Vericiguat

Indications

Vericiguat is used for: Heart Failure Risk Reduction

Adult Dose

Heart Failure Risk Reduction Indicated to reduce risk of cardiovascular death and heart failure (HF) hospitalization following a hospitalization for HF or need for outpatient IV diuretics, in adults with symptomatic chronic HF and ejection fraction <45% Initial: 2.5 mg PO once daily Maintenance: Double dose every 2 weeks as tolerated to target dose of 10 mg PO once daily Hepatic impairment Mild or moderate (Child-Pugh A or B): No dosage adjustment necessary Severe (Child-Pugh C): Not studied

Child Dose

Renal Dose

Renal impairment eGFR >15 mL/min/1.73m2 and not on dialysis: No dosage adjustment necessary eGFR <15 mL/min/1.73m2 or on dialysis: Not studied

Administration

Should be taken with food

Contra Indications

Coadministration with other soluble guanylate cyclase (sGC) stimulators May cause fetal harm when administered to pregnant females and its use is contraindicated

Precautions

May cause fetal harm; do not administer to pregnant females Exclude pregnancy before starting treatment To prevent pregnancy, females of reproductive potential must use effective forms of contraception during treatment and for 1 month after stopping treatment

Pregnancy-Lactation

Pregnancy Contraindicated; based on data from animal reproduction studies, may cause fetal harm when administered to pregnant females There are no available data regarding use in pregnant females Verify pregnancy status in females of reproductive potential before initiating Animal studies Administration to pregnant rabbits during organogenesis at ?4 times the human exposure (total AUC) with the maximum recommended human dose (MRHD) of 10 mg resulted in malformations of the heart and major vessels, as well as increased number of abortions and resorptions In a prenatal/postnatal toxicity study, oral administration to rats during gestation through lactation caused maternal toxicity, resulting in decreased pup body weight gain (>10 times the MRHD) and increased pup mortality (24 times the MRHD) during the preweaning period Contraception Advise females of reproductive potential to use effective contraception during treatment and for 1 month after final dose Lactation Data are not available on the presence of vericiguat in human milk, effects on breastfed infants, or effects on milk production Vericiguat is present in the milk of lactating rats and it is likely that vericiguat or its metabolites are present in human milk Owing to the potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment

Interactions

Coadministration with other sGC stimulators is contraindicated Coadministration with PDE-5 inhibitors not recommended owing to potential for hypotension

Side Effects

Side effects of Vericiguat : >10% Hypotension (16%); placebo (15%) 1-10% Anemia (10%); placebo (7%)

Mode of Action

Stimulates soluble guanylate-cyclase (sGC), the intracellular receptor for endogenous nitric oxide (NO), which catalyzes cyclic guanosine monophosphate (cGMP) production; cGMP plays a role in the regulation of vascular tone, cardiac contractility, and cardiac remodeling Heart failure is associated with impaired NO synthesis and decreased sGC activity, which may contribute to myocardial and vascular dysfunction By directly stimulating sGC, independently of and synergistically with NO, vericiguat augments levels of intracellular cGMP, leading to smooth muscle relaxation and vasodilation