Darunavir + Phenytoin = Prohibited

Effect on Concentration

Darunavir
Decrease
Applies within class?
No
Phenytoin
Decrease
Applies within class?
No

Pharmacologic Effects

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

Interaction History

N/A

Last Updated 30-Jul-2018

Summary

Sources

Protease Inhibitors versus Phenytoin ^

Study Design

The interaction between these two agents has not been formally studied, but based upon known mechanisms of drug metabolism, and package inserts, complex interactions may arise. Interaction studies exist between phenytoin and lopinavir/ritonavir, and the results can be expected to extrapolated to concomitant use of phenytoin with other protease inhibitors.

Study Results

Lopinavir/Ritonavir is a CYP3A4 inhibitor and substrate and may also induce CYP isozymes. Phenytoin (PHT) is a CYP3A4 inducer and CYP2C9/CYP2C19 substrate. Following the addition of PHT to patients on a LPV/RTV regimen, LPV C0h decreased by 46% and AUC0-12h decreased by 33%. Following the addition of LPV/RTV to patients on a PHT regimen, PHT C0h decreased by 33% and PHT AUC0-24h decreased by 31%. Concomitant LPV/RTV and PHT use results in a 2-way drug interaction. Phenytoin appears to increase LPV clearance via CYP3A4 induction, which is not offset by the presence of low-dose RTV. LPV/RTV may increase PHT clearance via CYP2C9 induction

Study Conclusions

Caution should be exercised in administering phenytoin with boosted protease inhibitors. Phenytoin levels should be monitored when the benefits of coadministration is deemed to outweigh the risks. Monitor closely for loss of virologic suppression or adverse effects of anticonvulsant toxicity.

References

Lim ML. Coadministration of lopinavir/ritonavir and phenytoin results in two-way drug interaction through cytochrome p-450 induction. Jaids: Journal Of The Acquired Immunodefiency Syndrome . 2004; : 1034-1040.