Indometacin is metabolized via O-demethylation and N-deacylation. Indometacin is not an inducer or an inhibitor of CYP enzymes in vivo. Risk for gastrointestinal adverse events in the form of nausea, vomiting and diarrhoea motivates vigilance against insufficient intake of food, especially of carbohydrate.

Chlorobenzoyl chloromethoxy metylindol acetic acid M=359. Practically insoluble in water.

Indometacin is indicated for the treatment of rheumatoid arthritis, arthrosis, MB Bechterew, and other supportive tissue inflammatory conditions. The inhibitory effect of cyclooxygenase-2 activity may counteract prostaglandin-caused prolongation of luteal progesterone production. Common side effects that can be potentially porphyrinogenic through reduction in carbohydrate intake and that also can be confused with an acute porphyria attack are dyspepsia, nausea, vomiting, abdominal pain and diarrhoea.

Probably significant.

Indometacin is metabolised via O-demethylation and N-deacylation. The first seems not to be dependent on CYP enzymes. In vitro data indicates that CYP2C9 is involved in the O-demethylation (Nakajima 1998 and Zhou 2009), with minor contribution by CYP1A2, CYP2C19 and CYP2D6 (Zhou 2009). The half-life elimination is 2-11 hours. In vitro data indicates that it has low potential to be a clinical inducer of hPXR (Sinz 2006). No drug-drug interactions with indomethacin as a perpetrator are observed (DRUID and Interaktionsdatabasen), which may indicate that indometacin is not an inhibitor or inducer of CYP enzymes.

C. Andersson; patient reports: tolerated (n=1).

Indomethacin is listed as safe for use in acute porphyria (Disler 1982, Kalman 1998, Moore 1997 and Palmieri 2004).

Uneventful use reported in 8 patients with acute porphyria.