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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for VERQUVO (VERQUVO).
| Breastfeeding | No data on vericiguat in human milk. In lactating rats, vericiguat or its metabolites were excreted in milk. M/P ratio not established for humans. Due to potential for serious adverse reactions in nursing infants (e.g., hypotension), advise against breastfeeding during therapy and for 1 month after last dose. |
| 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. |
■ 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 (sGC) stimulators. Concomitant use with phosphodiesterase-5 (PDE-5) inhibitors in patients with pulmonary arterial hypertension (PAH).
| 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. |
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| 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. |