Monograph

J01EE01 - Sulfamethoxazole and Trimethoprim

Porphyrinogenic

Rationale

The combination contains a notoriously porphyrinogenic sulfonamide component, inducer of CYP 3A4. Several references warn against it. Trimetoprim is substrate for CYP 2C9 and 3A4. Inhibits CYP 2C8, 2C19, 2D6,3A4. Warned against in three references.

Chemical description

sulfamethoxazol: Sulfonamide excreted in urine in unchanged form (20%), in acetylated form (60%) and in glucuronidated form (15%). trimethoprim: Bacteriostatic antibiotic perorally used (150-200 mg x 2) in urinary tract infections. About 10-20 % is metabolized in the liver.About 50 % is excreted by the kidneys in unchanged form within 24 hours. Sulfonamides: Australian list: unsafe/attacks. EPI-list: unsafe. French list: avoid. South African list: avoid /use with extreme caution only. Steim,Tchudy 1970: unsafe. Moore, Hift 1997: unsafe. Kalman, Bonkowsky: known to exacerbate disease. Andersson: Precipitates attacks (N=4) Trimethoprim: Martindale: unsafe/acute attacks. Australian list: unsafe. South African list: use with extreme caution only.

IPNet drug reports

Uneventful use reported in 3 patients with acute porphyria.

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