Darunavir + Ifosfamide = Precautionary

Effect on Concentration

Darunavir
Unknown
Applies within class?
No
Ifosfamide
Decrease
Applies within class?
No

Pharmacologic Effects

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

Interaction History

N/A

Last Updated 03-Aug-2018

Summary

Ifosfamide is a prodrug

Sources

Protease Inhibitors versus Ifosfamide ^

Study Design

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

Study Results

Protease inhibitors inhibit CYP3A and other CYP enzymes. In vitro studies have demonstrated the ability of ifosfamide to both inhibit and induce CYP3A4.

Study Conclusions

There is potential for ifosfamide to alter levels of protease inhibitors via modulation of CYP3A4 activity. Ifosfamide is metabolized by CYP3A4 and CYP2B6. Data with ketoconazole show that enzyme protease inhibitors may inhibit ifosfamide conversion to active metabolites, therefore decreasing its therapeutic effect. Close monitoring of ifosfamide induced toxicity is recommended.

References

Vanhoefer U, Schleucher N, Klaassen U, Seeber S, Harstrick A. Ifosfamide-based drug combinations: preclinical evaluation of drug interactions and translation into the clinic. Seminars In Oncology. 2000; 1: 8-13.