Verquvo

 Recommended Dosage

The recommended starting dose of VERQUVO is 2.5 mg orally once daily with food.

Double the dose of VERQUVO 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)].

 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)].

Pregnancy

Pregnancy Surveillance Program

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

Risk Summary

Based on data from animal reproduction studies, VERQUVO may cause fetal harm when administered to a pregnant woman and is contraindicated during pregnancy [see Contraindications (4)]. There are no available data with VERQUVO 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 increased number of abortions and resorptions (see Animal Data). 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 (≥10 times the MRHD) and increased pup mortality (24 times the MRHD) during the preweaning period (see Animal Data).

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Data

Animal Data

In an embryo-fetal development study in rabbits, vericiguat was administered orally to pregnant rabbits during the period of organogenesis from gestation day (GD) 6 to 20 at doses of 0.75, 2.5 or 7.5 mg/kg/day. An increased incidence of cardiac ventricular septal defect along with truncus arteriosus communis was observed at ≥2.5 mg/kg/day, which is ≥4 times the human exposure at the MRHD. Maternal toxicity (decreased food consumption and body weight loss), which may have resulted in late spontaneous abortions and resorptions was noted at ≥2.5 mg/kg/day (≥4 times the human exposure at the MRHD). There were no maternal toxicity or abortions/resorptions and no malformations of the heart and major vessels in rabbits at an exposure approximately equivalent to the human exposure at the MRHD.

In a prenatal developmental toxicity study in rats, vericiguat was administered orally to pregnant rats during the period of organogenesis from GD 6 to 17 at doses of 5, 15 or 50 mg/kg/day. No developmental toxicity was observed up to the highest dose (36 times the human exposure [total AUC] at the MRHD). Maternal toxicity (decreased body weight gain and food consumption) was observed at ≥15 mg/kg/day (≥10 times the human exposure at the MRHD). There was no maternal toxicity at 5 mg/kg/day (4 times the human exposure at the MRHD).

In a pre-postnatal development study in rats, vericiguat was administered orally at doses of 7.5, 15 or 30 mg/kg/day from GD 6 through lactation day 21. Maternal toxicity (decreases in food consumption and body weight gain) was observed at all dose levels ≥6 times the human exposure (total AUC) at the MRHD and resulted in decreased pup body weight gain at ≥15 mg/kg/day (≥10 times the human exposure at the MRHD) and pup mortality at 30 mg/kg/day (24 times the MRHD).

[14C]-vericiguat was administered orally to pregnant rats at a dose of 3 mg/kg. Vericiguat-related material was transferred across the placenta, with fetal plasma concentrations of approximately 67% maternal concentrations on GD 19.

 Lactation

Risk Summary

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 (see Data). Because of the potential for serious adverse reactions in breastfed infants from VERQUVO, advise women not to breastfeed during treatment with VERQUVO.

Data

[14C]-vericiguat was administered intravenously to lactating rats at a dose of 1 mg/kg. Vericiguat-related material was excreted into milk at concentrations approximately 12% maternal plasma concentrations on LD 8.

Females and Males of Reproductive Potential

Pregnancy Testing

Verify the pregnancy status in females of reproductive potential prior to initiating VERQUVO [see Dosage and Administration (2.2), Warnings and Precautions (5.1) and Use in Specific Populations (8.1)].

Contraception

Females

VERQUVO may cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment and for one month after the final dose [see Warnings and Precautions (5.1)].

Pediatric Use

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

Geriatric Use

No dosage adjustment of VERQUVO is required in geriatric patients. In VICTORIA, a total of 1,596 (63%) patients treated with VERQUVO were 65 years and older, and 783 (31%) patients treated with VERQUVO were 75 years and older. No overall differences in safety or efficacy of VERQUVO were observed between patients aged 65 years and older compared to younger patients, but greater sensitivity of some older individuals cannot be ruled out [see Clinical Pharmacology (12.3) and Clinical Studies (14)].

 Renal Impairment

No dosage adjustment of VERQUVO is recommended in patients with estimated glomerular filtration rate (eGFR) ≥15 mL/min/1.73m2 who are not on dialysis. VERQUVO has not been studied in patients with eGFR <15 mL/min/1.73m2 at treatment initiation or on dialysis [see Clinical Pharmacology (12.3) and Clinical Studies (14)].

 Hepatic Impairment

No dosage adjustment of VERQUVO is recommended in patients with mild or moderate hepatic impairment (e.g., Child-Pugh A or B). VERQUVO has not been studied in patients with severe hepatic impairment (e.g., Child-Pugh C) [see Clinical Pharmacology (12.3)].