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Drugs - Real World Outcomes Jun 2024The association between omeprazole and hypertension is poorly documented. The summary of product characteristics of omeprazole approved by major regulators did not...
INTRODUCTION
The association between omeprazole and hypertension is poorly documented. The summary of product characteristics of omeprazole approved by major regulators did not mention hypertension as an adverse drug event. Triggered by a locally reported case, this study was conducted to assess the possible causal relationship between omeprazole and hypertension.
METHODS
Globally reported cases of hypertension following use of omeprazole submitted to the World Health Organization global database, VigiBase, were retrieved on 5 March 2024 and analyzed descriptively. Besides this, a literature search was made to identify preclinical, clinical, and epidemiological information on the association between omeprazole and hypertension or increased blood pressure using different data sources. Relevant information, gathered from different data sources, was finally systematically organized into an Austin Bradford-Hill causality assessment framework to assess the causal relationship between omeprazole and hypertension.
RESULTS
VigiBase indicated a total of 1043 cases of hypertension related to omeprazole from 36 different countries. In the global database, a statistical signal was triggered (IC: 0.12) on association of omeprazole and hypertension. From the 1043 cases, 65.0% and 10.6% were reported as 'serious' and 'fatal', respectively. Hypertension resolved following withdrawal of omeprazole in 85 cases and recurred after re-introduction of the suspect drug in 14 cases. In 225 cases, omeprazole was the only suspected drug, while in 122 cases, omeprazole was the sole drug administered. When only these 122 cases were considered, 29 cases had positive dechallenge, four cases were with positive rechallenge and the median time-to-onset was 2 days. Literature search identified a possible biological mechanism and some experimental evidence that indicates omeprazole could possibly cause hypertension.
CONCLUSION
Currently available totality of evidence suggests there is a possible causal relationship between omeprazole and hypertension. Hence, it is recommended to monitor and report any incidence of hypertension related to omeprazole, and further epidemiological studies are recommended to corroborate the suggested causal association.
PubMed: 38907158
DOI: 10.1007/s40801-024-00441-2 -
Clinical Chemistry and Laboratory... Jun 2024
PubMed: 38905355
DOI: 10.1515/cclm-2024-0665 -
Frontiers in Pharmacology 2024Drug trials in neonates are scarce, and the neonates may consequently be at risk of adverse drug reactions (ADRs). Spontaneous ADR reporting is an important tool for...
INTRODUCTION
Drug trials in neonates are scarce, and the neonates may consequently be at risk of adverse drug reactions (ADRs). Spontaneous ADR reporting is an important tool for expanding the knowledge on drug safety in neonates. This study explores the quality of current neonatal ADR reports and the ADR reports of the most common drugs used in neonatal departments.
METHODS
An observational cross-sectional study focused on neonates was conducted using data on spontaneous reports extracted from the U.S. Food and Drug Administration Adverse Events Reporting System (FAERS) from the third quarter of 2014 up to December 2022. Only the primary suspect drugs given to neonates or subjects aged <30 days were included in the analysis.
RESULTS
Spontaneous reports from 13 million patients of all ages, totaling 50 million ADRs, were evaluated. Information regarding the age was missing in 40% of the reports, and data on 43,737 neonates with 948 different suspected drugs were identified and included in the analysis. We report the frequency of spontaneous ADR reports in the FAERS database for the ten most frequently administered drugs in neonatal intensive care units in the USA.
CONCLUSION
Overall, neonatal ADRs are still underreported. The FAERS database in its current form discriminates insufficiently between prenatal and postnatal drug exposures. Hence, improved neonatal pharmacovigilance systems are urgently needed.
PubMed: 38903999
DOI: 10.3389/fphar.2024.1395982 -
Frontiers in Pharmacology 2024Lorlatinib displays marked systemic and intracranial efficacy against anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC). We aimed to establish...
BACKGROUND
Lorlatinib displays marked systemic and intracranial efficacy against anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC). We aimed to establish the safety profile of lorlatinib based on the Food and Drug Administration Adverse Event Reporting System (FAERS).
METHODS
Reports from the FAERS between 2019 and 2023 were collected to conduct the disproportionality analysis. Reporting odds ratio (ROR) was employed to detect the potential adverse events (AEs) related to lorlatinib. The clinical characteristics, age and gender differences, time to onset of AEs were also investigated.
RESULTS
A total of 2,941 AE reports were found to be associated with lorlatinib among the 8,818,870 AE reports obtained from the FAERS database. 167 lorlatinib-related AE signals were identified. The frequently reported AEs including hypercholesterolemia, oedema, and cognitive disorder were in line with those observed in clinical trials and drug instruction. However, AEs such as interstitial lung disease and AV block indicated in the drug label require further evaluation. More attention should be paid to the new potential unexpected AEs including pulmonary arterial hypertension and radiation necrosis. Furthermore, we examined the specific high-risk AEs of different ages and genders. In addition, majority of AEs occurred within the first 2 months after lorlatinib initiation with a median onset time of 51 days.
CONCLUSION
Our study provides valuable insight into the post-marketing safety profile of lorlatinib, which can potentially benefit the rational and safe administration of lorlatinib in the clinic. Further prospective studies are needed to validate the associations between lorlatinib and the identified AEs.
PubMed: 38903993
DOI: 10.3389/fphar.2024.1385036 -
Cureus May 2024Toxic epidermal necrolysis (TEN) is a severe and potentially fatal adverse drug reaction. This case report presents a 19-year-old male with pulmonary tuberculosis...
Toxic epidermal necrolysis (TEN) is a severe and potentially fatal adverse drug reaction. This case report presents a 19-year-old male with pulmonary tuberculosis undergoing anti-tubercular therapy who developed TEN. The patient had multiple comorbidities including type 1 diabetes mellitus and multisystem atrophy. ChatGPT was utilized alongside conventional methods to assess causality. While conventional scoring systems estimated mortality at 58.3% (SCORTEN) and 12.3% (ABCD-10), ChatGPT yielded divergent scores. Causality assessment using WHO-Uppsala Monitoring Centre (UMC) and Naranjo's scale indicated rifampicin and isoniazid as probable causative agents. However, ChatGPT provided ambiguous results. The study underscores the potential of AI in pharmacovigilance but emphasizes caution due to discrepancies observed. Collaborative utilization of artificial intelligence (AI) with clinical judgment is advocated to enhance diagnostic accuracy and treatment decisions in adverse drug reactions. This case highlights the importance of integrating AI into drug safety systems while acknowledging its limitations to ensure optimal patient care.
PubMed: 38903274
DOI: 10.7759/cureus.60638 -
International Journal of Clinical... Jun 2024Endothelin receptor antagonists are commonly used in clinical practice, with concerns about their hepatotoxicity.
BACKGROUND
Endothelin receptor antagonists are commonly used in clinical practice, with concerns about their hepatotoxicity.
AIM
This study aimed to conduct a comprehensive pharmacovigilance study based on FDA adverse event reporting system data to evaluate the possible association between endothelin receptor antagonists and drug-induced liver injury.
METHOD
Adverse event reports from FDA adverse event reporting system between January 2004 and December 2022 were analyzed. Disproportionality algorithms, including reporting odds ratio and information component, were used to evaluate the association between endothelin receptor antagonists and liver injury. Sex- and age-stratified analyses of drug-induced liver injury events were also conducted in relation to endothelin receptor antagonists.
RESULTS
Significant associations between bosentan, macitentan, and liver injury were identified. Bosentan showed a strong link with liver injury, with reporting odds ratios for cholestatic injury at 7.59 (95% confidence interval: 6.90-8.35), hepatocellular injury at 5.63 (5.29-6.00), and serious drug-related hepatic disorders events at 1.33 (1.24-1.43). Drug-induced liver injury signals associated with bosentan were detected in all age groups. Macitentan was associated with liver injury, with reporting odds ratios for hepatic failure at 1.64 (1.39-1.94), cholestatic injury at 1.62 (1.43-1.83), and serious drug-related hepatic disorders events at 1.40 (1.29-1.51). No drug-induced liver injury signal was detected for ambrisentan, and no significant sex differences were observed in drug-induced liver injury events.
CONCLUSION
Both bosentan and macitentan are associated with liver injury. Routine monitoring of serum aminotransferase levels is recommended, especially in patients at higher risk of liver injury. Further research into drug-drug interactions involving endothelin receptor antagonists is warranted.
PubMed: 38902469
DOI: 10.1007/s11096-024-01757-3 -
The European Respiratory Journal Jun 2024Asthma is a common respiratory disease, which may be associated with an increased risk of herpes zoster (HZ), often a debilitating disease associated with severe pain.... (Review)
Review
BACKGROUND
Asthma is a common respiratory disease, which may be associated with an increased risk of herpes zoster (HZ), often a debilitating disease associated with severe pain. This was the first systematic review with the objective of summarizing evidence on HZ burden in adults with asthma.
METHODS
A global systematic literature review (SLR) and meta-analysis was conducted (Medline and Embase, 2003-2024), on HZ burden (incidence, risk, complications) in adults (≥18 years) with asthma.
RESULTS
There were 19 studies included on HZ outcomes in adults with asthma. Pooled HZ incidence per 1000 person-years was 5.71 (95% confidence interval [CI] 4.68-6.96) in ≥18-year-olds (4.20 [3.09-5.70] in <60-year-olds 10.33 [9.17-11.64] in ≥60-year-olds). The pooled rate ratio for developing HZ was 1.23 [1.11-1.35] in ≥18-year-olds, and 1.36 [1.15-1.61] in ≥50-year-olds. The risk of HZ was higher in people with asthma using systemic corticosteroids; long-acting beta-agonists plus inhaled corticosteroids; and "add-on therapy". Asthma was also associated with an increased risk of post-herpetic neuralgia (odds ratio, OR 1.21 [1.06-1.37]) and HZ ophthalmicus (OR 1.9 [1.1-3.2]).Differences in study design, setting, case definitions, and follow-up durations led to heterogeneity.
CONCLUSIONS
This SLR and meta-analysis found that adults with asthma have an increased risk of HZ, with higher risks in older age groups, and in those on certain treatments, such as oral corticosteroids. HZ vaccines are available for adults, including those with comorbidities such as asthma, and can be considered as part of integrated respiratory care.
PubMed: 38901886
DOI: 10.1183/13993003.00462-2024 -
General Hospital Psychiatry Jun 2024Valbenazine is commonly used to treat tardive dyskinesia, and we conducted a pharmacovigilance analysis using the Food and Drug Administration Adverse Event Reporting...
PURPOSE
Valbenazine is commonly used to treat tardive dyskinesia, and we conducted a pharmacovigilance analysis using the Food and Drug Administration Adverse Event Reporting System (FAERS) to evaluate neurological safety signals associated with valbenazine.
METHODS
Data was collected in FAERS from the second quarter of 2017 to the fourth quarter of 2023 for data cleaning. Neurological adverse event (AE) signals of valbenazine were mined by calculating reporting odds ratios (ROR), information component (IC) and empirical Bayesian geometric mean (EBGM). The serious and non-serious cases and signals were prioritized using a rating scale.
RESULTS
The number of neurological AE reports where the primary suspect (PS) drug was 8981 for valbenazine. Significant AE signals were identified by the preferred term (PT) analysis for valbenazine, including somnolence (ROR 19.69), tremor (ROR 15.17), and tardive dyskinesia (ROR 236.91), among which 18 AEs were identified as new signals. Patient age (p < 0.009) and sex (p = 0.197) might be associated with an increased risk of neurological AE severity. Notably, the association between valbenazine and neurological disorders remained when stratified by sex, age, and reporter type. AE timing analysis was performed for the drug and four moderate clinical priority signals [i.e., somnolence, balance disorder, parkinsonism, and akathisia (priorities 7)], showing the same early failure type profiles.
CONCLUSIONS
The increase in neurological safety signals is identified in the post-marketing research of valbenazine. Clinicians need to pay attention to not only common AEs but also be alert to new neurological AE signals when using valbenazine.
PubMed: 38901166
DOI: 10.1016/j.genhosppsych.2024.06.005 -
Expert Opinion on Drug Safety Jun 2024Lasmiditan offers a promising option for the treatment of migraines, particularly for individuals with cardiovascular concerns. It is crucial to gather comprehensive...
BACKGROUND
Lasmiditan offers a promising option for the treatment of migraines, particularly for individuals with cardiovascular concerns. It is crucial to gather comprehensive safety information of lasmiditan through large-scale post market monitoring.
RESEARCH DESIGN AND METHODS
This study assessed the safety profile of lasmiditan based on real-world data of FDA Adverse Event Reporting System (FAERS) database. Four disproportionality analysis methods were applied to mining the significant signals. The differences in adverse event signals among different subgroups were investigated concerning race, sex, age, weight, dose, and concomitant drug.
RESULTS
A total of 820 reports and 1,661 adverse events with lasmiditan as the primary suspected drug were identified. Two new adverse event signals related to nervous system disorders emerged. Females and males were more likely to develop paresthesia and dizziness, respectively. Most common adverse events were more likely to occur in the elderly patients and at high doses.
CONCLUSIONS
It is essential to be vigilant about the relation of potential nervous system disorders with lasmiditan. The importance of heightened clinical vigilance regarding paresthesia in females and dizziness in males was underscored. Additionally, it is advised to administer a lower initial dose for elderly patients.
PubMed: 38898801
DOI: 10.1080/14740338.2024.2371382 -
Expert Opinion on Drug Safety Jun 2024Drug efficacy and effectiveness are assessed respectively through clinical trials and pharmaco-epidemiological studies. However, relative and absolute benefits of drugs...
INTRODUCTION
Drug efficacy and effectiveness are assessed respectively through clinical trials and pharmaco-epidemiological studies. However, relative and absolute benefits of drugs are distinct measures that must be considered in relation to the baseline risk of disease incidence, complication or progression. On the other hand, adverse drug reactions are independent of the basic risk but depend on the characteristics of the population treated. Given these prerequisites, how can we balance the benefits and risks of drugs?
AREAS COVERED
We use the example of therapeutics evaluated during Covid to describe how assessing the benefit-risk balance of drugs is a complex process.
EXPERT OPINION
Clinical trials are not designed to identify rare adverse events, underscoring the necessity for a pharmacovigilance system. Evaluating the balance between the benefits and risks of drugs is an ongoing process, demanding the simultaneous analysis of data from clinical trials, potential drug-drug interactions, pharmacovigilance monitoring and pharmaco-epidemiological studies, to identify potential safety concerns. In addition, pharmacologists must play a major role in educating the general public about drugs, aiding in the accurate interpretation of the benefit-risk balance and preventing misinformation.
PubMed: 38898690
DOI: 10.1080/14740338.2024.2368811