scholarly journals Time trends of drug-specific actionable adverse events among patients on androgen receptor antagonists: Implications for remote monitoring

2021 ◽  
Vol 16 (3) ◽  
Author(s):  
Lauren Fleshner ◽  
Alejandro Berlin ◽  
Karen Hersey ◽  
Miran Kenk ◽  
Katherine Lajkosz ◽  
...  
Keyword(s):  
Adverse Events ◽  
Liver Dysfunction ◽  
Remote Monitoring ◽  
Cumulative Incidence ◽  
Time Trends ◽  
Chart Review ◽  
Liver Enzymes ◽  
Monitoring Methods ◽  
Patient Exposure ◽  
Elevated Liver Enzymes

Introduction: In light of COVID-19, reducing patient exposure via remote monitoring is desirable. Patients prescribed abiraterone/enzalutamide are scheduled for monthly in-person appointments to screen for adverse events (AEs). We determined time trends of drug-specific actionable AEs among users of abiraterone/enzalutamide to assess the safety of remote monitoring. Methods: A chart review was conducted on 828 prostate cancer patients prescribed abiraterone and/or enzalutamide. Data were collected to determine time to actionable first AEs, including hypertension, elevated liver enzymes (aspartate transaminase [AST], alanine transaminase [ALT]), hyperbilirubinemia, and hypokalemia. Survival analysis was used to determine time to AEs. Results: In this study, 425 and 403 patients received enzalutamide and abiraterone, respectively. In total, 25.6% of those who took enzalutamide experienced an AE, compared to 28.8% of patients on abiraterone. For patients using abiraterone and experiencing an AE, cumulative incidence of AEs at three, six, nine, and 12 months were: 67.2%, 81.9%, 90.5%, and 93.9%, respectively. Among enzalutamide users experiencing an AE, cumulative incidence of AEs at three, six, nine, and 12 months were 51.4%, 70.7%, 82.6%, and 88.1%, respectively. The AEs associated with enzalutamide were hypertension and liver dysfunction (77.1% and 22.9%, respectively). In the abiraterone group, associated AEs were liver dysfunction (47.4%), hypertension (47.4%), and hypokalemia (5.2%). Conclusions: Attaining AEs secondary to abiraterone/enzalutamide decreases over time and tends to occur within the first six months of therapy. Most actionable AEs can be remotely monitored. Given COVID-19, remote monitoring after six months of initiating abiraterone or enzalutamide appears appropriate.

Time trends of drug specific adverse events among patients on androgen receptor antagonists: Implications for remote monitoring.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 40-40
Author(s):  
Lauren Fleshner ◽  
Sophie O'Halloran ◽  
Katherine Lajkosz ◽  
Jacob Wise ◽  
Miran Kenk ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Adverse Events ◽  
Cancer Patients ◽  
Liver Dysfunction ◽  
Remote Monitoring ◽  
Cumulative Incidence ◽  
Time Trends ◽  
Advanced Prostate Cancer ◽  
Blood Pressure Monitoring ◽  
Elevated Liver Enzymes

40 Background: In light of the global pandemic, reducing patient exposure via remote monitoring is desirable. Currently, advanced prostate cancer patients prescribed Abiraterone or Enzalutamide are scheduled for an in-person appointment monthly, to screen for adverse events (AEs). We set out to determine time trends of drug specific AEs in order to determine whether reducing in-person visits for patients taking either Abiraterone or Enzalutamide is feasible. Methods: This chart review was conducted on 667 unique advanced prostate cancer patients, being either metastatic hormone sensitive or castration resistant and utilizing Abiraterone or Enzalutamide. Patients who switched courses of treatment and received both drugs were included twice in the data, resulting in 828 “subjects” overall. Data were collected via accessing electronic patient records, to determine the first sign of an AE related to either Abiraterone or Enzalutamide. These AEs include; hypertension, elevated liver enzymes (bilirubin, AST, ALT) or hypokalemia. Survival analysis was used to determine the time to adverse event. All grade AEs are included in this analysis. Results: In this study, 425 and 403 patients received Enzalutamide and Abiraterone, respectively. In total, 36.3% of those who took Enzalutamide experienced an AE, compared to 43.4% of patients on Abiraterone. For patients utilizing Abiraterone, cumulative incidence of AEs at 3,6,9 and 12 months were: 65.0%, 81.2%, 90.9% and 93.9%, respectively. Among Enzalutamide users, cumulative incidence of AEs at 3,6,9 and 12 months were: 46.8%, 67.5%, 81.2% and 88.3%, respectively. The primary first AEs associated with Enzalutamide consumption were hypertension and liver dysfunction (77.48% and 22.52%). In the Abiraterone group, the first associated AEs were liver dysfunction (48.78%), hypertension (46.34%), and hypokalemia (4.88%). Conclusions: These data suggest that the likelihood of attaining AEs associated with Abiraterone or Enzalutamide utilization decreases over time and tend to occur within the first 6 months of therapy. Furthermore, the vast majority of these AEs can be remotely monitored via outside laboratories and remote blood pressure monitoring. In light of the COVID-19 crisis, remote monitoring after 6 months of taking Abiraterone or Enzalutamide would appear appropriate. Efforts to further safely reduce in person visits should be explored.

scholarly journals Laboratory and clinical adverse events following initiation of dimethyl fumerate

2015 ◽  
Vol 42 (S1) ◽  
pp. S9-S9
Author(s):  
YM Al Malik ◽  
J Greenfield ◽  
W Wall ◽  
LM Metz
Keyword(s):  
Side Effects ◽  
Adverse Events ◽  
Real World ◽  
Clinical Setting ◽  
Liver Enzymes ◽  
First Line Therapy ◽  
Elevated Liver Enzymes ◽  
Relapsing Remitting ◽  
Treatment Naïve ◽  
Relapsing Remitting Multiple Sclerosis

Background: Dimethyl fumerate (DF) is a first line therapy for relapsing remitting multiple sclerosis (RRMS). This retrospective cohort study aims to determine adverse events (AEs) after initiation of DF in a real world clinical setting. Methods: Data from patients at the Calgary MS Clinic with RRMS who initiated DF between July 1, 2013 and December 31, 2014 were analyzed. Demographic, clinical and lab information were collected from patient electronic medical records and the clinic database. Results: This analysis included 170 patients. At treatment initiation mean age was 42.1 years, 75% were women, mean disease duration was 12.5 years, median EDSS was 2.0, and 24% were treatment naïve. Median follow-up was 6.4 months (range: 1.5-17.7). AEs occurred in 101 (59%); the most common were flushing (31%), gastrointestinal (GI) side effects (24%), and elevated liver enzymes (18%). Other less frequent AEs included lymphopenia (lymphocyte count < 0.5) (4%) and proteinuria (4%). DF was discontinued by 17 (10%); median time to discontinuation was 3.1 months. Fifteen (9%) discontinued due to AE. Conclusions: AE associated with DF in a real world clinical setting is comparable to the Canadian monograph for flushing, GI side effects, and lymphopenia but lower for elevated liver enzymes and proteinuria.

scholarly journals Sevoflurane-Induced Thrombocytopenia in Post-Robotic-Assisted Paraesophageal Hernia Repair

2020 ◽  
Vol 2020 ◽  
pp. 1-4
Author(s):  
Sara Alhaj ◽  
James Tran ◽  
Muhammad Nazim ◽  
Praveen Tumula ◽  
Hassan Ahmed
Keyword(s):  
Platelet Count ◽  
Hernia Repair ◽  
Liver Dysfunction ◽  
Paraesophageal Hernia ◽  
Liver Enzymes ◽  
Severe Thrombocytopenia ◽  
Paraesophageal Hernia Repair ◽  
Laboratory Findings ◽  
Liver Retraction ◽  
Elevated Liver Enzymes

Background. Transient transaminitis is an expected outcome from liver retraction after foregut surgeries. However, severe thrombocytopenia is usually not a sequela of that. We present a case in which sevoflurane is suspected of inducing thrombocytopenia as it was the only newly introduced medication to the patient during the hospital course. Thrombocytopenia may present in a variety of settings in hospitalized patients. However, managing this occurrence requires deep exploration of pathophysiology that can cause decreased platelets, which may be a challenging task in certain circumstances. The liver plays an important role in thrombopoiesis by releasing megakaryocyte growth factors. Therefore, liver dysfunction can present as thrombocytopenia or other platelet dysfunctions. Objective. To describe a presentation of thrombocytopenia possibly associated with anesthesia-induced transaminitis after a robotic paraesophageal hernia repair with mesh and fundoplasty with intraoperative esophagogastroduodenoscopy (EGD). Methods. A 55-year-old presented to the ED with abdominal pain and was found to have a large type IV paraesophageal hernia that was surgically treated with a robotic paraesophageal hernia repair with mesh. However, on the first postoperative day (POD) (#1), the patient developed new onset thrombocytopenia with transaminitis. Workup for thrombocytopenia failed to determine an etiology. With platelet transfusion, platelet count showed an upward trend. The patient was then evaluated and cleared for discharge by POD#5. Results. The patient’s POD#1 daily labs showed elevated values for liver function tests and a low platelet count of 10,000 platelets per microliter with an international normalized value (INR) of 1.3. She had received two doses of intravenous acetaminophen just prior to surgery. Her platelet count responded to two units of platelets but decreased again immediately after. She continued to have transaminitis with down-trending liver enzymes. Peripheral smear on review showed no evidence of schistocytes. A heparin-induced thrombocytopenia (HIT) screening was negative. The patient was regularly evaluated, and the platelets stabilized and slowly started to trend up. The patient recovered by the morning of her POD#5 and was cleared for discharge. Conclusion. We are reporting on a case of acute postoperative thrombocytopenia that was associated with transaminitis and elevated liver enzymes. We are linking the role of the liver dysfunction in noncirrhotic patients with surgical abdominal procedures. Although liver retraction transaminitis possibly played a role in the laboratory findings in the patient, the acute drop in her platelet count could be closely related to the use of sevoflurane anesthetic considering its potential hepatotoxic side effects. We also cannot rule out the sevoflurane directly affecting the platelet count.

Management of adverse events in patients with HER2+ metastatic breast cancer treated with tucatinib, trastuzumab, and capecitabine (HER2CLIMB).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1043-1043
Author(s):  
Alicia Frances Clare Okines ◽  
Elisavet Paplomata ◽  
Tanya A. Wahl ◽  
Gail Lynn Shaw Wright ◽  
Stephanie Sutherland ◽  
...  
Keyword(s):  
Breast Cancer ◽  
At Risk ◽  
Adverse Events ◽  
Median Time ◽  
Exposure Time ◽  
Liver Enzymes ◽  
Risk Exposure ◽  
Elevated Liver Enzymes ◽  
The Difference ◽  
Adjusted Incidence

1043 Background: Tucatinib (TUC) is an investigational TKI, highly selective for HER2 without significant inhibition of EGFR. HER2CLIMB is a randomized trial of TUC vs placebo in combination with trastuzumab and capecitabine in patients (pts) with HER2+ breast cancer (NCT02614794, Murthy NEJM 2019). The most common G ≥3 adverse events (AEs) with higher incidence on the TUC arm (diarrhea, palmar-plantar erythrodysesthesia syndrome [PPE], and elevated liver enzymes) are described herein. Methods: Given that pts on the TUC arm had a longer duration of tx than those on the control arm, time-at-risk exposure-adjusted incidence rates of diarrhea, AST, ALT, and PPE were calculated as the number of pts with an event divided by the total exposure time-at-risk of an initial occurrence of the event among pts in the tx group. Time-to-event analyses were conducted for AST/ALT/bilirubin (in aggregate), diarrhea, and PPE. Results: Diarrhea and elevated AST/ALT/bilirubin on both the TUC and control arms were primarily G1/2 and manageable with dose modifications, and in some cases of diarrhea, with antidiarrheal tx. Median time to diarrhea onset was shorter on the TUC arm compared to control. For AST/ALT/bilirubin and PPE, median time to first onset was Cycles 1 and 2. On the TUC arm, antidiarrheals were used in 49.7% of cycles in which diarrhea was reported (39.8% on the control arm), and when used, the median duration of use on each arm was 3 days per cycle. Prophylactic antidiarrheals were not required per protocol. When adjusted for exposure (time-at-risk exposure-adjusted incidence rate per 100 person-years), the difference in G ≥3 events between tx arms becomes similar for diarrhea and PPE (21 vs 17 and 21 vs 19). The difference in G ≥3 events between arms is reduced for AST and ALT (7 vs 1 and 8 vs 1). Conclusions: TUC with trastuzumab and capecitabine was well-tolerated. Rates of G ≥3 diarrhea and PPE were similar between tx arms. Elevated liver enzymes were higher on the TUC arm, but were transient and reversible. Discontinuation of TUC due to AEs was rare. Clinical trial information: NCT02614794 . [Table: see text]

The Neonatal Liver Part II: Assessment and Diagnosis of Liver Dysfunction

2003 ◽  
Vol 22 (2) ◽  
pp. 7-15 ◽  
Author(s):  
William Diehl-Jones ◽  
Debbie Fraser Askin
Keyword(s):  
Liver Disease ◽  
Liver Dysfunction ◽  
Plasma Proteins ◽  
Hepatic Dysfunction ◽  
Liver Enzymes ◽  
Neonatal Period ◽  
The Body ◽  
Hypoxic Injury ◽  
Elevated Liver Enzymes ◽  
Neonatal Liver

The liver, the largest organ in the body, performs many essential functions, including the storage and filtration of blood, production of bile, regulation of plasma proteins and glucose, and biotransformation of drugs and toxins. Many neonates display signs of hepatic dysfunction such as hyperbilirubinemia, hepatomegaly, or elevated liver enzymes. Primary liver disease in neonates is rare; much of the liver dysfunction seen in the neonatal period is secondary to systemic illness such as sepsis or hypoxic injury. It is important for the clinician to have the skills and knowledge necessary to distinguish intrinsic liver disease from liver dysfunction resulting from extrahepatic causes. Early intervention to address the cause of dysfunction is critical to successful management of liver disease. This article reviews the assessment of liver function in neonates and examines the techniques used to diagnose liver dysfunction.

scholarly journals Repaglinide induced Acute Hepatotoxicity

2009 ◽  
Vol 48 (174) ◽  
pp. 162-4 ◽  
Author(s):  
Suresh Jaiswal ◽  
R Mehta ◽  
M Musuku ◽  
L Tran ◽  
Jr W McNamee
Keyword(s):  
Case Report ◽  
Adverse Events ◽  
Side Effect ◽  
Liver Enzymes ◽  
Elevated Liver Enzymes ◽  
Rare Side Effect

Repaglinide is considered a safe drug; adverse events are mild to moderate which includes hypoglycemia, headache, nausea, vomiting, diarrhea and dyspepsia as similar to sulphonylureas. This case report describes a rare side effect of repaglinide. In rare cases, elevated liver enzymes have been noted. We report a case of acute hepatotoxicity in a 78 year old woman who developed acute hepatotoxicity while taking repaglinide.Key Words: hepatotoxicity, hypoglycemia, repaglinide,

scholarly journals SUN-495 Rapid Resolution of Hyperthyroidism Induced Hepatic Dysfunction with Methimazole

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Maryam Amir ◽  
Marie-Noel Rahhal ◽  
Jorge Calles-Escandon
Keyword(s):  
Liver Dysfunction ◽  
Hepatic Dysfunction ◽  
Liver Enzymes ◽  
Biliary Cirrhosis ◽  
Research Information ◽  
Free T4 ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Elevated Liver Enzymes ◽  
Elevated Transaminases

Abstract Background: Hepatic dysfunction in the setting of hyperthyroidism is difficult to diagnose and poses a challenge in therapy, since the classic medications used are potentially hepatotoxic. Clinical case: A 51-year-old female patient presented with fatigue, palpitations and tremors. BP 146/65 mmHg, HR 111 bpm and Temp 97.8 F. She was severely thyrotoxic with 3 + DTRs, tremors, enlarged thyroid gland with bruit on auscultation, clear lungs and no lower extremities edema. Blood tests showed TSH &lt;0.003 IU/ml (0.450-5.330 IU/ml), Free T4 5.33 ng/dL (0.45-1.80 ng/dL), Free T3 &gt; 30.0 pg/mL (2.3-4.2 pg/mL). Liver enzymes showed elevation in transaminases with ALT 319 IU/L (7-40 IU/L), AST 330 IU/L (7-40 IU/L) normal total Bilirubin 0.7 mg/dL (0.1-1.5 mg/dL) and Alkaline phosphatase 65 IU/L (40-200 IU/L). Transaminases were also elevated 3 weeks prior to presentation and this was extensively worked up with no identifiable etiology to explain the liver dysfunction. She was started on beta blocker therapy and admitted to the ICU. She had no clinical or echocardiographic evidence of cardiac dysfunction and remained hemodynamically stable. She was started on Methimazole 45 mg daily. The patient improved clinically and a pronounced decline in transaminase levels was documented in the first 72 hours. She was discharged home on day 3 of admission. On follow up visit her transaminases were found to have completely normalized within 14 days. Discussion: The diagnosis of elevated transaminases in hyperthyroidism is a challenge. This is due to the possibility of multiple etiologies including decreased cardiac output and/or liver congestion, concomitant primary liver disease or more specifically autoimmune hepatic disease such as primary biliary cirrhosis. (1-2). Incidentally Methimazole has been associated with transient asymptomatic transaminitis typically during the first three months of therapy (3). Our case indicates, that methimazole can be used in patients with a presumed diagnosis of hyperthyroidism induced hepatotoxicity after all possible etiologies are ruled out. Hyperthyroidism as the cause of liver dysfunction can only be entertained after all those etiologies are ruled out and upon resolution of transaminase elevation in conjunction with improvement in the hyperthyroid state itself, as was demonstrated in this case. Conclusion: Methimazole can be safely used in patients with severe hyperthyroidism and elevated liver enzymes when all other etiologies of liver dysfunction have been ruled out. References: 1. Khemichian S, Fong TL. Hepatic dysfunction in hyperthyroidism. Gastroenterol Hepatol (N Y). 2. Elias RM, Dean DS, Barsness GW. Hepatic dysfunction in hospitalized patients with acute thyrotoxicosis: a decade of experience. 3. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Bethesda (MD): Methimazole

scholarly journals SAT0137 METHOTREXATE ASSOCIATED ADVERSE EVENTS AND THEIR PREDICTORS IN METHOTREXATE-NAÏVE PATIENTS WITH RHEUMATOID ARTHRITIS: A SYSTEMATIC REVIEW

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1005.2-1006
Author(s):  
A. Sherbini ◽  
S. Sharma ◽  
J. Gwinnutt ◽  
K. Hyrich ◽  
S. Verstappen
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Events ◽  
Observational Studies ◽  
Liver Enzymes ◽  
Forest Plot ◽  
Research Support ◽  
High Baseline ◽  
Pooled Prevalence ◽  
Elevated Liver Enzymes ◽  
Increased Risk

Background:The adverse events (AEs) associated with methotrexate (MTX) treatment for rheumatoid arthritis (RA) have been studied extensively, but precise estimates of the incidence and prevalence of AEs are lacking. There is also limited published data on the predictors of AEs.Objectives:To summarise and pool incidence and prevalence rates of AEs in patients treated with MTX for RA, and to identify treatment, clinical and disease related predictors of AEs.Methods:A systematic literature search was carried out using Embase, Medline, and CENTRAL databases to identify relevant studies published between 1/1/2005 and 12/2/2019. The eligibility criteria included RCTs, non-randomized trials, and observational studies of first-time users of MTX in adults (≥ 18 years old) with RA and reported incidence, prevalence or predictors of the most common MTX related AEs, including: any AE, serious AEs, discontinuation due to AEs, elevated liver enzymes, gastrointestinal (GI), mucocutaneous (MC), central nervous system (CNS), and pulmonary AEs. Pooled proportions of GI AEs and elevated liver enzymes of patients treated with MTX monotherapy were estimated using random effects meta-analysis.Results:Of 3142 records screened, we included 46 articles (35 clinical trials and 11 cohort studies) with a total of 9646 patients, and a mean follow-up duration of 70±35 weeks (range: 13 - 104 weeks for RCTs, 40 - 156 weeks for observational cohorts).Six studies reported incidence rate (IR) of any AE (range: 196 - 595 per 100 person-years), and eight studies reported IR of serious AEs (range: 3.7 - 15.9 per 100 person-years). The percentage of patients with any AE, reported in 32 studies, varied between 37% and 100% in RCTs, and between 13% and 34% in observational studies. Discontinuation of MTX due to AEs ranged between 1% and 29% in RCTs, and between 8% and 38% in observational studies. The reported prevalence of MC events (4% - 54%), CNS events (12% - 59%) and pulmonary events (10% - 67%) varied between studies.The estimated pooled prevalence from studies with a MTX monotherapy arm was 14% (95% CI: 9%, 19%; N=7 studies) for liver enzymes elevation (Figure 1), and 29% (95% CI: 13%, 44%; N=7 studies) for GI AEs (Figure 2).Figure 1.Forest plot of pooled prevalence of elevated liver enzymesFigure 2.Forest plot of pooled prevalence of gastrointestinal adverse eventsNo statistically significant predictors of “any AE” were identified. For discontinuation of MTX due to AEs, RF positivity was associated with lower risk of MTX discontinuation due to MTX (HR 0.37, 95%CI: 0.21, 0.64), while other studies found that baseline HAQ score (OR 1.87, 95%CI: 1.11, 3.15) and BMI (OR 1.21, 95%CI: 1.02, 1.44) were associated with increased risk of MTX discontinuation due to AEs. ACPA positivity (OR 1.8, 95%CI: 1.1, 3.1), and high baseline alanine aminotransferase (ALT) (OR 3.1, 95%CI: 1.6, 6.2) were both independent predictors of two-fold elevation of ALT in one paper, and baseline creatinine (OR 1.03, 95%CI: 1.00, 1.07) and high baseline ALT (OR 1.03, 95%CI: 1.00, 1.06) were associated with increased risk of elevated ALT above the upper limit of normal in a different study.Conclusion:These findings affirm the high prevalence of GI AEs and elevated liver enzymes among patients treated with MTX for RA. The identified predictors of MTX withdrawal and elevated ALTs may be useful for identifying future patients likely to experience these AEs early in the course of treatment. However, the results of the predictors should be interpreted with caution, and further work is needed to replicate the results in studies with larger sample sizes and to assess the prognostic value of established predictors.Disclosure of Interests:Ahmad Sherbini: None declared, Seema Sharma: None declared, James Gwinnutt Grant/research support from: BMS, Kimme Hyrich Grant/research support from: Pfizer, UCB, BMS, Speakers bureau: Abbvie, Suzanne Verstappen Grant/research support from: BMS, Consultant of: Celltrion, Speakers bureau: Pfizer

Hepatitis A Antigen in Liver, Bile and Stool

1975 ◽  
Vol 33 ◽  
pp. 340-341
Author(s):  
D.R. Jackson ◽  
J.H. Hoofnagle ◽  
A.N. Schulman ◽  
J.L. Dienstag ◽  
R.H. Purcell ◽  
...  
Keyword(s):  
Hepatitis A ◽  
Liver Enzymes ◽  
Hepatitis A Virus ◽  
Type A ◽  
Initial Study ◽  
Virus Like Particle ◽  
Elevated Liver Enzymes ◽  
Ag Particles ◽  
Ag Particle ◽  
Human Stool

Using immune electron microscopy Feinstone et. al. demonstrated the presence of a 27 nm virus-like particle in acute-phase stools of patients with viral hepatitis, type A, These hepatitis A antigen (HA Ag) particles were aggregated by convalescent serum from patients with type A hepatitis but not by pre-infection serum. Subsequently Dienstag et. al. and Maynard et. al. produced acute hepatitis in chimpanzees by inoculation with human stool containing HA Ag. During the early acute disease, virus like particles antigenically, morphologically and biophysically identical to the human HA Ag particle were found in chimpanzee stool. Recently Hilleman et. al. have described similar particles in liver and serum of marmosets infected with hepatitis A virus (HAV). We have investigated liver, bile and stool from chimpanzees and marmosets experimentally infected with HAV. In an initial study, a chimpanzee (no.785) inoculated with HA Ag-containing stool developed elevated liver enzymes 21 days after exposure.

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