Expert Opinion on Drug Safety最新文献

Background: Pimavanserin is a new non-dopamine neurotransmitter antipsychotic drug. This study aimed to conduct a post-marketing pharmacovigilance study of pimavanserin, through data mining technology using the FDA Adverse Event Reporting System (FAERS) database.

Research design and methods: We analyzed adverse event reports for patients using pimavanserin. Data were classified using systematic organ classification (SOC) and preferred term (PT) of the Medical Dictionary for Regular Activities (MedDRA). Four signal algorithms [reporting odds ratio (ROR), proportional reporting ratio (PRR), multi-item gamma poisson shrinker (MGPS), and bayesian confidence propagation neural network (BCPNN)] were used to detect positive signals, and the median time-to-onset was determined.

Results: Adverse drug events (ADEs) related to pimavanserin (n = 31,852) were analyzed, exhibiting an annual linear upward trend (p = 0.027). The ADEs involved 27 SOCs, but only 'Psychiatric disorders' simultaneously satisfied four algorithms. Overall, 153 PTs simultaneously satisfied four algorithms. Subgroup analysis of differences in the top 30 signal intensity PTs according to sex yielded significant results for seven PTs (p < 0.05). The median time-to-onset was 97 days, the highest proportion occurred within the first 30 days (31.79%).

Conclusions: Some new PT signals not listed in the label were identified, and some PT signals showed differences according to sex.

Objectives: We aimed to evaluate and compare the risk of hematological adverse events (AEs) associated with CDK4/6 inhibitors using data from randomized controlled trials (RCTs) and Food and Drug Adverse Event Reporting System (FAERS) database.

Methods: The PubMed, Embase, and Cochrane Library databases were searched for RCTs related to abemaciclib, palbociclib, and ribociclib. A network meta-analysis (NMA) was conducted to compare the risks of hematological AEs, and a disproportionality analysis was performed to detect signals of hematological AEs.

Results: 16 RCTs comprising 16,350 breast cancer patients were included. Palbociclib and ribociclib had similar risks for hematological AEs, except a higher risk of grade 3-4 leukopenia observed with palbociclib (risk ratio [RR]: 7.84, 95% confidence interval [95%CI]: 1.33-41.28). Abemaciclib had a higher risk of anemia than both ribociclib (grade 1-4: RR: 2.23, 95% CI: 1.25 - 3.96; grade 3-4: RR: 3.52, 95% CI: 1.59 - 8.11) and palbociclib (grade 1-4: RR: 1.65, 95%CI: 1.03 - 2.59), but a lower risk of grade 3-4 of both leukopenia (RR: 0.12, 95%CI: 0.02 - 0.49) and neutropenia (RR: 0.15, 95%CI: 0.04 - 0.52) compared with palbociclib. Signals indicating occurrence of leukopenia, neutropenia, anemia, and thrombocytopenia were identified for three CDK4/6 inhibitors.

Conclusion: Abemaciclib, palbociclib, and ribociclib showed significant but inconsistent hematological toxicity risks.

Introduction: Adherence to therapy is fundamental for glaucoma management. Side effects of topical intraocular pressure (IOP)-lowering medications must be managed effectively to maintain adherence to the treatment plan and avoid disease progression. Ocular hyperemia is the most common side effect of topical IOP-lowering medications. It develops either as part of the mechanism of action of an IOP-lowering medication, usually requiring no medical intervention, or as a sign of allergy or toxicity, usually requiring intervention. Therefore, differentiating between types of ocular hyperemia is clinically important.

Areas covered: This clinically oriented narrative review explains the various types of topical glaucoma medication-induced ocular hyperemia, describing the underlying causes, mechanisms of development, and areas involved. Five types of ocular hyperemia associated with IOP-lowering medications are described, relating to the effects of preservatives and active ingredients in mono- and combination therapies. Relevant studies were identified through targeted searches of PubMed and Google Scholar, conducted in August 2024.

Expert opinion: Clinicians should identify the type and severity of ocular hyperemia related to IOP-lowering medications and, accordingly, remove allergenic or toxic agents from therapy. Patients should be advised to continue treatment if ocular hyperemia is mild, especially if it is an expected side effect of the medication.

Background: Immune and targeted anti-cancer therapies are associated with an increased risk of infectious complications. The objectives of the present study were to evaluate the infectious complications associated with immune and targeted anti-cancer drugs.

Research design and methods: This was a retrospective study for immune and targeted anti-cancer drugs submitted to the FDA Adverse Event Reporting System (FAERS) from 1996 to 20 March 2024. The primary outcome was the rate of infectious disease events, and the secondary outcomes were the incidence of febrile neutropenia (FN), all-cause mortality, and the top 10 infections in each class.

Results: Our study included 14 drug classes comprising 44 drugs. The incidence of infectious complications was 14.31% (110,671/773,130). The highest incidence rate was reported with IL-6 inhibitors (30.89%), the highest incidence of FN was reported with Histone deacetylase inhibitors (8.43%), and the highest all-cause mortality was reported with BCR-ABL tyrosine kinase inhibitors (17.17%).

Conclusion: Immune and targeted anti-cancer therapies vary in the incidence of infectious complications. Pirtobrutinib, copanlisib, sirolimus, vorinostat, and tocilizumab were associated with high infectious complications (>30%) that warrant emphasis in the clinical guidelines. Thus, clinicians should vigilantly monitor patients undergoing immune and targeted therapies for infectious complications and use antimicrobial prophylaxes when indicated.

Introduction: Bruton's tyrosine kinase (BTK) is a cytoplasmic signaling protein expressed across a variety of immune cells, terminally differentiated plasma cells, and natural killer cells. Due to the signal potential and targetable nature of BTK, the use of BTK inhibitors (BTKis) has been proposed for the management of several diseases. Currently, the use of BTKis is under investigations for several dermatological conditions such as pemphigus, systemic lupus erythematosus, hidradenitis suppurativa, atopic dermatitis, and chronic spontaneous urticaria (CSU).

Areas covered: The aim of this review is to delve into the use of BTKis in the management of CSU, in order to explore the potential of therapeutic inhibition of BTK in patients with CSU. A thorough analysis of the existing medical literature was conducted across the PubMed, Ovid, Scopus, Embase, and Cochrane Library databases up to 17 August 2024.

Expert opinion: BTK use may represent a breakthrough in the management of CSU. Indeed, their use is characterized by oral administration and a favorable mechanism of action that acts on a significant pathogenic pathway rather than a single molecule. However, long-term studies are needed to further investigate safety data, although data from registered trials appear to be reassuring.

Introduction: Venetoclax, an oral B-cell lymphoma-2 (BCL-2) inhibitor, shows promise in cancer treatment but has an unclear safety profile. This meta-analysis evaluates the safety of venetoclax, focusing on adverse events.

Methods: Data from PubMed, Embase, Cochrane databases, and ClinicalTrials.gov were retrieved up to August 2023. Nine studies were included based on specific inclusion and exclusion criteria. A random effects model was used to calculate risk ratios (RRs) and 95% confidence intervals (CIs).

Results: The meta-analysis included nine studies. Venetoclax was associated with increased risks of neutropenia (RR = 1.427, 95% CI = 1.118 to 1.822), diarrhea (RR = 1.889, 95% CI = 1.388 to 2.570), and cardiovascular events (RR = 1.726, 95% CI = 1.088 to 2.737). However, the risk of tumor lysis syndrome (TLS) with venetoclax was not increased compared to the comparators (RR = 1.478, 95% CI = 0.504 to 4.337).

Conclusions: Venetoclax increases the risk of hematological, gastrointestinal, and cardiac adverse events. Clinicians should monitor these side effects, especially in patients with preexisting conditions. Further research is needed to fully understand venetoclax's safety profile.

Protocol registration: https://inplasy.com/ identifier is INPLASY2023110041.

Background: Fulminant type 1 diabetes mellitus (FT1DM) is a severe subtype of type 1 diabetes characterized by rapid onset, metabolic disturbances, and irreversible insulin secretion failure. Recent studies have suggested associations between FT1DM and certain medications, warranting further investigation.

Objectives: This study aims to identify drugs associated with an increased risk of FT1DM using the FDA Adverse Event Reporting System (FAERS) database, evaluate reporting patterns, and provide actionable insights to reduce FT1DM occurrence and improve medication safety.

Methods: A retrospective analysis of FAERS data from 2013 to 2023 was conducted. Drug names were standardized using text mining tools, and safety signals were evaluated using reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS).

Results: A total of 706 FT1DM cases were identified, predominantly in older individuals and males. Nineteen drugs were implicated, including immune checkpoint inhibitors (nivolumab, ipilimumab, pembrolizumab, avelumab, durvalumab, atezolizumab), lenvatinib, eribulin, psychiatric drugs (atomoxetine, carbamazepine, lamotrigine), anti-infectives (sulfamethoxazole, trimethoprim, amoxicillin), and metabolic modulators (dapagliflozin, sitagliptin, hydrochlorothiazide, allopurinol).

Conclusion: This study highlights drugs potentially triggering FT1DM and emphasizes the need for pharmacovigilance and glucose monitoring in patients treated with these medications.

Background: Faricimab is predominantly prescribed for conditions such as age-related macular degeneration (AMD), diabetic macular edema (DME), and macular edema related to retinal vein occlusion (RVO-ME). Currently, a notable absence of large-scale, real-world studies focusing on the adverse reactions of faricimab exists.

Methods: This study assesses the side effects of faricimab by analyzing reports of adverse events (AEs) from the FDA's AE Reporting System (FAERS) database. Through disproportionality analysis, this study substantiates the drug's safety oversight.

Results: Our study revealed 2,746 instances of adverse events linked to faricimab, spanning 21 system organ classes (SOCs). The study retained 121 significant disproportionality preferred terms (PTs) that met criteria across all four analytical methods. Faricimab-associated AEs not documented in the drug instructions included visual impairment, blindness, retinal hemorrhage, anterior chamber inflammation, keratic precipitates, dry eye, chorioretinitis, diabetic retinopathy, and others.

Conclusion: The majority of our results align with earlier clinical studies and the details outlined in the product's manual. Additionally, we identified several unforeseen and potential AE signals related to faricimab use. These insights are instrumental for ongoing clinical surveillance and risk assessment associated with the drug.