VERQUVO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VERQUVO (VERQUVO).
Vericiguat stimulates soluble guanylate cyclase (sGC) directly and independently of nitric oxide (NO), increasing cyclic guanosine monophosphate (cGMP) production, leading to smooth muscle relaxation, vasodilation, and inhibition of platelet aggregation and vascular remodeling.
| Metabolism | Vericiguat is primarily metabolized by UGT1A1 and UGT1A9 to its major inactive glucuronide metabolite (M-1), with minor contributions from CYP1A2, CYP2C8, CYP2C9, and CYP3A4. |
| Excretion | Renal elimination accounts for approximately 70% of total clearance, with 30% excreted unchanged in urine; biliary/fecal elimination accounts for ~30% primarily as metabolites. |
| Half-life | Terminal elimination half-life is approximately 22 hours (range 18-26 h), supporting once-daily dosing. Steady-state reached within 5 days. |
| Protein binding | Approximately 98% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution at steady state is approximately 30 L (0.4 L/kg for a 70-kg individual), indicating extensive extravascular distribution. |
| Bioavailability | Absolute oral bioavailability is approximately 93% (range 80-100%), with food not significantly affecting absorption. |
| Onset of Action | Oral administration: Onset of symptomatic improvement in heart failure (e.g., dyspnea, edema) observed within 2-4 weeks; hemodynamic effects (reduction in NT-proBNP) seen as early as 1 week. |
| Duration of Action | Duration of clinical effect persists throughout the 24-hour dosing interval; consistent hemodynamic and functional improvement maintained with continuous therapy. |
| Molecular Weight | 426.5 Da |
Initial: 10 mg orally once daily; after 2 weeks, titrate to 20 mg once daily, then to 40 mg once daily as tolerated. Maximum: 40 mg once daily.
| Dosage form | TABLET |
| Renal impairment | eGFR >= 30 mL/min/1.73 m²: no adjustment; eGFR 15 to <30 mL/min/1.73 m²: avoid use due to limited data; eGFR <15 mL/min/1.73 m²: contraindicated. |
| Liver impairment | Child-Pugh A or B: no adjustment; Child-Pugh C: contraindicated. |
| Pediatric use | Safety and efficacy not established in pediatric patients; no dosing recommendations available. |
| Geriatric use | No specific dose adjustment; consider lower starting dose (10 mg) and cautious titration due to increased risk of hypotension and electrolyte disturbances; monitor renal function closely. |
| 1st trimester | Vericiguat is not recommended in first trimester due to potential fetal harm; animal studies show embryotoxicity and teratogenicity at supratherapeutic doses. |
| 2nd trimester | Avoid use in second trimester; inadequate human data and animal toxicities suggest risk of fetotoxicity. |
| 3rd trimester | Avoid use in third trimester; may cause fetal hypotension and renal impairment; use only if maternal benefit outweighs fetal risk. |
Clinical note
Comprehensive clinical and safety monograph for VERQUVO (VERQUVO).
| Placental transfer | Vericiguat and its active metabolite cross the placenta in animal studies; human transfer is expected given its molecular properties, but quantitative data are lacking. |
| Breastfeeding | No human data on excretion in breast milk; vericiguat is highly protein-bound and has high molecular weight, likely minimal transfer; however, due to potential adverse effects in nursing infants, breastfeeding is not recommended during therapy and for 1 month after last dose. |
■ FDA Black Box Warning
Vericiguat is contraindicated in patients with concomitant use of other soluble guanylate cyclase (sGC) stimulators. Vericiguat is contraindicated in patients with pulmonary arterial hypertension (PAH) who are treated with phosphodiesterase-5 (PDE-5) inhibitors. Use of vericiguat with PDE-5 inhibitors is contraindicated due to the potential for hypotension.
| Serious Effects |
Concomitant use with other soluble guanylate cyclase stimulators (e.g., riociguat)Severe hypotension (systolic BP <100 mmHg)Severe hepatic impairment (Child-Pugh C)History of hypersensitivity to vericiguat or any component
| Precautions | Embryo-fetal toxicity: Vericiguat may cause fetal harm when administered to pregnant women. Females of reproductive potential should use effective contraception. Hypotension: Vericiguat can cause hypotension. Monitor blood pressure. Risk of bleeding: Vericiguat may increase the risk of bleeding events. |
| Food/Dietary | No specific food interactions. VERQUVO can be taken with or without food. Avoid grapefruit juice if concurrent medications are sensitive to CYP3A4? Vericiguat is not a CYP3A4 substrate; no significant food interactions reported. |
Loading safety data…
| Lactation Rating | L4 - Possibly Hazardous |
| Teratogenic Risk | FDA Pregnancy Category C. Based on animal studies, vericiguat may cause fetal harm. There are no adequate and well-controlled studies in pregnant women. In rats and rabbits, vericiguat was associated with decreased fetal body weight and increased incidence of cardiovascular and skeletal malformations at exposures below the maximum recommended human dose. First trimester: potential risk of major malformations. Second and third trimesters: potential risk of fetal toxicity (growth restriction, oligohydramnios) due to maternal hypotension. Avoid use unless potential benefit justifies potential risk. |
| Fetal Monitoring | Monitor maternal blood pressure closely for hypotension. Assess fetal growth and amniotic fluid volume via ultrasound if used in second/third trimester. Monitor for signs of fetal distress. No specific fetal drug level monitoring recommended. |
| Fertility Effects | No human data on fertility effects. In animal studies, vericiguat did not impair male or female fertility at exposures up to 7 times the human exposure. However, theoretical risk due to potential hemodynamic effects on reproductive organs. |
| Clinical Pearls | VERQUVO (vericiguat) is indicated to reduce the risk of cardiovascular death and heart failure hospitalization following a hospitalization for heart failure or need for outpatient IV diuretics, in patients with symptomatic chronic HF and LVEF <45%. Initiate at 2.5 mg once daily, double every 2 weeks to target maintenance dose of 10 mg once daily. Avoid use with other soluble guanylate cyclase stimulators (e.g., riociguat). Monitor for hypotension, especially when co-administered with antihypertensives. Do not use in patients with concomitant PDE-5 inhibitors (e.g., sildenafil) due to risk of severe hypotension. Contraindicated in patients with concomitant nitrate therapy. |
| Patient Advice | Take VERQUVO exactly as prescribed, once daily with or without food. · Do not take VERQUVO with other heart failure medications called guanylate cyclase stimulators (e.g., riociguat). · Avoid taking VERQUVO with nitrates (e.g., nitroglycerin) or PDE-5 inhibitors (e.g., sildenafil, tadalafil) as this can cause a dangerous drop in blood pressure. · Inform your doctor if you experience dizziness, fainting, or low blood pressure symptoms. · Do not stop taking VERQUVO without consulting your healthcare provider. · Store at room temperature, away from moisture and heat. |