Reactions 1422 - 6 Oct 2012

SFlavocoxid/pregabalin

Acute liver injury: 4 case reportsThe Drug-Induced Liver Injury Network (DILIN) study

identified four patients who developed acute liver injuryduring treatment with oral flavocoxid [Limbrel], aproprietary blend of plant-derived bioflavonoids, includingbaicalin and catechins. One of the patients was alsoreceiving pregabalin [route not stated].

A 58-year-old woman with a history of coronary arterydisease, dyslipidaemia and mild renal insufficiency startedreceiving flavocoxid 500mg twice daily for spinal stenosisand osteoarthritis. About 10 weeks later, she presentedwith pruritus, fever, dark urine and fatigue. She had ALT,AST, ALP and total bilirubin levels of 1105 U/L, 1198 U/L,487 U/L and 42.7 µmol/L, respectively. A liver biopsyrevealed drug-induced liver injury, characterised by focalnecrosis and inflammation, portal lymphocyticinflammatory infiltrates with some eosinophils, and plasmacells. Flavocoxid was discontinued, and her liverabnormalities gradually normalised. The liver injury wasconsidered to be "very likely" due to flavocoxid, and theRoussel Uclaf Causality Assessment Method (RUCAM)score was 8 (probable).

A 57-year-old woman with a history of gastro-oesophageal reflux disease began receiving flavocoxid250mg twice daily for osteoarthritis. Approximately9 weeks later, she presented with a rash, generalisedpruritus and dark urine. Laboratory investigations revealedALT, AST, ALP and total bilirubin levels of 741 U/L, 233 U/L,286 U/L and 32.4 µmol/L, respectively. Flavocoxid wasdiscontinued, and she received prednisone. Her liverabnormalities resolved over the next 4 weeks. The liverinjury was judged as "very likely" due to flavocoxid, and theRUCAM score was 8 (probable).

A 61-year-old woman presented with jaundice, itchingand dark urine about 12 weeks after starting flavocoxid500mg twice daily and 7 weeks after starting pregabalin75mg thrice daily for fibromyalgia. Her medical historyincluded depression, hypertension, gastro-oesophagealreflux disease and deep vein thrombosis. She had ALT, AST,ALP and total bilirubin levels of 1178 U/L, 1108 U/L,426 U/L and 203.5 µmol/L, respectively. Flavocoxid andpregabalin were discontinued. A liver biopsy showedexpanded portal tracts with dense chronic inflammatorycell infiltrate, interface hepatitis and periportal collapse.Her liver abnormalities normalised over a period of6 weeks. Her clinical course was considered to be "highlylikely" due to drug-induced liver injury. The compound-specific causality score was 4 (possible) for flavocoxid and3 (probable) for pregabalin. The RUCAM score forflavocoxid was 2 (unlikely).

A 68-year-old obese woman with a history ofdyslipidaemia, hypertension, atrial fibrillation, irritablebowel syndrome and gastro-oesophageal reflux diseasebegan receiving flavocoxid 500mg twice daily forosteoarthritis. Four weeks later, she presented with darkurine and fatigue. Laboratory tests revealed ALT, AST, ALPand total bilirubin levels of 1375 U/L, 1050 U/L, 770 U/Land 71.8 µmol/L, respectively. Antinuclear antibody waspositive at 1:1280 dilution. Flavocoxid was discontinued,and her liver abnormalities gradually normalised. The liverinjury was judged as "very likely" due to flavocoxid, and theRUCAM score was 9 (highly probable).

Author comment: "Causality was assessed as very likelydue to flavocoxid in 3 patients and as possibly due toflavocoxid in 1 patient."Chalasani N, et al. Acute liver injury due to flavocoxid (Limbrel), A medical foodfor osteoarthritis: A case series. Annals of Internal Medicine 156: 857-860, No. 12,19 Jun 2012 - USA 803077982

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Reactions 6 Oct 2012 No. 14220114-9954/10/1422-0001/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved