Corazon

• Chronic Heart Failure with Reduced Ejection Fraction (HFrEF):
  Vericiguat is indicated to reduce the risk of cardiovascular death and heart failure hospitalization in adult patients with symptomatic chronic heart failure (NYHA Class II-IV) and an ejection fraction less than 45%, who have recently experienced worsening heart failure (e.g., hospitalization or need for intravenous diuretics).
• Off-label (Clinically Accepted):
  Use in other types of heart failure or earlier NYHA classes is not approved but may be considered investigational.

• Dosage Form: Oral tablets.
• Initial Dose: 2.5 mg once daily with food.
• Titration: Dose may be doubled every 2 weeks as tolerated to 5 mg, then 10 mg once daily (target maintenance dose).
• Maximum Dose: 10 mg once daily.
• Administration: Taken orally with food to improve absorption.
• Special Populations:
• Renal impairment: Use caution in severe impairment (eGFR <15 mL/min/1.73 m²); no dosage adjustment required for mild to moderate impairment.
• Hepatic impairment: Use caution in moderate impairment; not recommended in severe impairment.
• Elderly: No dose adjustment required.
• Duration: Long-term maintenance therapy.

Vericiguat is a soluble guanylate cyclase (sGC) stimulator. It sensitizes sGC to endogenous nitric oxide (NO) and directly stimulates sGC independently of NO, leading to increased cyclic guanosine monophosphate (cGMP) production. Elevated cGMP levels induce vasodilation, reduce cardiac remodeling, and improve myocardial function by enhancing myocardial relaxation and reducing cardiac fibrosis and hypertrophy. This mechanism improves hemodynamics and reduces the progression of heart failure symptoms.

• Absorption: Rapidly absorbed with peak plasma concentrations reached within 1 hour post-dose.
• Bioavailability: Approximately 93% when taken with food.
• Distribution: Volume of distribution ~57 L. Plasma protein binding ~98%.
• Metabolism: Mainly metabolized via phase II glucuronidation by UGT1A9 and UGT1A1 enzymes, minor involvement of CYP450 enzymes (mainly CYP1A1).
• Half-life: Approximately 30 hours.
• Excretion: Primarily excreted via urine (53%) and feces (45%) as metabolites.

• Pregnancy: No adequate human data. Animal studies show potential risk at high doses; use only if benefits outweigh risks. No FDA pregnancy category assigned (new labeling format).
• Lactation: Unknown if excreted in human milk; caution advised.
• Recommendation: Avoid use during pregnancy and breastfeeding unless clearly necessary.

• Primary Class: Soluble guanylate cyclase stimulator.
• Therapeutic Use: Treatment of chronic heart failure with reduced ejection fraction.

• Known hypersensitivity to vericiguat or any excipients.
• Concurrent use with nitrates or nitric oxide donors due to risk of hypotension.
• Use with phosphodiesterase-5 (PDE5) inhibitors contraindicated (e.g., sildenafil).
• Severe hepatic impairment (Child-Pugh Class C).

• Hypotension risk: Monitor blood pressure closely, especially in patients with low baseline blood pressure or volume depletion.
• Avoid use with PDE5 inhibitors or nitrates to prevent profound hypotension.
• Anemia: Monitor hemoglobin periodically as mild anemia has been observed.
• Renal function: Use cautiously in severe renal impairment.
• Pregnancy: Use only if benefit outweighs risk.

• Common:
• Hypotension
• Dizziness
• Headache
• Fatigue
• Nausea
• Serious but rare:
• Syncope
• Anemia
• Heart failure exacerbation (monitor clinical status)
• Side effects are usually mild to moderate and tend to appear early in therapy.

• Nitrates and Nitric Oxide Donors: Contraindicated; may cause severe hypotension.
• PDE5 Inhibitors (e.g., sildenafil): Contraindicated due to additive vasodilatory effects.
• UGT Enzyme Modulators: Drugs altering UGT1A9 or UGT1A1 activity may affect vericiguat metabolism.
• Antihypertensives: Additive blood pressure-lowering effects; monitor carefully.
• Diuretics: Monitor volume status and electrolytes due to risk of hypotension.

• The 2023 ACC/AHA/HFSA Guidelines recognize vericiguat as an option for reducing hospitalization and mortality in patients with worsening HFrEF despite standard therapy.
• No recent FDA safety warnings or dosage changes reported.
• Recommended as an adjunct to guideline-directed medical therapy (GDMT) in selected patients with HFrEF.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep tablets in original packaging until use.
• Avoid freezing or excessive heat.
• Keep out of reach of children.