Vericiguat (Monograph)

Brand name: Verquvo
Drug class: Vasodilating Agents, Miscellaneous
Chemical name: methyl N-[4,6-diamino-2-[5-fluoro-1-[(2-fluorophenyl)methyl]pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl]carbamate
Molecular formula: C₁₉H₁₆F₂N₈O₂
CAS number: 1350653-20-1

Medically reviewed by Drugs.com on Feb 13, 2023. Written by ASHP.

Introduction

Vericiguat, a soluble guanylate cyclase (sGC) stimulator, is a vasodilating agent.

Uses for Vericiguat

Vericiguat has the following uses:

Vericiguat is a soluble guanylate cyclase (sGC) stimulator, indicated to reduce the risk of cardiovascular death and heart failure (HF) hospitalization following a hospitalization for heart failure or need for outpatient IV diuretics, in adults with symptomatic chronic HF and ejection fraction less than 45%.

Vericiguat Dosage and Administration

General

Vericiguat is available in the following dosage form(s) and strength(s):

Tablets: 2.5 mg, 5 mg, and 10 mg.

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

• The recommended starting dose of vericiguat is 2.5 mg orally once daily with food.

• Double the dose of vericiguat approximately every 2 weeks to reach the target maintenance dose of 10 mg once daily, as tolerated by the patient.

• Tablets may be crushed and mixed with water for patients who have difficulty swallowing.

Cautions for Vericiguat

Contraindications

• Patients with concomitant use of other soluble guanylate cyclase (sGC) stimulators.

• Pregnancy.

Warnings/Precautions

Embryo-fetal Toxicity

Based on data from animal reproduction studies, vericiguat may cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential of the potential risk to a fetus. Obtain a pregnancy test before the start of treatment. Advise females of reproductive potential to use effective contraception during treatment with vericiguat and for at least one month after the final dose.

Specific Populations

Pregnancy

Risk Summary: Based on data from animal reproduction studies, vericiguat may cause fetal harm when administered to a pregnant woman and is contraindicated during pregnancy. There are no available data with vericiguat use in pregnant women. In animal reproduction studies, oral administration of vericiguat 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 pre/postnatal toxicity study, vericiguat administered orally to rats during gestation through lactation caused maternal toxicity, which resulted in decreased pup body weight gain (≥10 times the MRHD) and increased pup mortality (24 times the MRHD) during the preweaning period.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

If a patient becomes pregnant while receiving vericiguat, healthcare providers should report vericiguat exposure by calling 1-877-888-4231.

Animal Data: In an embryo-fetal development study in rabbits, vericiguat was administered orally to pregnant rabbits during the period of organogenesis from gestation day (GD) 6 to 20 at doses of 0.75, 2.5 or 7.5 mg/kg/day. An increased incidence of cardiac ventricular septal defect along with truncus arteriosus communis was observed at ≥2.5 mg/kg/day, which is ≥4 times the human exposure at the MRHD. Maternal toxicity (decreased food consumption and body weight loss), which may have resulted in late spontaneous abortions and resorptions was noted at ≥2.5 mg/kg/day (≥4 times the human exposure at the MRHD). There were no maternal toxicity or abortions/resorptions and no malformations of the heart and major vessels in rabbits at an exposure approximately equivalent to the human exposure at the MRHD.

In a prenatal developmental toxicity study in rats, vericiguat was administered orally to pregnant rats during the period of organogenesis from GD 6 to 17 at doses of 5, 15 or 50 mg/kg/day. No developmental toxicity was observed up to the highest dose (36 times the human exposure [total AUC] at the MRHD). Maternal toxicity (decreased body weight gain and food consumption) was observed at ≥15 mg/kg/day (≥10 times the human exposure at the MRHD). There was no maternal toxicity at 5 mg/kg/day (4 times the human exposure at the MRHD).

In a pre-postnatal development study in rats, vericiguat was administered orally at doses of 7.5, 15 or 30 mg/kg/day from GD 6 through lactation day 21. Maternal toxicity (decreases in food consumption and body weight gain) was observed at all dose levels ≥6 times the human exposure (total AUC) at the MRHD and resulted in decreased pup body weight gain at ≥15 mg/kg/day (≥10 times the human exposure at the MRHD) and pup mortality at 30 mg/kg/day (24 times the MHRD).

[¹⁴C]-vericiguat was administered orally to pregnant rats at a dose of 3 mg/kg. Vericiguat-related material was transferred across the placenta, with fetal plasma concentrations of approximately 67% maternal concentrations on GD 19.

Lactation

Risk Summary: There are no data on the presence of vericiguat in human milk, the effects on the breastfed infant, or the 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. Because of the potential for serious adverse reactions in breastfed infants from vericiguat, advise women not to breastfeed during treatment with vericiguat.

Data: [¹⁴C]-vericiguat was administered intravenously to lactating rats at a dose of 1 mg/kg. Vericiguat-related material was excreted into milk at concentrations approximately 12% maternal plasma concentrations on LD 8.

Females and Males of Reproductive Potential

Pregnancy Testing: Verify the pregnancy status in females of reproductive potential prior to initiating vericiguat.

Contraception for Females: Vericiguat may cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment and for one month after the final dose.

Pediatric Use

Safety and effectiveness of vericiguat have not been established in pediatric patients.

Geriatric Use

No dosage adjustment of vericiguat is required in geriatric patients. In VICTORIA, a total of 1,596 (63%) patients treated with vericiguat were 65 years and older, and 783 (31%) patients treated with vericiguat were 75 years and older. No overall differences in safety or efficacy of vericiguat were observed between patients aged 65 years and older compared to younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Renal Impairment

No dosage adjustment of vericiguat is recommended in patients with estimated glomerular filtration rate (eGFR) ≥15 mL/min/1.73m² who are not on dialysis. Vericiguat has not been studied in patients with eGFR <15 mL/min/1.73m² at treatment initiation or on dialysis.

Hepatic Impairment

No dosage adjustment of vericiguat is recommended in patients with mild or moderate hepatic impairment (e.g., Child-Pugh A or B). Vericiguat has not been studied in patients with severe hepatic impairment (e.g., Child-Pugh C).

Common Adverse Effects

Most common adverse reactions reported in ≥5% of patients receiving vericiguat are hypotension and anemia.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

• PDE-5 Inhibitors: Concomitant use is not recommended.

Actions

Mechanism of Action

Vericiguat is a stimulator of soluble guanylate cyclase (sGC), an important enzyme in the nitric oxide (NO) signaling pathway. When NO binds to sGC, the enzyme catalyzes the synthesis of intracellular cyclic guanosine monophosphate (cGMP), a second messenger that plays a role in the regulation of vascular tone, cardiac contractility, and cardiac remodeling. Heart failure is associated with impaired synthesis of NO and decreased activity of sGC, 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.

Advice to Patients

Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling.

If a dose is missed, it should be taken as soon as the patient remembers 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 one month after the final dose.

Advise women who are exposed to vericiguat during pregnancy to report their pregnancy to their healthcare provider.

Advise women not to breastfeed during treatment with vericiguat.

Additional Information

AHFSfirstRelease^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

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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