Monograph
C03DA01 - Spironolactone |
Porphyrinogenic |
P |
Rationale
Spironolactone has been associated with acute attacks of porphyria. Several references warn against its use. Spironolactone is known to induce CYP450. Sulfur metabolites of spironolactone are mechanism based inhibitors of CYP450 (degradation of prosthetic heme group). Two single observations of tolerance. Reported to have precipitated acute attacks.
Therapeutic characteristics
Mineralocorticoid antagonist, potassium saving diuretic.
Metabolism and pharmacokinetics
Extensively metabolized. The main metabolites7-alpha thiometyl-spironolactone and canrenone are excreted in urine and bile.
Preclinical data
The effect of spironolactone on the activity of delta-aminolevulinate synthase and on the formation of porphyrins and cytochrome P-450 were examined in the 18-day-old chick embryo liver in ovo(Anderson KE. Biochim Biophys Acta 1978). Spironolactone was found to induce delta-aminolevulinate synthase in this system. Spironolactone induces CYP activity. Sulfur metabolites inactivate CYP2C11 and 3A4 by degradation of the prosthetic heme group.
Personal communication
Thunell, patient report (n=1): tolerated. Andersson, patient report (n=1): tolerated.
Published experience
None
IPNet drug reports
Uneventful use reported in 2 patients with acute porphyria.
References
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