Verigat10 mg

Verigat is indicated, in combination with other heart failure therapies, to reduce the risk of cardiovascular death and heart failure hospitalization in adults with symptomatic chronic heart failure and an ejection fraction below 45%, following a recent episode of decompensation requiring hospitalization or outpatient intravenous diuretic treatment.

Evidence Classification

• FDA-approved, guideline-supported use: Add-on therapy for symptomatic chronic heart failure with reduced ejection fraction (HFrEF, EF <45%) after a recent decompensation event, used together with standard guideline-directed medical therapy (e.g., beta-blockers, ACE inhibitors/ARNI, mineralocorticoid receptor antagonists, SGLT2 inhibitors).
• Requires combination therapy: Verigat is not intended as monotherapy; it is added to existing standard-of-care heart failure treatment, not used as a substitute.
• Not established: Use in acutely decompensated heart failure requiring IV therapy, or in hemodynamically unstable patients, has not been studied and is not recommended.

Each film-coated tablet of Vericiguat contains vericiguat as the active ingredient, available in strengths of 2.5 mg, 5 mg, and 10 mg for oral administration.

Verigat is an oral soluble guanylate cyclase (sGC) stimulator developed for long-term management of chronic heart failure. It works by directly stimulating sGC, an enzyme in the nitric oxide signaling pathway, independent of and synergistically with endogenous nitric oxide, to increase cyclic guanosine monophosphate (cGMP) production. This helps improve vascular smooth muscle relaxation and cardiac and vascular function in patients with heart failure with reduced ejection fraction. Verigat is used as an add-on to standard heart failure therapy, particularly in patients who have recently been hospitalized or required intravenous diuretics for a worsening heart failure episode.

Soluble guanylate cyclase (sGC) stimulator; heart failure therapy agent — Verigat

Vericiguat is a stimulator of soluble guanylate cyclase (sGC), a key enzyme in the nitric oxide (NO)-sGC-cyclic guanosine monophosphate (cGMP) signaling pathway. In heart failure, endogenous nitric oxide production is often impaired, leading to reduced cGMP and worsening myocardial and vascular dysfunction. Vericiguat directly stimulates sGC independently of nitric oxide and also sensitizes sGC to low levels of endogenous nitric oxide, restoring cGMP production. Increased cGMP promotes vascular smooth muscle relaxation and has anti-fibrotic and anti-hypertrophic effects on the myocardium, together reducing the risk of cardiovascular death and heart failure hospitalization.

Vericiguat is absorbed orally, with peak plasma concentration reached within a few hours; taking it with food increases absorption. It is highly protein-bound and is metabolized mainly via glucuronidation (UGT1A1 and UGT1A9), with elimination divided between renal and fecal routes, and a half-life that supports once-daily dosing.

Verigat tablets should be taken orally once daily with food to improve absorption. Tablets should be swallowed whole; for patients unable to swallow tablets, they may be crushed and mixed immediately with water for oral administration, as advised by a physician. Do not skip doses; if a dose of Verigat is missed, take it as soon as remembered on the same day, but do not take two doses on the same day to make up for a missed dose.

Verigat has clinically significant interactions with the following agents. Concurrent use with other soluble guanylate cyclase (sGC) stimulators or PDE5 inhibitors is contraindicated (see Contraindications).

• Nitrates and nitric oxide donors (e.g., nitroglycerin, isosorbide): Combining with Verigat may cause additive vasodilation and significant hypotension; avoid combining unless directed by a physician who can monitor blood pressure closely.
• Antihypertensive agents: Concomitant use with other blood-pressure-lowering medicines may increase the risk of symptomatic hypotension with Verigat; dose titration and monitoring are advised.

The most commonly reported side effects of Verigat include:

• Hypotension (low blood pressure) — most common, generally manageable with gradual dose titration.
• Anemia (reduced red blood cell count) — periodic monitoring may be advised.
• Dizziness, related to blood pressure changes.
• Gastrointestinal symptoms such as nausea.

Patients taking Verigat should contact their physician if they experience persistent dizziness, fainting, unusual fatigue, or symptoms suggestive of low blood pressure.

Verigat is contraindicated in pregnancy due to the potential for embryo-fetal harm, based on findings in animal reproduction studies. A pregnancy test is recommended before starting Verigat, and patients who could become pregnant should use effective contraception during treatment and for one month after the last dose. If pregnancy is suspected or confirmed during treatment, a physician should be consulted immediately.

It is not known whether Verigat passes into human breast milk. Because of the potential for serious adverse reactions in a breastfed infant, breastfeeding is not recommended during treatment with Verigat. Use only if clearly needed and only under close medical supervision, with potential benefit weighed against potential risk; consult a physician before use during lactation.

Symptomatic hypotension: Verigat can cause symptomatic low blood pressure, particularly during dose titration. Treatment should be started at a low dose and increased gradually, with blood pressure monitored, especially in patients with a systolic blood pressure below 100 mmHg, elderly patients, or those with volume depletion or renal impairment.

Renal impairment: Use Verigat with caution in patients with severely reduced kidney function (eGFR below 15 mL/min/1.73m²) or those on dialysis, as clinical experience is limited.

Anemia: Verigat has been associated with a reduction in hemoglobin and anemia; periodic monitoring of hemoglobin/hematocrit is reasonable, particularly if signs or symptoms of anemia develop.

Pregnancy: See Contraindications and Pregnancy and Lactation for details on the pregnancy contraindication and contraception requirements for Verigat.

Overdose with Verigat may cause pronounced hypotension. There is no specific antidote for Verigat overdose. If overdose is suspected, seek immediate medical attention or contact a poison control center. Management generally involves general supportive measures, such as monitoring vital signs and blood pressure, with symptomatic and supportive care (e.g., fluids and positioning to support blood pressure) as directed by a physician; do not attempt specific home treatment.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

• Elderly: No dose adjustment of Verigat is required based on age alone; elderly patients may have a higher risk of hypotension, so careful titration and monitoring are advised.
• Renal impairment: No adjustment needed for mild-to-moderate impairment; use Verigat with caution in severe impairment or dialysis (see Dosage and Administration).
• Hepatic impairment: No adjustment needed for mild-to-moderate impairment; Verigat is not recommended in severe hepatic impairment.
• Pregnancy and lactation: See Pregnancy and Lactation section.
• Pediatric patients: See Pediatric Uses section.

Verigat is intended for long-term, ongoing use as part of chronic heart failure management. Treatment is typically continued indefinitely alongside other guideline-directed heart failure therapies, as advised by the treating physician, with periodic reassessment of blood pressure, hemoglobin, and clinical status.

Soluble guanylate cyclase (sGC) stimulator (Vericiguat)

Vericiguat stimulates soluble guanylate cyclase (sGC) directly and also sensitizes sGC to endogenous nitric oxide, increasing production of cyclic guanosine monophosphate (cGMP). This restores impaired nitric oxide-sGC-cGMP signaling seen in heart failure, promoting vasodilation and helping to counteract vascular and myocardial dysfunction associated with disease progression.

The safety and efficacy of Verigat in pediatric patients have not been established. Verigat is not recommended for use in children or adolescents outside of a clinical trial setting.