No Clinically Significant Pharmacokinetic Drug-Drug Interactions between Sofosbuvir (GS-7977) and the Immunosuppressants, Cyclosporine A or Tacrolimus in Healthy Volunteers.
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Study Design
In this single dose, healthy volunteer, open-label, randomized, 2-group, 3 period, cross-over design, Group 1 subjects (n=20) received sofosbuvir (SOF) 400 mg, high dose cyclosporine A (CsA) 600 mg and the combination of SOF + CsA. Group 2 (n=20) received SOF 400 mg, tacrolimus (Tac) 5 mg and SOF + Tac. PK samples were collected over 72 hours for Group 1 and over 96 hours for Group 2.
Study Results
No clinically relevant interaction was observed on coadministration of SOF and CsA or Tac. High-dose CsA increased systemic SOF exposure (AUC) by 4-fold corresponding to ~10% increase in total drug-related material (DRM) exposure and is not considered clinically significant. CsA had no affect on the GS-331007 (SOF major sytemic metabolite) AUCinf or AUCtau and caused a 40% decrease in the Cmax of GS-331007. SOF had no affect on the AUCinf or AUCtau, or Cmax of CsA.
A total of 19 subjects in Group 1 and 15 in Group 2 completed the study (1 and 2 discontinuations for adverse events [AE] in each group, respectively). All treatments were generally well tolerated; treatment emergent AEs were primarily related to administration of CsA or Tac.
SOF decreased Tac Cmax by 27%. Tac increased SOF AUCinf or AUCtau by 13% and decreased SOF Cmax by 4%, with no affect on GS-331007.
Study Conclusions
There is no clinically significant interaction between sofosbuvir and tacrolimus or cyclosporin.
Tac and CsA should still be monitored as in standard clinical practice.
References
Mathias A, Cornpropst A, Clemons D. No clinically significant pharmacokinetic drug-drug interactions between sofosbuvir (gs-7977) and the immunosuppressants, cyclosporine a or tacrolimus in healthy volunteers. Hepatology. 2012; 4S: 1063-1064.
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