Discovering clinical drug-drug interactions with known pharmacokinetics mechanisms using spontaneous reporting systems and electronic health records.

OBJECTIVE: Although the mechanisms behind pharmacokinetic (PK) drug-drug interactions (DDIs) are well-documented, bridging the gap between this knowledge and clinical evidence of DDIs, especially for serious adverse drug reactions (SADRs), remains challenging. While leveraging the FDA Adverse Event Reporting System (FAERS) database along with disproportionality analysis tends to detect a vast number of DDI signals, this abundance complicates further investigation, such as validation through clinical trials. Our study proposed a framework to efficiently prioritize these signals and assessed their reliability using multi-source Electronic Health Records (EHR) to identify top candidates for further investigation. METHODS: We analyzed FAERS data spanning from January 2004 to March 2023, employing four established disproportionality methods: Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), Multi-item Gamma Poisson Shrinker (MGPS), and Bayesian Confidence Propagating Neural Network (BCPNN). Building upon these models, we developed four ranking models to prioritize DDI-SADR signals and cross-referenced signals with DrugBank. To validate the top-ranked signals, we employed longitudinal EHRs from Vanderbilt University Medical Center and the All of Us research program. The performance of each model was assessed by counting how many of the top-ranked signals were confirmed by EHRs and calculating the average ranking of these confirmed signals. RESULTS: Out of 189 DDI-SADR signals identified by all four disproportionality methods, only two were documented in the DrugBank database. By prioritizing the top 20 signals as determined by each of the four disproportionality methods and our four ranking models, 58 unique DDI-SADR signals were selected for EHR validations. Of these, five signals were confirmed. The ranking model, which integrated the MGPS and BCPNN, demonstrated superior performance by assigning the highest priority to those five EHR-confirmed signals. CONCLUSION: The fusion of disproportionality analysis with ranking models, validated through multi-source EHRs, presents a groundbreaking approach to pharmacovigilance. Our study's confirmation of five significant DDI-SADRs, previously unrecorded in the DrugBank database, highlights the essential role of advanced data analysis techniques in identifying ADRs.

Analysis of the new and serious adverse drug reactions in our hospital from 2017 to 2021 / 中国现代医生

Objective To analyze the characteristics of the new and severe adverse drug reactions(ADR)in our hospital from 2017 to 2021,and to provide a reference for the rational use of drugs in the clinic and the reduction of ADR.Methods Retrospective classification and statistical methods were used to comprehensively analyze new and serious adverse drug reactions reported in our hospital.Results Among the 178 reports,the reporting staff was mainly pharmacists(163 cases,91.57%).Adverse reactions mainly occurred in patients over 65 years old(88 cases,49.44%).The dosage forms involved are mainly injections and tablets.Among the drugs involved,antitumor drugs accounted for the highest proportion(34.95%).ADR involved the most systemic/organ damage was hematological system(34.95%),followed by digestive system damage(29.03%).Conclusion Monitoring of new and serious ADR should be paid a close attention,especially antitumor drugs,to improve the reporting rate and ensure the safety of patients'medication.

Serious Adverse Drug Reactions and Safety Signals in Children: A Nationwide Database Study.

Children are more exposed to inappropriate medicine use and its consequent harms. Spontaneous reporting of suspected Serious Adverse Drug Reactions (SADR) increases knowledge and prevention of pharmacotherapy risk. Disproportionality measures are useful to quantify unexpected safety issues associated with a given drug-event pair (signals of disproportionality). This cross-sectional study aimed to assess SADR reporting and safety signals for Brazilian children from 0-12 years old, notified between January 2008 and December 2013 from the Brazilian Surveillance Agency (Notivisa). Information from serious reports (gender and age of the patient, event description, suspected drug) was included. Disproportionality analysis based on Reporting Odds Ratios with a confidence interval of 95% was conducted to identify possible signals of disproportionate reporting (SDR). Almost 30% of 1,977 suspected SADR was related to babies (0-1-year-old). 69% of reports happened with intravenous dosage forms, and 35% of suspected SADR involved off label use according to age. Laronidase, miglustat, imipenem/cilastatin, and clofarabine were involved in six or more suspected deaths among 75 deaths reported. There were 107 SDRs, of which 16 events (15%) were not described in the product labels. There was a relatively higher number of SADRs in Brazilian children compared with studies from other countries. SDRs found, (especially drug-event pairs 'imipenen/cilastatin-pneumonia' and 'laronidase-respiratory insufficiency') should be investigated more. The reports of SADR with IV dosage forms and OL drug use suggest the need for drug research and the use of better dosage forms for children in Brazil.

Detection of serious adverse drug reactions using diagnostic codes in the International Statistical Classification of Diseases and Related Health Problems.

Canadian hospitals are legally required to report serious adverse drug reactions (ADRs). This study aimed to assess the ability to detect serious ADRs from diagnostic codes and the potential benefit of adding stand-alone diagnostic codes to the regular process for detecting serious ADRs. In this descriptive study, clinical pharmacists and a reference work on drug-induced diseases allowed to identify diagnostic codes in the International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Canada (ICD-10-CA), reflecting clinical manifestations related to an ADR. Records for admissions to a large urban mother-child hospital in the fiscal year 2018-2019, as coded by medical archivists, were analysed. Of 69 ICD-10-CA diagnostic codes reflecting an ADR identified, 38 were included in the detailed analysis of patient records and 18 (which appeared in 130 admissions) deemed to indicate a serious ADR. Among the 130 admissions analysed, 70 serious ADRs were identified, of which 52 were previously detected by the regular process and 18 were not, increasing the detection of serious ADRs by 34.6% (18/52). These 18 serious ADRs were newly identified from 11 of the 18 codes reflecting clinical manifestation of a serious ADR. Adding ICD-10-CA diagnostic codes not associated with external cause codes can increase the capacity to detect serious ADRs in hospitals. Over a 12-month period, the use of 11 such diagnostic codes increased the detection capacity for serious ADRs by 34.6%.

Intravenous N-acetylcysteine in severe cutaneous drug reaction treatment: A case series.

Drug-induced serious adverse reaction is an unpleasant event with high rate of mortality. Stevens-Johnson Syndrome and toxic epidermal necrolysis are most common among the serious adverse drug reactions. There is no selective drug therapy for the management of serious adverse drug reactions-associated mucocutaneous blisters. The use of N-acetylcysteine in the treatment of mucocutaneous blisters has limited evidence worldwide. Three cases of toxic epidermal necrolysis or Stevens-Johnson Syndrome-associated mucocutaneous blisters are presented in this study where intravenous N-acetylcysteine (600 mg, every 8 h) was given in early hospitalization hours for the treatment of mucocutaneous fluid-filled blisters. Here, one patient with toxic epidermal necrolysis received intravenous immunoglobulin along with intravenous N-acetylcysteine and the other two patients (toxic epidermal necrolysis/Stevens-Johnson Syndrome) received only N-acetylcysteine intravenously. In response, mucocutaneous fluid-filled blisters stopped progressing within 48 h and were healed within 2 weeks of admission in the intensive care unit. Thus, intravenous N-acetylcysteine with or without having intravenous immunoglobulin in the treatment of serious adverse drug reactions-associated mucocutaneous blisters may be an effective therapeutic option for better clinical outcome.

An analysis of serious adverse drug reactions at a tertiary care teaching hospital.

OBJECTIVE: The objective of this study was to analyze the various aspects of serious adverse drug reactions (serious ADRs) such as clinical presentation, causality, severity, and preventability occurring in a hospital setting. MATERIALS AND METHODS: All serious ADRs reported from January 2010 to May 2015 at ADR Monitoring Centre, Department of Pharmacology, B. J. Medical College and Civil Hospital, Ahmedabad, were selected as per the World health Organization -Uppsala Monitoring Center (WHO-UMC) criteria. A retrospective analysis was carried out for clinical presentation, causality (as per the WHO-UMC scale and Naranjo's algorithm), severity (Hartwig and Siegel scale), and preventability (Schumock and Thornton criteria). RESULTS: Out of 2977 ADRs reported, 375 were serious in nature. The most common clinical presentation involved was skin and appendageal disorders (71, 18.9%). The common causal drug group was antitubercular (129, 34.4%) followed by antiretroviral (76, 20.3%) agents. The criteria for the majority of serious ADRs were intervention to prevent permanent impairment or damage (164, 43.7%) followed by hospitalization (158, 42.1%). Majority of the serious ADRs were continuing (191, 50.9%) at the time of reporting, few recovered (101, 26.9%), and two were fatal. The majority of serious ADRs were categorized as possible (182, 48.8%) followed by probable (173, 46.1%) in nature. CONCLUSION: Antitubercular, antiretroviral, and antimicrobial drugs were the most common causal drug groups for serious ADRs. This calls for robust ADR monitoring system and education of patients and prescribers for identification and effective management.