Adverse Event Profile of Tigecycline: Data Mining of the Public Version of the U.S. Food and Drug Administration Adverse Event Reporting System

Kadoyama, Kaori; Sakaeda, Toshiyuki; Tamon, Akiko; Okuno, Yasushi

doi:10.1248/bpb.35.967

Cited by 67 publications

(48 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally, this system was used to evaluate susceptibility to hypersensitivity reactions for 14 anticancer agents, and it was found that the number of co-occurrences was an important factor in signal detection 22, 23. Very recently, this system was applied to the evaluation of adverse drug events induced by statins 24, capecitabine 25 and tigecycline 26, and again the reproducibility of clinical observations was suggested, providing that the number of co-occurrences was large enough to detect a signal.…”

Section: Discussionmentioning

confidence: 99%

Omeprazole- and Esomeprazole-associated Hypomagnesaemia: Data Mining of the Public Version of the FDA Adverse Event Reporting System

Tamura

Sakaeda²,

Kadoyama³

et al. 2012

Int. J. Med. Sci.

Self Cite

View full text Add to dashboard Cite

Objective: Case reports showing that proton-pump inhibitors (PPIs), omeprazole and esomeprazole, can cause hypomagnesaemia have been accumulating since 2006. In this study, the reports submitted to the Adverse Event Reporting System (AERS) of the US Food and Drug Administration (FDA) were evaluated to assess omeprazole and esomeprazole in terms of susceptibility to hypomagnesaemia.Methods: After a revision of arbitrary drug names and the deletion of duplicated submissions, the reports involving omeprazole and esomeprazole were analyzed. Standardized official pharmacovigilance tools were used for the quantitative detection of a signal, i.e., an association between a drug and an adverse drug event, including the proportional reporting ratio, the reporting odds ratio, the information component given by a Bayesian confidence propagation neural network, and the empirical Bayes geometric mean.Results: A total of 22,017,956 co-occurrences were found in 1,644,220 reports from 2004 to 2009, where a co-occurrence was a pair of a drug and an adverse drug event. In total, 818 and 743 adverse drug events were listed as omeprazole- and esomeprazole-associated, with hypomagnesaemia ranking 85th and 135th, respectively. Although both PPIs were associated with hypomagnesaemia, the statistical metrics suggested that the association was more noteworthy for omeprazole.Conclusion: The data obtained in this study do not provide sufficient evidence to recommend systematic monitoring of magnesium levels in plasma, but chronic exposure to a PPI can lead to severe hypomagnesaemia.

show abstract

Section: Discussionmentioning

confidence: 99%

Omeprazole- and Esomeprazole-associated Hypomagnesaemia: Data Mining of the Public Version of the FDA Adverse Event Reporting System

Tamura

Sakaeda²,

Kadoyama³

et al. 2012

Int. J. Med. Sci.

Self Cite

View full text Add to dashboard Cite

show abstract

“…and Stenotrophomonas maltophilia) (3), and anaerobic bacteria (4) having relatively high sensitivities. Kadoyama et al (5) summarized a total of 248 tigecycline-related adverse reactions, the most common being nausea, vomiting, elevated levels of alanine aminotransferase, bilirubin, alkaline phosphatase, and aspartate aminotransferase, and hepatic dysfunction. In a number of studies, patients showed good tolerance of tigecycline, indicating that it is safe (6-7).…”

mentioning

confidence: 99%

Tigecycline Treatment Causes a Decrease in Fibrinogen Levels

Zhang

Zhou

2015

Antimicrob Agents Chemother

View full text Add to dashboard Cite

The objective of this study was to assess the impact of tigecycline treatment on coagulation parameters, specifically fibrinogen, in patients with severe infections. We examined 20 cases of tigecycline-treated patients with severe infections, including hospitalacquired pneumonia, complicated intra-abdominal infections, complicated skin and soft tissue infections, and bloodstream infections. We monitored the relative markers of coagulation and renal and liver function before, during, and after treatment. Fibrinogen (FIB) levels decreased significantly after the use of tigecycline and normalized after the cessation of treatment. FIB levels significantly decreased in the patients treated with the recommended dose or a higher treatment dose. The FIB levels decreased more in the higher-treatment-dose group. There was no difference in the decrease in FIB levels or the FIB level recovery by age. Prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT) were prolonged after tigecycline use. The TT decreased after the cessation of treatment, and the PT and APTT also decreased but not to a significant level. There was no change in platelet, alanine aminotransferase (ALT), or creatinine (Cr) levels associated with treatment. The use of tigecycline was associated with decreased FIB levels, which returned to normal after the cessation of treatment. A highdose treatment group showed greater decreases in FIB levels than did patients treated with the recommended dose. The decline in FIB was not related to patient age. The use of tigecycline was associated with prolonged PT, APTT, and TT.T igecycline is a novel broad-spectrum intravenous antibiotic that inhibits bacterial protein synthesis. Tigecycline functions by binding to the 30S ribosomal subunit and preventing aminoacylated tRNA molecules from entering the ribosomal A site. Tigecycline contains a glycylamino group substituted for the 9-minocycline group, a substitution rarely seen in any natural or semisynthetic tetracycline compound, which gives tigecycline unique microbiological properties. Tigecycline is not affected by the two major bacterial tetracycline resistance mechanisms, efflux and ribosomal protection mechanisms (1). Tigecycline has a very broad spectrum of antibacterial activity, with Grampositive cocci (including methicillin-resistant Staphylococcus aureus, [MRSA] and vancomycin-resistant enterococci [VRE]) (2), Gram-negative bacilli (including Acinetobacter spp. and Stenotrophomonas maltophilia) (3), and anaerobic bacteria (4) having relatively high sensitivities. Kadoyama et al. (5) summarized a total of 248 tigecycline-related adverse reactions, the most common being nausea, vomiting, elevated levels of alanine aminotransferase, bilirubin, alkaline phosphatase, and aspartate aminotransferase, and hepatic dysfunction. In a number of studies, patients showed good tolerance of tigecycline, indicating that it is safe (6-7). However, there were two case reports that tigecycline can induce decreases in fibrinogen (FIB) levels (...

show abstract

“…Pancreatitis has been identified in pharmacovigilance databases during post-approval use of tigecycline. 9,11,12 Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish causal relationship to drug exposure.…”

Section: Discussionmentioning

confidence: 99%

Pancreatitis in tigecycline Phase 3 and 4 clinical studies

McGovern

Wible

Korth‐Bradley

et al. 2013

Journal of Antimicrobial Chemotherapy

View full text Add to dashboard Cite

ObjectivesTo examine the incidence of pancreatitis among subjects enrolled in the tigecycline clinical trial programme, summarize cases and examine concomitant use of other pancreatitis-causing medications.MethodsSubject data from Phase 3 and 4 comparative tigecycline studies were included in the analysis; investigator-reported adverse events of ‘pancreatitis’, ‘necrotizing pancreatitis’ or ‘pancreas disorder’ were reviewed. Data were summarized and cases were reported. No statistical comparisons were made. The incidence of overall pancreatitis with 95% CIs was calculated. The Wilson score method was used to calculate CIs.ResultsNineteen subjects with investigator-determined pancreatitis were identified from the programme database, which included 3788 subjects treated with tigecycline and 3646 subjects treated with a comparator. There were 9 cases identified among the tigecycline-treated subjects [9 of 3788 (0.24%; 95% CI, 0.11–0.45)] and 10 cases among the comparator-treated subjects [10 of 3646 (0.27%; 95% CI, 0.13–0.50)]. The demographic characteristics of the subjects with pancreatitis were similar between treatment groups. The median duration of tigecycline therapy was 8.0 days compared with 11.0 days of comparator treatment. Concomitant or prior exposure to a Badalov class I medication was evident in the majority of subjects who developed pancreatitis. A numerically higher number of tigecycline-treated subjects were exposed to furosemide prior to the onset of pancreatitis than comparator-treated subjects.ConclusionsPancreatitis was uncommon in subjects treated with tigecycline, with an occurrence of <1%. Concomitant medications known to cause pancreatitis should be considered when prescribing tigecycline, but may not identify those at risk of developing pancreatitis.

show abstract

Adverse Event Profile of Tigecycline: Data Mining of the Public Version of the U.S. Food and Drug Administration Adverse Event Reporting System

Cited by 67 publications

References 19 publications

Omeprazole- and Esomeprazole-associated Hypomagnesaemia: Data Mining of the Public Version of the FDA Adverse Event Reporting System

Omeprazole- and Esomeprazole-associated Hypomagnesaemia: Data Mining of the Public Version of the FDA Adverse Event Reporting System

Tigecycline Treatment Causes a Decrease in Fibrinogen Levels

Pancreatitis in tigecycline Phase 3 and 4 clinical studies

Contact Info

Product

Resources

About