limbrel and Chemical-and-Drug-Induced-Liver-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

The dried root of the angiosperm Scutellaria baicalensis, also known as Chinese skullcap or Baikal skullcap, is widely used in traditional Chinese medicine, Korean traditional medicine and as a nutritional supplement; several studies have indicated that both the supplement and some of its ingredients may have clinically beneficial actions. However, the National Institutes of Health official guidance states that the use of Scutellaria "has been implicated in rare instances of clinically apparent liver injury" and that "the onset of symptoms and jaundice occurred within 6-24 weeks of starting skullcap, and the serum enzyme pattern was typically hepatocellular", with marked increases in serum alanine transaminase, aspartate transaminase, alkaline phosphatase and bilirubin levels. Careful perusal of all such published case reports showed that in each case the patient was concurrently taking at least one other supplement which had an established association with hepatic dysfunction. The authors hypothesised that long-term supplementation with Scutellaria baicalensis does not lead to hepatic dysfunction. The aim of this study was to test this hypothesis by assessing liver function before and after starting supplementation with Scutellaria baicalensis. Pre- and post-supplementation serum assays of alanine transaminase, aspartate transaminase, alkaline phosphatase and bilirubin were carried out in 17 patients (16 female) of average age 38.6 (standard error 4.4) years who had each taken 1335 mg dried root daily for an average of 444 (71) days. The mean baseline versus follow-up values for each liver function test were: alanine transaminase: 25.7 (2.6) IU/L v. 25.1 (1.7) IU/L; aspartate transaminase: 22.1 (1.1) IU/L v. 23.5 (1.3) IU/L; alkaline phosphatase: 63.7 (4.6) IU/L v. 63.3 (3.9) IU/L; and bilirubin: 6.1 (0.6) μM v. 6.0 (0.7) μM. None of these changes was statistically significant; indeed, three of the four parameters showed a non-significant decrease over time. Furthermore, none manifested clinical symptoms or signs of hepatic dysfunction during Scutellaria supplementation. These results suggest that daily intake of a relatively high level of Scutellaria baicalensis for over a year is not associated with any biochemical or clinical evidence of hepatic dysfunction. Indeed, Scutellaria baicalensis has been shown in murine experiments to have hepatoprotective actions.

Topics: Adult; Alanine Transaminase; Alkaline Phosphatase; Aspartate Aminotransferases; Bilirubin; Biomarkers; Catechin; Chemical and Drug Induced Liver Injury; Dietary Supplements; Drug Combinations; Drugs, Chinese Herbal; Female; Follow-Up Studies; Herb-Drug Interactions; Humans; Male; Phytotherapy; Plant Roots; Scutellaria baicalensis; Tea

Flavocoxid is a prescription medical food that is used to treat osteoarthritis. It is a proprietary blend of 2 flavonoids, baicalin and catechins, which are derived from the botanicals Scutellaria baicalensis and Acacia catechu, respectively.. To describe characteristics of patients with acute liver injury suspected of being caused by flavocoxid.. Case series.. Drug-Induced Liver Injury Network Prospective Study ongoing at multiple academic medical centers since 2004.. Four adults with liver injury.. Clinical characteristics, liver biochemistry values, and outcomes.. Among 877 patients enrolled in the prospective study, 4 had liver injury suspected to have been caused by flavocoxid. All were women; ages ranged from 57 to 68 years. All developed symptoms and signs of liver injury within 1 to 3 months after initiating flavocoxid. Liver injury was characterized by marked elevations in levels of alanine aminotransferase (mean peak, 1268 U/L; range, 741 to 1540 U/L), alkaline phosphatase (mean peak, 510 U/L; range, 286 to 770 U/L), and serum bilirubin (mean peak, 160.7 µmol/L [9.4 mg/dL]; range, 34.2 to 356 µmol/L [2.0 to 20.8 mg/dL]). Liver biochemistry values decreased to the normal range within 3 to 12 weeks after flavocoxid was stopped, and all patients recovered without experiencing acute liver failure or chronic liver injury. Causality was adjudicated as highly likely in 3 patients and as possible in 1 patient.. The frequency and mechanism of liver injury could not be assessed.. Flavocoxid can cause clinically significant liver injury, which seems to resolve within weeks after cessation.

Topics: Aged; Alanine Transaminase; Alkaline Phosphatase; Bilirubin; Catechin; Chemical and Drug Induced Liver Injury; Dietary Supplements; Drug Combinations; Female; Humans; Middle Aged; Osteoarthritis; Prospective Studies

Topics: Catechin; Chemical and Drug Induced Liver Injury; Dietary Supplements; Drug Combinations; Humans; Legislation, Food; Osteoarthritis; United States; United States Food and Drug Administration

Topics: Aged; Alanine Transaminase; Alkaline Phosphatase; Bilirubin; Catechin; Chemical and Drug Induced Liver Injury; Dietary Supplements; Drug Combinations; Female; Humans; Middle Aged; Osteoarthritis; Prospective Studies