Vericiguat

Last updated

Vericiguat
Vericiguat Structural formula V1.svg
Clinical data
Trade names Verquvo
License data
Pregnancy
category
Routes of
administration 		By mouth
Drug class Soluble guanylate cyclase activator
ATC code
Legal status
Legal status
Identifiers
  • methyl N-[4,6-diamino-2-[5-fluoro-1-[(2-fluorophenyl)methyl]pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl]carbamate
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.247.370 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C19H16F2N8O2
Molar mass 426.388 g·mol−1
3D model (JSmol)
  • COC(=O)NC1=C(N=C(N=C1N)C2=NN(C3=C2C=C(C=N3)F)CC4=CC=CC=C4F)N
  • InChI=1S/C19H16F2N8O2/c1-31-19(30)25-14-15(22)26-17(27-16(14)23)13-11-6-10(20)7-24-18(11)29(28-13)8-9-4-2-3-5-12(9)21/h2-7H,8H2,1H3,(H,25,30)(H4,22,23,26,27)
  • Key:QZFHIXARHDBPBY-UHFFFAOYSA-N

Vericiguat, sold under the brand name Verquvo, is a medication used to reduce the risk of cardiovascular death and hospitalization in certain patients with heart failure after a recent acute decompensation event. [3] [4] [8] It is taken by mouth. [3] [4] [8] Vericiguat is a soluble guanylate cyclase (sGC) stimulator. [3]

Contents

Common side effects include low blood pressure and low red cell count (anemia). [4] [8]

It was approved for medical use in the United States in January 2021, [4] [9] and for use in the European Union in July 2021. [8] The U.S. Food and Drug Administration considers it to be a first-in-class medication. [10]

Medical uses

Vericiguat is indicated to reduce the risk of cardiovascular death and hospitalization for heart failure following a prior hospitalization for heart failure or need for outpatient intravenous diuretics, in adults with symptomatic chronic heart failure and an ejection fraction of less than 45%. [3] [4]

Vericiguat is usually given orally once every day with food. No dose adjustments are required in the elderly, in people with mild-to-moderate liver failure, or in those with impaired kidney function. As of 2024, no studies have found information for patients with severely impaired kidney function, severe liver failure, or are on dialysis.

Vericiguat is contraindicated in pregnancy. While there are no studies on its safety when used by pregnant women, animals studies suggest higher rates of birth defects, as well as increased number of abortions and resorptions. It may also pass into breast milk, but the effects on breastfed infants is unknown. The manufacturer advises that child-bearing age patients should be on contraception and assessed for pregnancy before starting treatment.

Adverse effects

The most common side effects of vericiguat include symptomatic low blood pressure and anemia. [3] Patients taking other soluble guanylate cyclase inhibitors should not take vericiguat. [3]

Pharmacology

Vericiguat is a direct stimulator of soluble guanylate cyclase, an important enzyme in vascular smooth muscle cells. Specifically, vericiguat binds to the beta-subunit of the target site on the soluble guanylate cyclase enzyme. [11] Soluble guanylate cyclase catalyzes the formation of cyclic GMP upon interaction with nitric oxide to activate a number of downstream signaling cascades, which can compensate for defects in this pathway and resulting losses in regulatory myocardial and vascular cellular processes due to cardiovascular complications. [11] [ vague ][ clarification needed ]

Pharmacokinetics

After vericiguat is administered (100 mg by mouth once daily), the average steady state and Cmax and AUC for patients with cardiovascular failure is 350 mcg/L and 6,680 mcg/h/L with a Tmax of one hour. Vericiguat has a positive food effect, and therefore patients are advised to consume food with the drug for an oral bioavailability of 93%. [11] Vericiguat is extensively protein bound in plasma. [11] Vericiguat is primarily metabolized via phase 2 conjugation reactions, with a minor CYP-mediated oxidative metabolite. The major metabolite is glucuronidated and inactive. The typical half-life profile for patients with heart failure is 30 hours. Vericiguat has a decreased clearance in patients with systolic heart failure. [11]

History

The U.S. Food and Drug Administration (FDA) approved vericiguat based on evidence from a clinical trial (NCT02861534) which consisted of 5,050 participants aged 23 to 98 years old with worsening heart failure. [4] The trial was conducted at 694 sites in 42 countries in Europe, Asia, North and South America. [4] The trial enrolled participants with symptoms of worsening heart failure. [4] Participants were randomly assigned to receive vericiguat or a placebo pill once a day. [4] Neither the participants nor the health care professionals knew if the participants were given vericiguat or placebo pills until after the trial was complete. [4] It was awarded a fast track designation on 19 January 2021. [12]

Society and culture

On 20 May 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for vericiguat, intended for the treatment of symptomatic chronic heart failure in adults with reduced ejection fraction. [13] The applicant for this medicinal product is Bayer AG. Vericiguat was approved for medical use in the European Union in July 2021. [8] [14]

Related Research Articles

<span class="mw-page-title-main">Valsartan</span> Angiotensin II receptor antagonist

Valsartan, sold under the brand name Diovan among others, is a medication used to treat high blood pressure, heart failure, and diabetic kidney disease. It belongs to a class of medications referred to as angiotensin II receptor blockers (ARBs). It is a reasonable initial treatment for high blood pressure. It is taken by mouth.

<span class="mw-page-title-main">Ivabradine</span> Heart medication

Ivabradine, sold under the brand name Procoralan among others, is a medication, which is a pacemaker current (If) inhibitor, used for the symptomatic management of heart-related chest pain and heart failure. Patients who qualify for use of ivabradine for coronary heart failure are patients who have symptomatic heart failure, with reduced ejection volume, and heart rate at least 70 bpm, and the condition not able to be fully managed by beta blockers.

<span class="mw-page-title-main">Dronedarone</span> Medication

Dronedarone, sold under the brand name Multaq, is a class III antiarrhythmic medication developed by Sanofi-Aventis. It was approved by the US Food and Drug Administration (FDA) in July 2009. Besides being indicated in arrhythmias, it was recommended as an alternative to amiodarone for the treatment of atrial fibrillation and atrial flutter in people whose hearts have either returned to normal rhythm or who undergo drug therapy or electric shock treatment i.e. direct current cardioversion (DCCV) to maintain normal rhythm. It is a class III antiarrhythmic drug. The FDA label includes a claim for reducing hospitalization, but not for reducing mortality, as a reduction in mortality was not demonstrated in the clinical development program. A trial of the drug in heart failure was stopped as an interim analysis showed a possible increase in heart failure deaths, in people with moderate to severe congestive heart failure.

Tocilizumab, sold under the brand name Actemra among others, is an immunosuppressive drug, used for the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis, polyarticular juvenile idiopathic arthritis, giant cell arteritis, cytokine release syndrome, COVID‑19, and systemic sclerosis-associated interstitial lung disease (SSc-ILD). It is a humanized monoclonal antibody against the interleukin-6 receptor (IL-6R). Interleukin 6 (IL-6) is a cytokine that plays an important role in immune response and is implicated in the pathogenesis of many diseases, such as autoimmune diseases, multiple myeloma and prostate cancer. Tocilizumab was jointly developed by Osaka University and Chugai, and was licensed in 2003 by Hoffmann-La Roche.

<span class="mw-page-title-main">Soluble guanylyl cyclase</span>

Soluble guanylyl cyclase (sGC) is one of the gasoreceptors for nitric oxide, NO. It is soluble, i.e. completely intracellular. Most notably, this enzyme is involved in vasodilation. In humans, it is encoded by the genes GUCY1A2, GUCY1A3, GUCY1B2 and GUCY1B3.

<span class="mw-page-title-main">Dapagliflozin</span> Diabetes medication

Dapagliflozin, sold under the brand names Farxiga (US) and Forxiga (EU) among others, is a medication used to treat type 2 diabetes. It is also used to treat adults with heart failure and chronic kidney disease. It reversibly inhibits sodium-glucose co-transporter 2 (SGLT-2) in the renal proximal convoluted tubule to reduce glucose reabsorption and increase urinary glucose excretion.

<span class="mw-page-title-main">Ethyl eicosapentaenoic acid</span> Medication

Ethyl eicosapentaenoic acid, sold under the brand name Vascepa among others, is a medication used to treat dyslipidemia and hypertriglyceridemia. It is used in combination with changes in diet in adults with hypertriglyceridemia ≥ 150 mg/dL. Further, it is often required to be used with a statin.

<span class="mw-page-title-main">Riociguat</span> Chemical compound

Riociguat, sold under the brand name Adempas, is a medication by Bayer that is a stimulator of soluble guanylate cyclase (sGC). It is used to treat two forms of pulmonary hypertension (PH): chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH). Riociguat constitutes the first drug of the class of sGC stimulators. The drug has a half-life of 12 hours and will decrease dyspnea associated with pulmonary arterial hypertension.

<span class="mw-page-title-main">Canagliflozin</span> Chemical compound

Canagliflozin, sold under the brand name Invokana among others, is a medication used to treat type 2 diabetes. It is used together with exercise and diet. It is not recommended in type 1 diabetes. It is taken by mouth.

<span class="mw-page-title-main">Sacubitril/valsartan</span> Combination medication

Sacubitril/valsartan, sold under the brand name Entresto among others, is a fixed-dose combination medication for use in heart failure. It consists of the neprilysin inhibitor sacubitril and the angiotensin receptor blocker valsartan. The combination is sometimes described as an "angiotensin receptor-neprilysin inhibitor" (ARNi). In 2016, the American College of Cardiology/American Heart Association Task Force recommended it as a replacement for an ACE inhibitor or an angiotensin receptor blocker in people with heart failure with reduced ejection fraction.

Empagliflozin, sold under the brand name Jardiance, among others, is an antidiabetic medication used to improve glucose control in people with type 2 diabetes. It is taken by mouth.

<span class="mw-page-title-main">Finerenone</span> Chemical compound

Finerenone, sold under the brand name Kerendia and Firialta, is a medication used to reduce the risk of kidney function decline, kidney failure, cardiovascular death, non-fatal heart attacks, and hospitalization for heart failure in adults with chronic kidney disease associated with type 2 diabetes. Finerenone is a non-steroidal mineralocorticoid receptor antagonist (MRA). It is taken orally.

Sotagliflozin, sold under the brand name Inpefa among others, is a medication used to reduce the risk of death due to heart failure. It is a sodium-glucose cotransporter 2 (SGLT2) inhibitor. It is taken by mouth.

<span class="mw-page-title-main">Pemigatinib</span> Pharmaceutical drug

Pemigatinib, sold under the brand name Pemazyre, is an anti-cancer medication used for the treatment of bile duct cancer (cholangiocarcinoma). Pemigatinib works by blocking FGFR2 in tumor cells to prevent them from growing and spreading.

<span class="mw-page-title-main">Casirivimab/imdevimab</span> Antiviral combination medication

Casirivimab/imdevimab, sold under the brand name REGEN‑COV among others, is a combination medicine used for the treatment and prevention of COVID‑19. It consists of two human monoclonal antibodies, casirivimab and imdevimab that must be mixed together and administered as an infusion or subcutaneous injection. The combination of two antibodies is intended to prevent mutational escape. It is also available as a co-formulated product. It was developed by the American biotechnology company Regeneron Pharmaceuticals.

Avalglucosidase alfa, sold under the brand name Nexviazyme, is an enzyme replacement therapy medication used for the treatment of glycogen storage disease type II.

<span class="mw-page-title-main">Tirzepatide</span> Anti-diabetic and weight loss medication

Tirzepatide is an antidiabetic medication used for the treatment of type 2 diabetes and for weight loss. Tirzepatide is administered via subcutaneous injections. It is sold under the brand names Mounjaro for diabetes treatment, and Zepbound for weight loss.

<span class="mw-page-title-main">Asciminib</span> Chemical compound

Asciminib, sold under the brand name Scemblix, is a medication used to treat Philadelphia chromosome-positive chronic myeloid leukemia. Asciminib is a protein kinase inhibitor.

<span class="mw-page-title-main">Mavacamten</span> Chemical compound

Mavacamten, sold under the brand name Camzyos, is a medication used to treat obstructive hypertrophic cardiomyopathy.

Soluble guanylate cyclase (sGC) stimulators are a class of drugs developed to treat heart failure, pulmonary hypertension, and other diseases. The first-in-class medication was riociguat, approved in 2013 for pulmonary hypertension. They have also been investigated for hypertension, systemic sclerosis, and sickle cell disease.

References

  1. 1 2 "Verquvo". Therapeutic Goods Administration (TGA). 29 November 2021. Retrieved 28 December 2021.
  2. ↑ "Updates to the Prescribing Medicines in Pregnancy database". Therapeutic Goods Administration (TGA). 12 May 2022. Retrieved 13 May 2022.
  3. 1 2 3 4 5 6 7 8 "Verquvo- vericiguat tablet, film coated". DailyMed. Retrieved 9 February 2021.
  4. 1 2 3 4 5 6 7 8 9 10 11 "Drug Trials Snapshot: Verquvo". U.S. Food and Drug Administration (FDA). 8 February 2021. Retrieved 8 February 2021.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  5. ↑ "Details for: Verquvo". Health Canada . 19 September 2023. Retrieved 3 March 2024.
  6. ↑ "Notice: Multiple additions to the Prescription Drug List (PDL) [2023-06-23]". Health Canada . 23 June 2023. Retrieved 3 January 2024.
  7. ↑ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA . Retrieved 22 October 2023.
  8. 1 2 3 4 5 6 "Verquvo EPAR". European Medicines Agency (EMA). 19 May 2021. Retrieved 14 September 2021.
  9. ↑ "Drug Approval Package: Verquvo". U.S. Food and Drug Administration (FDA). 17 February 2021. Retrieved 14 September 2021.
  10. ↑ Advancing Health Through Innovation: New Drug Therapy Approvals 2021 (PDF). U.S. Food and Drug Administration (FDA) (Report). 13 May 2022. Archived from the original on 6 December 2022. Retrieved 22 January 2023.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  11. 1 2 3 4 5 "Vericiguat". go.drugbank.com. Retrieved 9 April 2022.
  12. ↑ Hochron, Adam. "FDA Grants Fast Track Designation for Heart Failure Developmental Treatment". www.mdalert.com. Retrieved 9 April 2022.
  13. ↑ "Verquvo: Pending EC decision". European Medicines Agency. 20 May 2021. Archived from the original on 21 July 2021. Retrieved 23 May 2021. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  14. ↑ "Verquvo Product information". Union Register of medicinal products. Retrieved 3 March 2023.

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.