limbrel and Acute-Kidney-Injury

Flavocoxid is a prescription medical food used to manage osteoarthritis (OA) symptoms. Safety concerns based on case reports raised an association with acute liver injury and hypersensitivity pneumonitis. We determined incidence rates (IR) of these safety events in a cohort of new users of flavocoxid and prescription non-steroidal anti-inflammatory drugs (NSAIDs).. MarketScan® claims data (2006-2017) was used to identify patients initiating flavocoxid or NSAIDs. Propensity score matching (1:2 ratio) was used to balance patient characteristics. Outcomes included hospitalization for hypersensitivity pneumonitis, liver injury, gastrointestinal bleeding, myocardial infarction, and acute kidney injury. Poisson regression was used to calculate IRs and Cox regression for calculating adjusted hazard ratios (aHR).. 3,337 flavocoxid and 6,674 NSAID users met eligibility criteria. Before matching, flavocoxid users were older (mean 57 vs 51 years), had more polypharmacy (68% vs 29% taking ≥11 medications). After matching, characteristics were well balanced. The rate of hypersensitivity pneumonitis was 1.1 (95% CI 0.0-5.9) per 1,000 PY for flavocoxid and 0.0 (95% CI 0.0-2.2) for NSAIDs. For hospitalized liver injury, it was 3.2 (95% CI 0.7-9.3) for flavocoxid and 2.4 (95% CI 0.7-6.1) for NSAIDs, aHR = 1.16, 95% CI 0.23-6.01. A lower rate of GI bleed was observed, IR: 5.3 (1.7-12.3) for flavocoxid and 10.2 (5.9-16.3) for NSAIDs, aHR 0.49 (0.18-1.68). There were no significant differences for MI or AKI.. The rate of hypersensitivity pneumonitis and liver injury associated with flavocoxid was low and minimally elevated compared to NSAIDs. Flavocoxid users had a significantly lower risk for hospitalized GI bleeding. The risk-benefit profile of flavocoxid may warrant reevaluation in light of these findings.

Topics: Acute Kidney Injury; Adult; Aged; Alveolitis, Extrinsic Allergic; Anti-Inflammatory Agents, Non-Steroidal; Catechin; Chemical and Drug Induced Liver Injury; Drug Combinations; Female; Gastrointestinal Hemorrhage; Hospitalization; Humans; Male; Middle Aged; Myocardial Infarction; Osteoarthritis; Polypharmacy; Proportional Hazards Models

Gentamicin is a widely used antibiotic against serious and life-threatening infections; however, its usefulness is limited by the development of nephrotoxicity. The present study was designed to determine whether flavocoxid has a protective effect against gentamicin-induced nephrotoxicity in rats. For this purpose, we quantitatively evaluated gentamicin-induced renal structural and functional alterations using histopathological and biochemical approaches. Furthermore, the effect of flavocoxid on gentamicin induced hypersensitivity of urinary bladder rings to acetylcholine (ACh) was determined. Twenty-four male Wistar albino rats were randomly divided into three groups, namely control, gentamicin (100 mg/kg, i.p.) and gentamicin plus flavocoxid (20 mg/kg, orally). At the end of the study, all rats were sacrificed and then blood, urine samples and kidneys were collected for further analysis. Gentamicin administration caused a severe nephrotoxicity which was evidenced by an elevated renal somatic index (RSI), serum creatinine, blood urea nitrogen, serum lactate dehydrogenase, and protein in urine with a concomitant reduction in serum albumin and normalized creatinine clearance value as compared with the controls. Moreover, a significant increase in renal contents of malondialdehyde, myeloperoxidase, and tumor necrosis factor-alpha with a significant decrease in renal reduced glutathione and superoxide dismutase activities was detected upon gentamicin administration together with increasing the sensitivity of isolated urinary bladder rings to ACh. Exposure to gentamicin induced necrosis of renal tubular epithelial cells. Flavocoxid protected kidney tissue against the oxidative damage and the nephrotoxic effect caused by gentamicin treatment. In addition, flavocoxid significantly reduced the responses of isolated bladder rings to ACh. The results from our study indicate that flavocoxid supplement attenuates gentamicin-induced renal injury via the amelioration of oxidative stress and inflammation of renal tubular cells.

Topics: Acute Kidney Injury; Animals; Anti-Bacterial Agents; Catechin; Dose-Response Relationship, Drug; Drug Combinations; Gentamicins; Male; Organ Culture Techniques; Rats; Rats, Wistar; Urinary Bladder