Verigat Tablet

Verigat Tablet 5 mg is an oral soluble guanylate cyclase (sGC) stimulator used to reduce the risk of cardiovascular death and hospitalization in adults with symptomatic chronic heart failure following a recent worsening event. It enhances the nitric oxide (NO)-sGC-cGMP signaling pathway by directly stimulating sGC, increasing cyclic guanosine monophosphate (cGMP) production, and improving myocardial and vascular function.

By restoring impaired cGMP signaling, vericiguat helps improve cardiac performance and reduce disease progression in patients with heart failure. Its long half-life supports convenient once-daily dosing.

Verigat Tablet 5 mg is a soluble guanylate cyclase stimulator used to reduce heart failure-related hospitalization and cardiovascular death in patients with chronic systolic heart failure.

Verigat Tablet 5 mg is indicated in adults with symptomatic, chronic heart failure and an ejection fraction of 5

• Cardiovascular Mortality
• Heart Failure Hospitalization

By directly stimulating the increased production of intracellular cyclic guanosine monophosphate (cGMP), vericiguat causes the relaxation of vascular smooth muscle and vasodilation. Verigat Tablet 5 mg has a relatively long half-life (~30h) that allows for once-daily dosing.

Animal reproduction studies have demonstrated the potential for embryo-fetal toxicity when vericiguat is administered to pregnant females - defects in major vessel and heart formation, as well as spontaneous abortions/resorptions, were observed when vericiguat was administered to pregnant rabbits during organogenesis. The possibility of pregnancy should be excluded prior to beginning therapy with vericiguat, and adequate contraception should be used throughout therapy and for one month following cessation of treatment.

Heart failure (HF) involves, amongst other morphologic and physiologic changes, the impaired synthesis of nitric oxide (NO) and decreased activity of soluble guanylate cyclase (sGC). Functioning normally, NO binds to sGC and stimulates the synthesis of intracellular cyclic guanosine monophosphate (cGMP), a second messenger involved in the maintenance of vascular tone, as well as cardiac contractility and remodeling. Defects in this pathway are thought to contribute to the myocardial and vascular dysfunction associated with heart failure and are therefore a desirable target in its treatment.

Verigat Tablet 5 mg directly stimulates sGC by binding to a target site on its beta-subunit, bypassing the need for NO-mediated activation, and in doing so causes an increase in the production of intracellular cGMP that results in vascular smooth muscle relaxation and vasodilation.

Following the administration of 10mg of vericiguat by mouth once daily, the average steady-state C_max and AUC in patients with heart failure is 350 mcg/L and 6,680 mcg•h/L, respectively, with a T_max of 1 hour. The absolute bioavailability of orally-administered vericiguat is approximately 93% when taken with food - co-administration with meals has been shown to reduce pharmacokinetic variability, increase T_max to roughly 4 hours, and increase C_max and AUC by 41% and 44%, respectively.

In healthy subjects the steady-state volume of distribution of vericiguat is approximately 44 liters.

Verigat Tablet 5 mg is extensively (~98%) protein-bound in plasma, primarily to serum albumin.

Following the oral administration of radiolabeled vericiguat, approximately 53% of the administered radioactivity was recovered in the urine and 45% in the feces. A human mass balance study found that the portion recovered in the urine comprised approximately 40.8% N-glucuronide metabolite, 7.7% other metabolites, and 9% unchanged parent drug, while virtually the entire portion recovered in the feces comprised unchanged vericiguat.

In patients with heart failure, the half-life of vericiguat is 30 hours.

Verigat Tablet 5 mg is a low-clearance drug, with an observed plasma clearance of 1.6 L/h in healthy volunteers and 1.3 L/h in patients with systolic heart failure.

Data regarding overdosage with vericiguat are unavailable. Doses of up to 15mg once daily (50% greater than the recommended maintenance dose) have been studied and found to be well-tolerated. Symptoms of overdose are likely to be consistent with the adverse effect profile of vericiguat and may therefore involve significant hypotension for which symptomatic and supportive measures should be provided. Dialysis is unlikely to be of benefit in vericiguat overdose given its high degree of protein binding.

• Take with food. Administration with food has been shown to reduce pharmacokinetic variability and significantly improve absorption.