Do we titrate Verquvo (Vericiguat) up to 10 mg?

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Verquvo (Vericiguat) Titration to 10 mg

Yes, titrate Verquvo up to the target maintenance dose of 10 mg once daily, doubling the dose approximately every 2 weeks as tolerated by the patient. 1

Standard Titration Protocol

The FDA-approved dosing regimen for Verquvo is straightforward and should be followed systematically 1:

  • Starting dose: 2.5 mg orally once daily with food 1
  • Titration schedule: Double the dose approximately every 2 weeks 1
    • Week 0-2: 2.5 mg once daily
    • Week 2-4: 5 mg once daily
    • Week 4+: 10 mg once daily (target maintenance dose)
  • Target dose: 10 mg once daily 1

This titration strategy was validated in the VICTORIA trial, which demonstrated that vericiguat 10 mg once daily reduced the composite endpoint of cardiovascular death or heart failure hospitalization (hazard ratio 0.90; 95% CI 0.82-0.98; P=0.02) compared to placebo 2.

Tolerability Considerations

The phrase "as tolerated by the patient" in the FDA label means you should slow or pause titration only if specific adverse effects occur 1:

Primary Concerns During Titration

  • Hypotension: Occurred in 16% of patients on vericiguat vs 15% on placebo in VICTORIA 1

    • Monitor blood pressure at each dose escalation
    • If symptomatic hypotension develops, consider holding the current dose until symptoms resolve before attempting further titration
  • Anemia: Occurred in 10% of patients on vericiguat vs 7% on placebo 1

    • Monitor hemoglobin periodically during titration

Reassuring Safety Data

Vericiguat demonstrated excellent tolerability in phase I studies with doses up to 10 mg, with no serious adverse events or deaths reported 3. The 10 mg dose was well tolerated in patients with chronic coronary syndromes without clinically relevant QT prolongation 4. Discontinuation rates were low across all dose levels in clinical trials 5.

Clinical Context for 10 mg Target

The 10 mg dose is the evidence-based target that demonstrated clinical benefit in the pivotal VICTORIA trial 2. This trial specifically enrolled high-risk patients with:

  • Recent heart failure hospitalization (75% of patients) or outpatient IV diuretic use (25%) 2
  • Ejection fraction <45% 2
  • NYHA class II-IV symptoms 2

The median treatment duration was 10.8 months, confirming long-term tolerability of the 10 mg dose 2.

Special Populations

No dose adjustment is required for renal impairment or hepatic impairment based on pharmacokinetic studies 6. Vericiguat is primarily metabolized via glucuronidation (UGT1A9 and UGT1A1) with 53% urinary excretion and 45% fecal excretion 6.

Critical Safety Mandate

Exclude pregnancy before starting Verquvo and ensure effective contraception throughout treatment and for one month after discontinuation 1. Vericiguat is contraindicated in pregnancy due to embryo-fetal toxicity demonstrated in animal studies 1.

Drug Interactions

Vericiguat has minimal drug-drug interaction potential 6:

  • Contraindicated: Concomitant use with other soluble guanylate cyclase stimulators 1
  • Not recommended: Concomitant use with PDE-5 inhibitors due to potential for hypotension 1
  • No dose adjustment needed: When co-administered with common heart failure medications including sacubitril/valsartan, digoxin, or warfarin 6

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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