Darunavir + Milk Thistle = Unknown or no reaction

Effect on Concentration

Darunavir
No change
Applies within class?
No
Milk Thistle
No change
Applies within class?
No

Pharmacologic Effects

Darunavir
Effect
N/A
Applies within class?
No
Milk Thistle
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 17-Jul-2018

Summary

Sources

Darunavir versus Milk Thistle ^

Study Design

In an open-label, fixed-sequence study, the concomitant use of milk thistle and darunavir/ritonavir (DRV/r) was evaluated in HIV-infected patients (n=15). Patients who had been receiving antiretroviral (ARV) therapy with DRV/r 600/100 mg twice daily (BID) for at least 4 weeks received milk thistle containing 150 mg of silymarin every 8 hours (q8h) for 14 days. Plasma samples for analysis of DRV/r were obtained predose and at 1, 2, 4, 6, 8,10, and12 hours after a morning dose of DRV/r on day 0.1 Plasma samples for analysis of DRV/r plus milk thistle were obtained on day 14.

Study Results

Coadministration of DRV/r (600/100 mg BID) and milk thistle (150 mg of silymarin q8h) for 14 days resulted in slightly decreased pharmacokinetic (PK) parameters of both DRV and ritonavir. The geometric mean ratios (GMRs; milk thistle + DRV/r / DRV/r) [90% CIs] of DRV were: 0.83 [0.70, 0.98] for Cmax, 0.86 [0.70, 1.05] for AUC, and 0.94 [0.73, 1.19] for Cmin GMRs (milk thistle + DRV/r / DRV/r) [90% CIs] of ritonavir were: 0.90 [0.72, 1.14] for Cmax, 0.89 [0.72, 1.09] for AUC, and 0.94 [0.75, 1.16] for Cmin

Study Conclusions

Based on the study results, milk thistle does not significantly affect the PKs of both DRV and ritonavir in HIV-infected patients. The investigators concluded that no dose adjustment for DRV/r is necessary when co-administering with milk thistle. However, in vitro studies suggest that different milk thistle formulations may have various effects (i.e. increase/ decrease/ no meaningful effects) on CYP3A4 enzymes due to great variability in silymarin content among different milk thistle brands. Therefore, use milk thistle cautiously in patients taking CYP3A4 substrates, such as DRV and ritonavir, until further data is available.

References

Molto J, Valle M, Miranda C, Cedeno S, Negredo E, Clotet B. Effect of milk thistle on the pharmacokinetics of darunavir-ritonavir in hiv-infected patients. Antimicrobial Agents And Chemotherapy . 2012; 6: 2837-2841.