Usage
- Vericiguat is prescribed to reduce the risk of cardiovascular death and heart failure (HF) hospitalization in adults with symptomatic chronic heart failure and reduced ejection fraction (less than 45%) following a hospitalization for heart failure or need for outpatient IV diuretics. It’s used in conjunction with other heart failure therapies.
- Pharmacological Classification: Soluble guanylate cyclase (sGC) stimulator.
- Mechanism of Action: Vericiguat directly stimulates sGC, enhancing the production of cyclic guanosine monophosphate (cGMP). This leads to vasodilation and smooth muscle relaxation, improving cardiac function.
Alternate Names
How It Works
- Pharmacodynamics: Vericiguat directly stimulates soluble guanylate cyclase (sGC), independent of and synergistically with nitric oxide (NO). Increased cGMP production causes smooth muscle relaxation and vasodilation, reducing cardiac workload.
- Pharmacokinetics:
- Absorption: Oral administration, preferably with food.
- Metabolism: Primarily hepatic, mainly by glucuronidation via UGT1A9 and UGT1A1.
- Elimination: Multiple routes, including renal and fecal excretion.
Dosage
Standard Dosage
Adults:
- Initial: 2.5 mg orally once daily with food.
- Maintenance: Double the dose approximately every 2 weeks, as tolerated, to a target maintenance dose of 10 mg orally once daily.
Children:
- Safety and efficacy not established.
Special Cases:
- Elderly Patients (≥65 years): No dosage adjustment needed.
- Patients with Renal Impairment (eGFR ≥15 mL/min/1.73 m2 and not on dialysis): No dosage adjustment needed. Not recommended for patients with eGFR <15 mL/min/1.73 m2 or on dialysis.
- Patients with Hepatic Dysfunction (Mild or Moderate): No dosage adjustment needed. Not recommended for patients with severe hepatic impairment (Child-Pugh C).
- Patients with Comorbid Conditions: Dose adjustments may be necessary based on individual patient characteristics and concomitant medications. Close monitoring of blood pressure is recommended, especially in patients with hypotension or taking antihypertensives.
Clinical Use Cases
Vericiguat is not specifically indicated for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations like status epilepticus or cardiac arrest. Its primary use is for chronic heart failure management in the outpatient setting.
Dosage Adjustments
- If symptomatic hypotension (SBP<90 mmHg) occurs, consider dose reduction or discontinuation.
- No adjustments are recommended based on renal or hepatic impairment (except severe) or geriatric population.
Side Effects
Common Side Effects
Rare but Serious Side Effects
- Symptomatic hypotension or syncope
Long-Term Effects
- Unknown at this time, as vericiguat is a relatively new medication. Long-term monitoring is crucial.
Adverse Drug Reactions (ADR)
Contraindications
- Pregnancy
- Concomitant use of other sGC stimulators
Drug Interactions
- PDE5 inhibitors (e.g., sildenafil): Not recommended due to increased risk of hypotension.
- Antihypertensives: May increase risk of hypotension.
- Long-acting nitrates: Potential for increased hypotension.
- Strong CYP3A4 inducers (e.g., rifampin): Caution advised.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Contraindicated in pregnancy. Vericiguat can cause fetal harm. Females of reproductive potential should have a negative pregnancy test before starting treatment and use effective contraception during and for one month after treatment.
- Breastfeeding: Not recommended as vericiguat may be present in breast milk and could cause adverse effects in infants.
Drug Profile Summary
- Mechanism of Action: Stimulates sGC, increasing cGMP, leading to vasodilation.
- Side Effects: Hypotension, anemia.
- Contraindications: Pregnancy, concomitant sGC stimulators.
- Drug Interactions: PDE5 inhibitors, antihypertensives.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy and not recommended while breastfeeding.
- Dosage: Initial: 2.5 mg daily, titrate to 10 mg daily as tolerated.
- Monitoring Parameters: Blood pressure, hemoglobin.
Popular Combinations
- Vericiguat is often combined with standard heart failure therapies like beta-blockers, ACE inhibitors/ARBs/ARNIs, and MRAs.
Precautions
- General Precautions: Monitor blood pressure, especially during dose titration. Assess for anemia.
- Specific Populations:
- Pregnant Women: Contraindicated.
- Breastfeeding Mothers: Not recommended.
- Children & Elderly: No dose adjustments needed for elderly; not established for children.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Vericiguat?
A: The starting dose is 2.5 mg orally once daily, taken with food. The dose is doubled every 2 weeks, as tolerated, up to a maximum of 10 mg once daily.
Q2: What is the mechanism of action of Vericiguat?
A: Vericiguat is a soluble guanylate cyclase stimulator that works by increasing intracellular cGMP, leading to vasodilation and a reduction in cardiac workload.
Q3: What are the common side effects of Vericiguat?
A: The most common side effects include hypotension and anemia.
Q4: Is Vericiguat safe to use during pregnancy?
A: No, Vericiguat is contraindicated in pregnancy as it can cause fetal harm.
Q5: What are the contraindications for Vericiguat?
A: Contraindications include pregnancy and concomitant use of other sGC stimulators.
Q6: How should Vericiguat be administered?
A: Vericiguat is administered orally once daily with food. Tablets may be crushed and mixed with water for patients who have difficulty swallowing.
Q7: Does Vericiguat require dose adjustments in elderly patients?
A: No, dose adjustments are generally not needed in elderly patients.
Q8: Are there any drug interactions with Vericiguat?
A: Yes, concomitant use of PDE5 inhibitors (like sildenafil) is not recommended due to increased risk of hypotension. Caution is advised when co-administering with other antihypertensives or long-acting nitrates.
Q9: What should be monitored in patients taking Vericiguat?
A: Blood pressure, particularly during dose titration, and hemoglobin levels should be monitored.
Q10: What if a patient misses a dose of Vericiguat?
A: The patient should take the missed dose as soon as possible on the same day. They should not double up on doses.
