12 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2019/05/10

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

The Adverse Drug Reactions From Patient Reports in Social Media Project: Protocol for an Evaluation Against a Gold Standard.

JMIR Res Protoc. 2019 May 07;8(5):e11448

Authors: Arnoux-Guenegou A, Girardeau Y, Chen X, Deldossi M, Aboukhamis R, Faviez C, Dahamna B, Karapetiantz P, Guillemin-Lanne S, Lillo-Le Louët A, Texier N, Burgun A, Katsahian S

Abstract
BACKGROUND: Social media is a potential source of information on postmarketing drug safety surveillance that still remains unexploited nowadays. Information technology solutions aiming at extracting adverse reactions (ADRs) from posts on health forums require a rigorous evaluation methodology if their results are to be used to make decisions. First, a gold standard, consisting of manual annotations of the ADR by human experts from the corpus extracted from social media, must be implemented and its quality must be assessed. Second, as for clinical research protocols, the sample size must rely on statistical arguments. Finally, the extraction methods must target the relation between the drug and the disease (which might be either treated or caused by the drug) rather than simple co-occurrences in the posts.
OBJECTIVE: We propose a standardized protocol for the evaluation of a software extracting ADRs from the messages on health forums. The study is conducted as part of the Adverse Drug Reactions from Patient Reports in Social Media project.
METHODS: Messages from French health forums were extracted. Entity recognition was based on Racine Pharma lexicon for drugs and Medical Dictionary for Regulatory Activities terminology for potential adverse events (AEs). Natural language processing-based techniques automated the ADR information extraction (relation between the drug and AE entities). The corpus of evaluation was a random sample of the messages containing drugs and/or AE concepts corresponding to recent pharmacovigilance alerts. A total of 2 persons experienced in medical terminology manually annotated the corpus, thus creating the gold standard, according to an annotator guideline. We will evaluate our tool against the gold standard with recall, precision, and f-measure. Interannotator agreement, reflecting gold standard quality, will be evaluated with hierarchical kappa. Granularities in the terminologies will be further explored.
RESULTS: Necessary and sufficient sample size was calculated to ensure statistical confidence in the assessed results. As we expected a global recall of 0.5, we needed at least 384 identified ADR concepts to obtain a 95% CI with a total width of 0.10 around 0.5. The automated ADR information extraction in the corpus for evaluation is already finished. The 2 annotators already completed the annotation process. The analysis of the performance of the ADR information extraction module as compared with gold standard is ongoing.
CONCLUSIONS: This protocol is based on the standardized statistical methods from clinical research to create the corpus, thus ensuring the necessary statistical power of the assessed results. Such evaluation methodology is required to make the ADR information extraction software useful for postmarketing drug safety surveillance.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/11448.

PMID: 31066711 [PubMed]

A Multicenter, Randomized, Open-Label Study to Compare Micafungin with Fluconazole in the Prophylaxis of Invasive Fungal Infections in Living-Donor Liver Transplant Recipients.

J Gastrointest Surg. 2019 May 07;:

Authors: Kang WH, Song GW, Lee SG, Suh KS, Lee KW, Yi NJ, Joh JW, Kwon CHD, Kim JM, Choi DL, Kim JD, Kim MS

Abstract
BACKGROUND: Although invasive fungal infections (IFIs) contribute to substantial morbidity and mortality in liver transplant recipients, only a few randomized studies analyzed the results of antifungal prophylaxis with echinocandins. The aim of this open-label, non-inferiority study was to evaluate the efficacy and safety of micafungin in the prophylaxis of IFIs in living-donor liver transplantation recipients (LDLTRs), with fluconazole as the comparator.
METHODS: LDLTRs (N = 172) from five centers were randomized 1:1 to receive intravenous micafungin 100 mg/day or fluconazole 100~200 mg/day (intravenous or oral). A non-inferiority of micafungin was tested against fluconazole.
RESULTS: The per-protocol set included 144 patients without major clinical trial protocol violations: 69 from the micafungin group and 75 from the fluconazole group. Mean age of the study patients was 54.2 years and mean model for end-stage liver disease (MELD) score amounted to 16.5. Clinical success rates in the micafungin and fluconazole groups were 95.65% and 96.10%, respectively (difference: - 0.45%; 90% confidence interval [CI]: - 6.93%, 5.59%), which demonstrated micafungin's non-inferiority (the lower bound for the 90% CI exceeded - 10%). The study groups did not differ significantly in terms of the secondary efficacy endpoints: absence of IFIs at the end of the prophylaxis and the end of the study, time to proven IFI, fungal-free survival, and adverse reactions. A total of 17 drug-related adverse events were observed in both groups; none of them was serious and all resolved.
CONCLUSION: Micafungin can be used as an alternative to fluconazole in the prevention of IFIs in LDLTRs.
CLINICAL TRIALS REGISTRATION: NCT01974375 .

PMID: 31066013 [PubMed - as supplied by publisher]

Identification of potentially inappropriate medications with risk of major adverse cardiac and cerebrovascular events among elderly patients in ambulatory setting and long-term care facilities.

Clin Interv Aging. 2019;14:535-547

Authors: Aguiar JP, Heitor Costa L, Alves da Costa F, Leufkens HG, Martins AP

Abstract
Purpose: Cardiovascular diseases (CVDs) are extremely common among the elderly, but information on the use of potentially inappropriate medications (PIMs) with cardiovascular risk is scarce. We aimed to determine the prevalence of PIMs with risk of cardiac and cerebrovascular adverse events (CCVAEs), including major adverse cardiac and cerebrovascular events (MACCE).
Patients and methods: A cross-sectional study was performed using a convenience sample from four long-term care facilities and one community pharmacy in Portugal. Patients were included if they were aged 65 or older and presented at least one type of medication in their medical and pharmacotherapeutic records from 2015 until December 2017. The main outcome was defined as the presence of PIMs with risk of MACCE and was assessed by applying a PIM-MACCE list that was developed from a previous study. All medications included in this list were assessed for their availability in Portugal.
Results: A total of 680 patients were included. Of those, 428 (63%) were female with a mean age of 78.4±8.1 years. Four-hundred and four (59.4%) patients were taking medications associated with CCVAEs risk (mean =1.7±1.0 drugs/patient), including 264 patients (38.8%) who used drugs with MACCE risk (mean =1.4±0.8 drugs/patient). Fifty percent of patients with a previous history of CVD (n=521) were taking PIMs with risk of CCVAEs, including 30.0% with risk of MACCE.
Conclusion: Our findings show that 50% of patients with previous history of CVD were taking drugs with risk of CCAVEs and 30% with risk of MACCE. More tailored tools for the management of drug therapy in elderly patients with CVD are of major importance in clinical practice.

PMID: 30880934 [PubMed - indexed for MEDLINE]

Evaluating the Efficacy and Safety of Silodosin on Nocturia in Patients With Benign Prostatic Hyperplasia: A Multicenter, Prospective, Open-label, Single-arm, Phase IV Trial.

Urology. 2018 Nov;121:153-157

Authors: Cho KJ, Lee JZ, Song YS, Choi JB, Kim DK, Kim YT, Kim JC

Abstract
OBJECTIVE: To evaluate the efficacy and safety of silodosin on nocturia in patients with benign prostatic hyperplasia (BPH).
MATERIALS AND METHODS: This was a 12-week, single-arm, open-label, prospective, multicenter study. The study included men aged 50 years or older with nocturia (≥2 events/night) based on a voiding diary, an International Prostate Symptom Score (IPSS) ≥8, and a quality of life score ≥3. Enrolled patients received 8 mg of silodosin once daily for 12 weeks. We evaluated changes in the mean number of nocturia episodes (using a voiding diary) from baseline to the final assessment. Safety assessments included the rate of adverse events and adverse drug reactions.
RESULTS: There were 118 patients included in the safety evaluation analysis, and 112 patients in the full analysis set group. The number of nocturia episodes decreased significantly after 12 weeks of treatment with silodosin (-1.12 ± 1.05, P < .0001). The secondary efficacy variables, including IPSS, overactive bladder symptom score and International Consultation on Incontinence Questionnaire-Nocturia score, also improved with treatment (P < .0001). There were abnormal drug reactions in 11.8% of patients. The most common adverse drug reaction was an ejaculatory disorder (7.6%). There were no significant adverse drug reactions reported.
CONCLUSION: Silodosin was found to be safe and effective in the treatment of nocturia in patients with BPH.

PMID: 30098325 [PubMed - indexed for MEDLINE]

No side-effects of single intranasal oxytocin administration in middle childhood.

Psychopharmacology (Berl). 2018 Aug;235(8):2471-2477

Authors: Verhees MWFT, Houben J, Ceulemans E, Bakermans-Kranenburg MJ, van IJzendoorn MH, Bosmans G

Abstract
BACKGROUND: Despite growing interest in the (therapeutic) use of intranasal oxytocin administration in children, the potential side-effects of intranasal oxytocin have remained largely unclear to date. The current study is the first double-blind randomized controlled trial to examine side-effects following single administration of oxytocin nasal spray in elementary school-aged children.
METHODS: One hundred children (8-12 years old) were randomly assigned to receive oxytocin or placebo nasal spray. We assessed side-effects by means of a standardized, drug-specific questionnaire and an open-ended question at two time points: 90 min after nasal spray administration and 24 h after administration.
RESULTS: There were no significant associations between nasal spray condition and total frequency of reported side-effects or reports of specific side-effects. Children and their mothers were unable to correctly guess nasal spray allocation, further supporting that the subjective experience of oxytocin versus placebo nasal spray effects was similar. Moreover, the majority of reported side-effects were classified as mild and ceased within 24 h after the procedure, indicating that the nasal sprays were well tolerated.
CONCLUSION: In all, this study is the first randomized controlled trial to provide information on the safety of intranasal oxytocin administration in middle childhood. The current study suggests that single administration of intranasal oxytocin is likely safe in elementary school-aged children.

PMID: 29915962 [PubMed - indexed for MEDLINE]

How to integrate monoclonal antibodies targeting the calcitonin gene-related peptide or its receptor in daily clinical practice.

J Headache Pain. 2019 May 06;20(1):49

Authors: Tiseo C, Ornello R, Pistoia F, Sacco S

Abstract
BACKGROUND: Migraine is a major public health issue associated with significant morbidity, considerable negative impact on quality of life, and significant socioeconomic burden. Preventive treatments are required to reduce the occurrence and the severity of acute attacks and to minimize the use of abortive medications and the associate risk of drug-related adverse events, as well as the onset of medication-overuse headache and chronification of migraine. We performed a review of all available evidence on the safety and efficacy of monoclonal antibodies targeting the calcitonin gene-related peptide or its receptor for the preventive treatment of migraine to provide evidence-based guidance on their use in clinical practice. Monoclonal antibodies targeting the calcitonin gene-related peptide or its receptor are mechanism-specific drugs for the preventive treatment of migraine. Double-blind randomized clinical trials have shown that monoclonal antibodies targeting the calcitonin gene-related peptide or its receptor are effective across all the spectrum of migraine patients who require prevention and have a good safety and tolerability profile. Nevertheless, high costs limit the affordability of those drugs at the moment.
CONCLUSIONS: Specificity, long half-life, efficacy, tolerability, and ease of use make monoclonal antibodies targeting the calcitonin gene-related peptide or its receptor an appealing treatment option for migraine prevention. Optimal strategies to manage treatment over time still need to be clarified with real-life data.

PMID: 31060490 [PubMed - in process]

Emerging evolutionary paradigms in antibiotic discovery.

J Ind Microbiol Biotechnol. 2019 Mar;46(3-4):257-271

Authors: Chevrette MG, Currie CR

Abstract
Antibiotics revolutionized medicine and remain its cornerstone. Despite their global importance and the continuous threat of resistant pathogens, few antibiotics have been discovered in recent years. Natural products, especially the secondary metabolites of Actinobacteria, have been the traditional discovery source of antibiotics. In nature, the chemistry of antibiotic natural products is shaped by the unique evolution and ecology of their producing organisms, yet these influences remain largely unknown. Here, we highlight the ecology of antibiotics employed by microbes in defensive symbioses and review the evolutionary processes underlying the chemical diversity and activity of microbe-derived antibiotics, including the dynamics of vertical and lateral transmission of biosynthetic pathways and the evolution of efficacy, targeting specificity, and toxicity. We argue that a deeper understanding of the ecology and evolution of microbial interactions and the metabolites that mediate them will allow for an alternative, rational approach to discover new antibiotics.

PMID: 30269177 [PubMed - indexed for MEDLINE]

Safety pharmacology methods and regulatory considerations evolve together.

J Pharmacol Toxicol Methods. 2018 Sep - Oct;93:1-6

Authors: Pugsley MK, Harter ML, de Korte T, Connaughton C, Authier S, Curtis MJ

PMID: 29936032 [PubMed - indexed for MEDLINE]

15 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2019/05/07

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

The importance of correct estimation of renal function for drug treatment in hospitalized elderly patients, especially women: A prospective observational study
.

Clin Nephrol. 2019 Apr;91(4):254-264

Authors: Helldén A, Bergman U, Odar-Cederlöf I

Abstract
AIM: To compare renal function by several GFR formulas (particularly cystatin C eGFR-"CAPA") in relation to renal risk drugs (RRDs) in patients admitted to two geriatric wards in a university geriatric department.
MATERIALS AND METHODS: This was a prospective quality improvement study including 108 patients, 2/3 women, age ≥ 75 years, admitted with multimorbidity. Renal function tests were performed with Cockcroft & Gault with uncalibrated (C&Guc) and calibrated creatinine (C&Gcc), and 3 - 4 points' iohexol clearance (mGFR) in mL/min, and eGFR with MDRD4, CKD-EPI, CAPA, and BIS2 clearance in mL/min/1.73m2. Agreement was tested by Bland & Altman analysis. The number and type of RRDs were analyzed.
RESULTS: Measured GFR, C&Gcc, and C&Guc were mean 37, 39, and 32 mL/min, respectively. Estimated GFR by MDRD4, CKD-EPI, CAPA, and BIS2 were mean 56, 52, 45, and 40 mL/min/1.73m2, respectively. Compared to mGFR, women had significantly higher clearance for all estimates except for C&Gcc and C&Guc. C&Gcc, C&Guc, and BIS2 showed the lowest bias. 38 RRDs were identified. 96 patients used a mean of 2.3 RRDs per patient, and 1.7 RRDs needed dose adjustments. Cardiovascular drugs and analgesics were the most frequent RRDs.
DISCUSSION: The C&Gcc, C&Guc, and BIS2 equations gave the best estimate of kidney function in relation to mGFR for drug dosing in the elderly. The eGFR methods showed significantly higher clearance than mGFR, C&Gcc, C&Guc, and BIS2. RRDs that needed dose adjustment were common in this geriatric population. If the eGFR formulas (MDRD4, CKD-EPI, and CAPA) are used instead of C&Gcc, C&Guc, and BIS2, higher and potentially more risky doses of RRDs may be administered to geriatric patients over 75 years, women in particular.

PMID: 30686288 [PubMed - indexed for MEDLINE]

Apremilast ameliorates carfilzomib-induced pulmonary inflammation and vascular injuries.

Int Immunopharmacol. 2019 Jan;66:260-266

Authors: Imam F, Al-Harbi NO, Al-Harbi MM, Qamar W, Aljerian K, Belali OM, Alsanea S, Alanazi AZ, Alhazzani K

Abstract
Acute lung injury (ALI) due to chemotherapy occurs frequently. It presents a challenge for clinicians managing therapies for different types of cancers. Carfilzomib (Kyprolis™) is a new proteasome inhibitor that shows promise for the treatment of relapsing multiple myeloma. However, several cases of severe ALI have raised concern about the use of carfilzomib against relapsed multiple myelomas. To improve the efficacy of carfilzomib, a new anti-inflammatory drug for psoriasis treatment, apremilast (Otezla™) was investigated for its protective effects against carfilzomib-induced ALI in rats. RT-PCR analyses revealed that carfilzomib administration in rats markedly increased the levels of tumor necrosis factor-alpha and nuclear factor-kappa B and myeloperoxidase activity with a concomitant increase in lipid peroxidation. The anti-inflammatory cytokine, interleukin-10, was downregulated following carfilzomib administration. Reduction in glutathione levels indicated diminished cellular antioxidant defenses in response to carfilzomib-induced ALI. ALI was confirmed by histopathological observations in lung tissue slices. Apremilast administration reduced lung inflammation in terms of reduction in myeloperoxidase activity and levels of tumor necrosis factor-alpha and alveolar infiltrating cells. Apremilast reversed all observed toxic effects of carfilzomib and prevented ALI in rats.

PMID: 30500623 [PubMed - indexed for MEDLINE]

Pill-count and the arithmetic of risk: Evidence that polypharmacy is a health status marker rather than a predictive surrogate for the risk of adverse drug events.

Int J Clin Pharmacol Ther. 2018 Dec;56(12):572-576

Authors: Haefeli WE, Meid AD

Abstract
With advancing age there is an increase in the disease burden and thus in the number of drugs prescribed to this patient group. It is often assumed that an increase in pill count is associated per se with an increase in the number of medication errors (e.g., potentially inappropriate prescribing, PIP) and the frequency of adverse drug events (ADE). However, prescribing more drugs can also mean more successful treatment, making it important to critically assess the benefit/risk balance of the medications prescribed in each patient. Whether a prescribed medication is appropriate depends on the clinical state of the patient (diagnoses), treatment goals, comedication/drug interactions, patient preferences, whether the patient tolerates the drug, a measure of how frail the patient is, etc. It is often argued that the number of prescribed drugs should be restricted, but we hold the view that this should only be done after careful consideration of the factors mentioned above. In our study, we remodeled the findings of two large cohort studies investigating the association between the number of drugs prescribed and clinical endpoints. The graphic illustrations obtained confirmed that targeting pill count, as a measure to reduce ADEs and mortality, fails to impact patient well-being because the number of drugs prescribed is likely determined by patient characteristics affecting drug response, namely, disease burden, patient functionality, and specific patient needs, all of which must be taken into account in order to reduce the risk of PIMs and the occurrence ADEs.
.

PMID: 30369395 [PubMed - indexed for MEDLINE]

Safety and effectiveness of iguratimod in patients with rheumatoid arthritis: Final report of a 52-week, multicenter postmarketing surveillance study.

Mod Rheumatol. 2019 Mar;29(2):314-323

Authors: Mimori T, Harigai M, Atsumi T, Fujii T, Kuwana M, Matsuno H, Momohara S, Takei S, Tamura N, Takasaki Y, Yamamoto K, Ikeuchi S, Kushimoto S, Koike T

Abstract
OBJECTIVES: We evaluated the long-term (52 weeks) safety and effectiveness of iguratimod (IGU) in patients with rheumatoid arthritis (RA).
METHODS: This multicenter, prospective, observational study included all evaluable RA patients who received IGU since its market launch in 2012. We evaluated adverse events (AEs); adverse drug reactions (ADRs); ADRs of special interest, including liver and renal dysfunctions, interstitial lung disease, gastrointestinal and blood disorders, and infection; and change in Disease Activity Score 28-C-reactive protein (DAS28-CRP) at week 52.
RESULTS: Safety and effectiveness were analyzed in 2666 and 1614 patients, respectively. The incidences of AEs, serious AEs, ADRs, and serious ADRs were 46.92, 7.35, 38.26, and 4.58%, respectively. The incidence of ADRs peaked at approximately 4 weeks of treatment. Subsequently, the ADR incidence did not increase over time. Improvement of RA activity was shown up to week 52.
CONCLUSION: Long-term treatment with IGU in patients with RA resulted in a tolerable safety profile and an improvement in RA activity. IGU could be considered a useful treatment option for patients with RA.

PMID: 29611761 [PubMed - indexed for MEDLINE]

Use of intravenous iron polymaltose in the management of iron deficiency in pregnancy: A retrospective cohort study.

Aust N Z J Obstet Gynaecol. 2018 Apr;58(2):163-169

Authors: Qassim A, Gergis RG, Jeffries B, Grivell RM, Grzeskowiak LE

Abstract
BACKGROUND: Intravenous iron polymaltose (IPM) is commonly utilised in pregnancy when oral treatment is not tolerated or where rapid replenishment of iron stores is required, but data on use in pregnancy is scarce.
AIM: To examine the use, safety and efficacy of intravenous IPM in pregnancy.
METHODS: Retrospective cohort study of pregnant women administered intravenous IPM between January 2014 and January 2016 at a Tertiary teaching hospital in Adelaide, Australia. Data on maternal characteristics, intravenous iron infusion details, and haematological parameters were collected from case notes and electronic records. Main outcome measures included indication for intravenous iron infusion, prevalence of infusion reactions, change in haemoglobin and correction of anaemia prior to delivery.
RESULTS: Intravenous IPM was administered in 213 pregnancies, 62.0% of women with iron deficiency anaemia (IDA) and the remainder (38.0%) with non-anaemic iron deficiency. Adverse drug reactions (ADRs) occurred in 24% of women, of which 32% required infusion cessation. Anaemia was still present at delivery among 7%, and 17% of women with mild, and moderate/severe anaemia respectively. Approximately one in five anaemic women received an intravenous IPM dose below that recommended by the local guideline, particularly in women with a body mass index ≥ 25 kg/m2 compared with <25 kg/m2 (30.9% vs 6.3%; P < 0.001). Doses 'at recommended' resulted in a greater increase in haemoglobin from treatment until delivery than doses 'below recommended' (adjusted beta coefficient 8.4 g/L; 95% CI 2.7-14.1 g/L).
CONCLUSION: Intravenous IPM is effective in treating IDA in pregnancy but is associated with a high prevalence of ADRs and treatment cessation.

PMID: 28608544 [PubMed - indexed for MEDLINE]

[Importance and specificity of pharmacovigilance in the pediatric population].

Rev Med Suisse. 2019 Apr 03;15(645):743-747

Authors: Rodieux F, Ing-Lorenzini K, Rollason V

Abstract
Clinical trials are usually conducted in a limited time and on a selected population, most often excluding children. These clinical trials provide a first safety profile of the drugs, undeniably essential but often partial, highlighting only the most common adverse drug reactions. In addition in pediatrics, due to growth and physiologic maturation, adverse drug reactions may differ between children and adults and extrapolation of data obtained in adults to children, including safety data, may be inaccurate. Pharmacovigilance, which is based on spontaneous notifications of adverse drug reactions, helps to refine the risk/benefit ratio of drugs and to increase their safety after market launch. This article aims to highlight the importance of pharmacovigilance in general and in particular in the pediatric population and to remind the modalities of reporting in Switzerland.

PMID: 30942973 [PubMed - in process]

Study of serious adverse drug reactions using FDA-approved drug labeling and MedDRA.

BMC Bioinformatics. 2019 Mar 14;20(Suppl 2):97

Authors: Wu L, Ingle T, Liu Z, Zhao-Wong A, Harris S, Thakkar S, Zhou G, Yang J, Xu J, Mehta D, Ge W, Tong W, Fang H

Abstract
BACKGROUND: Adverse Drug Reactions (ADRs) are of great public health concern. FDA-approved drug labeling summarizes ADRs of a drug product mainly in three sections, i.e., Boxed Warning (BW), Warnings and Precautions (WP), and Adverse Reactions (AR), where the severity of ADRs are intended to decrease in the order of BW > WP > AR. Several reported studies have extracted ADRs from labeling documents, but most, if not all, did not discriminate the severity of the ADRs by the different labeling sections. Such a practice could overstate or underestimate the impact of certain ADRs to the public health. In this study, we applied the Medical Dictionary for Regulatory Activities (MedDRA) to drug labeling and systematically analyzed and compared the ADRs from the three labeling sections with a specific emphasis on analyzing serious ADRs presented in BW, which is of most drug safety concern.
RESULTS: This study investigated New Drug Application (NDA) labeling documents for 1164 single-ingredient drugs using Oracle Text search to extract MedDRA terms. We found that only a small portion of MedDRA Preferred Terms (PTs), 3819 out of 21,920 or 17.42%, were observed in a whole set of documents. In detail, 466/3819 (12.0%) PTs were in BW, 2023/3819 (53.0%) were in WP, and 2961/3819 (77.5%) were in AR sections. We also found a higher overlap of top 20 occurring BW PTs with WP sections compared to AR sections. Within the MedDRA System Organ Class levels, serious ADRs (sADRs) from BW were prevalent in Nervous System disorders and Vascular disorders. A Hierarchical Cluster Analysis (HCA) revealed that drugs within the same therapeutic category shared the same ADR patterns in BW (e.g., nervous system drug class is highly associated with drug abuse terms such as dependence, substance abuse, and respiratory depression).
CONCLUSIONS: This study demonstrated that combining MedDRA standard terminologies with data mining techniques facilitated computer-aided ADR analysis of drug labeling. We also highlighted the importance of labeling sections that differ in seriousness and application in drug safety. Using sADRs primarily related to BW sections, we illustrated a prototype approach for computer-aided ADR monitoring and studies which can be applied to other public health documents.

PMID: 30871458 [PubMed - in process]

Managing the adverse events associated with lenvatinib therapy in radioiodine-refractory differentiated thyroid cancer.

Semin Oncol. 2019 02;46(1):57-64

Authors: Cabanillas ME, Takahashi S

Abstract
Lenvatinib is a multikinase inhibitor of vascular endothelial growth factor (VEGF) receptors 1-3, fibroblast growth factor receptors 1-4, RET, KIT, and platelet-derived growth factor receptor-α. Lenvatinib is approved as a monotherapy for the treatment of radioiodine-refractory differentiated thyroid cancer and in combination with everolimus for the second-line treatment of advanced renal cell carcinoma. Lenvatinib is also under investigation for the treatment of several malignancies including unresectable hepatocellular carcinoma. Although lenvatinib is associated with favorable efficacy, it is associated with adverse events (AEs) that the clinician will have to closely monitor for and proactively manage. Most of these AEs are known class effects of VEGF-targeted therapies, including hypertension, diarrhea, fatigue or asthenia, decreased appetite, and weight loss. This review summarizes the safety profile of lenvatinib and offers guidance for the management of both frequent and rare AEs. We discuss the potential mechanisms underlying these AEs and present practical recommendations for managing toxicities. The development of treatment plans that include prophylactic and therapeutic strategies for the management of lenvatinib-associated AEs has the potential to improve patient quality of life, optimize adherence, minimize the need for dose reductions, treatment interruptions, or discontinuations, and maximize patient outcomes.

PMID: 30685073 [PubMed - in process]

Adverse events associated with oral administration of melatonin: A critical systematic review of clinical evidence.

Complement Ther Med. 2019 Feb;42:65-81

Authors: Foley HM, Steel AE

Abstract
While melatonin was once thought of simply as a sleep-inducing hormone, recent research has resulted in development of a deeper understanding of the complex physiological activity of melatonin in the human body. Along with this understanding has come widespread, increasing use of melatonin supplementation, extending beyond its traditional use as a sleep aid into novel fields of application. This increased use often involves off-label and self-prescription, escalating the importance of safety data. In order to examine the current knowledge relating to safety of the exogenous neurohormone, we conducted a comprehensive, critical systematic review of clinical evidence. We examined controlled studies of oral melatonin supplementation in humans when they presented any statistical analysis of adverse events. Of the fifty articles identified, twenty-six found no statistically significant adverse events, while twenty-four articles reported on at least one statistically significant adverse event. Adverse events were generally minor, short-lived and easily managed, with the most commonly reported adverse events relating to fatigue, mood, or psychomotor and neurocognitive performance. A few studies noted adverse events relating to endocrine (e.g. reproductive parameters, glucose metabolism) and cardiovascular (e.g. blood pressure, heart rate) function, which appear to be influenced by dosage, dose timing and potential interactions with antihypertensive drugs. Oral melatonin supplementation in humans has a generally favourable safety profile with some exceptions. Most adverse effects can likely be easily avoided or managed by dosing in accordance with natural circadian rhythms. Further research is required to explore the potential for melatonin to interact with endogenous hormones and pharmaceuticals.

PMID: 30670284 [PubMed - in process]

The Persistent Challenge of Understanding Preventable Adverse Drug Events.

Pediatrics. 2018 09;142(3):

Authors: Schroeder L, Stockwell DC

PMID: 30097526 [PubMed - in process]