Expanding the donor pool: Hepatitis C, hepatitis B and human immunodeficiency virus-positive donors in liver transplantation

Table 2 Drug-drug interactions among direct-acting antivirals and calcineurin inhibitors

	Cyclosporine (CSA)	Tacrolimus (TAC)	Sirolimus (SRL)	Everolimus (EVR)
Sofosbuvir (SOF)	4.5-fold ↑ in SOF AUC No dose adjustment necessary	13% ↑ in SOF AUC No dose adjustment necessary	Not studied, no interaction expected No dose adjustment necessary	Not studied, no interaction expected No dose adjustment necessary
Ledipasvir	Not studied, no interaction expected	Not studied, no interaction expected	Not studied, no interaction expected	Not studied, may increase EVR concentrations due to mild inhibition of P-gp by ledipasvir
Paritaprevir / ritonavir / ombitasvir + dasabuvir (PrOD)	5.8-fold ↑ in CSA AUC Modeling suggests using 1/5 of CSA dose during PrOD treatment Frequent monitoring necessary	57-fold ↑ in TAC AUC Modeling suggests TAC 0.5 mg every 7 days during PrOD treatment	38-fold ↑ in SRL AUC Do NOT co-administer	27.1-fold ↑ in EVR AUC Do NOT co-administer
Elbasvir / grazoprevir (EBR/GZR)	15-fold ↑ in GZR AUC and 2-fold ↑ in EBR AUC Do NOT co-administer	43% ↑ in TAC AUC No a priori dose adjustment necessary	Not studied, may increase SRL concentrations due to mild inhibition of P-gp by elbasvir	Not studied, may increase EVR concentrations due to mild inhibition of P-gp by elbasvir
Velpatasvir	No interaction observed; no a priori dose adjustment necessary	No data; no a priori dose adjustment necessary	No data; no a priori dose adjustment necessary	Not studied, may increase EVR concentrations due to mild inhibition of P-gp by velpatasvir
Glecaprevir / pibrentasvir (GLE/PIB)	5-fold ↑ in GLE AUC with higher doses (400 mg) of CSA Not recommended in patients requiring stable CSA doses > 100 mg/day	1.45-fold ↑ in TAC AUC No a priori dose adjustment, monitor TAC levels and titrate TAC dose as needed	Not studied, may increase SRL concentrations due to mild inhibition of P-gp by pibrentasvir	Not studied, may increase EVR concentrations due to mild inhibition of P-gp by pibrentasvir
Sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX)	9.4-fold ↑ in VOX AUC Do NOT co-administer	No data; no a priori dose adjustment	Not studied, may increase SRL concentrations due to mild inhibition of P-gp by velpatasvir and voxilaprevir	Not studied, may increase EVR concentrations due to mild inhibition of P-gp by velpatasvir and voxilaprevir

Adapted from http://www.hcvguidelines.org and http://www.hep-druginteractions.org. CsA: Cyclosporine; TAC: Tacrolimus; SRL: Sirolimus; EVR: Everolimus; SOF: Sofosbuvir; AUC: Area under the curve; PrOD: Paritaprevir/ritonavir, ombitasvir, and dasabuvir; ELB/GRZ: Elbasvir/grazoprevir; P-gp: P-glycoprotein; VOX: Voxilaprevir; VEL: Velpatasvir.