Vericiguat

V03A - All other therapeutic products ATC C01DX22 Small molecule approved 2021 Oral First-in-class Black-box warning

JFDA label: Verquvo Film-coated tablet

⚠ Black-Box Warning

teratogenicity — ChEMBL drug_warning (Black Box Warning) | United States
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 contracept

Mechanism of Action

Activator of Soluble guanylate cyclase — Soluble guanylate cyclase activator

Target	Action	Gene / class
Soluble guanylate cyclase efficacy	ACTIVATOR

Indications

Approved

Cardiovascular Diseases — cardiovascular disease
Heart Failure — heart failure

Contraindications

Source: openFDA

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 ) Absolute

Dosing

Source: openFDA

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. For patients at risk of symptomatic hypotension, the recommended starting dose is 2.5 mg orally once daily with food [see Clinical Trials Experience (6.1) ]. Double the dose approximately every 2 weeks to reach the target maintenance dose of 10 mg once daily, as tolerated by the patient. For patients who are unable to swallow whole tablets, VERQUVO may be crushed and mixed with water immediately before administration [see Clinical Pharmacology (12.3) ] . 2.2 Pregnancy Testing in Females of Reproductive Potential Obtain a pregnancy test in females of reproductive potential prior to initiating treatment with VERQUVO [see Warnings and Precautions (5.1) and Use in Specific Populations (8.3) ].

Warnings & Precautions

Source: openFDA

Boxed 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. Do not administer VERQUVO to a pregnant female because it may cause fetal harm. ( 4 , 5.1 , 8.1 ) 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. ( 2.2 , 5.1 , 8.3 )

Embryo-Fetal Toxicity Based on data from animal reproduction studies,

Embryo-Fetal Toxicity Based on data from animal reproduction studies, VERQUVO may cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential of the potential risk to a fetus. Obtain a pregnancy test before the start of treatment. Advise females of reproductive potential to use effective contraception during treatment with VERQUVO and for at least one month after the final dose [see Dosage and Administration (2.2) and Use in Specific Populations (8.1 , 8.3) ].

Chemistry & Properties

Formula	C19H16F2N8O2
Molecular weight	426.39 g/mol
IUPAC name	methyl N-[4,6-diamino-2-[5-fluoro-1-[(2-fluorophenyl)methyl]pyrazolo[5,4-b]pyridin-3-yl]pyrimidin-5-yl]carbamate
CAS	1350653-20-1
PubChem CID	54674461
InChIKey	`QZFHIXARHDBPBY-UHFFFAOYSA-N`
logP	2.56 (XLogP 1.5)
Polar surface area	146.86 Å²
H-bond acceptors / donors	9 / 3
Drug-likeness (QED)	0.45
Lipinski violations	0

SMILES

COC(=O)Nc1c(N)nc(-c2nn(Cc3ccccc3F)c3ncc(F)cc23)nc1N

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	10.0%
Half-life	0.807 h
Volume of distribution	0.712 L/kg
Protein binding	80.4%
BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP1A2	Inhibitor	—
CYP3A4	Substrate	—

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)BCRP (Substrate)P-gp (Substrate)

Registered Products (3)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Verquvo Film-coated tablet	Film-Coated Tablet 5 mg	14 tab	Khoury Drug Store	51.420
Verquvo Film-coated tablet	Film-Coated Tablet 2.5 mg	14 tab	Khoury Drug Store	51.420
Verquvo Film-coated tablet	Film-Coated Tablet 10 mg	28 tab	Khoury Drug Store	102.840