scholarly journals United States Pharmacopeia (USP) Safety Review of Gamma-Aminobutyric Acid (GABA)

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2742
Author(s):  
Hellen A. Oketch-Rabah ◽  
Emily F. Madden ◽  
Amy L. Roe ◽  
Joseph M. Betz
Keyword(s):  
Blood Pressure ◽  
Adverse Events ◽  
Dietary Supplement ◽  
Clinical Studies ◽  
Case Reports ◽  
Endocrine System ◽  
Chronic Administration ◽  
Fermented Milk ◽  
Gamma Aminobutyric Acid ◽  
Serious Adverse Events

Gamma-amino butyric acid (GABA) is marketed in the U.S. as a dietary supplement. USP conducted a comprehensive safety evaluation of GABA by assessing clinical studies, adverse event information, and toxicology data. Clinical studies investigated the effect of pure GABA as a dietary supplement or as a natural constituent of fermented milk or soy matrices. Data showed no serious adverse events associated with GABA at intakes up to 18 g/d for 4 days and in longer studies at intakes of 120 mg/d for 12 weeks. Some studies showed that GABA was associated with a transient and moderate drop in blood pressure (<10% change). No studies were available on effects of GABA during pregnancy and lactation, and no case reports or spontaneous adverse events associated with GABA were found. Chronic administration of GABA to rats and dogs at doses up to 1 g/kg/day showed no signs of toxicity. Because some studies showed that GABA was associated with decreases in blood pressure, it is conceivable that concurrent use of GABA with anti-hypertensive medications could increase risk of hypotension. Caution is advised for pregnant and lactating women since GABA can affect neurotransmitters and the endocrine system, i.e., increases in growth hormone and prolactin levels.

Serious Adverse Events Reported with Dietary Supplement Use in the United States: A 2.5 Year Experience

2018 ◽  
Vol 17 (2) ◽  
pp. 227-248 ◽  
Author(s):  
Stephen M. Schmitz ◽  
Hector L. Lopez ◽  
Douglas Mackay ◽  
Haiuyen Nguyen ◽  
Paula E. Miller
Keyword(s):  
United States ◽  
Adverse Events ◽  
Dietary Supplement ◽  
The United States ◽  
Serious Adverse Events ◽  
Supplement Use ◽  
Dietary Supplement Use

scholarly journals Pharmacology and Adverse Events of Emergency-Use Authorized Medication in Moderate to Severe COVID-19

2021 ◽  
Vol 14 (10) ◽  
pp. 955
Author(s):  
Jen-Yu Hsu ◽  
Yan-Chiao Mao ◽  
Po-Yu Liu ◽  
Kuo-Lung Lai
Keyword(s):  
Adverse Events ◽  
Metabolic Pathways ◽  
Case Reports ◽  
Secondary Infection ◽  
Treatment Strategies ◽  
Serious Adverse Events ◽  
Small Molecule Drugs ◽  
Post Market ◽  
Inflammatory Processes ◽  
Effective Drugs

Some effective drugs have been approved or issued an Emergency Use Authorization for the treatment of COVID-19 in hospitalized patients, but post-market surveillance is warranted to monitor adverse events. We reviewed clinical trials and case reports in patients with moderate-to-severe COVID-19 infection who received remdesivir, baricitinib, tocilizumab, or sarilumab. The drug-specific pharmacokinetics, toxicity, and drug interactions are summarized in this study. Remdesivir and baricitinib are small-molecule drugs that are mainly metabolized by the kidneys, while tocilizumab and sarilumab are monoclonal antibody drugs with metabolic pathways that are currently not fully understood. The most common adverse events of these drugs are alterations in liver function, but serious adverse events have rarely been attributed to them. Only a few studies have reported that remdesivir might be cardiotoxic and that baricitinib might cause thromboembolism. Biological agents such as baricitinib, tocilizumab, and sarilumab could inhibit the pathway of inflammatory processes, leading to immune dysregulation, so the risk of secondary infection should be assessed before prescribing. Further recognition of the pathogenic mechanism and risk factors of adverse events is essential for optimizing treatment strategies.

Abstract 14387: Dose-Related Reductions in Blood Pressure With a RNA Interference (RNAi) Therapeutic Targeting Angiotensinogen in Hypertensive Patients: Interim Results From a First-In-Human Phase 1 Study of ALN-AGT01

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Stephen A Huang ◽  
Jorg Taubel ◽  
Giuseppe Fiore ◽  
Peter Dewland ◽  
George L Bakris ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Single Dose ◽  
Adverse Events ◽  
Phase 1 ◽  
Serious Adverse Events ◽  
Therapeutic Targeting ◽  
Dose Administration ◽  
Hypertensive Patients ◽  
Single Dose Administration ◽  
Angiotensin Peptides

Background: Angiotensinogen (AGT) is the sole precursor of all angiotensin peptides and plays a key role in hypertension pathogenesis. We evaluated the effect of ALN-AGT01, a subcutaneous investigational RNAi therapeutic targeting hepatic AGT synthesis, on blood pressure in hypertensive patients. Methods: As part of a phase 1 program designed to assess the safety and tolerability of ALN-AGT01, we conducted a multicenter study randomizing patients aged 18-65 years with mild to moderate hypertension (mean seated systolic blood pressure [SBP] of >130 and ≤165 mmHg after washout of antihypertensive medication) 2:1 to ascending single doses of ALN-AGT01 or placebo. Change from baseline in BP at 8 weeks was measured by ambulatory BP monitoring (ABPM). We report interim results as of May 14, 2020. Results: Sixty patients (mean age 52 years, 45% female, mean baseline 24h SBP 139 +/- 7 mm Hg) were enrolled in ascending dose cohorts of 10 mg, 25 mg, 50 mg, 100 mg, or 200 mg. Dose-related reductions in serum AGT levels were observed (figure), with reductions >90% in the 100 and 200 mg dose cohorts. AGT remained durably reduced through 12 weeks after single dose administration. Concomitant reductions in BP from baseline were observed with AGT knockdown, with an over 10 mm Hg reduction of mean 24-hour SBP observed at Week 8 after single doses of 100 mg or 200 mg. No symptomatic hypotension, treatment-related serious adverse events, or clinically significant elevations in blood creatinine or potassium were seen. Conclusions: Single dose administration of ALN-AGT01 to hypertensive patients resulted in dose-related reductions in serum AGT and BP over 8 weeks without hypotension or other related serious adverse events. Durable AGT knockdown to 12 weeks supports further evaluation of once quarterly or potentially less frequent dose administration.

scholarly journals Impact of cumulative SBP and serious adverse events on efficacy of intensive blood pressure treatment

2019 ◽  
Vol 37 (5) ◽  
pp. 1058-1069 ◽  
Author(s):  
Oscar L. Rueda-Ochoa ◽  
Lyda Z. Rojas ◽  
Shahzad Ahmad ◽  
Cornelia M. van Duijn ◽  
Mohammad A. Ikram ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Adverse Events ◽  
Pressure Treatment ◽  
Serious Adverse Events ◽  
Blood Pressure Treatment ◽  
Intensive Blood Pressure

scholarly journals Invasive Fungal Infections in Infants—Focus on Anidulafungin

2013 ◽  
Vol 7 ◽  
pp. CMPed.S8028 ◽  
Author(s):  
Michael H. Wilke
Keyword(s):  
Risk Factors ◽  
Adverse Events ◽  
Safety Profile ◽  
Fungal Infections ◽  
Case Reports ◽  
Small Body ◽  
Pediatric Intensive Care ◽  
Invasive Fungal Infections ◽  
Serious Adverse Events ◽  
Good Safety Profile

Introduction Invasive fungal infection in pediatric intensive care units (PICU) is a rising challenge. Candida species are the most common microorganisms in these infections. Due to growing resistance against fluconazole, echinocandins are being used for the appropriate therapy. However, the recent IDSA guidelines recommend them only in cases where fluconazole or Amphotericin B cause treatment failure or are contraindicated. In a literature review, the importance of invasive fungal infections in PICU settings and the role of anidulafungin shall be examined. Materials and Methods Articles were retrieved form PubMed covering the years 2000–2012. Various search terms were used. Then the articles were clustered in different types like ‘review,’ ‘pharmacokinetics,’ ‘case reports’ and others. Results From 67 search results, 14 articles were selected. Of these, 7 were related to anidulafungin, while 7 were related to echinocandins or fungal infections in the PICU. Anidulafungin was examined in 4 PK/PD studies where a good safety profile was found. No serious adverse events occurred. The articles reporting risk factors show that central venous catheters, receipt of antibiotics, receipt of parenteral nutrition, and neutropenia are the most important independent risk factors for invasive fungal infections in PICU. Three reviews of antifungal agents show that echinocandins may be useful due to their safety profile; micafungin is the best examined one and further trials are needed. Discussion The published literature on invasive fungal infections in PICU settings has grown over the years. There are only a few articles, however, which are directly related to the use of anidulafungin in this setting. A most recent publication showed good PK/PD dynamics and a good safety profile for anidulafungin. So far, no RCT in the area of invasive candidiasis in infants and neonates has been published. A review of currently registered trials at ClinicalTrials.gov has shown one more trial related to PK/PD and two trials that investigate the use of anidulafungin or anidulafungin in combination with Voriconazole in pediatrics. Conclusion The small body of existing literature on anidulafungin in infants shows success in treatment, no drug-related adverse events, and good pharmacodynamics. A dosing of 0.75 mg/kg/day or 1.5 mg/kg/day is as effective as 50 mg/day or 100 mg/day in adults. More trials on the use in clinical reality of PICU or NICU should follow.

A cocktail of synthetic stimulants found in a dietary supplement associated with serious adverse events

2014 ◽  
Vol 6 (6) ◽  
pp. 578-581 ◽  
Author(s):  
Bastiaan Venhuis ◽  
Peter Keizers ◽  
Antoinette van Riel ◽  
Dries de Kaste
Keyword(s):  
Adverse Events ◽  
Dietary Supplement ◽  
Serious Adverse Events

Abstract P179: The Magnitude, And Not Direction, Of Blood Pressure Change Influences The Risk Of Serious Adverse Events In SPRINT

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Michael Buhnerkempe ◽  
Vivek Prakash ◽  
Albert Botchway ◽  
Oritsegbubemi Adekola ◽  
John M Flack
Keyword(s):  
Blood Pressure ◽  
Adverse Events ◽  
Systolic Blood Pressure ◽  
Proportional Hazards ◽  
Pressure Change ◽  
Cox Proportional Hazards ◽  
Intensive Treatment ◽  
Atherosclerotic Cardiovascular Disease ◽  
Serious Adverse Events ◽  
Ascvd Risk

Background: The landmark Systolic Blood Pressure Intervention Trial (SPRINT) showed that more intensive systolic blood pressure treatment (SBP < 120 mm Hg) was associated with lower risk for cardiovascular events and mortality but higher risk for serious adverse events (SAEs). However, it is unclear if the magnitude and/or the direction of the BP change determines SAE risk. In this study, we aim to determine how the magnitude and direction of BP change impacts SAE risk. Methods: This is a secondary analysis of 7922 participants in SPRINT. Time-varying Cox proportional hazards models were used to explore the relationship between visit-to-visit BP change and SAE risk. BP change was categorized using five intervals: 1) decreases ≥30 mm Hg, 2) decreases 10-29 mm Hg, 3) increases or decreases <10 mm Hg (reference category), 4) increases 10-29 mm Hg, and 5) increases ≥30 mm Hg. Additional variables adjusted for in the model included: age, gender, race, estimated glomerular filtration rate, treatment group, and baseline atherosclerotic cardiovascular disease (ASCVD) risk. Hypotension was excluded as an SAE to prevent bias in SAE risk in the large BP decrease category. Results: The hazard ratio (HR) for SAEs compared to the minimal BP change category was greatest for BP increases above 30 mm Hg (HR = 1.62, 95% confidence interval [1.30, 2.01]). However, the HR was similar for sharp BP decreases over 30 mm Hg (HR = 1.52 [1.23, 1.87]). Milder BP increases and decreases were associated with lower SAE risk (HR = 1.18 [1.06, 1.32] and HR = 1.10 [0.98, 1.22] for BP changes 10 to 30 mm Hg and -30 to -10 mm Hg, respectively). There were no significant interactions between BP change, intensive treatment, and baseline ASCVD risk. Conclusions: SAE risk was similar for similarly sized increases and decreases in BP between visits, with higher magnitude changes associated with higher SAE risk. When accounting for the magnitude of BP change, no significant effect of intensive treatment or baseline ASCVD risk was found.

scholarly journals The effects of caffeine in adults with neurogenic orthostatic hypotension: a systematic review

2021 ◽  
Author(s):  
Jake Ryan Gibbon ◽  
James Frith
Keyword(s):  
Systematic Review ◽  
Blood Pressure ◽  
Orthostatic Hypotension ◽  
Case Reports ◽  
Meta Analysis ◽  
Evidence Base ◽  
Original Research ◽  
Neurogenic Orthostatic Hypotension ◽  
Serious Adverse Events ◽  
Evidence Based Treatments

Abstract Purpose To systematically review the evidence base for the effectiveness and safety of caffeine for the treatment of neurogenic orthostatic hypotension in adults. Methods Eight electronic databases were searched in January 2021. Original research studies or case reports involving adults with neurogenic orthostatic hypotension were included if caffeine was an intervention and outcomes included symptoms, blood pressure or adverse effects. Relevant studies were screened and underwent qualitative analysis. Insufficient reporting precluded meta-analysis. Results Five studies were identified: four crossover studies and one case report summation. Study size ranged from 5 to 16 participants. Participants had neurogenic orthostatic hypotension, with a mean standing systolic blood pressure of 86 mmHg. Two studies evaluated caffeine alone. Three studies administered caffeine in combination with ergotamine. Caffeine dose ranged from 100 to 300 mg. Nature and timing of outcomes measured varied between studies, with measurements being recorded from 30 to 480 min after intervention. Caffeine/ergotamine improved symptoms in one study and reduced orthostatic blood pressure drop in two studies. Caffeine/ergotamine increased seated blood pressure in three studies, whilst the results for caffeine alone were inconsistent. No serious adverse events were reported. All studies demonstrated high risk of bias. Conclusion Caffeine should only be considered as a treatment for adults with neurogenic orthostatic hypotension when evidence-based treatments have been exhausted. Systematic review registration PROSPERO ID: CRD42020124589. Date of registration: 30/10/2020

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