Table 6.

Effects of vericiguat on the pharmacokinetics of other drugs

Interaction drug	Changes in the PK parameters of interaction drugs
	PK parameter	N	Point estimate	90% confidence interval	Clinical comment in relation to the VICTORIA study
Midazolam	AUC	32	0.822	0.776–0.871	No dose adjustment of co-medications metabolized by CYP3A4
	Cmax	32	0.769	0.683–0.865
In combination with drugs prescribed in cardiovascular disease
R-warfarin	AUC	23	0.985	0.967–1.003	No dose adjustment of warfarin
	Cmax	23	0.994	0.960–1.031
S-warfarin	AUC	23	0.978	0.957–0.999	No dose adjustment of warfarin
	Cmax	23	0.983	0.947–1.021
Digoxin	AUCτ,md	22	1.042	0.994–1.093	No dose adjustment of digoxin
	Ctrough	22	1.000	0.947–1.055
Sacubitril	AUC0–12,md	14	1.080	0.992–1.177	No dose adjustment of sacubitril/valsartan
	Cmax,md	14	1.182	0.891–1.569
LBQ657	AUC0–12,md	14	1.013	0.972–1.056	No dose adjustment of sacubitril/valsartan
	Cmax,md	14	1.016	0.971–1.063
Valsartan	AUC0–12,md	14	1.117	0.953–1.309	No dose adjustment of sacubitril/valsartan
	Cmax,md	14	1.127	0.976–1.301
In combination with drugs affecting the NO signaling pathway
Sildenafila	AUC0–22	30	1.130	0.873–1.461	Currently excluded from the phase III VICTORIA study as patient safety data is not available
	Cmax	30	1.171	0.906–1.513

AUC area under the concentration–time curve, AUC_0–12,md AUC from time 0 to 12 h after multiple dose administration, AUC_(0–22) AUC from time 0 to 22 h, AUC_τ,md AUC within the dosing interval after multiple dosing, C_max maximum concentration within a dosing interval, C_max,md C_max within a dosing interval after multiple dose administration, C_trough trough concentration within a dosing interval, CYP cytochrome P450, DDI drug–drug interaction, NO nitric oxide, PK pharmacokinetic

^aData for the highest dose of sildenafil administered (100 mg)