationally by manufacturers are still available in some countries. The wide variation in the numbers of drug withdrawals and restrictions among countries indicates the need to improve drug surveillance systems and regulatory communication networks.
Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Drug Utilization/*economics/statistics & numerical data ; Female ; Gross Domestic Product/*statistics & numerical data ; *Health Status Indicators ; Humans ; Infant ; Infant, Newborn ; Internationality ; *Life Expectancy ; Male ; Middle Aged ; Product Surveillance, Postmarketing/*economics/statistics & numerical data ; Safety-Based Drug Withdrawals/*economics/statistics & numerical data ; Social Welfare/economics/statistics & numerical data ; Socioeconomic Factors ; Statistics as Topic ; Young Adult

Idiosyncratic adverse drug reactions (IDR) induce severe medical complications or even death in patients. Alert structure in drugs can be metabolized as reactive metabolite (RM) in the bodies, which is one of the major factors to induce IDR. Structure modification and avoidance of alert structure in the drug candidates is an efficient method for reducing toxicity risks in drug design. This review briefly summarized the recent development of the methodologies for structure optimization strategy to reduce the toxicity risks of drug candidates. These methods include blocking metabolic site, altering metabolic pathway, reducing activity, bioisosterism, and prodrug.
Binding Sites ; Cytochrome P-450 Enzyme System ; metabolism ; Drug Design ; Drug Discovery ; methods ; Drug Recalls ; Drug-Related Side Effects and Adverse Reactions ; prevention & control ; Humans ; Structure-Activity Relationship