Elbasvir/Grazoprevir + Rosuvastatin = Precautionary

Effect on Concentration

Elbasvir/Grazoprevir
No change
Applies within class?
No
Rosuvastatin
Increase
Applies within class?
No

Pharmacologic Effects

Elbasvir/Grazoprevir
Effect
N/A
Applies within class?
No
Rosuvastatin
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 18-Jul-2018

Summary

Sources

Elbasvir/Grazoprevir versus Rosuvastatin ^

Study Design

In an open-label, 2-part study, the PK effects between Rosuvastatin and Grazoprevir (GZR)/Elbasvir (EBR) were assessed. 24 healthy subjects participated in the study. In Period 1, each participant received a single 10mg dose of rosuvastatin on day 1. This was followed by a 3 day washout period. In Period 2, subjects received Grazoprevir (GZR) 200mg daily on days 1 through 9. Rosuvastatin 10mg was coadministered on day 7. In period 3, subjects received GZR 200mg + elbasvir (EBR) 50mg daily on days 1 through 11. A single dose of rosuvastatin 10mg was coadministered on day 9. There was no washout between periods 2 and 3.

Study Results

Results Drug AUC GMR (90% CI) Cmax GMR (90% CI) C24 GMR (90%CI) Rosuvastatin (GZR + Rosuvastatin) 1.85 (1.56-2.19) 4.25 (3.25 -5.56) 0.80 (0.70-0.91) GZR (GZR + Rosuvastatin ) 1.16 (0.94-1.44) 1.13 (0.77-1.65) 0.93 (0.84-1.03) Rosuvastatin (Rosuvastatin + GZR + EBR) 2.68 (2.26 -3.17) 5.49 (4.29-7.04) 0.98 (0.84-1.13) GZR (Rosuvastatin + GZR + EBR) 1.01 (0.79-1.28) 0.97 (0.63-1.50) 0.95 (0.87-1.04) EBR (Rosuvastatin + GZR + EBR) 1.09 (0.98-1.21) 1.11 (0.99-1.26) 0.96 (0.86-1.08) Results showed a significant increase in both AUC and Cmax when Rosuvastatin was co-administered with both GZR and GZR/EBR. Rosuvastatin had no significant impact on GZR or EBR pharmacokinetics.

Study Conclusions

Use caution if rosuvastatin and GZR/EBR are used concomitantly as this may increase rosuvastatin concentration.1 If coadministration of rosuvastatin with GZR/EBR is required, initiate rosuvastatin at 5 mg once daily and do not exceed rosuvastatin doses of 10 mg daily due to an increased risk of statin toxicity.1,2 During the therapy, monitor the patient for signs and symptoms of statin toxicity, such as myopathy or rhabdomyolysis, etc.

References

L Caro, W Marshall, H Feng, et al. Coadministration of hcv protease inhibitor grazoprevir with hcv ns5a inhibitor elbasvir has no effect on pravastatin but increases rosuvastatin exposure in healthy subjects. 16th International Workshop On Clinical Pharmacology Of Hiv And Hepatitis Therapy. Washington, DC. ; 2015.