Changes in emergency department visits for zolpidem-attributed adverse drug reactions after FDA Drug Safety Communications.

Pharmacoepidemiol Drug Saf. 2020 Mar;29(3):352-356

Authors: Geller AI, Zhou EH, Budnitz DS, Lovegrove MC, Dal Pan GJ

Abstract
Purpose: To identify possible changes in U.S. emergency department (ED) visits from zolpidem-attributed adverse drug reactions (ADRs) after 2013 Food and Drug Administration (FDA) Drug Safety Communications (DSCs), which notified the public about FDA's new dosing recommendations for zolpidem.
Methods: We estimated the occurrence of ED visits from zolpidem-attributed ADRs using nationally representative, public health surveillance of medication harms (National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project, 2010-2017). We estimated the number of zolpidem prescriptions using IQVIA National Prescription Audit, 2010-2017. We calculated rates of ED visits for zolpidem-attributed ADRs per 10 000 dispensed zolpidem prescriptions and identified time trends and potential inflection points using joinpoint regression. For comparison, we repeated these analyses for sedating antidepressants commonly used to treat disordered sleep (trazodone, doxepin, and mirtazapine).
Results: The best-fit regression model for rates of ED visits for zolpidem-attributed ADRs by 6-month intervals identified a single inflection point in the second half of 2014 (P = .024) with a 6.7% biannual decrease from 2010 to 2014 ([-13.1%, 0.3%], P = .059) and a 13.9% biannual increase from the second half of 2014 through 2017 ([-1.1%, 31.3%], P = .068). No change or inflection points were identified for rates of ED visits for sedating antidepressant-attributed ADRs.
Conclusions: While there was a nominal decline in the rate of ED visits for ADRs in the time period before and for 18 months after FDA's 2013 zolpidem DSCs, the decrease was not sustained, and thus questions remain concerning the long-term impact of the zolpidem DSCs on ADRs.

PMID: 32483401 [PubMed - in process]

Economic Impact of Reducing Inappropriate Inhaled Corticosteroids Use in Patients With Chronic Obstructive Pulmonary Disease: ISPOR's Guidance on Budget Impact in Practice.

Value Health. 2019 10;22(10):1092-1101

Authors: Fens T, van der Pol S, Kocks JWH, Postma MJ, van Boven JFM

Abstract
OBJECTIVES: To assess the budget impact of restricting inappropriate inhaled corticosteroids (ICS) use according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD)-guidelines indication for ICS use in the chronic obstructive pulmonary disease (COPD)-population, taking The Netherlands as a reference case.
METHODS: A budget impact model was developed and closely aligned with the International Society for Pharmacoeconomics and Outcomes Research best-practice guidelines. The model estimates the impact of pharmacologic COPD maintenance treatments on clinical events (exacerbations and pneumonias) and associated healthcare utilization and costs. The current treatment mix included all maintenance treatments including long-acting muscarinic antagonists (LAMA), long-acting β2-agonists (LABA), LABA/ICS, LABA/LAMA, and triple therapy (LABA/LAMA/ICS). We modeled a situation where 25% of patients would use ICS-containing treatments and compared this to the current Dutch situation with 60% ICS use. A 5-year time horizon with a Dutch healthcare payer's perspective was used. In sensitivity analyses, a range of values for absolute ICS reduction (20%-40%), relative risks of exacerbations and pneumonia events, and other input parameters were explored.
RESULTS: Over a period of 5 years, the new treatment mix with Global Initiative for Chronic Obstructive Lung Disease guideline recommended ICS, and LABA/LAMA use resulted in potential avoidance of 17 405 exacerbations and 11 984 pneumonias and accompanied savings of €84 million in the base-case scenario. Savings were consistent in various sensitivity analyses, indicating cost savings between €30 and €200 million.
CONCLUSION: Reducing inappropriate ICS use and increasing use of LABA/LAMA in COPD patients could result in a reduction of exacerbations and pneumonias, corresponding with a reduction in total costs for COPD in The Netherlands.

PMID: 31563251 [PubMed - indexed for MEDLINE]

U.S. Emergency Department Visits Resulting From Nonmedical Use of Pharmaceuticals, 2016.

Am J Prev Med. 2019 05;56(5):639-647

Authors: Geller AI, Dowell D, Lovegrove MC, McAninch JK, Goring SK, Rose KO, Weidle NJ, Budnitz DS

Abstract
INTRODUCTION: National data on morbidity from nonmedical use of pharmaceuticals are limited. This study used nationally representative, public health surveillance data to characterize U.S. emergency department visits for acute harms from nonmedical use of pharmaceuticals and to guide prevention efforts.
METHODS: Data collected in 2016 from the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project were analyzed in 2018 to calculate national estimates of emergency department visits for harms from nonmedical use of pharmaceuticals.
RESULTS: Based on 5,130 surveillance cases, there were an estimated 358,247 emergency department visits (95% CI=280,675, 435,819) in 2016 for harms from nonmedical use of pharmaceuticals and 41.1% resulted in hospitalization (95% CI=32.3%, 49.8%). One half (50.9%, 95% CI=46.6%, 55.3%) of estimated visits involved patients aged ≤34 years; more than one half of estimated visits also involved non-pharmaceutical substances (52.9%, 95% CI=49.7%, 56.1%), including illicit drugs in 34.1% (95% CI=30.9%, 37.2%) and alcohol in 21.8% (95% CI=19.8%, 23.9%). Overall, benzodiazepines were implicated in 46.9% (95% CI=42.5%, 51.2%) of estimated emergency department visits for nonmedical use of pharmaceuticals but were the only substance implicated in just 6.5% (95% CI=5.1%, 7.9%). Prescription opioids were implicated in 36.2% (95% CI=30.8%, 41.7%) of estimated emergency department visits and were the only substance implicated in 11.3% (95% CI=8.6%, 14.0%).
CONCLUSIONS: Although prescription opioids or benzodiazepines are frequently implicated in emergency department visits for nonmedical use, because other substances and additional pharmaceuticals are most often involved, prescribing clinicians should consider implementing specific screening to address polysubstance use and, when warranted, treatment interventions.

PMID: 30851991 [PubMed - indexed for MEDLINE]

20 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 2020/06/02

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.

20 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 2020/06/02

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.

Testicular pain following initiation of elexacaftor/tezacaftor/ivacaftor in males with cystic fibrosis.

J Cyst Fibros. 2020 May 26;:

Authors: Rotolo SM, Duehlmeyer S, Slack SM, Jacobs HR, Heckman B

Abstract
Elexacaftor/tezacaftor/ivacaftor (Trikafta) was approved by the Food and Drug Administration in October 2019 for treatment of cystic fibrosis (CF) in patients 12 years and older with at least one F508del mutation in the CFTR protein. There were no documented reports of testicular pain during clinical trials. In this case series, we discuss 7 males between 17 and 39 years of age who reported testicular pain or discomfort within the first two weeks of starting therapy. The precise mechanism of this side effect is unknown, but it may be related to restoration of CFTR function in the male reproductive tract. All patients experienced resolution of this side effect within a week after onset, regardless of the management, except for one. Further research is needed to determine short- and long-term impact of this drug on male fertility. Until more data is available, the authors recommend counseling patients on contraceptive options.

PMID: 32471772 [PubMed - as supplied by publisher]

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 2020/05/30

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.

Biomarkers of pre-existing risk of Torsade de Pointes under Sotalol treatment.

J Electrocardiol. 2020 May 04;60:177-183

Authors: Cruces PD, Torkar D, Arini PD

Abstract
INTRODUCTION: Antiarrhythmic drugs therapies are currently going through a turning point. The high risk that exists during the treatments has led to an ongoing search for new non-invasive toxicity risk biomarkers.
METHODS: We propose the use of spatial biomarkers obtained through the quaternion algebra, evaluating the dynamics of the cardiac electrical vector in a non-invasive way in order to detect abnormal changes in ventricular heterogeneity. In groups of patients with and without history of Torsade de Pointes undergoing a Sotalol challenge, we compute the radius and the linear and angular velocities of QRS complex and T-wave loops. From these signals we extract significant features in order to compute a risk patient classifier.
RESULTS: Using machine learning techniques and statistical analysis, the combinations of few indices reach a pair of sensitivity/specificity of 100%/100% when separating patients with arrhythmogenic substrate. Several biomarkers not only measure drug-induced changes significantly but also observe differences in at-risk patients outperforming current standards.
DISCUSSION: Alternative biomarkers were able to describe pre-existing risk of patients. Given the high levels of significance and performance, these results could contribute to a better understanding of the torsadogenic substrate and to the safe development of drug therapies.

PMID: 32464371 [PubMed - as supplied by publisher]

Panniculitis following baricitinib initiation for treatment of rheumatoid arthritis.

Joint Bone Spine. 2020 May 04;:

Authors: Fike A, Kent R, Biehl A, Ward MM

PMID: 32461123 [PubMed - as supplied by publisher]

Hemodialysis for treatment of levofloxacin-induced neurotoxicity.

Hemodial Int. 2019 Apr;23(2):E40-E45

Authors: Idrees N, Almeqdadi M, Balakrishnan VS, Jaber BL

Abstract
Levofloxacin, a third-generation fluoroquinolone antibiotic, is rarely associated with neurotoxicity. Patients with advanced kidney disease are particularly vulnerable to this adverse effect. We present two elderly patients with kidney failure who developed levofloxacin-induced neurotoxicity, which was successfully treated with frequent hemodialysis, resulting in the full resolution of their symptoms. Neurotoxicity is a well-known side effect of fluoroquinolone antibiotics. Postulated mechanisms include inhibition of the gamma-aminobutyric acid A receptors and activation of the excitatory N-methyl-D-aspartate receptors. Risk factors include older age, kidney disease, pre-existing neurological disorders, and drug-drug interactions. While management of levofloxacin-induced neurotoxicity includes discontinuation of the drug and supportive care, hemodialysis is not recommended, despite available pharmacokinetic data in support of its dialyzability. The successful use of hemodialysis for the treatment of levofloxacin-induced neurotoxicity observed in our two patients with kidney failure should be further considered for rapid resolution of this rare fluoroquinolone-related adverse effect in patients with impaired kidney function.

PMID: 30255655 [PubMed - indexed for MEDLINE]

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 2020/05/28

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.

11 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 2020/05/28

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.

Szisztémás gyógyszerek szemészeti mellékhatásai.

Orv Hetil. 2020 Jun;161(23):951-961

Authors: Czakó C, Sándor G, Horváth H, Szepessy Z, Nagy ZZ, Kovács I

Abstract
Systemic medications of various diseases can have adverse effects on the eye that range from asymptomatic lesions to potentially blinding complications such as toxic retinopathy and optic neuropathy. In the course of ophthalmological screening, with the early detection of toxic effects, the majority of drug-induced eye disorders can be prevented and even be reversed. Our review focuses on major drugs with common and significant ocular side effects. Physicians prescribing medications need to be keenly aware of ocular toxicity risks and the importance of regular screening. Orv Hetil. 2020; 161(23): 951-961.

PMID: 32453698 [PubMed - as supplied by publisher]

Safety, Tolerability, and Efficacy of Viltolarsen in Boys With Duchenne Muscular Dystrophy Amenable to Exon 53 Skipping: A Phase 2 Randomized Clinical Trial.

JAMA Neurol. 2020 May 26;:

Authors: Clemens PR, Rao VK, Connolly AM, Harper AD, Mah JK, Smith EC, McDonald CM, Zaidman CM, Morgenroth LP, Osaki H, Satou Y, Yamashita T, Hoffman EP, CINRG DNHS Investigators

Abstract
Importance: An unmet need remains for safe and efficacious treatments for Duchenne muscular dystrophy (DMD). To date, there are limited agents available that address the underlying cause of the disease.
Objective: To evaluate the safety, tolerability, and efficacy of viltolarsen, a novel antisense oligonucleotide, in participants with DMD amenable to exon 53 skipping.
Design, Setting, and Participants: This phase 2 study was a 4-week randomized clinical trial for safety followed by a 20-week open-label treatment period of patients aged 4 to 9 years with DMD amenable to exon 53 skipping. To enroll 16 participants, with 8 participants in each of the 2 dose cohorts, 17 participants were screened. Study enrollment occurred between December 16, 2016, and August 17, 2017, at sites in the US and Canada. Data were collected from December 2016 to February 2018, and data were analyzed from April 2018 to May 2019.
Interventions: Participants received 40 mg/kg (low dose) or 80 mg/kg (high dose) of viltolarsen administered by weekly intravenous infusion.
Main Outcomes and Measures: Primary outcomes of the trial included safety, tolerability, and de novo dystrophin protein production measured by Western blot in participants' biceps muscles. Secondary outcomes included additional assessments of dystrophin mRNA and protein production as well as clinical muscle strength and function.
Results: Of the 16 included boys with DMD, 15 (94%) were white, and the mean (SD) age was 7.4 (1.8) years. After 20 to 24 weeks of treatment, significant drug-induced dystrophin production was seen in both viltolarsen dose cohorts (40 mg/kg per week: mean [range] 5.7% [3.2-10.3] of normal; 80 mg/kg per week: mean [range] 5.9% [1.1-14.4] of normal). Viltolarsen was well tolerated; no treatment-emergent adverse events required dose reduction, interruption, or discontinuation of the study drug. No serious adverse events or deaths occurred during the study. Compared with 65 age-matched and treatment-matched natural history controls, all 16 participants treated with viltolarsen showed significant improvements in timed function tests from baseline, including time to stand from supine (viltolarsen: -0.19 s; control: 0.66 s), time to run/walk 10 m (viltolarsen: 0.23 m/s; control: -0.04 m/s), and 6-minute walk test (viltolarsen: 28.9 m; control: -65.3 m) at the week 25 visit.
Conclusions and Relevance: Systemic treatment of participants with DMD with viltolarsen induced de novo dystrophin production, and clinical improvement of timed function tests was observed.
Trial Registration: ClinicalTrials.gov Identifier: NCT02740972.

PMID: 32453377 [PubMed - as supplied by publisher]

Quality of adverse event reporting in phase III randomized controlled trials of breast and colorectal cancer: A systematic review.

Cancer Med. 2020 May 26;:

Authors: Komorowski AS, MacKay HJ, Pezo RC

Abstract
BACKGROUND: Clinical trial reports often emphasize efficacy over harms, leading to misinterpretation of the risk-to-benefit ratio of new therapies. Clear and sufficiently detailed reporting of methods and results is especially important in the abstracts of trial reports, as readers often base their assessment of a trial on such information. In this study, we evaluated the quality of adverse event (AE) reporting and abstract quality in phase III randomized controlled trials (RCTs) of systemic therapies in breast and colorectal cancer.
METHODS: Medline, EMBASE, Cochrane Database of RCTs, and Cochrane Database of Systematic Reviews were searched from November 2005 to September 2018. Phase III RCTs evaluating systemic therapies in breast or colorectal cancer were included. Each article was independently reviewed by two investigators using a standardized data extraction form based on guidelines developed by the Consolidated Standards of Reporting Trials (CONSORT) group. Descriptive statistics, bivariate analysis, and multivariable linear regression were used to analyze data. All statistical tests were two-sided.
RESULTS: Of 166 RCTs identified, 99.4% reported harms in the manuscript body, and 59.6% reported harms in the abstract. Reporting was restricted to severe harms in 15.6% of RCTs. Statistical comparison of AE rates went unreported in 59.0% of studies. Information regarding AEs leading to dose reductions, treatment discontinuations, or study withdrawals went unreported in 59.3%, 18.7%, and 86.8% of studies, respectively. Recently published RCTs (P = .009) and those sponsored at least partially by for-profit companies (P = .003) had higher abstract quality scores.
CONCLUSIONS: Breast and colorectal cancer phase III RCTs inadequately report CONSORT-compliant AE data. Improved guideline adherence and abstract reporting is required to properly weigh benefits and harms of new oncologic therapies.
SYSTEMATIC REVIEW REGISTRATION NUMBER: CRD42019140673.

PMID: 32452660 [PubMed - as supplied by publisher]

Improvement of Paclitaxel-Associated Adverse Reactions (ADRs) via the Use of Nano-Based Drug Delivery Systems: A Systematic Review and Network Meta-Analysis.

Int J Nanomedicine. 2020;15:1731-1743

Authors: Chou PL, Huang YP, Cheng MH, Rau KM, Fang YP

Abstract
Background: Paclitaxel is wildly used in chemotherapy, however, the adverse drug reactions (ADRs) occurred frequently. Various novel nano-based paclitaxel delivery systems were developed. The aim performed systemically review and meta-analyses to evaluate the effect adverse drug reactions (ADRs) of paclitaxel and its nano-based delivery systems.
Methods: Systematically searched PubMed, Embase, Web of Science, Cochrane, Clinicalkey, Clinicaltrial.com, ASCO and ESMO. Data of adverse effect were analyzed to odds ratio (ORs) with 95% confidence interval (CI). The quality of studies was assessed with CASP Randomised Controlled Trial Checklist. Statistical analysis was used WinBUGS software (version 1.4.3) with the NetMetaXL interface (version 1.6.1).
Results: Twenty-one studies, including 7011 patients and 6 paclitaxel formulations fulfilled the inclusion criteria. In all grade hypersensitivity reactions, comparing to SB-P, people with Lip-P had 0.19 times (95% CI= 0.02, 1.3) of chance, with Nab-P had 0.47 times (95% CI= 0.11, 1.40) of chance, with PPX had 0.44 times (95% CI= 0.03, 5.7) of chance for all grade adverse effect. In All grad neutropenia, comparing to Lip-P, people with SB-P had 0.83 times (95% CI= 0.15, 4.81) of chance for all grade adverse effect; comparing to PM-P, people with SB-P had 0.73 times (95% CI= 0.22, 2.42) of chance for all grade adverse effect. In leucopenia, comparing to Nab-P, people with SB-P had 0.66 times (95% CI= 0.50, 0.87) of chance for all grade adverse effect; comparing to PM-P, people with SB-P had 0.64 times (95% CI= 0.32, 1.16) of chance for all grade adverse effect. The rate of incidence in peripheral sensory neuropathy, myalgias and arthralgias tend to no significant differences between different formulations.
Conclusion: Nano-based paclitaxel delivery resulted in fewer hypersensitivity reactions than solvent-based delivery. However, the incidence of neutropenia and leucopenia was higher in nano-based than solvent-based paclitaxel delivery. Dose-dependent ADRs were more frequent in paclitaxel anticancer treatment.

PMID: 32210563 [PubMed - indexed for MEDLINE]

Pancreatitis in pre-adolescent children: a 10 year experience in the pediatric emergency department.

BMC Emerg Med. 2019 11 21;19(1):71

Authors: Randall MM, McDaniels S, Kyle K, Michael M, Giacopuzzi J, Brown LA

Abstract
BACKGROUND: The diagnosis of pediatric pancreatitis has been increasing over the last 15 years but the etiology of this is uncertain. The population of pre-adolescent patients with pancreatitis in the emergency department has not been specifically described. Our objective was to determine the characteristics of these patients to illuminate this population and disease in order to better identify them and avoid a delay in diagnosis and treatment.
METHODS: This was a retrospective descriptive study of consecutive pediatric patients under the age of 13 years between 2006 and 2016 who presented to our pediatric emergency department with a diagnosis of atraumatic pancreatitis. Patient characteristics, lab and imaging results, identified etiology of pancreatitis, and recurrence rates were recorded and evaluated.
RESULTS: There were 139 visits, of which 85 were for a first episode of acute pancreatitis, and 54 were patients with an episode of recurrent pancreatitis. The median age for all visits was 8 years (IQ range 5-11). Of the acute cases, 26% had uncertain or undetermined etiologies of which half were thought to likely be viral related; 20% had systemic inflammatory or autoimmune diseases; 19% were associated with medications, with the most common being valproic acid; 16% were cholelithiasis-related; and 15% were found to have a genetic, congenital or structural etiology. No patients had elevated triglycerides. Those with cholelithiasis and genetic or structural defects were found to have a higher recurrence rate than those with other etiologies. There were only four patients diagnosed with chronic pancreatitis.
CONCLUSIONS: The etiology of pancreatitis in pre-adolescent children has a different distribution than in adolescents and adults, with gallstone disease less frequent and concurrent contributing illness more common. Patients on pancreatitis-causing medications or with known genetic risk or structural pancreatic problems should be tested for pancreatitis if presenting with concerning symptoms. Hypertriglyceridemia and chronic pancreatitis with evidence of pancreatic exocrine insufficiency is uncommon in this population.

PMID: 31752694 [PubMed - indexed for MEDLINE]

Efficacy and safety of levoketoconazole in the treatment of endogenous Cushing's syndrome (SONICS): a phase 3, multicentre, open-label, single-arm trial.

Lancet Diabetes Endocrinol. 2019 11;7(11):855-865

Authors: Fleseriu M, Pivonello R, Elenkova A, Salvatori R, Auchus RJ, Feelders RA, Geer EB, Greenman Y, Witek P, Cohen F, Biller BMK

Abstract
BACKGROUND: Levoketoconazole is a ketoconazole stereoisomer in development for treatment of Cushing's syndrome and has not been assessed previously in a clinical trial in patients with Cushing's syndrome. We aimed to investigate the efficacy and safety of levoketoconazole in patients with endogenous Cushing's syndrome.
METHODS: SONICS is a phase 3, multicentre, open-label, non-randomised, single-arm study in which we recruited adults (≥18 years) with confirmed Cushing's syndrome and a mean 24-h urinary free cortisol (mUFC) of at least 1·5 times the upper limit of normal from 60 hospital and community sites in 19 countries (15 countries in Europe, and Canada, Israel, Turkey, and the USA). Patients were treated with oral levoketoconazole in a 2-21 week incremental dose-titration phase starting at 150 mg twice daily (150 mg increments until mUFC normalisation, maximum 600 mg twice daily) and a 6-month maintenance phase. The primary outcome was the proportion of patients with mUFC normalisation at end of maintenance, without dose increase during the maintenance phase (in the intention-to-treat population). Prespecified adverse events of special interest were potential liver toxicity, corrected QT prolongation, and adrenal insufficiency. This trial is registered with ClinicalTrials.gov, NCT01838551.
FINDINGS: Between July 30, 2014, and June 30, 2017, 201 individuals were screened and 94 patients were enrolled and received at least one dose of study medication. Of the 94 patients, 80 (85%) had pituitary Cushing's syndrome. Mean mUFC at baseline was 671·4 nmol/24 h (243·3 μg/24 h), which is 4·9 times the upper limit of normal. Of the 77 patients who advanced to the maintenance phase, 62 (81%) had mUFC normalisation by end-of-dose titration. At the end of the 6-month maintenance phase, 29 (31%) of 94 patients were responders; the least-squares mean estimate of the proportion of responders was 0·30 (95% CI 0·21-0·40; p=0·0154 vs null hypothesis of ≤0·20). The most common adverse events in the 94 patients were nausea (30 [32%]) and headache (26 [28%]). Adverse events led to study discontinuation in 12 (13%) of 94 patients. Two patients had a QT interval (Fridericia corrected) of more than 500 ms, and three patients had suspected adrenal insufficiency. Alanine aminotransferase reversibly increased to more than three times the upper limit of normal in ten (11%) patients. Four patients had serious adverse events that were considered probably or definitely related to the study drug: abnormal liver function test results (n=1), prolonged QT interval (n=2), and adrenal insufficiency (n=1). One person died from colon carcinoma unrelated to study medication.
INTERPRETATION: Twice-daily oral levoketoconazole treatment led to sustained improvements in urinary free cortisol, with an acceptable safety and tolerability profile. Levoketoconazole might represent a useful therapeutic option for the medical treatment of Cushing's syndrome.
FUNDING: Strongbridge Biopharma.

PMID: 31542384 [PubMed - indexed for MEDLINE]

17 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 2020/05/26

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.

Role of Thiopurines in Pediatric Inflammatory Bowel Diseases: A Real-Life Prospective Cohort Study.

J Pediatr Gastroenterol Nutr. 2020 Jun;70(6):825-832

Authors: Atia O, Ledder O, Ben-Moshe T, Lev-Tzion R, Rachmen Y, Meyer EO, Beeri R, Renbaum P, Shamasneh I, Shteyer E, Turner D

Abstract
OBJECTIVES: Use of thiopurines for inflammatory bowel diseases (IBDs) is declining in some parts of the world. We aimed to explore outcomes of thiopurines and predictors of response in a real-world prospective cohort of children with dose optimization.
METHODS: Children with IBD treated with thiopurines without biologics were enrolled. Dosing was guided by thiopurine S-methyltransferase-activity at baseline and by clinical response and toxicity at 4 months; 1 year into the study, therapeutic drug monitoring at 4 months was also considered in the decision making. The primary outcome was steroid-free remission without treatment escalation by 12 months (SFR), using the intention-to-treat approach.
RESULTS: A total of 129 children were included (74% Crohn disease [CD] and 26% ulcerative colitis [UC]). SFR was achieved in 37 (39%) CD and 13 (39%) UC patients, and SFR with normal erythrocyte sedimentation rate/C-reactive protein in 20 (21%) and 9 (27%), respectively. At 4 months, mean corpuscular volume/white blood cell ratio and Δ absolute neutrophil count weakly correlated with 6-thioguanine (r = 0.33, P = 0.02 and r = 0.32, P = 0.02, respectively). In CD, SFR was associated with 4-month median weighted Pediatric Crohn Disease Activity Index (2.5 [IQR 0-7.5] in responders vs 5 in nonresponders [0-12.5], P = 0.048) and Δabsolute neutrophil count (1.7 [IQR 0.7-4.1] vs 0.05 [-2.3-0.9]; P = 0.03). Mild drug-related adverse events were recorded in 30 children (22%), 3 required stopping the drug.
CONCLUSIONS: In this real-life prospective cohort using dose optimization, thiopurines were safe and effective in 21% of CD and 27% of UC patients, including normalization of C-reactive protein and erythrocyte sedimentation rate. Thiopurines remain a viable option in the treatment algorithm of mild-moderate pediatric IBD, especially in girls whose risk for lymphoma is lower.

PMID: 32443042 [PubMed - as supplied by publisher]