Verquvo

/ Bayer

Vericiguat is administered in conjunction with other heart failure therapies.
Before starting vericiguat, care should be taken to optimise volume status and diuretic therapy to stabilise patients after the decompensation event, particularly in patients with very high NT-proBNP levels.
The recommended starting dose is 2.5 mg vericiguat once daily. The dose should be doubled approximately every 2 weeks to reach the target maintenance dose of 10 mg once daily, as tolerated by the patient.
If patients experience tolerability issues (symptomatic hypotension or systolic blood pressure [SBP] less than 90 mmHg), temporary down-titration or discontinuation of vericiguat is recommended.
Treatment should not be initiated in patients with SBP <100 mmHg.
Missed dose: If a dose is missed, it should be taken as soon as the patient remembers on the same day of the missed dose. Patients should not take two doses of vericiguat on the same day.
Elderly: No dose adjustment is required for elderly patients.
Renal impairment: No dose adjustment is required in patients with estimated glomerular filtration rate (eGFR)>15 mL/min/1.73 m2 (without dialysis). Treatment with vericiguat is not recommended in patients with eGFR <15 mL/min/1.73 m2 at treatment initiation or on dialysis.
Hepatic impairment: No dose adjustment is required in patients with mild or moderate hepatic impairment. Treatment with vericiguat is not recommended in patients with severe hepatic impairment.
Paediatric population: The safety and efficacy of vericiguat in children and adolescents aged below 18 years have not yet been established. No clinical data are available. Undesirable effects were observed on growing bone in non-clinical studies.

This medicinal product 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%.

Hypersensitivity to the active substance or to any of the excipients.
Concomitant use of other soluble guanylate cyclase (sGC) stimulators, such as riociguat. See prescribing information for full details.

Symptomatic hypotension: Vericiguat may cause symptomatic hypotension. Patients with SBP less than 100 mmHg or symptomatic hypotension at treatment initiation were not studied. The potential for symptomatic hypotension should be considered in patients with hypovolaemia, severe left ventricular outflow obstruction, resting hypotension, autonomic dysfunction, history of hypotension, or concomitant treatment with antihypertensives or organic nitrates. If patients experience tolerability issues (symptomatic hypotension or SBP less than 90 mmHg), temporary down-titration or discontinuation of vericiguat is recommended.
Concomitant use of vericiguat and PDE5 inhibitors, such as sildenafil, has not been studied in patients with heart failure and is therefore not recommended due to the potential increased risk for symptomatic hypotension.
Renal impairment: Patients with eGFR <15 mL/min/1.73 m2 at treatment initiation or on dialysis have not been studied, therefore treatment with vericiguat is not recommended in these patients.
Hepatic impairment: Patients with severe hepatic impairment have not been studied, therefore treatment with vericiguat is not recommended in these patients.
Excipients:
Lactose: This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
Sodium: This medicinal product contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially “sodium-free”.

Very common: Hypotension
Common: Anaemia, Dizziness, headache, nausea, dyspepsia, vomiting
gastro-oesophageal reflux disease.

Pharmacodynamic interactions
Vericiguat co-administration with haemodynamic active substances did not result in a more than additive effect. In addition, vericiguat reduced systolic blood pressure by approximately 1 to 2 mmHg when co-administered with other medicinal products used in patients with heart failure.
Other soluble guanylate cyclase (sGC) stimulators:
Verquvo is contraindicated in patients with concomitant use of other soluble guanylate cyclase (sGC) stimulators, such as riociguat.
PDE5 inhibitors:
Addition of single doses of sildenafil (25, 50, or 100 mg) to multiple doses of vericiguat (10 mg) once daily in healthy subjects was associated with additional seated blood pressure (BP) reduction of less than or equal to 5.4 mmHg (systolic/diastolic BP, mean arterial pressure [MAP]) compared to administration of vericiguat alone. No dose-dependent trend was observed with the different sildenafil doses.
Co-administration was not associated with a clinically relevant effect on the exposure (AUC and Cmax) of either medicinal product.
Concomitant use of vericiguat and PDE5 inhibitors, such as sildenafil, has not been studied in patients with heart failure and is therefore not recommended due to the potential increased risk for symptomatic hypotension.
Acetylsalicylic acid:
Administration of a single dose of vericiguat (15 mg) in healthy subjects did not alter the effect of acetylsalicylic acid (500 mg) on bleeding time or platelet aggregation. Bleeding time or platelet aggregation did not change under treatment with vericiguat (15 mg) alone.
Co-administration of acetylsalicylic acid was not associated with a clinically relevant effect on the exposure (AUC and Cmax) of vericiguat.
Warfarin:
Administration of multiple doses of vericiguat (10 mg) once daily in healthy subjects did not alter the effect of a single dose of warfarin (25 mg) on prothrombin time and the activities of Factors II, VII, and X.
Co-administration was not associated with a clinically relevant effect on the exposure (AUC and Cmax) of either medicinal product.
Combination of sacubitril/valsartan
Addition of multiple doses of vericiguat (2.5 mg) to multiple doses of sacubitril/valsartan (97/103 mg) in healthy subjects had no additional effect on seated blood pressure compared to administration of sacubitril/valsartan alone.
Co-administration was not associated with a clinically relevant effect on the exposure (AUC and Cmax) of either medicinal product.
Organic nitrates:
Co-administration of multiple doses of vericiguat increased to 10 mg once daily did not significantly alter the seated blood pressure effects of short- and long-acting nitrates (nitroglycerin spray and isosorbide mononitrate [ISMN]) in patients with coronary artery disease. In patients with heart failure, concomitant use of short-acting nitrates was well tolerated. There is limited experience with concomitant use of vericiguat and long-acting nitrates in patients with heart failure.
Pharmacokinetic interactions:
Vericiguat is eliminated via multiple routes in humans. The dominant route is glucuronidation via UGT1A9 and UGT1A1, and vericiguat does not affect the pharmacokinetics of other medicinal products.
UGT1A9/1A1 inhibitors:
Vericiguat is metabolised by UGT1A9 and UGT1A1. Inhibitors of these UGTs may result in increased exposure of vericiguat.
No clinically meaningful effect on vericiguat exposure was observed when vericiguat was co- administered with mefenamic acid (weak to moderate UGT1A9 inhibitor).
As strong inhibition of UGT1A9 or combined UGT1A9/1A1 has not been tested in clinical drug-drug interaction studies due to the lack of available inhibitors, the clinical consequences of co- administration with these medicinal products are currently unknown.
Concomitant use with medicinal products that increase gastric pH:
Co-treatment with medicinal products that increase gastric pH, such as proton pump inhibitors (omeprazole), H2-receptor antagonists or antacids (aluminium hydroxide/magnesium hydroxide) did not affect vericiguat exposure when vericiguat was taken as directed with food in heart failure patients.
No significant interactions:
Concomitant administration of medicinal products affecting one or more of vericiguat´s elimination pathways does not have a clinically relevant effect on the pharmacokinetics of vericiguat.
No clinically meaningful effect on vericiguat exposure was observed when vericiguat was co-administered with ketoconazole (multi-pathway CYP and transporter inhibitor), or rifampicin (multi-pathway UGT, CYP and transporter inducer).
No clinically meaningful effect on midazolam (CYP3A substrate) or digoxin (P-gp substrate) exposure was observed when vericiguat was co-administered with these medicinal products.

Pregnancy:
There are no data from the use of vericiguat in pregnant women. Studies in animals have shown reproductive toxicity in presence of maternal toxicity. As a precautionary measure, vericiguat should not be used during pregnancy and in women of childbearing potential not using contraception.
Breast-feeding:
There is no information regarding 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. A risk to the breastfed child cannot be excluded.
A decision must be made whether to discontinue breast-feeding or to discontinue or abstain from vericiguat therapy, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
Fertility:
There are no data available on the effect of vericiguat on human fertility. In a study with male and female rats, vericiguat showed no impairment of fertility.

Overdose of vericiguat may lead to hypotension. If necessary, symptomatic treatment should be provided. The medicinal product is unlikely to be removed by haemodialysis due to high protein binding.