scholarly journals Safety Profile of Ibrutinib: An Analysis of the WHO Pharmacovigilance Database

2021 ◽  
Vol 12 ◽  
Author(s):  
Marion Allouchery ◽  
Cécile Tomowiak ◽  
Thomas Lombard ◽  
Marie-Christine Pérault-Pochat ◽  
Francesco Salvo
Keyword(s):  
Safety Profile ◽  
Large Scale ◽  
Reference Group ◽  
Heart Diseases ◽  
Proportional Reporting Ratio ◽  
World Health ◽  
Safety Database ◽  
Potential Safety ◽  
Pharmacovigilance Database ◽  
Safety Signals

As ibrutinib has become a standard of care in B-cell malignancies in monotherapy or in combination with other agents, definition of its safety profile appears essential. The aim of this study was to further characterize the safety profile of ibrutinib through the identification of potential safety signals in a large-scale pharmacovigilance database. All serious individual case safety reports (ICSRs) in patients aged ≥18 years involving ibrutinib suspected in the occurrence of serious adverse drug reactions or drug interacting from November 13th, 2013 to December 31st, 2020 were extracted from VigiBase, the World Health Organization global safety database. Disproportionality reporting was assessed using the information component (IC) and the proportional reporting ratio (PRR), with all other anticancer drugs used as the reference group. To mitigate the confounding of age, two subgroups were considered: patients aged<75 years and ≥75 years. A signal of disproportionate reporting (SDR) was defined if both IC and PRR were significant. A total of 16,196 ICSRs were included. The median age of patients was 72.9 years, 42.6% of ICSRs concerned patients aged ≥75 years, and 64.2% male patients. More than half (56.2%) of ICSRs resulted in hospitalization or prolonged hospitalization. Among 713 SDRs, 36 potential safety signals emerged in ibrutinib-treated patients, mainly ischemic heart diseases, pericarditis, uveitis, retinal disorders and fractures. All potential safety signals having arisen in this analysis may support patient care and monitoring of ongoing clinical trials. However, owing to the mandatory limitations of this study, our results need further confirmation using population-based studies.

Drug safety profiling for assessment of drug combinations in oncology

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 15037-15037
Author(s):  
S. N. Voss ◽  
A. Czarnecki
Keyword(s):  
Ovarian Cancer ◽  
Drug Safety ◽  
Gastrointestinal Disorders ◽  
Safety Database ◽  
New Drug ◽  
Combination Treatments ◽  
Potential Safety ◽  
Drug Regimens ◽  
Safety Signals ◽  
System Organ

15037 Background: It is important to understand the safety profile (SP)/toxicity of new drug regimens in oncology. We compared SPs of gemcitabine (Gem) + carboplatin (Carbo) in NSCLC with Gem alone and in different combinations and also tested the methodology of drug safety profiling (DSP). Methods: Spontaneous cases for the period of 1995–2005 were reviewed on the Lilly Safety Database (LSD). DSP was used to evaluate differences in the SPs of several combinations: Gem+Carbo in NSCLC, Gem+Carbo in ovarian cancer, Gem+ cisplatin (Cis) in NSCLC, Gem+Carbo in all indications, and Gem regardless of treatment regimen, for all indications. Frequencies of adverse events (AEs) for all MedDRA System Organ Classes (SOCs) were used for each regimen. In addition, the MedDRA Preferred Terms (PTs) were reviewed to detect potential safety signals. The numbers of AEs in different SOCs were assessed as proportions of the total reports for the Gem combinations in the LSD. Results: With the exception of the Investigations SOC, the proportions of AEs for patients treated for NSCLC with Gem+Carbo were consistent with those for patients treated for NSCLC with Gem+Cis and with Gem for all indications. However, the frequency in the Investigations SOC was consistent with that reported for Gem+Carbo in all indications (14.2% v. 12.0%). A greater frequency of AEs was seen in the Gastrointestinal Disorders SOC for patients treated with Gem+Carbo for ovarian cancer compared to patients treated with Gem+Carbo for NSCLC. The review of individual PTs for Gem+Carbo did not reveal any safety signals. Conclusions: The SP of Gem+Carbo in NSCLC using DSP showed similar patterns to all other Gem combinations with only some differences due to the indication. DSP is a useful tool in assessing the new drug combination treatments in existing or new indications. [Table: see text]

scholarly journals Associations between osteoporosis and drug exposure: a post-marketing study of the World Health Organization pharmacovigilance database (VigiBase®)

Bone ◽  
2021 ◽  
pp. 116137
Author(s):  
Benjamin Batteux ◽  
Youssef Bennis ◽  
Sandra Bodeau ◽  
Kamel Masmoudi ◽  
Anne-Sophie Hurtel-Lemaire ◽  
...  
Keyword(s):  
World Health Organization ◽  
Drug Exposure ◽  
World Health ◽  
The World ◽  
Pharmacovigilance Database ◽  
Post Marketing ◽  
Health Organization

scholarly journals Coadministration of tizanidine and ciprofloxacin: a retrospective analysis of the WHO pharmacovigilance database

2021 ◽  
Author(s):  
Annette Rudolph ◽  
Hendrike Dahmke ◽  
Hugo Kupferschmidt ◽  
Andrea Burden ◽  
Stefan Weiler
Keyword(s):  
Real World ◽  
Safety Issue ◽  
Demographic Data ◽  
Fatal Outcome ◽  
Individual Case ◽  
World Health ◽  
Global Database ◽  
The Usa ◽  
Pharmacovigilance Database ◽  
The Impact

Abstract Purpose Tizanidine, an alpha-adrenergic substance with antinociceptive and antihypertensive effects, is extensively metabolized via cytochrome P450 (CYP) 1A2. Therefore, coadministration with potent CYP1A2 inhibitors, such as ciprofloxacin, is contraindicated. However, both drugs are broadly utilized in various countries. Their concomitant use bears an inherent high risk for clinically significant symptoms, especially in multimorbid patients experiencing polypharmacy. This study aims to investigate the impact of coadministration of tizanidine and ciprofloxacin using real-world pharmacovigilance data and to raise awareness of this potentially underestimated safety issue. Methods We conducted a retrospective study including Individual Case Safety Reports (ICSR) registered until March 1, 2017, in the World Health Organization (WHO) global database. Demographic data, drug administration information, the course of the adverse drug reaction (ADR), its severity, and outcomes were analyzed for cases reporting ciprofloxacin comedication. Results In 91 (2.0%) of the identified 4192 worldwide ICSR on tizanidine, coadministration of ciprofloxacin was reported. Most of the patients were female (n = 59, 64.8%) with a median age of 54 years (range 13–85 years). The countries contributing most reports were the USA (n = 54, 59.3%) and Switzerland (n = 16, 17.6%). ADRs reported most often affected the nervous system and the cardiac function, especially with large tizanidine doses or drugs with CNS and cardiovascular depressant effects. In two cases, a fatal outcome was reported. Conclusion Despite the existing formal contraindication, the concomitant use of tizanidine and ciprofloxacin can be observed in real-world clinical practice. Reactions mainly affected the central nervous and the cardiovascular system resulting in potentially severe adverse effects. The concomitant use of tizanidine and ciprofloxacin should absolutely be avoided.

Atrial fibrillation in patients treated with intravenous zoledronic or pamidronic acid: a pharmacoepidemiological study

2021 ◽  
Vol 184 (3) ◽  
pp. 441-448
Author(s):  
Luc Pijnenburg ◽  
Joe-Elie Salem ◽  
Bénédicte Lebrun-Vignes ◽  
Jean Sibilia ◽  
Rose-Marie Javier ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Zoledronic Acid ◽  
Pamidronic Acid ◽  
Real Life ◽  
World Health ◽  
Disproportionality Analysis ◽  
Pharmacoepidemiological Study ◽  
Systematic Analysis ◽  
The World ◽  
Pharmacovigilance Database

Objective Atrial fibrillation (AF) may be triggered by intravenous bisphosphonates (IVBPs) such as zoledronic acid or pamidronic acid. Our objective was to confirm the association between AF and IVBPs in a real-life large pharmacovigilance database. Design A systematic analysis of VigiBase, the World Health Organization's pharmacovigilance database. Methods Analysis of adverse events reported as ‘atrial fibrillation’ (according to the Medical Dictionary for Drug Regulatory Activities) associated with the use of zoledronic acid or pamidronic acid, in VigiBase, the World Health Organization's global Individual Case Safety Report (ICSR) database. All ICSRs reporting AF associated with zoledronic acid or pamidronic acid were included in a disproportionality analysis determining the lower end of the 95% credibility interval for the information component (IC025), showing a statistical association when >0. Results 530 ICSRs reporting on the association between AF and IVBPs were extracted. Bayesian disproportionality analysis detected a significant association between AF and use of zoledronic acid (IC025 = 1.83) and pamidronic acid (IC025 = 2.16). Further analysis of these ICSRs determined that AF was severe in 85.0% of cases and with a mortality of 17.7%. The risk of severe AF was increased (OR: 2.98 (95% CI: 1.17–7.57), P = 0.02) following zoledronic acid vs pamidronic acid, after adjustment for age and gender. Conclusions This is the first VigiBase pharmacoepidemiological study confirming the association between IVBPs and AF. Most AF were severe, with a high frequency of lethal outcome. The risk of severe AF was increased following zoledronic acid use compared to pamidronic acid, advocating for a cautious use of IVBPs.

scholarly journals Comparison of tolerability between quetiapine and haloperidol in schizophrenia

2012 ◽  
Vol 1 (1) ◽  
pp. 59-64
Author(s):  
Naba Raj Koirala ◽  
Manisha Chapagain ◽  
Pratikchya Tulachan ◽  
Siquafa Zafreen
Keyword(s):  
Safety Profile ◽  
Negative Symptoms ◽  
Life Time ◽  
Assessment Instrument ◽  
New Drugs ◽  
World Health ◽  
Typical Antipsychotic ◽  
Mental Health Systems ◽  
Medical College ◽  
Health Organization

Schizophrenia is a serious, disabling, often lifetime condition, which can produce severe functional impairment in patients. The life time morbidity risk for schizophrenia is estimated to be 1% and account for 2.8% of the total global YLDs. The World Health Organization Assessment Instrument for Mental Health Systems report of 2006 done in Nepal states in Nepal states that 12% of the patients are diagnosed as schizophrenia in out-patient mental facilities, 14% in community based psychiatry inpatient units and 34% in mental hospital. Atypical antipsychotics are the first line agents recommended for the treatment of schizophrenia considering better efficacy at least in the negative symptoms and better side-effect profile compared with typical antipsychotic. Haloperidol has been used as a standard comparator in numerous trials and new drugs have been compared to it to establish their efficacy, and safety profile. As the authors could not find out any such study which had compared the safety profile of quetipine against conventional antipsychotic, hence this present study is purposed to carry as an attempt to address this issue among Nepalese population.DOI: http://dx.doi.org/10.3126/jonmc.v1i1.7289 Journal of Nobel Medical College Vol.1(1) 2011 59-64

Impact of the “French Levothyrox crisis” on signal detection in the World Health Organization pharmacovigilance database

2018 ◽  
Vol 27 (12) ◽  
pp. 1427-1428 ◽  
Author(s):  
Charles Khouri ◽  
Bruno Revol ◽  
Marion Lepelley ◽  
Michel Mallaret ◽  
Jean-Luc Cracowski
Keyword(s):  
Signal Detection ◽  
World Health Organization ◽  
World Health ◽  
The World ◽  
Pharmacovigilance Database ◽  
Health Organization
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