St. John’s Wort + Indinavir

• Indinavir AUC ¯ 57%
• Indinavir trough (C8h) ¯ by 81% (range 49-99%)
  • I.e., ¯ by factor of 10 (0.49 ug/mL --> 0.048 ug/mL)

[Piscitelli et al. Lancet 2000;355:547-8]

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Piscitelli SC, Burstein AH, Chaitt D, Alfaro RM, Falloon J. Indinavir concentrations and St John's wort. Lancet 2000 Feb 12;355(9203):547-8.Abstract: St John's wort reduced the area under the curve of the HIV-1 protease inhibitor indinavir by a mean of 57% (SD 19) and decreased the extrapolated 8-h indinavir trough by 81% (16) in healthy volunteers. A reduction in indinavir exposure of this magnitude could lead to the development of drug resistance and treatment failure.

de Maat et al. 1st Int Wkshp HIV Clin Pharmacol 2000, #2.8:

• Case report of an HIV-infected patient receiving nevirapine as part of a combination regimen. Addition of St. John Wort caused a 20% ¯ in nevirapine Css vs. historical data; Investigators suggest possible interaction due to CYP450 induction.

• These findings, along with other interaction reports led to the issuing of an FDA Advisory ((JAMA 2000;283:1679):

St. John’s Wort should be avoided in patients taking indinavir as sole protease inhibitor. It is also reasonable to avoid its use with other protease inhibitors and NNRTIs. The use of low-dose ritonavir may prevent interaction (?), but the optimal dosage has not yet been defined.