scholarly journals Paracetamol safety in COVID-19

2021 ◽  
Vol 1 (1) ◽  
pp. 5-9
Author(s):  
B. K. Romanov
Keyword(s):  
Clinical Trials ◽  
Side Effects ◽  
Safety Issue ◽  
Initial Period ◽  
Safety Data ◽  
Medicinal Products ◽  
Safety Issues ◽  
Safety Concerns ◽  
State Register ◽  
Pharmacovigilance Database

The relevance of paracetamol safety assessment is associated with broad recommendations for its use as a symptomatic agent in COVID-19 and an agent for adverse events following vaccination to prevent COVID-19.Objectives. Conducting a review of global paracetamol safety data during the initial period of COVID-19 pandemic (in 2020 and in the first half of 2021).Materials and methods. 2,356 scientific articles and their abstracts on paracetamol safety in electronic libraries; data on 2,272 clinical trials of paracetamol in ClinicalTrials.gov and the State Register of Medicines of the Ministry of Health of the Russian Federation; 173,707 individual reports of adverse drugs reactions of paracetamol in the international pharmacovigilance database VigiBase. The data were evaluated by statistical methods in the VigiLyze analytical system (authorized expert access).Results. No publications and completed clinical trials were found on the safety issue of paracetamol use in COVID-19. During the initial period of COVID-19 pandemic (from January 1, 2020 to July 31, 2021), the number of reports of paracetamol safety issues included in VigiBase decreased by 22,1%, which may be due to a decrease in the number of specialists sending reports on safety, with an increase of their duties and with a switching attention of these specialists and patients to other problems associated with the COVID-19 pandemic. No changes have been identified in the sources of safety data and trade names for paracetamol medicinal products. It has been established that the main part (99,4% of cases) of side effects associated with paracetamol develops outside the use of vaccines for the prevention of COVID-19. Pre-COVID and COVID data include information on 2,692 and 2,527 names of various paracetamol safety concerns, respectively. These data overlap the list of side effects specified in instructions for medical use and include new symptoms not described in instructions for medical use.Conclusions. The lack of safety signals may be due to the lack of alertness of specialists and marketing authorization holders regarding paracetamol. During the COVID period, the structure and frequency of paracetamol safety concerns codified in terms of MedDRA (version 24.0) have changed, which can be studied in future studies of paracetamol, ibuprofen and other medicinal products.

scholarly journals Safety of Hydroxychloroquine among Outpatient Clinical Trial Participants for COVID-19

2020 ◽  
Author(s):  
SARAH M LOFGREN ◽  
Melanie R Nicol ◽  
Ananta S Bangdiwala ◽  
Katelyn A Pastick ◽  
Elizabeth C Okafor ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Side Effects ◽  
Side Effect ◽  
Randomized Clinical Trials ◽  
Safety Data ◽  
Post Exposure Prophylaxis ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Gastrointestinal Side Effects ◽  
Exposure Prophylaxis

Introduction: Use of hydroxychloroquine in hospitalized patients with COVID-19, especially in combination with azithromycin, has raised safety concerns. Here, we report safety data from three outpatient randomized clinical trials. Methods: We conducted three randomized, double-blind, placebo-controlled trials investigating hydroxychloroquine as pre-exposure prophylaxis, post-exposure prophylaxis and early treatment for COVID-19. We excluded individuals with contraindications to hydroxychloroquine. We collected side effects and serious adverse events. We report descriptive analyses of our findings. Results: We enrolled 2,795 participants. The median age of research participants was 40 (IQR 34-49) years, and 59% (1633/2767) reported no chronic medical conditions. Overall 2,324 (84%) participants reported side effect data, and 638 (27%) reported at least one medication side effect. Side effects were reported in 29% with daily, 36% with twice weekly, 31% with once weekly hydroxychloroquine compared to 19% with placebo. The most common side effects were upset stomach or nausea (25% with daily, 18% with twice weekly, 16% with weekly, vs. 10% for placebo), followed by diarrhea, vomiting, or abdominal pain (23% for daily, 16% twice weekly, 12% weekly, vs. 6% for placebo). Two individuals were hospitalized for atrial arrhythmias, one on placebo and one on twice weekly hydroxychloroquine. No sudden deaths occurred. Conclusion: Data from three outpatient COVID-19 trials demonstrated that gastrointestinal side effects were common but mild with the use of hydroxychloroquine, while serious side effects were rare. No deaths occurred related to hydroxychloroquine. Randomized clinical trials can safely investigate whether hydroxychloroquine is efficacious for COVID-19.

scholarly journals Safety Profile of L-Glutamine in Patients with Sickle Cell Disease: Data from Post-Marketing Surveillance

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4184-4184
Author(s):  
Bhawna Rastogi ◽  
Sunita Rani ◽  
Meiko Mayuzumi ◽  
Rafael Razon ◽  
Rajani Singh ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Abdominal Pain ◽  
Back Pain ◽  
Chest Pain ◽  
Side Effects ◽  
Sickle Cell Disease ◽  
Cell Disease ◽  
Safety Concerns ◽  
Post Marketing Surveillance ◽  
Post Marketing

Abstract Background: L-glutamine (Endari ®) was approved by the US Food and Drug Administration (FDA) in July 2017 to reduce the acute complications of sickle cell disease (SCD) in adult and pediatric patients, aged 5 years and older. Data collected during the phase 2 and phase 3 trials demonstrated a rather mild adverse event profile at the approved doses (approximately 0.3 g/kg administered twice daily). The combined data from the clinical trials encompassed 187 patients assigned to the L-glutamine arm and 111 patients assigned to the placebo arm. The most common side effects observed were constipation, nausea, headache, abdominal pain, cough, pain in extremity, back pain, and chest pain. Since 2017, safety data for L-glutamine has been collected through several sources. Aim: To determine whether new safety concern signals for L-glutamine in the treatment of SCD have emerged over the post-marketing period since July of 2017. Methods: Individual case safety reports (ICSR) received from consumers, physicians, pharmacies, and other healthcare professionals that were processed in the global safety database in real time were reviewed. Continuous safety evaluations that were performed when evaluating ICSRs were collected. Additionally, signal management activities performed quarterly since July 2017, which included screening of literature and regulatory websites for the identification of potential safety information, were evaluated. Results: Overall, 1791 case reports were received with 2954 adverse events between July 07, 2017 (the date of approval) and July 06, 2021. A summary of frequently reported adverse events during the post-marketing phase is presented in Figure 1. No new safety concerns have been identified upon evaluation of these events, which has been performed on a quarterly basis from the approval date. Conclusion: Post-marketing surveillance data indicates that L-glutamine administered at approximately 0.3 g/kg twice daily is safe and well-tolerated. The most common side effects observed during clinical trials were constipation, nausea, headache, abdominal pain, cough, pain in extremity, back pain, and chest pain (Table 1). These same side effects have been observed in the post-marketing phase with the exception of "cough." Side effects reported during the post-marketing phase that were not reported in the clinical trials were abdominal discomfort, diarrhea, malaise, and pain. The majority of these reports were categorized as non-serious (Figure 1). Information pertaining to these events was limited or the event could be explained by the underlying condition or concomitant medication; therefore, these events were not considered to be new safety concerns. In summary, there were no new safety concerns identified with L-glutamine for the treatment of SCD in the post-marketing period. Figure 1 Figure 1. Disclosures Mayuzumi: Emmaus Medical, Inc: Current Employment. Razon: Emmaus Medical, Inc: Current Employment. Singh: Emmaus Medical, Inc: Current Employment. Goodrow: Emmaus Medical, Inc: Current Employment. Becerra: Emmaus Medical, Inc: Current Employment. Stark: Emmaus Medical, Inc: Current Employment. Niihara: Emmaus Lifesciences, Inc.: Current Employment.

scholarly journals Optimizing Collection of Adverse Event Data in Cancer Clinical Trials Supporting Supplemental Indications

2010 ◽  
Vol 28 (34) ◽  
pp. 5046-5053 ◽  
Author(s):  
Lee D. Kaiser ◽  
Allen S. Melemed ◽  
Alaknanda J. Preston ◽  
Hilary A. Chaudri Ross ◽  
Donna Niedzwiecki ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Concomitant Medication ◽  
Safety Data ◽  
Drug Effects ◽  
Statistical Analysis Plan ◽  
Marketing Approval ◽  
Safety Issues ◽  
Adverse Event Data ◽  
Grade 3 ◽  
Optimal Approach

Purpose Although much is known about the safety of an anticancer agent at the time of initial marketing approval, sponsors customarily collect comprehensive safety data for studies that support supplemental indications. This adds significant cost and complexity to the study but may not provide useful new information. The main purpose of this analysis was to assess the amount of safety and concomitant medication data collected to determine a more optimal approach in the collection of these data when used in support of supplemental applications. Methods Following a prospectively developed statistical analysis plan, we reanalyzed safety data from eight previously completed prospective randomized trials. Results A total of 107,884 adverse events and 136,608 concomitant medication records were reviewed for the analysis. Of these, four grade 1 to 2 and nine grade 3 and higher events were identified as drug effects that were not included in the previously established safety profiles and could potentially have been missed using subsampling. These events were frequently detected in subsamples of 400 patients or larger. Furthermore, none of the concomitant medication records contributed to labeling changes for the supplemental indications. Conclusion Our study found that applying the optimized methodologic approach, described herein, has a high probability of detecting new drug safety signals. Focusing data collection on signals that cause physicians to modify or discontinue treatment ensures that safety issues of the highest concern for patients and regulators are captured and has significant potential to relieve strain on the clinical trials system.

scholarly journals Biosimilars: the science of extrapolation

Blood ◽  
2014 ◽  
Vol 124 (22) ◽  
pp. 3191-3196 ◽  
Author(s):  
Martina Weise ◽  
Pekka Kurki ◽  
Elena Wolff-Holz ◽  
Marie-Christine Bielsky ◽  
Christian K. Schneider
Keyword(s):  
Decision Making ◽  
European Union ◽  
Clinical Trials ◽  
Safety Data ◽  
Real Life ◽  
Medical Community ◽  
The European Union ◽  
Efficacy And Safety ◽  
Medicinal Products ◽  
Regulatory Decision

Abstract Despite the establishment of a specific approval pathway, the issuance of detailed scientific guidelines for the development of similar biological medicinal products (so-called “biosimilars”) and the approval of several biosimilars in the European Union, acceptance of biosimilars in the medical community continues to be low. This is especially true in therapeutic indications for which no specific clinical trials with the biosimilar have been performed and that have been licensed based on extrapolation of efficacy and safety data from other indications. This article addresses the concerns frequently raised in the medical community about the use of biosimilars in such extrapolated indications and explains the underlying scientific and regulatory decision making including some real-life examples from recently licensed biosimilars.

Safety and Tolerability of the Anxiolytic and Nootropic Drug Phenibut: A Systematic Review of Clinical Trials and Case Reports

2020 ◽  
Vol 53 (05) ◽  
pp. 201-208 ◽  
Author(s):  
Einars Kupats ◽  
Jelena Vrublevska ◽  
Baiba Zvejniece ◽  
Edijs Vavers ◽  
Gundega Stelfa ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Side Effects ◽  
Clinical Symptoms ◽  
Gabab Receptor ◽  
Case Reports ◽  
Safety Data ◽  
Cardiovascular Effects ◽  
Nootropic Drug ◽  
The One

AbstractPhenibut is a nootropic drug that exerts anxiolytic and antinociceptive effects by acting on the GABAB receptor and the α2-δ subunit of voltage-dependent calcium channels. An increased number of reports of dependence to and intoxication by phenibut purchased online on the one hand and the wide prescription of phenibut in Eastern Europe for more than half a century on the other hand have resulted in a number of controversies regarding its use. In this review, we have summarized currently available information from case reports of phenibut dependence and intoxication and safety data from clinical trials. We included 14 dependence and intoxication case reports (16 patients) and reviewed 11 phenibut clinical trials (583 patients). The clinical symptoms in the case reports included cardiovascular effects, insomnia, anxiety and agitation, hallucinations, and depressed level of consciousness. In addition, the doses used (0.5–100 g/day) were much higher than the recommended daily dose (0.25–2 g/day). An analysis of phenibut side effects described in the clinical trials showed adverse events in only 5.66% of patients, and the most reported side effect was somnolence (1.89%). There are discrepancies in the reported side effects of phenibut in clinical trials compared to those reported in cases of online-purchased phenibut dependence and intoxication. The current systematic review provides evidence that, at therapeutic doses, phenibut is safe and well tolerated with minor adverse effects, but questions regarding the quality of phenibut obtained online and the contribution of alcohol and other drug abuse to phenibut dependence and intoxication remain open.

scholarly journals Safety of Hydroxychloroquine Among Outpatient Clinical Trial Participants for COVID-19

2020 ◽  
Vol 7 (11) ◽  
Author(s):  
Sarah M Lofgren ◽  
Melanie R Nicol ◽  
Ananta S Bangdiwala ◽  
Katelyn A Pastick ◽  
Elizabeth C Okafor ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Side Effects ◽  
Early Treatment ◽  
Side Effect ◽  
Randomized Clinical Trials ◽  
Safety Data ◽  
Postexposure Prophylaxis ◽  
Serious Adverse Events ◽  
Once Daily ◽  
Exposure Prophylaxis

Abstract Background Use of hydroxychloroquine in hospitalized patients with coronavirus disease 2019 (COVID-19), especially in combination with azithromycin, has raised safety concerns. Here, we report safety data from 3 outpatient randomized clinical trials. Methods We conducted 3 randomized, double-blind, placebo-controlled trials investigating hydroxychloroquine as pre-exposure prophylaxis, postexposure prophylaxis, and early treatment for COVID-19 using an internet-based design. We excluded individuals with contraindications to hydroxychloroquine. We collected side effects and serious adverse events. We report descriptive analyses of our findings. Results We enrolled 2795 participants. The median age of research participants (interquartile range) was 40 (34–49) years, and 59% (1633/2767) reported no chronic medical conditions. Overall 2544 (91%) participants reported side effect data, and 748 (29%) reported at least 1 medication side effect. Side effects were reported in 40% with once-daily, 36% with twice-weekly, 31% with once-weekly hydroxychloroquine, compared with 19% with placebo. The most common side effects were upset stomach or nausea (25% with once-daily, 19% with twice-weekly, and 18% with once-weekly hydroxychloroquine, vs 11% for placebo), followed by diarrhea, vomiting, or abdominal pain (23% for once-daily, 17% twice-weekly, and 13% once-weekly hydroxychloroquine, vs 7% for placebo). Two individuals were hospitalized for atrial arrhythmias, 1 on placebo and 1 on twice-weekly hydroxychloroquine. No sudden deaths occurred. Conclusions Data from 3 outpatient COVID-19 trials demonstrated that gastrointestinal side effects were common but mild with the use of hydroxychloroquine, while serious side effects were rare. No deaths occurred related to hydroxychloroquine. Randomized clinical trials, in cohorts of healthy outpatients, can safely investigate whether hydroxychloroquine is efficacious for COVID-19. ClinicalTrials.gov Identifier NCT04308668 for postexposure prophylaxis and early treatment trials; NCT04328467 for pre-exposure prophylaxis trial.

scholarly journals Tuberculosis and viral hepatitis in patients treated with certolizumab pegol in Asia-Pacific countries and worldwide: real-world and clinical trial data

2020 ◽  
Author(s):  
Chak Sing Lau ◽  
Yi-Hsing Chen ◽  
Keith Lim ◽  
Marc de Longueville ◽  
Catherine Arendt ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Viral Hepatitis ◽  
Central Europe ◽  
Real World ◽  
Certolizumab Pegol ◽  
Safety Data ◽  
Asia Pacific ◽  
Hbv Reactivation ◽  
Post Marketing

Abstract Introduction/objectives To evaluate the incidence rate (IR) of tuberculosis (TB) and viral hepatitis B and C (HBV/HCV) during certolizumab pegol (CZP) treatment, worldwide and in Asia-Pacific countries, across clinical trials and post-marketing reports (non-interventional studies and real-world practice). Method CZP safety data were pooled across 49 clinical trials from 1998 to June 2017. Post-marketing reports were from initial commercialization until March 2015 (TB)/February 2017 (HBV/HCV). All suspected TB and HBV/HCV cases underwent centralized retrospective review by external experts. Incidence rates (IRs) were calculated per 100 patient-years (PY) of CZP exposure. Results Among 11,317 clinical trial patients (21,695 PY), 62 TB cases were confirmed (IR 0.29/100 PY) including 2 in Japan (0.10/100 PY) and 3 in other Asia-Pacific countries (0.58/100 PY). From > 238,000 PY estimated post-marketing CZP exposure, there were 31 confirmed TB cases (0.01/100 PY): 5 in Japan (0.05/100 PY), 1 in other Asia-Pacific countries (0.03/100 PY). Reported regional TB IRs were highest in eastern Europe (0.17/100 PY), central Europe (0.09/100 PY), and Mexico (0.16/100 PY). Across clinical trials, there was 1 confirmed HBV reactivation and no HCV cases. From > 420,000 PY estimated post-marketing CZP exposure, 5 HBV/HCV cases were confirmed (0.001/100 PY): 2 HCV reactivations; 1 new HCV; plus 2 HBV reactivations in Japan (0.008/100 PY). Conclusions CZP TB risk is aligned with nationwide TB rates, being slightly higher in Asia-Pacific countries excluding Japan. Overall, TB and HBV/HCV risk with CZP treatment is currently relatively low, as risk can be minimized with patient/physician education, screening, and vigilant treatment, according to international guidelines. Key Points:• TB rates were highest in eastern/central Europe, Mexico, and Asia-Pacific regions.• With the implementation of stricter TB screening and risk evaluations in 2007, especially in high TB incidence countries, there was a notable reduction TB occurrence.• Safety profile of biologics in real-world settings complements controlled studies.• TB and hepatitis (HBV/HCV) risk with certolizumab pegol (CZP) treatment is low.

The Use of Methotrexate in Rheumatoid Arthritis

1985 ◽  
Vol 19 (5) ◽  
pp. 349-358 ◽  
Author(s):  
Peter W. Letendre ◽  
Douglas J. DeJong ◽  
Donald R. Miller
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Trials ◽  
Folic Acid ◽  
Side Effects ◽  
Adverse Effects ◽  
Systemic Administration ◽  
Refractory Disease ◽  
Controlled Clinical Trials ◽  
Folic Acid Antagonist ◽  
Acid Antagonist

The use of methotrexate in rheumatoid arthritis is reviewed. Methotrexate, a folic acid antagonist, is sometimes employed in an attempt to symptomatically control patients whose disease does not respond adequately to conventional therapies. Systemic administration of 7.5–15 mg/wk in a “pulse” fashion appears to be effective without precipitating severe adverse effects. However, concern over potentially serious side effects and a lack of well-controlled clinical trials have limited its use to severe, refractory disease. Further studies are needed before its role in rheumatoid arthritis can justifiably be expanded.

scholarly journals Manual on the proper use of sodium astatide ([211At]NaAt) injections in clinical trials for targeted alpha therapy (1st edition)

2021 ◽  
Author(s):  
Tadashi Watabe ◽  
Makoto Hosono ◽  
Seigo Kinuya ◽  
Takahiro Yamada ◽  
Sachiko Yanagida ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Japanese Society ◽  
Radiation Safety ◽  
Safety Management ◽  
Evaluation Methodology ◽  
Targeted Alpha Therapy ◽  
Safety Issues ◽  
Safety Standards ◽  
And Training ◽  
Alpha Therapy

AbstractWe present the guideline for use of [211At] sodium astatide (NaAt) for targeted alpha therapy in clinical trials on the basis of radiation safety issues in Japan. This guideline was prepared by a study supported by the Ministry of Health, Labour, and Welfare, and approved by the Japanese Society of Nuclear Medicine on 8th Feb, 2021. The study showed that patients receiving [211At]NaAt do not need to be admitted to a radiotherapy room and outpatient treatment is possible. The radiation exposure from the patient is within the safety standards of the ICRP and IAEA recommendations for the general public and caregivers. Precautions for patients and their families, safety management associated with the use of [211At]NaAt, education and training, and disposal of medical radioactive contaminants are also included in this guideline. Treatment using [211At]NaAt in Japan should be carried out according to this guideline. Although this guideline is applied in Japan, the issues for radiation protection and evaluation methodology shown here are considered internationally useful as well.

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