Darunavir + Etoposide = Precautionary

Effect on Concentration

Darunavir
No change
Applies within class?
No
Etoposide
Increase
Applies within class?
No

Pharmacologic Effects

Darunavir
Effect
N/A
Applies within class?
No
Etoposide
Effect
N/A
Applies within class?
No

Interaction History

Prohibited, 27-Jun-2018;

Last Updated 27-Jun-2018

Summary

While boosted protease inhibitors are not expected to have their concentrations altered by concomitant administration of etoposide, levels of etoposide may be increased.

Sources

MDR-and CYP3A4-mediated drug–drug interactions. ^

Study Design

Interaction studies comparing the pharmacokinetics of etoposide and atazanavir have not been conducted, and theoretical interactions are based upon what is known of the metabolic pathways of these medications.

Study Results

Etoposide is partly metabolized by CYP3A4 to reactive catechol metabolites, though several other pathways of metabolism exist, including glucuronidation by UGT1A1.

Study Conclusions

O-demethylation of etoposide occurs through the cytochrome P450 pathway. Darunavir/ritonavir could potentially increase etoposide exposure. Close monitoring of etoposide induced toxicity is recommended.

References

Pal D, Mitra AK. Mdr-and cyp3a4-mediated drug–drug interactions. Journal Of Neuroimmune Pharmacology. 2006; 3: 323-329.