Flavocoxid is a

medical food Medical foods are foods that are specially formulated and intended for the dietary management of a disease that has distinctive nutritional needs that cannot be met by normal diet alone. In the United States they were defined in the Food and Drug A ...

consisting of plant derived

flavonoid Flavonoids (or bioflavonoids; from the Latin word ''flavus'', meaning yellow, their color in nature) are a class of polyphenolic secondary metabolites found in plants, and thus commonly consumed in the diets of humans. Chemically, flavonoids ...

s which have anti-inflammatory activity and are used to provide nutritional support to people with chronic

osteoarthritis Osteoarthritis (OA) is a type of degenerative joint disease that results from breakdown of joint cartilage and underlying bone which affects 1 in 7 adults in the United States. It is believed to be the fourth leading cause of disability in the w ...

. Flavocoxid has been approved for use as a medical food in the United States since 2004 and is available by prescription for use in chronic osteoarthritis in tablets of 500 mg under the commercial name Limbrel. Flavocoxid has been linked to occasional minor elevations in serum enzyme levels during therapy and to rare instances of clinically apparent liver injury.

Hepatotoxicity

In clinical trials, serum

aminotransferase Transaminases or aminotransferases are enzymes that catalyze a transamination reaction between an amino acid and an α-keto acid. They are important in the synthesis of amino acids, which form proteins. Function and mechanism An amino acid co ...

elevations occurred in up to 10% of patients on flavocoxid therapy, but elevations above 3 times the upper limit of normal occurred in only 1% to 2% of recipients. However, there have been several reports of clinically apparent acute liver injury attributed to flavocoxid. Most cases have occurred in women (who are more likely to take flavocoxid). The time to onset has been 1 to 5 months and the pattern of enzyme elevations was usually hepatocellular or mixed. Most cases have been moderate in severity and no instance of acute liver failure or death has been reported. Complete resolution upon stopping flavocoxid has occurred in 2 to 12 weeks. Immunoallergic features have been mild and autoantibodies are not common. At least one instance of recurrence upon rechallenge has been reported.

Mechanism of Injury

Flavocoxid is a proprietary mixture of molecules extracted from plants and it is unclear which component(s) might be responsible for liver injury. The mixture includes extracts from

Scutellaria baicalensis ''Scutellaria baicalensis'', with the common name Baikal skullcap or Chinese skullcap, is a species of flowering plant in the family Lamiaceae. Distribution The plant is native to China, Korea, Mongolia, and Russia in the Russian Far East and Si ...

(containing the

phytochemical Phytochemicals are chemical compounds produced by plants, generally to help them resist fungi, bacteria and plant virus infections, and also consumption by insects and other animals. The name comes . Some phytochemicals have been used as poisons ...

baicalin As baicalin is a flavone glycoside, it is a flavonoid. It is the glucuronide of baicalein. Natural occurrences Baicalin is found in several species in the genus ''Scutellaria'', including ''Scutellaria baicalensis'', and '' Scutellaria lateri ...

) and

Acacia catechu ''Senegalia catechu'' is a deciduous, thorny tree which grows up to in height. The plant is called ''khair''
in H ...

(

catechin Catechin is a flavan-3-ol, a type of secondary metabolite providing antioxidant roles in plants. It belongs to the subgroup of polyphenols called flavonoids. The name of the catechin chemical family derives from ''catechu'', which is the tannic ...

)), both of which have been implicated in causing idiosyncratic acute liver injury, but the mechanism is unknown.

Outcome and management

No instances of acute liver failure or chronic liver injury have been linked to flavocoxid use and all cases have been self-limited, without subsequent

chronic hepatitis Hepatitis is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes (jaundice), poor appetite, vomiting, tiredness, abdominal pain ...

or vanishing bile duct syndrome. Recurrence upon re-exposure has been reported and rechallenge should be avoided. There is no information on possible cross sensitivity of hepatic injury with other medications or herbal agents such as skull cap or green tea.

References

{{reflist Dosage forms Medical food

Hepatotoxicity

Mechanism of Injury

Outcome and management

See also

References