Chemistry:Vericiguat
 | |
| 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 | |
| |
| CAS Number | |
| PubChem CID | |
| DrugBank | |
| ChemSpider | |
| UNII | |
| KEGG | |
| ChEBI | |
| ChEMBL | |
| Chemical and physical data | |
| Formula | C19H16F2N8O2 |
| Molar mass | 426.388 g·mol−1 |
| 3D model (JSmol) | |
| |
| |
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][6] It is taken by mouth.[3][4][6] Vericiguat is a soluble guanylate cyclase (sGC) stimulator.[3]
Common side effects include low blood pressure and low red cell count (anemia).[4][6]
It was approved for medical use in the United States in January 2021,[4][7] and for use in the European Union in July 2021.[6] The U.S. Food and Drug Administration considers it to be a first-in-class medication.[8]
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]
Adverse effects
Vericiguat causes harm to the unborn baby and should not be given to pregnant women.[4] It is not known to what extent vericiguat passes into breastmilk; therefore, breastfeeding patients should not take vericiguat.
The most common side effects of vericiguat include 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.[9] 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.[9][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%.[9] Vericiguat is extensively protein bound in plasma.[9] 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. [9]
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 pill until after the trial was complete.[4] It was awarded a fast track designation on 19 January 2021. [10]
Society and culture
Legal status
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.[11] The applicant for this medicinal product is Bayer AG. Vericiguat was approved for medical use in the European Union in July 2021.[6][12]
References
- ↑ 1.0 1.1 "Verquvo". 29 November 2021. https://www.tga.gov.au/apm-summary/verquvo.
- ↑ "Updates to the Prescribing Medicines in Pregnancy database". 12 May 2022. https://www.tga.gov.au/resources/resource/guidance/updates-prescribing-medicines-pregnancy-database.
- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 "Verquvo- vericiguat tablet, film coated". https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=17056d73-1b1b-4bf2-9c07-b7a9367f0d6d.
- ↑ 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 "Drug Trials Snapshot: Verquvo". 8 February 2021. https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshot-verquvo.
This article incorporates text from this source, which is in the public domain.
- ↑ "Notice: Multiple additions to the Prescription Drug List (PDL) [2023-06-23"]. 23 June 2023. https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/prescription-drug-list/notices-changes/multiple-additions-2023-06-23.html.
- ↑ 6.0 6.1 6.2 6.3 6.4 6.5 "Verquvo EPAR". 19 May 2021. https://www.ema.europa.eu/en/medicines/human/EPAR/verquvo.
- ↑ "Drug Approval Package: Verquvo". 17 February 2021. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214377Orig1s000TOC.cfm.
- ↑ (PDF) Advancing Health Through Innovation: New Drug Therapy Approvals 2021 (Report). 13 May 2022. https://www.fda.gov/media/155227/download. Retrieved 22 January 2023. This article incorporates text from this source, which is in the public domain.
- ↑ 9.0 9.1 9.2 9.3 9.4 "Vericiguat". https://go.drugbank.com/drugs/DB15456.
- ↑ Hochron, Adam. "FDA Grants Fast Track Designation for Heart Failure Developmental Treatment". https://www.mdalert.com/ms/chf/article/fda-grants-fast-track-designation-heart-failure.
- ↑ "Verquvo: Pending EC decision". 20 May 2021. https://www.ema.europa.eu/en/medicines/human/summaries-opinion/verquvo. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
- ↑ "Verquvo Product information". https://ec.europa.eu/health/documents/community-register/html/h1561.htm.
Further reading
- "Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction". N Engl J Med 382 (20): 1883–1893. May 2020. doi:10.1056/NEJMoa1915928. PMID 32222134.
External links
- Clinical trial number NCT02861534 for "A Study of Vericiguat in Participants With Heart Failure With Reduced Ejection Fraction (HFrEF) (MK-1242-001) (VICTORIA)" at ClinicalTrials.gov
 |  |
