VERICIGUAT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VERICIGUAT (VERICIGUAT).
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.
| 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. |
| Molecular Weight | 426.46 |
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. |
| 1st trimester | Teratogenic in animal studies; avoid use due to risk of fetal harm. |
| 2nd trimester | Limited human data; potential for fetal harm based on animal studies and mechanism of action (vasodilation). Avoid use. |
| 3rd trimester | May cause uterine relaxation and fetal hypotension; avoid use, especially near term. |
Clinical note
Comprehensive clinical and safety monograph for VERICIGUAT (VERICIGUAT).
| Placental transfer | Maternal-fetal transfer expected based on molecular weight (<400 Da) and lipophilicity; animal studies demonstrate placental passage. |
| Breastfeeding | No human data on presence in breast milk; based on molecular weight and animal studies, likely present. Risk of infant hypotension and gastrointestinal effects. Not recommended during breastfeeding. |
■ 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.
| Serious Effects |
Concomitant use with PDE-5 inhibitors (e.g., sildenafil)Concomitant use with soluble guanylate cyclase stimulators (e.g., riociguat)Pregnancy
| 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. |
| Food/Dietary | Take with food to reduce risk of hypotension. No specific dietary restrictions; avoid grapefruit juice as it may alter drug metabolism. |
Loading safety data…
| Lactation Rating |
| L5 - Contraindicated |
| 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. |
| Fetal Monitoring | Monitor maternal blood pressure and heart rate regularly. Assess for symptomatic hypotension, syncope, or bleeding. Fetal monitoring via ultrasound for growth and wellbeing if used during pregnancy. Monitor for fetal distress in third trimester. |
| Fertility Effects | In animal studies, vericiguat did not impair fertility in male or female rats at exposures up to 7 times human exposure. No human data available. |
| Clinical Pearls | Vericiguat is a soluble guanylate cyclase stimulator used for heart failure with reduced ejection fraction (HFrEF) after recent decompensation. Monitor for hypotension and syncope, especially in elderly or volume-depleted patients. Avoid use with PDE-5 inhibitors (e.g., sildenafil) due to risk of severe hypotension. Dose adjustment required for severe renal impairment (eGFR <15 mL/min/1.73 m²). Not recommended in patients with systolic BP <100 mmHg. |
| Patient Advice | Take vericiguat exactly as prescribed, typically once daily with food. · Avoid taking sildenafil, tadalafil, or other PDE-5 inhibitors while on this medication. · Report symptoms of low blood pressure such as dizziness, lightheadedness, or fainting. · Do not stop or change dose without consulting your doctor. · Inform all healthcare providers that you are taking vericiguat. · Store at room temperature away from moisture and heat. |