Overview
11 DESCRIPTION VERQUVO tablets contains vericiguat, a soluble guanylate cyclase stimulator. The chemical name of vericiguat is methyl {4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b] pyridin-3-yl] pyrimidin-5-yl} carbamate. The molecular formula is C 19 H 16 F 2 N 8 O 2 and the molecular weight is 426.39 g/mol.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Vericiguat is a stimulator of soluble guanylate cyclase (sGC), an important enzyme in the nitric oxide (NO) signaling pathway. When NO binds to sGC, the enzyme catalyzes the synthesis of intracellular cyclic guanosine monophosphate (cGMP), a second messenger that plays a role in the regulation of vascular tone, cardiac contractility, and cardiac remodeling. Heart failure is associated with impaired synthesis of NO and decreased activity of sGC, which may contribute to myocardial and vascular dysfunction. By directly stimulating sGC, independently of and synergistically with NO, vericiguat augments levels of intracellular cGMP, leading to smooth muscle relaxation and vasodilation. 12.
Indications
- 1 INDICATIONS AND USAGE VERQUVO ® is indicated to reduce the risk of cardiovascular death and heart failure (HF) hospitalization following a hospitalization for heart failure or need for outpatient IV diuretics, in adults with symptomatic chronic HF and ejection fraction less than 45% [see Clinical Studies (14) ] . VERQUVO is a soluble guanylate cyclase (sGC) stimulator, indicated to reduce the risk of cardiovascular death and heart failure (HF) hospitalization following a hospitalization for heart failure or need for outpatient IV diuretics, in adults with symptomatic chronic HF and ejection...
Common Doses
- 5 mg
- 2.5 mg
- 10 mg
Dosage
2 DOSAGE AND ADMINISTRATION The recommended starting dose of VERQUVO is 5 mg orally once daily with food. ( 2.1 ) For patients at risk of symptomatic hypotension, the recommended starting dose is 2.5 mg orally once daily with food. ( 2.1 ) Double the dose after approximately every 2 weeks to reach the target maintenance dose of 10 mg once daily, as tolerated by the patient. ( 2.1 ) Tablets may be crushed and mixed with water for patients unable to swallow whole tablets. ( 2.1 ) 2.1 Recommended Dosage The recommended starting dose of VERQUVO is 5 mg orally once daily with food.
Black Box Warning
WARNING: EMBRYO-FETAL TOXICITY Females of reproductive potential: Exclude pregnancy before the start of treatment. To prevent pregnancy, females of reproductive potential must use effective forms of contraception during treatment and for one month after stopping treatment. Do not administer VERQUVO to a pregnant female because it may cause fetal harm [see Dosage and Administration (2.2) , Warnings and Precautions (5.1) , and Use in Specific Populations (8.3) ] . WARNING: EMBRYO-FETAL TOXICITY See full prescribing information for complete boxed warning.
Contraindications
- 4 CONTRAINDICATIONS VERQUVO is contraindicated in patients with concomitant use of other soluble guanylate cyclase (sGC) stimulators [see Drug Interactions (7.1) ] . VERQUVO is contraindicated in pregnancy [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1) ]. Patients with concomitant use of other soluble guanylate cyclase (sGC) stimulators. ( 4 , 7.1 ) Pregnancy ( 4 )
Side Effects
- 6 ADVERSE REACTIONS Most common adverse reactions reported in ≥5% are hypotension and anemia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Merck Sharp & Dohme LLC at 1-877-888-4231 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Interactions
- 7 DRUG INTERACTIONS PDE-5 Inhibitors: Concomitant use is not recommended. ( 7.2 ) 7.1 Other Soluble Guanylate Cyclase Stimulators VERQUVO is contraindicated in patients with concomitant use of other soluble guanylate cyclase (sGC) stimulators [see Contraindications (4) ] . 7.2 PDE-5 Inhibitors Concomitant use of VERQUVO with PDE-5 inhibitors is not recommended because of the potential for hypotension [see Clinical Pharmacology (12.2) ] .