VERICIGUAT

Clinical safety rating: caution

Comprehensive clinical and safety monograph for VERICIGUAT (VERICIGUAT).

How it works

Vericiguat is a soluble guanylate cyclase (sGC) stimulator. It directly stimulates sGC, enhancing the sensitivity of sGC to endogenous nitric oxide (NO), thereby increasing cyclic guanosine monophosphate (cGMP) production. This leads to smooth muscle relaxation, vasodilation, and inhibition of vascular remodeling and fibrosis.

What the body does with it

Metabolism	Primarily metabolized by UGT1A9 and to a minor extent by CYP1A2, CYP2C8, CYP2C9, and CYP3A4.
Excretion	Vericiguat is eliminated primarily via non-renal routes, with approximately 53% of the dose recovered in feces and 40% in urine. Renal excretion of unchanged drug is minimal (<5% of the dose).
Half-life	The terminal elimination half-life is approximately 4-5 hours in patients with chronic heart failure, allowing twice-daily dosing. In severe renal impairment, half-life may be prolonged (up to 8 hours).
Protein binding	Approximately 95% bound to plasma proteins, mainly serum albumin.
Volume of Distribution	The volume of distribution is approximately 0.25 L/kg (18 L for a 70 kg individual), indicating distribution primarily in extracellular fluid and limited tissue binding.
Bioavailability	Absolute oral bioavailability is approximately 70-80% under fasting conditions. Food has no significant effect on bioavailability.
Onset of Action	Oral administration: Clinical effects, including reduction in NT-proBNP levels and improvement in exercise capacity, are observed within 1-2 weeks of starting therapy. Immediate pharmacodynamic effects on cyclic GMP signaling occur within hours.
Duration of Action	The duration of clinical effect after oral dosing is approximately 12 hours, supporting twice-daily administration. Continuous exposure is required for sustained reduction in hospitalization risk.

Classification & Brands

Dosing & administration

1.25 mg orally three times daily with food; increase in 1.25 mg increments every 2 weeks as tolerated to target maintenance dose of 2.5 mg three times daily.

Dosage form	TABLET
Renal impairment	No dose adjustment required for GFR ≥15 mL/min/1.73 m²; not recommended for GFR <15 mL/min/1.73 m² or on dialysis.
Liver impairment	Child-Pugh A and B: no dose adjustment required; Child-Pugh C: not recommended due to lack of data.
Pediatric use	Safety and efficacy not established; no dosing recommendations available.
Geriatric use	No specific dose adjustment recommended; monitor renal function due to age-related decline.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for VERICIGUAT (VERICIGUAT).

Breastfeeding	No data on presence in human milk, effects on breastfed infant, or milk production. Present in rat milk. M/P ratio unknown. Use caution; consider developmental and health benefits of breastfeeding along with mother's clinical need.
Teratogenic Risk	Based on animal studies, vericiguat is teratogenic in rats and rabbits at exposures 7 and 5 times the human exposure, respectively. There are no adequate human studies. Risk cannot be excluded in the first trimester. Second and third trimester risks include potential fetal harm due to pharmacodynamic effects; use only if benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

Do not use vericiguat with phosphodiesterase-5 (PDE-5) inhibitors (e.g., sildenafil, tadalafil) or other sGC stimulators. Concomitant use may cause severe hypotension.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Concomitant use with phosphodiesterase-5 (PDE-5) inhibitors (e.g., sildenafil, tadalafil).","Concomitant use with other soluble guanylate cyclase (sGC) stimulators.","Not recommended during pregnancy due to potential fetal harm."]

Clinical Precautions

Precautions

["Hypotension: Can cause symptomatic hypotension, especially in patients with pre-existing low blood pressure.","Bleeding risk: Use with caution in patients with severe bleeding or hemoptysis.","Fertility impairment: May impair spermatogenesis and fertility in males."]

Clinical Tips & Counseling

Drug interactions

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VERICIGUAT

Clinical safety rating: caution

Comprehensive clinical and safety monograph for VERICIGUAT (VERICIGUAT).

How it works

What the body does with it

Metabolism	Primarily metabolized by UGT1A9 and to a minor extent by CYP1A2, CYP2C8, CYP2C9, and CYP3A4.
Excretion	Vericiguat is eliminated primarily via non-renal routes, with approximately 53% of the dose recovered in feces and 40% in urine. Renal excretion of unchanged drug is minimal (<5% of the dose).
Half-life	The terminal elimination half-life is approximately 4-5 hours in patients with chronic heart failure, allowing twice-daily dosing. In severe renal impairment, half-life may be prolonged (up to 8 hours).
Protein binding	Approximately 95% bound to plasma proteins, mainly serum albumin.
Volume of Distribution	The volume of distribution is approximately 0.25 L/kg (18 L for a 70 kg individual), indicating distribution primarily in extracellular fluid and limited tissue binding.
Bioavailability	Absolute oral bioavailability is approximately 70-80% under fasting conditions. Food has no significant effect on bioavailability.
Onset of Action	Oral administration: Clinical effects, including reduction in NT-proBNP levels and improvement in exercise capacity, are observed within 1-2 weeks of starting therapy. Immediate pharmacodynamic effects on cyclic GMP signaling occur within hours.
Duration of Action	The duration of clinical effect after oral dosing is approximately 12 hours, supporting twice-daily administration. Continuous exposure is required for sustained reduction in hospitalization risk.

Classification & Brands

Dosing & administration

1.25 mg orally three times daily with food; increase in 1.25 mg increments every 2 weeks as tolerated to target maintenance dose of 2.5 mg three times daily.

Dosage form	TABLET
Renal impairment	No dose adjustment required for GFR ≥15 mL/min/1.73 m²; not recommended for GFR <15 mL/min/1.73 m² or on dialysis.
Liver impairment	Child-Pugh A and B: no dose adjustment required; Child-Pugh C: not recommended due to lack of data.
Pediatric use	Safety and efficacy not established; no dosing recommendations available.
Geriatric use	No specific dose adjustment recommended; monitor renal function due to age-related decline.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for VERICIGUAT (VERICIGUAT).

Breastfeeding	No data on presence in human milk, effects on breastfed infant, or milk production. Present in rat milk. M/P ratio unknown. Use caution; consider developmental and health benefits of breastfeeding along with mother's clinical need.
Teratogenic Risk	Based on animal studies, vericiguat is teratogenic in rats and rabbits at exposures 7 and 5 times the human exposure, respectively. There are no adequate human studies. Risk cannot be excluded in the first trimester. Second and third trimester risks include potential fetal harm due to pharmacodynamic effects; use only if benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

Do not use vericiguat with phosphodiesterase-5 (PDE-5) inhibitors (e.g., sildenafil, tadalafil) or other sGC stimulators. Concomitant use may cause severe hypotension.