Verquvo (vericiguat)

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Vericiguat primarily undergoes glucuronidation by uridine diphosphate-glucuronosyltransferase (UGT) enzymes 1A9 and, to a lesser extent, by UGT1A1 to form an inactive N-glucuronide metabolite. Vericiguat is not an inhibitor of UGT1A1, 1A4, 1A6, 1A9, 2B4, or 2B7 in vitro.

In vitro studies suggest that vericiguat is not an inhibitor of cytochrome P-450 (CYP) isoenzymes 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 3A4 and is not an inducer of CYP1A2, 2B6, or 3A4.

Vericiguat is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) transporters in vitro. In vitro studies suggest vericiguat is not a substrate of organic cation transporter (OCT) 1 or organic anion transporting (OAT) polypeptides OATP1B1 and OATP1B3 and not an inhibitor of P-gp, BCRP, bile salt export pump (BSEP), OATP1B1/1B3, OAT1, OAT3, OCT1, OCT2, multidrug and toxin extrusion (MATE) 1, or MATE2K.

There are no contraindication interactions for this drug.

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Vericiguat/Pde Inhibitors

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Vericiguat stimulates the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate (cGMP) pathway and also increases cGMP.(1) Aminophylline, avanafil, dipyridamole, sildenafil, tadalafil, theophylline, and vardenafil inhibit phosphodiesterase (PDE), which is responsible for the breakdown of cGMP.(1-6)

CLINICAL EFFECTS: The concurrent use of PDE inhibitors and vericiguat potentiates the hypotensive effects of both agents, which may result in dizziness, syncope, heart attack, or stroke.(1)

PREDISPOSING FACTORS: Plasma levels of the PDE type-5 inhibitors may be higher in the following patients: those older than 65, with hepatic impairment, or with severe renal impairment. This may increase the severity of the interaction.

PATIENT MANAGEMENT: The manufacturer of vericiguat states that administration of vericiguat to patients receiving PDE inhibitors, including specific PDE-5 inhibitors (avanafil,(2) sildenafil,(3) tadalafil,(4,5) or vardenafil(6)) and nonspecific PDE inhibitors (aminophylline, dipyridamole, theophylline) is not recommended.(1) The manufacturers of the PDE-5 inhibitors state that concurrent use of guanylate cyclase stimulators is contraindicated.(2-6)

DISCUSSION: Concomitant use of vericiguat 10 mg with single doses of sildenafil (25, 50, or 100 mg) was associated with additional seated BP reduction of up to 5.4 mm Hg (systolic/diastolic BP, MAP), compared to administration of vericiguat alone.(1)

There are no moderate interactions for this drug.

*Pregnancy.

*Concomitant therapy with other soluble guanylate cyclase stimulators.

• Pregnancy

There are no severe contraindications for this drug.

There are no moderate contraindications for this drug.

The most common adverse reactions reported in >=5% of patients receiving vericiguat are hypotension and anemia.

More Frequent

• Anemia
• Hypotension

There are no less severe adverse reactions for this drug.

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Safety and effectiveness of vericiguat have not been established in pediatric patients.

Based on data from animal reproduction studies, vericiguat may cause embryo-fetal toxicity when administered to a pregnant woman and is contraindicated during pregnancy. There are no available data with vericiguat use in pregnant women.

In animal reproduction studies, oral administration of vericiguat to pregnant rabbits during organogenesis, at >=4 times the human exposure (total AUC) with the maximum recommended human dose (MRHD) of 10 mg, resulted in malformations of the heart and major vessels, as well as an increased number of abortions and resorptions. In a pre/postnatal toxicity study, vericiguat administered orally to rats during gestation through lactation caused maternal toxicity, which resulted in decreased pup body weight gain (dosage >=10 times the MRHD) and increased pup mortality (dosage 24 times the MRHD) during the preweaning period. (14C)-vericiguat was administered orally to pregnant rats at a dose of 3 mg/kg and vericiguat-related material was transferred across the placenta, with fetal plasma concentrations of approximately 67% maternal concentrations on gestation day 19.

There is a Pregnancy Surveillance Program that monitors pregnancy outcomes in women exposed to vericiguat during pregnancy. Healthcare providers should report any prenatal exposure to vericiguat by calling 1-877-888-4231 or at https://pregnancyreporting.verquvo-us.com.

There are no data on the presence of vericiguat in human milk, the effects on the breastfed infant, or the effects on milk production. Vericiguat is present in the milk of lactating rats and it is likely that vericiguat or its metabolites are present in human milk. Because of the potential for serious adverse reactions in breastfed infants from vericiguat, advise women not to breastfeed during treatment with vericiguat.

No dosage adjustment is required in geriatric patients; however, greater sensitivity of some older patients cannot be ruled out.

No dosage adjustment of vericiguat is required in geriatric patients. In the VICTORIA study, a total of 1,596 (63%) patients treated with vericiguat were 65 years of age and older, and 783 (31%) patients treated with vericiguat were 75 years of age and older. No overall differences in safety or efficacy of vericiguat were observed between patients 65 years of age and older compared to younger patients, but greater sensitivity of some older individuals cannot be ruled out.