Peringatan Keamanan

Data regarding overdosage with vericiguat are unavailable. Doses of up to 15mg once daily (50% greater than the recommended maintenance dose) have been studied and found to be well-tolerated. Symptoms of overdose are likely to be consistent with the adverse effect profile of vericiguat and may therefore involve significant hypotension for which symptomatic and supportive measures should be provided. Dialysis is unlikely to be of benefit in vericiguat overdose given its high degree of protein binding.L31153

Vericiguat

DB15456

small molecule approved investigational

Deskripsi

Vericiguat is a direct stimulator of soluble guanylate cyclase (sGC) used in the management of systolic heart failure to reduce mortality and hospitalizations.L31153 A key component of the NO-sGC-cGMP signaling pathway that helps to regulate the cardiovascular system, sGC enzymes are intracellular enzymes found in vascular smooth muscle cells (amongst other cell types) that catalyze the synthesis of cyclic guanosine monophosphate (cGMP) in response to activation by nitric oxide (NO).A227458,A227488 Cyclic GMP acts as a second messenger, activating a number of downstream signaling cascades that elicit a broad variety of effects, and these diverse cellular effects have implicated deficiencies in its production (primarily due to insufficient NO bioavailability) in the pathogenesis of various cardiovascular diseases.A227458 As a direct stimulator of sGC, vericiguat mitigates the need for a functional NO-sGC-cGMP axis and thereby helps to prevent the myocardial and vascular dysfunction associated with decreased sGC activity in heart failure.L31178

Vericiguat was approved by the FDA in January 2021 - developed by Merck under the brand name Verquvo - for use in certain patients with systolic heart failure.L31178 Although not the first sGC stimulator to be granted FDA approval (riociguat was approved in 2013 for use in pulmonary hypertension),L3955 vericiguat is unique amongst its peers in that modifications to its structure have dramatically decreased its susceptibility to oxidative metabolism,A227458 resulting in a relatively long half-life and allowing for once-daily dosing.

Struktur Molekul 2D

Berat 426.388
Wujud solid

Peta Jejaring Molekuler
Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) In patients with heart failure, the half-life of vericiguat is 30 hours.[L31153]
Volume Distribusi In healthy subjects the steady-state volume of distribution of vericiguat is approximately 44 liters.[L31153]
Klirens (Clearance) Vericiguat is a low-clearance drug, with an observed plasma clearance of 1.6 L/h in healthy volunteers and 1.3 L/h in patients with systolic heart failure.[L31153,A227478]

Absorpsi

Following the administration of 10mg of vericiguat by mouth once daily, the average steady-state Cmax and AUC in patients with heart failure is 350 mcg/L and 6,680 mcg•h/L, respectively, with a Tmax of 1 hour.L31153 The absolute bioavailability of orally-administered vericiguat is approximately 93% when taken with food - co-administration with meals has been shown to reduce pharmacokinetic variability, increase Tmax to roughly 4 hours, and increase Cmax and AUC by 41% and 44%, respectively.L31153

Metabolisme

Vericiguat is primarily metabolized via phase II conjugation reactions, with CYP-mediated oxidative metabolism comprising a small (<5%) portion of its overall biotransformation. The major inactive metabolite, vericiguat N-glucuronide (M1), is formed by UGT1A9 and, to a lesser extent, UGT1A1.L31153 Other identified metabolites include a denbenzylated compoundA227458 and an M15 metabolite thought to be the result of oxidative metabolism,A227478 although these metabolites are poorly characterized.

Rute Eliminasi

Following the oral administration of radiolabeled vericiguat, approximately 53% of the administered radioactivity was recovered in the urine and 45% in the feces.L31153 A human mass balance study found that the portion recovered in the urine comprised approximately 40.8% N-glucuronide metabolite, 7.7% other metabolites, and 9% unchanged parent drug, while virtually the entire portion recovered in the feces comprised unchanged vericiguat.A227478

Interaksi Makanan

1 Data
  • 1. Take with food. Administration with food has been shown to reduce pharmacokinetic variability and significantly improve absorption.

Interaksi Obat

317 Data
Duloxetine The risk or severity of orthostatic hypotension and syncope can be increased when Vericiguat is combined with Duloxetine.
Levodopa The risk or severity of hypotension and orthostatic hypotension can be increased when Vericiguat is combined with Levodopa.
Risperidone Vericiguat may increase the hypotensive activities of Risperidone.
Aripiprazole Aripiprazole may increase the hypotensive activities of Vericiguat.
Aripiprazole lauroxil Aripiprazole lauroxil may increase the hypotensive activities of Vericiguat.
Nicorandil Nicorandil may increase the hypotensive activities of Vericiguat.
Linezolid Linezolid may increase the orthostatic hypotensive activities of Vericiguat.
Furazolidone Furazolidone may increase the orthostatic hypotensive activities of Vericiguat.
Procaine Procaine may increase the orthostatic hypotensive activities of Vericiguat.
Tranylcypromine Tranylcypromine may increase the orthostatic hypotensive activities of Vericiguat.
Phenelzine Phenelzine may increase the orthostatic hypotensive activities of Vericiguat.
Minaprine Minaprine may increase the orthostatic hypotensive activities of Vericiguat.
Selegiline Selegiline may increase the orthostatic hypotensive activities of Vericiguat.
Procarbazine Procarbazine may increase the orthostatic hypotensive activities of Vericiguat.
Moclobemide Moclobemide may increase the orthostatic hypotensive activities of Vericiguat.
Isocarboxazid Isocarboxazid may increase the orthostatic hypotensive activities of Vericiguat.
Rasagiline Rasagiline may increase the orthostatic hypotensive activities of Vericiguat.
Pargyline Pargyline may increase the orthostatic hypotensive activities of Vericiguat.
Clorgiline Clorgiline may increase the orthostatic hypotensive activities of Vericiguat.
Iproniazid Iproniazid may increase the orthostatic hypotensive activities of Vericiguat.
Nialamide Nialamide may increase the orthostatic hypotensive activities of Vericiguat.
Safinamide Safinamide may increase the orthostatic hypotensive activities of Vericiguat.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the orthostatic hypotensive activities of Vericiguat.
Hydracarbazine Hydracarbazine may increase the orthostatic hypotensive activities of Vericiguat.
Pirlindole Pirlindole may increase the orthostatic hypotensive activities of Vericiguat.
Toloxatone Toloxatone may increase the orthostatic hypotensive activities of Vericiguat.
Benmoxin Benmoxin may increase the orthostatic hypotensive activities of Vericiguat.
Mebanazine Mebanazine may increase the orthostatic hypotensive activities of Vericiguat.
Octamoxin Octamoxin may increase the orthostatic hypotensive activities of Vericiguat.
Pheniprazine Pheniprazine may increase the orthostatic hypotensive activities of Vericiguat.
Phenoxypropazine Phenoxypropazine may increase the orthostatic hypotensive activities of Vericiguat.
Pivhydrazine Pivhydrazine may increase the orthostatic hypotensive activities of Vericiguat.
Safrazine Safrazine may increase the orthostatic hypotensive activities of Vericiguat.
Caroxazone Caroxazone may increase the orthostatic hypotensive activities of Vericiguat.
Harmaline Harmaline may increase the orthostatic hypotensive activities of Vericiguat.
Brofaromine Brofaromine may increase the orthostatic hypotensive activities of Vericiguat.
Butabarbital Butabarbital may increase the hypotensive activities of Vericiguat.
Butalbital Butalbital may increase the hypotensive activities of Vericiguat.
Pentobarbital Pentobarbital may increase the hypotensive activities of Vericiguat.
Secobarbital Secobarbital may increase the hypotensive activities of Vericiguat.
Methohexital Methohexital may increase the hypotensive activities of Vericiguat.
Thiopental Thiopental may increase the hypotensive activities of Vericiguat.
Primidone Primidone may increase the hypotensive activities of Vericiguat.
Methylphenobarbital Methylphenobarbital may increase the hypotensive activities of Vericiguat.
Thiamylal Thiamylal may increase the hypotensive activities of Vericiguat.
Phenobarbital Phenobarbital may increase the hypotensive activities of Vericiguat.
Amobarbital Amobarbital may increase the hypotensive activities of Vericiguat.
Hexobarbital Hexobarbital may increase the hypotensive activities of Vericiguat.
Barbital Barbital may increase the hypotensive activities of Vericiguat.
Barbexaclone Barbexaclone may increase the hypotensive activities of Vericiguat.
Aldesleukin The risk or severity of adverse effects can be increased when Aldesleukin is combined with Vericiguat.
Streptokinase The risk or severity of adverse effects can be increased when Streptokinase is combined with Vericiguat.
Valsartan The risk or severity of adverse effects can be increased when Valsartan is combined with Vericiguat.
Ramipril The risk or severity of adverse effects can be increased when Ramipril is combined with Vericiguat.
Esmolol The risk or severity of adverse effects can be increased when Esmolol is combined with Vericiguat.
Betaxolol The risk or severity of adverse effects can be increased when Betaxolol is combined with Vericiguat.
Reserpine The risk or severity of adverse effects can be increased when Reserpine is combined with Vericiguat.
Torasemide The risk or severity of adverse effects can be increased when Torasemide is combined with Vericiguat.
Methyclothiazide The risk or severity of adverse effects can be increased when Methyclothiazide is combined with Vericiguat.
Metoprolol The risk or severity of adverse effects can be increased when Metoprolol is combined with Vericiguat.
Ropinirole The risk or severity of adverse effects can be increased when Ropinirole is combined with Vericiguat.
Isradipine The risk or severity of adverse effects can be increased when Isradipine is combined with Vericiguat.
Olmesartan The risk or severity of adverse effects can be increased when Olmesartan is combined with Vericiguat.
Morphine The risk or severity of adverse effects can be increased when Morphine is combined with Vericiguat.
Ropivacaine The risk or severity of adverse effects can be increased when Ropivacaine is combined with Vericiguat.
Bupivacaine The risk or severity of adverse effects can be increased when Bupivacaine is combined with Vericiguat.
Chlorthalidone The risk or severity of adverse effects can be increased when Chlorthalidone is combined with Vericiguat.
Tolcapone The risk or severity of adverse effects can be increased when Tolcapone is combined with Vericiguat.
Nitroprusside The risk or severity of adverse effects can be increased when Nitroprusside is combined with Vericiguat.
Olanzapine The risk or severity of adverse effects can be increased when Olanzapine is combined with Vericiguat.
Atenolol The risk or severity of adverse effects can be increased when Atenolol is combined with Vericiguat.
Diltiazem The risk or severity of adverse effects can be increased when Diltiazem is combined with Vericiguat.
Minoxidil The risk or severity of adverse effects can be increased when Minoxidil is combined with Vericiguat.
Clozapine The risk or severity of adverse effects can be increased when Clozapine is combined with Vericiguat.
Timolol The risk or severity of adverse effects can be increased when Timolol is combined with Vericiguat.
Amlodipine The risk or severity of adverse effects can be increased when Amlodipine is combined with Vericiguat.
Triamterene The risk or severity of adverse effects can be increased when Triamterene is combined with Vericiguat.
Nimodipine The risk or severity of adverse effects can be increased when Nimodipine is combined with Vericiguat.
Nisoldipine The risk or severity of adverse effects can be increased when Nisoldipine is combined with Vericiguat.
Pramipexole The risk or severity of adverse effects can be increased when Pramipexole is combined with Vericiguat.
Spironolactone The risk or severity of adverse effects can be increased when Spironolactone is combined with Vericiguat.
Nitric Oxide The risk or severity of adverse effects can be increased when Nitric Oxide is combined with Vericiguat.
Bendroflumethiazide The risk or severity of adverse effects can be increased when Bendroflumethiazide is combined with Vericiguat.
Prazosin The risk or severity of adverse effects can be increased when Prazosin is combined with Vericiguat.
Imipramine The risk or severity of adverse effects can be increased when Imipramine is combined with Vericiguat.
Chlorpromazine The risk or severity of adverse effects can be increased when Chlorpromazine is combined with Vericiguat.
Nabilone The risk or severity of adverse effects can be increased when Nabilone is combined with Vericiguat.
Sotalol The risk or severity of adverse effects can be increased when Sotalol is combined with Vericiguat.
Fosinopril The risk or severity of adverse effects can be increased when Fosinopril is combined with Vericiguat.
Trandolapril The risk or severity of adverse effects can be increased when Trandolapril is combined with Vericiguat.
Metolazone The risk or severity of adverse effects can be increased when Metolazone is combined with Vericiguat.
Lercanidipine The risk or severity of adverse effects can be increased when Lercanidipine is combined with Vericiguat.
Benazepril The risk or severity of adverse effects can be increased when Benazepril is combined with Vericiguat.
Propranolol The risk or severity of adverse effects can be increased when Propranolol is combined with Vericiguat.
Clonidine The risk or severity of adverse effects can be increased when Clonidine is combined with Vericiguat.
Enalapril The risk or severity of adverse effects can be increased when Enalapril is combined with Vericiguat.
Doxazosin The risk or severity of adverse effects can be increased when Doxazosin is combined with Vericiguat.
Amiloride The risk or severity of adverse effects can be increased when Amiloride is combined with Vericiguat.
Labetalol The risk or severity of adverse effects can be increased when Labetalol is combined with Vericiguat.
Bisoprolol The risk or severity of adverse effects can be increased when Bisoprolol is combined with Vericiguat.

Target Protein

Retinal guanylyl cyclase 1 GUCY2D
Guanylate cyclase soluble subunit beta-1 GUCY1B1

Referensi & Sumber

Synthesis reference: Follmann M, Ackerstaff J, Redlich G, Wunder F, Lang D, Kern A, Fey P, Griebenow N, Kroh W, Becker-Pelster EM, Kretschmer A, Geiss V, Li V, Straub A, Mittendorf J, Jautelat R, Schirok H, Schlemmer KH, Lustig K, Gerisch M, Knorr A, Tinel H, Mondritzki T, Trubel H, Sandner P, Stasch JP: Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure. J Med Chem. 2017 Jun 22;60(12):5146-5161. doi: 10.1021/acs.jmedchem.7b00449. Epub 2017 Jun 12.
Artikel (PubMed)
  • PMID: 28557445
    Follmann M, Ackerstaff J, Redlich G, Wunder F, Lang D, Kern A, Fey P, Griebenow N, Kroh W, Becker-Pelster EM, Kretschmer A, Geiss V, Li V, Straub A, Mittendorf J, Jautelat R, Schirok H, Schlemmer KH, Lustig K, Gerisch M, Knorr A, Tinel H, Mondritzki T, Trubel H, Sandner P, Stasch JP: Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure. J Med Chem. 2017 Jun 22;60(12):5146-5161. doi: 10.1021/acs.jmedchem.7b00449. Epub 2017 Jun 12.
  • PMID: 33277825
    Tomasoni D, Adamo M, Anker MS, von Haehling S, Coats AJS, Metra M: Heart failure in the last year: progress and perspective. ESC Heart Fail. 2020 Dec 5. doi: 10.1002/ehf2.13124.
  • PMID: 32458378
    Boettcher M, Gerisch M, Lobmeyer M, Besche N, Thomas D, Gerrits M, Lemmen J, Mueck W, Radtke M, Becker C: Metabolism and Pharmacokinetic Drug-Drug Interaction Profile of Vericiguat, A Soluble Guanylate Cyclase Stimulator: Results From Preclinical and Phase I Healthy Volunteer Studies. Clin Pharmacokinet. 2020 Nov;59(11):1407-1418. doi: 10.1007/s40262-020-00895-x.
  • PMID: 31853617
    Friebe A, Sandner P, Schmidtko A: cGMP: a unique 2nd messenger molecule - recent developments in cGMP research and development. Naunyn Schmiedebergs Arch Pharmacol. 2020 Feb;393(2):287-302. doi: 10.1007/s00210-019-01779-z. Epub 2019 Dec 18.

Contoh Produk & Brand

Produk: 39 • International brands: 1
Produk
  • Verquvo
    Tablet, film coated • 10 mg • Oral • EU • Approved
  • Verquvo
    Tablet, film coated • 10 mg • Oral • EU • Approved
  • Verquvo
    Tablet, film coated • 10 mg • Oral • EU • Approved
  • Verquvo
    Tablet, film coated • 10 mg • Oral • EU • Approved
  • Verquvo
    Tablet, film coated • 10 mg • Oral • EU • Approved
  • Verquvo
    Tablet, film coated • 10 mg • Oral • EU • Approved
  • Verquvo
    Tablet, film coated • 10 mg • Oral • EU • Approved
  • Verquvo
    Tablet, film coated • 10 mg • Oral • EU • Approved
Menampilkan 8 dari 39 produk.
International Brands
  • Verquvo — Merck

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.
© 2025 Digital Pharmacy Research - Universitas Esa Unggul