Reporting of adverse events for marketed drugs: Need for strengthening safety database

Background: Drug change (DC) is a common challenge in Danish hospitals. It affects the work of hospital personnel and has potentially serious patient safety consequences. Focus on medication safety is becoming increasingly important in the prevention of adverse events. The aim of this study is to identify and describe patient safety challenges related to DCs, and to explore potential facilitators to improve patient safety in the medication process in Danish hospital setting. Method: Two qualitative methods were combined. Data were obtained from the Danish Patient Safety Database (DPSD) containing incidents reports of adverse events related to DCs. Additionally, five semi-structured focus group interviews with hospital personnel (doctors, nurses, pharmacists and pharmacy technicians) from the five regions of Denmark were held. Results: The DPSD search identified 88 incidents related to DCs due to tender or drug shortage. The incidents were linked to prescribing errors, incorrect dose being dispensed/administered, and delayed/omitted treatment. Four themes from the interviews emerged: (1) challenges related to the drug itself; (2) situational challenges; (3) challenges related to the organization/IT systems/personnel; (4) facilitators/measures to ensure patient safety. Conclusion: DC is as a complex challenge, especially related to drug shortage. The results allow for a deeper understanding of the challenges and possible facilitators of DCs on the individual and organizational level. Pharmacy personnel were identified to play a key role in ensuring patient safety of DCs in hospitals. Indeed, this emphasizes that pharmacy personnel should be engaged in developing patient safety strategies and support hospital personnel around drug changes.

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Pregnancy Outcomes of Patients Exposed to Adalimumab in Japan

Digestive Diseases ◽

10.1159/000493462 ◽

2018 ◽

Vol 37 (2) ◽

pp. 123-130 ◽

Cited By ~ 5

Author(s):

Yumi Kawai ◽

Tsuyoshi Tsuchiya ◽

Shigeru Aoki

Keyword(s):

Adverse Events ◽

Pregnancy Outcomes ◽

Outcome Data ◽

Full Term ◽

Third Trimester ◽

Serious Adverse Events ◽

Additional Risk ◽

Safety Database ◽

Induced Abortions ◽

Adalimumab Treatment

Background: This is the first retrospective report of pregnancy outcomes after exposure to adalimumab treatment in Japan. Methods: Using the AbbVie safety database, we analyzed pregnancy outcome data from patients who received adalimumab treatment from April 16, 2008, to May 15, 2017. Results: Data were extracted retrospectively for 74 pregnancies in 73 patients. More than half of the patients included in the study received adalimumab for the treatment of Crohn’s disease (37.8%) or ulcerative colitis (20.3%), while 9.5% received adalimumab for rheumatoid arthritis. Of the 53 pregnancies with available outcome data, 45 newborns (45/53 [84.9%]) were delivered. Of these births, 30 were full-term, 2 were preterm, and 13 were unknown. Apgar scores were available for 11 of the 16 newborns whose mothers were exposed to adalimumab in the third trimester; all scores were within the normal range. Low birth weight was observed in 5 infants out of the 30 full-term deliveries. There were also 5 miscarriages (5/53 [9.4%]), 2 induced abortions (2/53 [3.8%]), and 1 stillbirth (1/53 [1.9%]). Eight maternal adverse events were observed in 5 pregnancies; no serious adverse events occurred. Conclusion: Although safety concerns were inconclusive, these data do not report additional risk to pregnancy outcomes with adalimumab exposure.

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Response to “Analysis of adverse events of potential autoimmune aetiology in a large integrated safety database of AS04 adjuvanted vaccines” by Verstraeten et al.

Vaccine ◽

10.1016/j.vaccine.2009.01.028 ◽

2009 ◽

Vol 27 (19) ◽

pp. 2529 ◽

Cited By ~ 1

Author(s):

Allan Hildesheim ◽

Mark Schiffman ◽

Diane Solomon ◽

Sholom Wacholder ◽

Ana Cecilia Rodriguez ◽

...

Keyword(s):

Adverse Events ◽

Safety Database ◽

Autoimmune Aetiology

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Use of Identical INN “Imiglucerase” for Different Drug Products: Impact Analysis of Adverse Events in a Proprietary Global Safety Database

Drug Safety ◽

10.1007/s40264-021-01125-4 ◽

2022 ◽

Author(s):

So-Fai Tsang ◽

Shirali Pandya ◽

Kristina Barakov ◽

Joan Keutzer ◽

Grace Lewis ◽

...

Keyword(s):

Adverse Events ◽

Impact Analysis ◽

Safety Database ◽

Drug Products

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702. Hepatic Safety Among Patients Treated with Anti-Fungal Triazole Agent Posaconazole: Characterization of Adverse events in a Manufacturer’s Safety Database

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.770 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S317-S317

Author(s):

Yun-Ping Zhou ◽

Rose O’Flynn ◽

Hetty Waskin ◽

Ronald W Leong ◽

Walter Straus

Keyword(s):

Adverse Events ◽

Drug Exposure ◽

Entire Group ◽

Cell Transplant ◽

Medical Conditions ◽

Hepatocellular Injury ◽

Hematopoietic Stem ◽

Safety Database ◽

Concomitant Medications ◽

Anti Fungal

Abstract Background Second-generation triazoles including posaconazole are highly efficacious for the prophylaxis and salvage treatment of life-threatening invasive fungal diseases. All triazoles have been associated with hepatic adverse events (AEs), which may affect their clinical use; however, risk factors for those AEs are poorly defined. Methods Reports of hepatobiliary AEs for posaconazole from clinical trials and post-market use in our company’s global safety database were reviewed to characterize concomitant medical conditions and drug exposure. Results As of 2018, 444 cases of hepatic AEs were reported; 139 (31%) led to discontinuation of posaconazole. Most hepatic AEs had a time to onset >20 days (55.5%). The most frequent AEs reported (per Medical Dictionary for Regulatory Activities) were: Hyperbilirubinaemia (17%); Hepatotoxicity (13.5%); Hepatic function abnormal (11.5%); and Hepatocellular injury (11.3%). Most patients were adults (18–64 years old) (65%). Hematological malignancy (128 cases, 29%) and hematopoietic stem cell transplant (91 cases, 20%) were leading concurrent medical conditions. Notably, 75% of the cases reported exposure to other drugs (often multiple ones) with known risks for drug-induced liver injury (DILI, e.g., acetaminophen, cytarabine, cyclosporine). Among 139 cases in which posaconazole treatment was discontinued due to hepatic AEs, 6 of the 20 most frequently used co-medications (used by >4.5% of the cases) were classified by the FDA in its DILIRank as “Most-DILI-Concern” (resulting in drug withdrawal, or prominent labeling for severe DILI risk in boxed warning or warnings and precautions), and 7 were “Less-DILI-concern” drugs (DILI risk language in warnings and precautions or adverse reactions). Similarly, of the top 35 concomitant medications for the entire group, 9 are classified as “Most-DILI-Concern” and 12 are “Less-DILI Concern” drugs. Conclusion The use of concomitant medications with known risks for hepatic injury appears to be an important contributor to the development of hepatotoxicity in patients treated with posaconazole. Co-administration of these drugs with anti-fungal triazole agents such as posaconazole, when needed, will continue to be carefully monitored. Disclosures All authors: No reported disclosures.

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Rebuttal Letter to the Letter to the Editor to “Analysis of adverse events of potential autoimmune aetiology in a large integrated safety database of AS04 adjuvanted vaccines” by T. Verstraeten et al.

Vaccine ◽

10.1016/j.vaccine.2009.01.123 ◽

2009 ◽

Vol 27 (19) ◽

pp. 2530 ◽

Cited By ~ 2

Author(s):

Thomas Verstraeten

Keyword(s):

Adverse Events ◽

Safety Database ◽

Letter To The Editor ◽

Autoimmune Aetiology

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Frequency and Clinical Impact of Serious Adverse Events on Post-Stroke Recovery with NeuroAiD (MLC601) versus Placebo: The CHInese Medicine Neuroaid Efficacy on Stroke Recovery Study

Cerebrovascular Diseases ◽

10.1159/000506070 ◽

2020 ◽

Vol 49 (2) ◽

pp. 192-199

Author(s):

Narayanaswamy Venketasubramanian ◽

Rajesh B. Moorakonda ◽

Qingshu Lu ◽

Christopher L.H. Chen ◽

Keyword(s):

Chinese Medicine ◽

Adverse Events ◽

Safety Data ◽

Clinical Impact ◽

Stroke Recovery ◽

Serious Adverse Events ◽

Double Blind ◽

Safety Database ◽

Post Stroke ◽

Life Threatening

Background: Most comparative clinical trials are designed to assess the treatment effect for efficacy endpoints, with less emphasis on the analysis of safety outcomes. However, an extensive analysis of safety data could demonstrate beneficial results in terms of effectiveness by reducing serious adverse events (SAEs), and their unfavourable clinical impact on the study population. We aimed to conduct an exploratory analysis of the CHInese Medicine Neuroaid Efficacy on Stroke recovery (CHIMES) study safety database comparing the frequency of SAEs and their clinical impacts among subjects having received MLC601 or placebo during the first 3 months post-stroke. Methods: Analyses were performed by using the safety database of the multicentre, randomised, double-blind, placebo-controlled CHIMES study of 3 months of NeuroAiD versus placebo in subjects with acute ischaemic stroke of intermediate severity in the preceding 72 h. SAEs as reported by investigators at any time-point during the 3-month study were analysed on their frequency and that of any of their outcomes (death, and life threatening, new and/or prolonged hospitalisation, disability, and medical importance, in surviving subjects), as well as their time to onset and resolution. Results: Of the 1,099 subjects in the CHIMES study, 1,087 were included in the safety analysis (MLC601 = 542) and (placebo = 545); the 12 who did not receive study treatment were excluded. There was a total of 135 subjects with SAEs (MLC601 = 60, placebo = 75). At baseline, overall, subjects with SAEs were older and had lower MMSE score. In the MLC601 group, they had higher NIHSS score, and more frequently a history of ischaemic heart disease and hyperlipidaemia. The number of SAEs per subjects was statistically significantly lower in the MLC601 group than placebo one, especially for subjects with ≥2 SAEs (6.7 vs. 29.3%; p < 0.001). This benefit was seen throughout the study period and during the initial hospitalisation. The main clinical impact of SAEs was an increase in hospitalisation time, reduced in the MLC601 arm with the rate of subjects hospitalised for a prolonged period being significantly threefold lower in surviving subjects (1.1 vs. 3.7%; p < 0.01). Conclusions: This post hoc analysis of SAEs from the CHIMES study database shows that subjects receiving a 3-month course of MLC601 experienced fewer SAEs, with lower rates of harmful clinical impacts, especially in terms of hospitalisation duration. These findings could translate to a benefit in terms of reduction of both healthcare burden and additional medical costs.

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