Verquvo

Vericiguat.

Verquvo 2.5 mg film-coated tablets: Each film-coated tablet contains 2.5 mg vericiguat.
Excipient with known effect: Each film-coated tablet contains 58.14 mg lactose (as monohydrate), see Precautions.
Verquvo 5 mg film-coated tablets: Each film-coated tablet contains 5 mg vericiguat.
Excipient with known effect: Each film-coated tablet contains 55.59 mg lactose (as monohydrate), see Precautions.
Verquvo 10 mg film-coated tablets: Each film-coated tablet contains 10 mg vericiguat.
Excipient with known effect: Each film-coated tablet contains 111.15 mg lactose (as monohydrate), see Precautions.
Excipients/Inactive Ingredients: Tablet core: Microcrystalline cellulose, Croscarmellose sodium, Hypromellose 2910, Lactose monohydrate, Magnesium stearate, Sodium laurilsulfate.
Film-coat: Hypromellose 2910, Talc, Titanium dioxide (E 171), Iron oxide red (E 172) (Verquvo 5 mg only), Iron oxide yellow (E 172) (Verquvo 10 mg only).

Pharmacotherapeutic group: Cardiac therapy, other vasodilators used in cardiac diseases. ATC code: C01DX22.
Pharmacology: Pharmacodynamics: Mechanism of action: Vericiguat is a stimulator of soluble guanylate cyclase (sGC). Heart failure is associated with impaired synthesis of nitric oxide (NO) and decreased activity of its receptor, sGC. Deficiency in sGC-derived cyclic guanosine monophosphate (cGMP) contributes to myocardial and vascular dysfunction. Vericiguat restores the relative deficiency in the NO-sGC-cGMP signalling pathway by directly stimulating sGC, independently of and synergistically with NO, to augment the levels of intracellular cGMP, which may improve both myocardial and vascular function.
Pharmacodynamic effects: The pharmacodynamic effects of vericiguat are consistent with the mode of action of a sGC stimulator resulting in smooth muscle relaxation and vasodilation.
In a 12-week placebo-controlled dose-finding study (SOCRATES-REDUCED) in patients with heart failure, vericiguat demonstrated a dose-dependent reduction in NT-proBNP, a biomarker in heart failure, compared to placebo when added to standard of care. In VICTORIA, the estimated reduction from baseline NT-proBNP at week 32 was greater in patients who received vericiguat compared with placebo (see Clinical efficacy and safety as follows).
Cardiac electrophysiology: In a dedicated QT study in patients with stable coronary artery disease, administration of 10 mg of vericiguat at steady-state did not prolong the QT interval to a clinically relevant extent, i.e. the maximum mean prolongation of the QTcF interval did not exceed 6 ms (upper bound of the 90% CI <10 ms).
Clinical efficacy and safety: The safety and efficacy of vericiguat were evaluated in a randomised, parallel-group, placebo-controlled, double-blind, event-driven, multi-centre trial (VICTORIA) comparing vericiguat and placebo in 5,050 adult patients with symptomatic chronic heart failure (NYHA class II-IV) and left ventricular ejection fraction (LVEF) less than 45% following a worsening heart failure (HF) event. A worsening chronic HF event was defined as heart failure hospitalisation within 6 months before randomisation or use of outpatient IV diuretics for heart failure within 3 months before randomisation.
Patients were treated up to the target maintenance dose of vericiguat 10 mg once daily or matching placebo in combination with other HF therapies. Therapy was initiated at 2.5 mg vericiguat once daily and increased in approximately 2 week intervals to 5 mg once daily and then 10 mg once daily, as tolerated. After approximately 1 year, 89% of vericiguat-treated patients and 91% of placebo-treated patients received the 10 mg target dose in addition to other HF therapies.
The primary endpoint was the time to first event of the composite of cardiovascular (CV) death or hospitalisation for HF. The median follow-up for the primary endpoint was 11 months. Patients on vericiguat were treated for a mean duration of 1 year and up to 2.6 years.
The mean age of the studied population was 67 years, a total of 1,596 (63%) patients treated with vericiguat were 65 years and older, and 783 (31%) patients treated with vericiguat were 75 years and older. At randomisation, 58.9% of patients were NYHA Class II, 39.7% were NYHA Class III, and 1.3% were NYHA Class IV. The mean LVEF was 28.9%, approximately half of all patients had an LVEF <30%, and 14.3% of patients had an LVEF between 40% and 45%. The most frequently reported medical history conditions other than HF included hypertension (79%), coronary artery disease (58%), hyperlipidaemia (57%), diabetes mellitus (47%), atrial fibrillation (45%), and myocardial infarction (42%). At randomisation, the mean eGFR was 62 mL/min/1.73 m² (88% of patients >30 mL/min/1.73 m²; 10% of patients ≤30 mL/min/1.73 m²). 67% of the patients in VICTORIA were enrolled within 3 months of a HF hospitalisation; 17% were enrolled within 3 to 6 months of HF hospitalisation and 16% were enrolled within 3 months of outpatient treatment with IV diuretics. The median NT-proBNP level was 2,816 pg/mL at randomisation.
At baseline, more than 99% of patients were treated with other HF therapies which included beta blockers (93%), angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARB) (73%), mineralocorticoid receptor antagonists (MRA) (70%), a combination of an angiotensin receptor and neprilysin inhibitor (ARNI) (15%), ivabradine (6%), implantable cardiac defibrillators (28%), and biventricular pacemakers (15%). 91% of patients were treated with 2 or more HF medicinal products (beta blocker, any renin-angiotensin system [RAS] inhibitor, or MRA) and 60% of patients were treated with all 3. 3% of patients were on a sodium glucose co-transporter 2 (SGLT2) inhibitor.
Vericiguat was superior to placebo in reducing the risk of CV death or HF hospitalisation based on a time-to-event analysis. Over the course of the study, the annualised absolute risk reduction (ARR) was 4.2% with vericiguat compared with placebo. Therefore, 24 patients would need to be treated over an average of 1 year to prevent 1 primary endpoint event. The treatment effect reflected a reduction in the risk of CV death, HF hospitalisation, all-cause mortality or HF hospitalisation and total number of HF hospitalisation (see Table 1 and Figure 1).

Click on icon to see table/diagram/image


Click on icon to see table/diagram/image

A wide range of demographic characteristics, baseline disease characteristics and baseline concomitant medicinal products were examined for their influence on outcomes. The results of the primary composite endpoint were generally consistent across subgroups. Results of select pre-specified subgroup analyses are shown in Figure 2. (See Figure 2.)

Click on icon to see table/diagram/image

Patients with very high NT-proBNP may not be fully stabilised and require further optimisation of volume status and diuretic therapy (see Indications/Uses and Dosage & Administration).
Paediatric population: The European Medicines Agency has deferred the obligation to submit the results of studies with Verquvo in one or more subsets of the paediatric population in the treatment of left ventricular failure (see Dosage & Administration for information on paediatric use).
Pharmacokinetics: General introduction: Vericiguat shows time-independent pharmacokinetics with low to moderate variability when administered with food. Pharmacokinetics are dose proportional in healthy volunteers and slightly less than dose proportional in heart failure patients. Vericiguat accumulates in plasma up to 155-171% and reaches pharmacokinetic steady-state after approximately 6 days. The mean steady-state population pharmacokinetic parameters of vericiguat in heart failure patients are summarised in Table 2. Steady-state exposure is estimated to be about 20% higher in heart failure patients when compared to healthy volunteers. (See Table 2.)

Click on icon to see table/diagram/image

Absorption: The absolute bioavailability of vericiguat is high (93%) when taken with food. Bioavailability (AUC) and peak plasma levels (C_max) of vericiguat administered orally as a crushed tablet in water are comparable to that of a whole tablet (see Dosage & Administration).
Effect of food: Administration of vericiguat with a high-fat, high-calorie meal increases T_max from about 1 hour (fasted) to about 4 hours (fed), reduces PK variability, and increases vericiguat exposure by 19% (AUC) and 9% (C_max) for the 5 mg tablet and by 44% (AUC) and 41% (C_max) for the 10 mg tablet as compared with the fasted state. Similar results were obtained when vericiguat was administered with a low-fat, high-carbohydrate meal. Therefore, Verquvo should be taken with food (see Dosage & Administration).
Distribution: The mean steady-state volume of distribution of vericiguat in healthy subjects is approximately 44 L. Plasma protein binding of vericiguat is about 98%, with serum albumin being the main binding component. Plasma protein binding of vericiguat is not altered by renal or hepatic impairment.
Biotransformation: Glucuronidation is the major biotransformation pathway of vericiguat to form an N-glucuronide, which is pharmacologically inactive and the major drug-related component in plasma, accounting for 72% of the total drug-related AUC, with the parent vericiguat accounting for 28% of the total drug-related AUC. N-glucuronidation is catalysed predominantly by UGT1A9, as well as UGT1A1. CYP-mediated metabolism is a minor clearance pathway (<5%).
The potential effect of UGT-related genetic polymorphism has not been investigated given the low-to-moderate inter-individual variability of vericiguat (see Table 2). Titration of vericiguat mitigates the clinical impact of potential changes in exposure (see Dosage & Administration).
Elimination: Vericiguat is a low-clearance drug (1.6 L/h in healthy subjects). The half-life is about 20 hours in healthy subjects and 30 hours in heart failure patients. Following oral administration of [¹⁴C]-vericiguat to healthy subjects, approximately 53% of the dose was excreted in urine (primarily as the N-glucuronide), and 45% of the dose was excreted in faeces (primarily as vericiguat, likely due to excretion of the N-glucuronide into bile followed by hydrolysis back to vericiguat by intestinal microflora).
Special populations: Renal impairment: In patients with heart failure with mild, moderate, and severe renal impairment not requiring dialysis, the mean exposure (AUC) of vericiguat was increased by 5%, 13%, and 20% respectively, compared to patients with normal renal function. These differences in exposure are not considered clinically relevant. The pharmacokinetics of vericiguat have not been studied in patients with eGFR <15 mL/min/1.73 m² at treatment initiation or on dialysis (see Dosage & Administration and Precautions).
In a dedicated clinical pharmacology study, otherwise healthy participants with mild, moderate, and severe renal impairment, had 8%, 73%, and 143% respectively, higher mean vericiguat exposure (unbound AUC normalised for body weight) after a single dose compared to healthy controls.
The apparent discrepancy of the effect of renal impairment on vericiguat exposure between the dedicated clinical pharmacology study and the analysis in patients with heart failure may be attributed to differences in study design and size.
Hepatic impairment: No relevant increase in exposure (unbound AUC) was observed for subjects with mild hepatic impairment (Child-Pugh A) with mean exposure to vericiguat 21% higher compared to healthy subjects with normal hepatic function. In subjects with moderate hepatic impairment (Child-Pugh B), mean exposure to vericiguat was approximately 47% higher compared to their healthy subjects with normal hepatic function. The pharmacokinetics of vericiguat have not been studied in patients with severe hepatic impairment (Child-Pugh C) (see Dosage & Administration and Precautions).
Effects of age, body weight, gender, ethnicity, race and baseline NT-proBNP: Based on an integrated population pharmacokinetic analysis of vericiguat in patients with heart failure, age (23-98 years), body weight, gender, ethnicity, race and baseline NT-proBNP do not have a clinically meaningful effect on the pharmacokinetics of vericiguat (see Pharmacodynamics as previously mentioned).
Paediatric population: No studies with vericiguat have been performed yet in paediatric patients.
In vitro assessment of medicinal product interactions: Vericiguat is a substrate for UGT1A9, as well as UGT1A1 (see Interactions). In vitro studies indicate that vericiguat and its N-glucuronide are neither inhibitors of major CYP isoforms (CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6 and 3A4) or UGT isoforms (UGT1A1, 1A4, 1A6, 1A9, 2B4, and 2B7), nor inducers of CYP1A2, 2B6 and 3A4, at clinically relevant concentrations.
Vericiguat is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) transporters and is not a substrate of organic cation transporter (OCT1) or organic anion transporting polypeptides (OATP1B1, OATP1B3). Vericiguat and its N-glucuronide are not inhibitors of drug transporters, including P-gp, BCRP, BSEP, OATP1B1/1B3, OAT1, OAT3, OCT1, OCT2, MATE1, and MATE2K, at clinically relevant concentrations.
Overall, these data indicate that the administration of vericiguat is unlikely to affect the pharmacokinetics of concurrently administered medicinal products that are substrates of these enzymes or transporters.
Toxicology: Preclinical safety data: Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, and male and female fertility.
In repeat-dose toxicity studies, the toxicological profile was characterised by effects secondary to exaggerated pharmacodynamics. Secondary to smooth muscle relaxation haemodynamic and gastrointestinal effects were noted in all species investigated.
In adolescent rapidly-growing rats, reversible bone effects consisting of hypertrophy of growth plate and hyperostosis and remodelling of metaphyseal and diaphyseal bone were seen. These effects were not observed after chronic administration of vericiguat to adult rats and almost full-grown dogs. A study in pregnant rats showed that vericiguat is transferred to the foetus through the placenta. Developmental toxicity studies in rats with vericiguat administered orally during organogenesis showed no developmental toxicity up to at least 21 times the human exposure (based on unbound AUC) at the maximum recommended human dose (MRHD) of 10 mg. In rabbits, late abortions and resorptions were observed, at maternally toxic doses at ≥6 times the human exposure at the MRHD. In a pre-/postnatal toxicity study in rats, at maternal toxic doses decreased pup body weight gain resulting in a slight delay in incisor eruption and a slight delay in vaginal opening was observed at approximately ≥21 times the human exposure at the MRHD. An increased incidence of stillbirths and decreased pup survival and a delay in balano-preputial separation were observed at 49 times the human exposure at the MRHD.

Verquvo is indicated for the treatment of symptomatic chronic heart failure in adult patients with reduced ejection fraction who are stabilised after a recent decompensation event requiring IV therapy (see Pharmacology: Pharmacodynamics under Actions).

Posology: 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 (see Pharmacology: Pharmacodynamics under Actions).
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 (see Precautions).
Treatment should not be initiated in patients with SBP <100 mmHg (see Precautions).
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.
Special populations: Elderly: No dose adjustment is required for elderly patients (see Pharmacology: Pharmacodynamics and Pharmacokinetics under Actions).
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 (see Precautions and Pharmacology: Pharmacokinetics under Actions).
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 (see Precautions and Pharmacology: Pharmacokinetics under Actions).
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 (see Pharmacology: Toxicology: Preclinical safety data under Actions).
Method of administration: For oral use. Verquvo should be taken with food (see Pharmacology: Pharmacokinetics under Actions).
Crushed tablets: For patients who are unable to swallow whole tablets, Verquvo may be crushed and mixed with water immediately before administration (see Pharmacology: Pharmacokinetics under Actions).

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.

Hypersensitivity to the active substance or to any of the excipients listed in Description.
Concomitant use of other soluble guanylate cyclase (sGC) stimulators, such as riociguat (see Interactions).

Symptomatic hypotension: Vericiguat may cause symptomatic hypotension (see Adverse Reactions). 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 (see Interactions). If patients experience tolerability issues (symptomatic hypotension or SBP less than 90 mmHg), temporary down-titration or discontinuation of vericiguat is recommended (see Dosage & Administration).
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 (see Interactions).
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 (see Dosage & Administration and Pharmacology: Pharmacokinetics under Actions).
Hepatic impairment: Patients with severe hepatic impairment have not been studied, therefore treatment with vericiguat is not recommended in these patients (see Dosage & Administration and Pharmacology: Pharmacokinetics under Actions).
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".
Effects on ability to drive and use machines: Vericiguat has minor influence on the ability to drive or use machines. When driving vehicles or operating machines it should be taken into account that dizziness may occur occasionally.

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 (see Pharmacology: Toxicology: Preclinical safety data under Actions). 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 (see Pharmacology: Toxicology: Preclinical safety data under Actions).

Summary of the safety profile: The most frequently reported adverse reaction under treatment with vericiguat was hypotension (16.4%).
Tabulated list of adverse reactions: The safety of vericiguat was evaluated in a phase III study (VICTORIA) which included a total of 2,519 patients treated with vericiguat (up to 10 mg once daily) (see Pharmacology: Pharmacodynamics under Actions). The mean duration of vericiguat exposure was 1 year and the maximum duration was 2.6 years.
The adverse reactions reported with vericiguat obtained from clinical studies are listed in the following table by MedDRA system organ class and by frequency. Frequencies are defined as very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), and very rare (<1/10,000). (See Table 3.)

Click on icon to see table/diagram/image

Description of selected adverse reactions: Hypotension: Over the course of the VICTORIA study, the mean reduction in systolic blood pressure was approximately 1 to 2 mmHg greater in patients who received vericiguat compared with placebo. In VICTORIA, hypotension was reported in 16.4% of vericiguat-treated patients compared with 14.9% of placebo-treated patients. This includes also orthostatic hypotension that was reported in 1.3% of vericiguat-treated patients compared with 1.0% of placebo-treated patients. Symptomatic hypotension was reported in 9.1% of vericiguat-treated and 7.9% of placebo-treated patients, and was considered as a serious adverse event in 1.2% of vericiguat-treated patients and 1.5% of placebo-treated patients (see Precautions).
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions.

Pharmacodynamic interactions: Vericiguat co-administration with haemodynamic active substances did not result in a more than additive effect (see Precautions and Pharmacology: Pharmacodynamics under Actions). 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 (see Adverse Reactions).
Other soluble guanylate cyclase (sGC) stimulators: Verquvo is contraindicated in patients with concomitant use of other soluble guanylate cyclase (sGC) stimulators, such as riociguat (see Contraindications).
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 C_max) 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 (see Precautions).
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 C_max) 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 C_max) 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 C_max) 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 (see Precautions).
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 (see Pharmacology: Pharmacokinetics under Actions).
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 (see Dosage & Administration).
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.

Special precautions for disposal: Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
Incompatibilities: Not applicable.

Do not store above 30°C.

Other Cardiovascular Drugs

C01DX22 - vericiguat ; Belongs to the class of other vasodilators used in cardiac diseases.

P₁S₁S₃