Coadministration of sofosbuvir and tacrolimus (5 mg single dose) decreased tacrolimus Cmax by 27%, but increased AUC by 9%. Sofosbuvir Cmax decreased by 3%, but AUC increased by 13%. The Cmax of GS-331007 decreased by 3% and there was no change in AUC. No dose adjustment of sofosbuvir or tacrolimus is required at initiation of co-administration. Afterwards, close monitoring and potential dose adjustment of tacrolimus may be required.
The pharmacokinetics of drugs that are metabolized by the liver (e.g. immunosuppressive agents such as calcineurin inhibitors) may be impacted by changes in liver function during DAA therapy, related to clearance of HCV.

The interaction between sofosbuvir and tacrolimus was evaluated in clinical trials and no dose adjustment is needed for either drug. Coadministration of tacrolimus (5 mg single dose) and sofosbuvir (400 mg single dose) was studied in 16 subjects. Sofosbuvir Cmax decreased by 3% and AUC increased by 13%. GS-331007 Cmax decreased by 3% and there was no change in AUC. Tacrolimus Cmax decreased by 27%, but AUC increased by 9%.
Frequent monitoring of relevant drug concentrations of concomitant medications such as cytochrome P450 substrates with a narrow therapeutic index (e.g. certain immunosuppressants) is recommended to ensure safe and effective use. Dose adjustments of concomitant medications may be necessary.

A single-centre retrospective study of 108 patients with solid organ transplants examined immunosuppression doses before and during DAA treatment in patients, 91% of whom were taking tacrolimus. Secondary outcome measures were new or worsening rejection, graft dysfunction, and SVR12. The most common DAA regimen given was simepravir + sofosbuvir (33.9%), followed by ledipasvir/sofosbuvir (26.6%). There were no statistically significant changes in immunosuppressant doses or exposure after 4 weeks of DAA therapy. Only 1 patient experienced new or worsening rejection. Five patients experienced new or worsening graft dysfunction. Ninety-eight per-cent of patients achieved SVR12. The rejection rate was similar to historic controls in the literature and the cure rate is likewise similar to the general population. The authors conclude there was no drug interaction between the immunosuppressants and the DAAs.