Darunavir + Ledipasvir/Sofosbuvir = Precautionary

Effect on Concentration

Darunavir
No change
Applies within class?
No
Ledipasvir/Sofosbuvir
Increase
Applies within class?
No

Pharmacologic Effects

Darunavir
Effect
N/A
Applies within class?
No
Ledipasvir/Sofosbuvir
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 16-Jul-2018

Summary

Use caution if using with TDF as part of the NRTI backbone as increases in TFV concentration may increase risk of adverse events.

Sources

Drug–Drug Interaction Profile of the Fixed-Dose Combination Tablet Regimen Ledipasvir/Sofosbuvir. ^

Study Design

The drug-drug interaction potential of ledipasvir (LDV) with ritonavir-boosted darunavir was assessed in a pharmacokinetic evaluation in healthy patients. DRV/r was administered as 800mg/100mg QD and LDV as 90mg QD (n=23).

Study Results

Co-administration of DRV/r with LDV resulted in increased exposure of LDV; AUC, Cmax and Cmin was 1.39 (1.28-1.49),1.45 (1.34-1.56) and 1.39 (1.29-1.51), respectively. DRV PK was unaffected (PK parameters not reported), however, ritonavir AUC and Cmax increased by 37% and 33%, respectively, with LDV co-administration.

Study Conclusions

*If coadministration is necessary, the manufacturer of LDV/SOF (Harvoni) recommends close monitoring for tenofovir-associated adverse reactions when DRV/r is administered with tenofovir DF + emtricitabine and LDV/SOF. Refer to VIREAD or TRUVADA prescribing information for recommendations on renal monitoring.

References

German P, Mathias A, Brainard DM, Kearney BP. Drug–drug interaction profile of the fixed-dose combination tablet regimen ledipasvir/sofosbuvir. Clinical Pharmacokinetics. 2018; : 1-15.