Vericiguat (Monograph)

Brand name: Verquvo
Drug class:

Medically reviewed by Drugs.com on Apr 10, 2024. Written by ASHP.

Introduction

Vasodilator; soluble guanylate cyclase (sGC) stimulator.

Uses for Vericiguat

Heart Failure

Treatment of adults with symptomatic (i.e., recent heart failure [HF] hospitalization, need for outpatient IV diuretics) chronic HF and ejection fraction (LVEF) <45%.

Has been shown to reduce the risk of cardiovascular death and HF hospitalization.

Experts state vericiguat may be considered in selected high-risk patients with HFrEF (stage C, New York Heart Association [NYHA] class II-IV) and recent worsening of HF (recent HF hospitalization, IV diuretics) already on guideline-directed medical therapy (e.g., angiotensin-converting enzyme [ACE] inhibitor, angiotensin II receptor antagonist, angiotensin receptor-neprilysin inhibitor [ARNI], beta-adrenergic blocking agent, aldosterone receptor antagonist, sodium-glucose cotransporter 2 [SGLT2] inhibitor).

Vericiguat Dosage and Administration

General

Pretreatment Screening

• Obtain a pregnancy test in females of reproductive potential prior to start of treatment with vericiguat.

Administration

Oral Administration

Administer orally with food.

If a dose is missed, may administer as soon as possible on the same day of missed dose. Do not administer 2 doses on the same day.

For patients unable to swallow whole tablets, may be crushed and mixed with water immediately before administration.

Dosage

Adults

Heart Failure

Oral

Initially, 2.5 mg once daily.

Double the dose approximately every 2 weeks as tolerated to reach target maintenance dosage of 10 mg once daily.

Special Populations

Hepatic Impairment

No dosage recommendation. Not studied in patients with severe (Child Pugh class C) hepatic impairment.

Renal Impairment

No dosage recommendation. Not studied in patients with eGFR <15 mL/minute per 1.73 m²or on dialysis.

Geriatric Patients

No dosage adjustment required; however, greater sensitivity of some older patients cannot be ruled out.

Related/similar drugs

Verquvo

Cautions for Vericiguat

Contraindications

• Pregnancy.

• Concomitant therapy with other soluble guanylate cyclase stimulators.

Warnings/Precautions

Warnings

Embryo-fetal Toxicity

May cause fetal harm (see Boxed Warning); embryo-fetal toxicity demonstrated in animals.

Exclude pregnancy prior to initiation of therapy.

Apprise of potential fetal hazard; use effective contraception during and for ≥1 month after the final dose.

Specific Populations

Pregnancy

Based on data from animal studies, may cause embryo-fetal toxicity; contraindicated during pregnancy.

No data in pregnant women.

Exclude pregnancy prior to initiation of therapy.

Apprise of potential fetal hazard; use effective contraception during and for ≥1 month after the final dose.

Report any prenatal exposure to the Pregnancy Surveillance Program by calling 1-877-888-4231 or at [Web].

Lactation

Excreted into milk of lactating rats. No data on presence of vericiguat in human milk, effects on the breastfed infant, or effects on milk production.

Advise women not to breastfeed during treatment with vericiguat.

Females and Males of Reproductive Potential

Exclude pregnancy in females of childbearing potential prior to initiation. Apprise of potential fetal hazard; use effective contraception during and for ≥1 month after the final dose.

Pediatric Use

Safety and efficacy not established in pediatric patients.

Geriatric Use

No overall differences in safety or efficacy relative to younger patients.

Hepatic Impairment

Safety and efficacy not established in patients with severe hepatic impairment (Child-Pugh class C).

Renal Impairment

Safety and efficacy not established in patients with with eGFR <15 mL/minute per 1.73 m²at treatment initiation or on dialysis.

Common Adverse Effects

Most common adverse reactions (≥5%): hypotension, anemia.

Drug Interactions

Metabolized by UGT1A9 and 1A1.

Substrate of P-gp and BCRP.

Drugs Affecting Uridine Diphosphate Glucuronosyltransferase Enzymes

UGT1A9 inhibitor (i.e., mefenamic acid): No clinically siginificant difference on vericiguat pharmacokinetics.

UGT1A1 inhibitor (i.e., atazanavir): No clinically siginificant difference on vericiguat pharmacokinetics predicted.

Drugs Affecting Gastric Acidity

Less soluble at neutral than at acidic pH.

No clinically significant differences observed with coadministration of drugs that increase gastric pH (e.g., proton pump inhibitors, H₂-receptor antagonists, antacids) when vericiguat was taken with food.

Phosphodiesterase Type 5 Inhibitors

Not recommended due to potential for hypotension.

Soluble Guanylate Cyclase Stimulators

Contraindicated.

Vericiguat Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability 93% when taken with food.

Comparable results when tablet crushed and mixed with water.

Food

AUC and peak concentration increased.

Distribution

Protein Binding

98%; primarily albumin.

Elimination

Metabolism

Glucuronidation by uridine diphosphate glucuronosyltransferase; N-glucuronide metabolite inactive.

Elimination Route

Urine: 53%; primarily inactive metabolite.

Feces: 45%; primarily unchanged drug.

Half-life

Patients with heart failure: 30 hours.

Steady-state: approximately 6 days.

Special Populations

Exposure increased in patients with mild and moderate hepatic impairment (Child-Pugh class A and B) or mild, moderate, and severe renal impairment not requiring dialysis.

No clinically significant differences observed based on age, sex, race/ethnicity (Black, white, Asian, Hispanic, Latino), body weight, or baseline NT-proBNP.

Stability

Storage

Oral

Tablets

20–25°C (excursions permitted between 15–30°C).

Actions

• Soluble guanylate cyclase (sGC) is an important enzyme in the nitric oxide (NO) signaling pathway.

• NO binds to sGC and intracellular cGMP is synthesized to regulate vascular tone, cardiac contractility, and cardiac remodeling.

• Vericiguat promotes smooth muscle relaxation and vasodilation by directly stimulating sGC, independently of and synergistically with NO.

Advice to Patients

• Advise the patient to read the FDA-approved patient labeling (Medication Guide).

• If a dose is missed, advise patient it should be taken as soon as it is remembered on the same day of the missed dose. Patients should not take two doses of vericiguat on the same day.

• Advise pregnant women and females of reproductive potential of the potential risk to a fetus and to inform their healthcare provider of a known or suspected pregnancy. Advise females of reproductive potential to use effective contraception during treatment with vericiguat and for at least one month after the final dose.

• Advise women who are exposed to vericiguat during pregnancy to report the pregnancy to their healthcare provider. Health care providers should report any prenatal exposure to vericiguat by calling 1-877-888-4231 or at [Web].

• Advise women not to breastfeed during treatment with vericiguat.

• Advise patients that vericiguat tablets should be administered with food and swallowed whole.

• Advise patients unable to swallow a whole vericiguat tablet they may crush the tablet(s) and mix with water right before taking the dose.

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.

• Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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