Vericiguat

Vericiguat
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Kosar Doraghi, M.D.[2]

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Black Box Warning

WARNING: EMBRYO-FETAL TOXICITY See full prescribing information for complete Boxed Warning. Do not administer VERQUVO to a pregnant female because it may cause fetal harm. Females of reproductive potential: Exclude pregnancy before the start of treatment. To prevent pregnancy, females of reproductive potential must use effective forms of contraception during treatment and for one month after stopping treatment

Overview

Vericiguat is a soluble guanylate cyclase (sGC) stimulator that is FDA approved for the treatment of heart failure with reduced ejection fraction (HFrEF), 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%. There is a Black Box Warning for this drug as shown here. Common adverse reactions include hypotension and anemia.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

• Start VERQUVO at a recommended dose of 2.5 mg orally once daily with food.
• Double the dose approximately every 2 weeks until reaching the target maintenance dose of 10 mg once daily, as tolerated by the patient.
• For patients who have difficulty swallowing, tablets can be crushed and mixed with water.

Off-Label Use and Dosage (Adult)

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding Vericiguat FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

Off-Label Use and Dosage (Pediatric)

Contraindications

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

• Pregnancy

Warnings

WARNING: EMBRYO-FETAL TOXICITY See full prescribing information for complete Boxed Warning. Do not administer VERQUVO to a pregnant female because it may cause fetal harm. Females of reproductive potential: Exclude pregnancy before the start of treatment. To prevent pregnancy, females of reproductive potential must use effective forms of contraception during treatment and for one month after stopping treatment

• VERQUVO may pose a risk of embryo-fetal toxicity when administered to pregnant women, based on animal reproduction studies.
• Females of reproductive potential should be informed about this potential risk to a fetus.
• A pregnancy test should be obtained before initiating treatment with VERQUVO.
• Females of reproductive potential should use effective contraception during VERQUVO treatment and for at least one month after the final dose.

Adverse Reactions

Clinical Trials Experience

• low blood pressure
• low red blood cells (anemia)

Postmarketing Experience

There is limited information regarding Vericiguat Postmarketing Experience in the drug label.

Drug Interactions

• PDE-5 Inhibitors: Concomitant use is not recommended

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): may cause fetal harm when administered to a pregnant woman and is contraindicated during pregnancy
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Vericiguat in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Vericiguat during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Vericiguat in women who are nursing.

Pediatric Use

There is no FDA guidance on the use of Vericiguat in pediatric settings.

Geriatic Use

• No dosage adjustment of VERQUVO is needed in geriatric patients.
• In the VICTORIA trial, 63% of patients treated with VERQUVO were aged 65 years and older, and 31% were aged 75 years and older.
• While no significant differences in safety or efficacy were observed between older and younger patients, the potential for greater sensitivity in some older individuals cannot be ruled out.

Gender

There is no FDA guidance on the use of Vericiguat with respect to specific gender populations.

Race

There is no FDA guidance on the use of Vericiguat with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Vericiguat in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Vericiguat in patients with hepatic impairment.

Females of Reproductive Potential and Males

Verify the pregnancy status in females of reproductive potential prior to initiating VERQUVO

• females of reproductive potential to use effective contraception during treatment and for one month after the final dose

Immunocompromised Patients

There is no FDA guidance one the use of Vericiguat in patients who are immunocompromised.

Administration and Monitoring

Administration

• VERQUVO 2.5 mg: round, biconvex, white film-coated tablets with "2.5" on one side and "VC" on the other side.
• VERQUVO 5 mg: round, biconvex, brown-red film-coated tablets with "5" on one side and "VC" on the other side.
• VERQUVO 10 mg: round, biconvex, yellow-orange film-coated tablets with "10" on one side and "VC" on the other side.

Monitoring

There is limited information regarding Vericiguat Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Vericiguat and IV administrations.

Overdosage

There is limited information regarding Vericiguat overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

There is limited information regarding Vericiguat Pharmacology in the drug label.

Mechanism of Action

Vericiguat acts as a stimulator of soluble guanylate cyclase (sGC), a crucial enzyme in the nitric oxide (NO) signaling pathway. In this pathway, when NO binds to sGC, the enzyme triggers the production of cyclic guanosine monophosphate (cGMP), an intracellular second messenger that regulates vascular tone, cardiac contractility, and cardiac remodeling. Heart failure is often linked with reduced NO synthesis and sGC activity, which can contribute to dysfunction in the myocardium and vasculature. Vericiguat directly stimulates sGC, augmenting intracellular cGMP levels independently and synergistically with NO. This mechanism leads to smooth muscle relaxation and vasodilation, thereby addressing aspects of heart failure pathophysiology.

Structure

VERQUVO tablets contains vericiguat, a soluble guanylate cyclase stimulator. The chemical name of vericiguat is methyl 4,6-diamino-2-5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo 3,4-b pyridin-3-yl pyrimidin-5-yl carbamate. The molecular formula is C19H16F2N8O2 and the molecular weight is 426.39 g/mol.

Pharmacodynamics

• Blood Pressure Effects: VERQUVO led to a slightly greater reduction in systolic blood pressure compared to placebo.
• NT-proBNP Reduction: VERQUVO demonstrated dose-dependent reduction in NT-proBNP, a heart failure biomarker, compared to placebo when added to standard care.
• Cardiac Electrophysiology: Vericiguat showed no pro-arrhythmic risk or inhibition of cardiac ion channels at recommended doses, indicating no clinically meaningful QTc prolongation.
• Drug Interactions:
• No significant differences in bleeding time or platelet aggregation were observed with aspirin.
• No significant changes in prothrombin time or coagulation factor activities were seen with warfarin.
• VERQUVO did not significantly affect blood pressure when used with sacubitril/valsartan or nitrates.
• Concomitant use with sildenafil led to additional blood pressure reduction, but limited data exists on its combination with PDE-5 inhibitors in heart failure patients.

Pharmacokinetics

• Vericiguat steady-state pharmacokinetics show mean Cmax of 350 mcg/L (29%) and AUC of 6,680 mcg•h/L (33.9%) following VERQUVO 10 mg administration in heart failure patients, increasing slightly less than dose-proportionally.
• Plasma vericiguat accumulates up to 155-171% and reaches steady-state in about 6 days.
• Vericiguat has 93% absolute bioavailability when taken with food, with comparable results regardless of tablet administration method.
• Food intake delays Tmax to about 4 hours, reduces pharmacokinetic variability, and increases AUC by 44% and Cmax by 41% compared to fasting.
• The mean steady-state volume of distribution is approximately 44 L, with 98% protein binding to serum albumin.
• Vericiguat has a half-life of 30 hours in heart failure patients, with clearance of 1.6 L/h in healthy subjects.
• Primary metabolism occurs through glucuronidation by UGT1A9 and, to a lesser extent, by UGT1A1, with minor clearance via CYP-mediated pathways.
• Following oral administration, approximately 53% of vericiguat is excreted in urine (primarily as inactive metabolite) and 45% in feces (mostly unchanged drug).
• Drugs that increase gastric pH, such as proton pump inhibitors or antacids, can decrease vericiguat exposure by approximately 30% when taken on an empty stomach. However, this effect is mitigated when vericiguat is taken with food.
• Co-administration of mefenamic acid, ketoconazole, rifampin, digoxin, warfarin, aspirin, sildenafil, or sacubitril/valsartan did not significantly affect vericiguat pharmacokinetics in healthy subjects.
• Similarly, vericiguat did not significantly alter the pharmacokinetics of midazolam, digoxin, warfarin, sildenafil, or sacubitril/valsartan when co-administered with these drugs in healthy subjects.

Nonclinical Toxicology

• Carcinogenicity studies conducted in mice and rats did not indicate a carcinogenic effect of vericiguat.
• In mice, doses up to 150 mg/kg/day (males) or 250 mg/kg/day (females) did not show carcinogenic effects, with exposures 41 times (males) or 78 times (females) the human exposure at the maximum recommended human dose (MRHD) of 10 mg/day.
• Similarly, in rats, doses up to 20 mg/kg/day did not result in vericiguat-related tumor or hyperplastic findings, with exposures of 16 (males) and 21 times (females) the human exposure at the MRHD.

Clinical Studies

• The VICTORIA trial was a double-blind, placebo-controlled study involving 5,050 adult patients with symptomatic chronic heart failure (NYHA class II-IV) and reduced ejection fraction (<45%) following a recent heart failure event.
• Patients were randomized to receive VERQUVO 10 mg or placebo, with dosage adjustments based on tolerability.
• The primary endpoint was a composite of cardiovascular death or heart failure hospitalization, with a median follow-up of 11 months.
• The study population was diverse, with most patients being Caucasian, male, and with a mean age of 67 years.
• At baseline, patients had a high burden of comorbidities, including hypertension, coronary artery disease, and diabetes mellitus.
• The majority of patients were on multiple heart failure medications, including beta-blockers, ACE inhibitors/ARBs, and MRAs.
• VERQUVO demonstrated superiority over placebo in reducing the risk of cardiovascular death or heart failure hospitalization, with a 4.2% annualized absolute risk reduction. This effect was driven by reductions in both cardiovascular death and heart failure hospitalization.

The Kaplan-Meier curve shows time to first occurrence of the primary composite endpoint of CV death or heart failure hospitalization.

• Secondary endpoints in the VICTORIA trial, other than the primary composite endpoint, were evaluated using a hierarchical testing approach to manage the family-wise type I error rate.
• VERQUVO demonstrated superiority over placebo in reducing the risk of total (first and recurrent) events of heart failure hospitalization.
• Additionally, VERQUVO was effective in reducing the risk of the first occurrence of either all-cause mortality or heart failure hospitalization compared to placebo.

How Supplied

VERQUVO (vericiguat) is available as round, film-coated, biconvex tablets in the following configurations:

10 blister cards of 10 tablets

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (between 59°F to 86°F). See USP for Controlled Room Temperature.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

• Females must not be pregnant when starting VERQUVO, and a pregnancy test is required before treatment initiation.
• Effective forms of birth control must be used during VERQUVO treatment and for one month after discontinuation.
• Patients should promptly notify their healthcare provider if they become pregnant during VERQUVO treatment.
• There is a Pregnancy Surveillance Program for monitoring pregnancy outcomes in women exposed to VERQUVO during pregnancy.
• VERQUVO is prescribed for adults with chronic heart failure and reduced ejection fraction (less than 45%), following recent hospitalization or intravenous medication, to reduce the risk of death and hospitalization.
• Prior to taking VERQUVO, inform your healthcare provider about all medical conditions, including breastfeeding or plans to breastfeed, as VERQUVO's passage into breast milk is unknown.
• Discuss feeding options for your baby with your healthcare provider if you are taking VERQUVO and breastfeeding.
• Inform your healthcare provider about all medications, including prescriptions, over-the-counter drugs, vitamins, and herbal supplements, as certain medications may interact with VERQUVO.
• Take VERQUVO exactly as prescribed by your healthcare provider, typically once daily with food.
• Swallow VERQUVO tablets whole; if unable to swallow, they may be crushed and mixed with water just before ingestion.
• Your healthcare provider may adjust your dose initially to determine the most suitable dosage and assess your tolerance.
• If you miss a dose, take it as soon as remembered on the same day. Do not take two doses to compensate for a missed one.
• In case of overdose, contact your healthcare provider or seek emergency medical assistance immediately.

Verquvo ®

(vericiguat) tablets

5 mg

Dispense the accompanying Medication Guide to each patient.

Each tablet contains 5 mg vericiguat.

Rx only

30 Tablets

Precautions with Alcohol

Alcohol-Vericiguat interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Vericiguat Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Vericiguat Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.