Vericiguat

Vericiguat
Names
Trade namesVerquvo
IUPAC name
  • methyl N-[4,6-diamino-2-[5-fluoro-1-[(2-fluorophenyl)methyl]pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl]carbamate
Clinical data
Drug classSoluble guanylate cyclase activator
Main usesHeart failure[1]
Side effectsLow blood pressure, low red blood cells[2][3]
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
Routes of
use		By mouth
Typical dose10 mg OD[3]
External links
AHFS/Drugs.comMonograph
Legal
License data
Legal status
Chemical and physical data
FormulaC19H16F2N8O2
Molar mass426.388 g·mol−1
3D model (JSmol)
SMILES
  • COC(=O)NC1=C(N=C(N=C1N)C2=NN(C3=C2C=C(C=N3)F)CC4=CC=CC=C4F)N
InChI
  • 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 in heart failure after a recent worsening to reduce the risk of heart related death and hospitalization.[1][3] It is only used in those with an ejection fraction less than 45%.[1] It is taken by mouth.[3]

Common side effects include low blood pressure and low red blood cells.[2][3] Use in pregnancy may harm the baby.[2] It is a soluble guanylate cyclase (sGC) stimulator, and should not be used with other medications in this class.[1][3]

Vericiguat was approved for medical use in the United States and Europe in 2021.[2][3] In the United States it costs about 615 USD per month as of 2022.[6] This amount in the United Kingdom costs the NHS about £100.[7]

Medical uses

Vericiguat is used 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%.[1][2] It decreases this risk from 38.5% to 35.5% over a year.[3]

Dosage

It is started at 2.5 mg once per day and may be doubled every 2 weeks to a typical dose of 10 mg once per day.[3]

Side effects

Vericiguat may cause harm to the unborn baby and should not be given to pregnant women.[2] It is also not known how vericiguat passes into breastmilk, therefore patients should not take vericiguat The most common side effects of vericiguat include low blood pressure and anemia.[1] Patients taking other soluble guanylate cyclase inhibitors should also not be taking vericiguat.[1]

Pharmacology

Vericiguat is a direct stimulator of soluble guanylate cyclase enzyme, an important enzyme in vascular smooth muscle cells. Specifically, vericiguat will bind to the beta-subunit of the target site on the soluble guanylate cyclase enzyme.[8] Soluble guanylate cyclase enzymes catalyzes the formation of cyclic GMP upon interaction with nitric oxide to activate a number of downstream signaling cascade which can compensate for defects in this pathway and resulting losses in regulatory myocardial and vascular cellular processes due to cardiovascular complications. [8]

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%. [8] Vericiguat is extensively protein-bound in plasma . [8] Vericiguat is primarily metabolized via phase II 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 and was observed to have a 1.6 g/L clearance in patients with systolic heart failure. [8]

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.[2] The trial was conducted at 694 sites in 42 countries in Europe, Asia, North and South America.[2] The trial enrolled participants with symptoms of worsening heart failure.[2] Participants were randomly assigned to receive vericiguat or a placebo pill once a day.[2] Neither the participants nor the health care professionals knew if the participants were given vericiguat or placebo pill until after the trial was complete.[2] It was awarded a fast track designation on January 19th, 2021. [9]

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.[10] The applicant for this medicinal product is Bayer AG. Vericiguat was approved for medical use in the European Union in July 2021.[3]

References

  1. 1 2 3 4 5 6 7 8 9 "Verquvo- vericiguat tablet, film coated". DailyMed. Archived from the original on 6 September 2021. Retrieved 9 February 2021.
  2. 1 2 3 4 5 6 7 8 9 10 11 12 "Drug Trials Snapshot: Verquvo". U.S. Food and Drug Administration (FDA). 8 February 2021. Archived from the original on 9 February 2021. Retrieved 8 February 2021. Public Domain This article incorporates text from this source, which is in the public domain.
  3. 1 2 3 4 5 6 7 8 9 10 11 "Verquvo EPAR". European Medicines Agency (EMA). 19 May 2021. Archived from the original on 15 September 2021. Retrieved 14 September 2021.
  4. 1 2 "Verquvo". Therapeutic Goods Administration (TGA). 29 November 2021. Archived from the original on 28 December 2021. Retrieved 28 December 2021.
  5. ↑ "Updates to the Prescribing Medicines in Pregnancy database". Therapeutic Goods Administration (TGA). 12 May 2022. Archived from the original on 3 April 2022. Retrieved 13 May 2022.
  6. ↑ "Verquvo". Archived from the original on 23 October 2022. Retrieved 23 October 2022.
  7. ↑ "Vericiguat". SPS - Specialist Pharmacy Service. 17 October 2016. Archived from the original on 3 March 2022. Retrieved 23 October 2022.
  8. 1 2 3 4 5 "Vericiguat". go.drugbank.com. Archived from the original on 9 April 2022. Retrieved 9 April 2022.
  9. ↑ Hochron, By Adam. "FDA Grants Fast Track Designation for Heart Failure Developmental Treatment". www.mdalert.com. Archived from the original on 23 October 2022. Retrieved 9 April 2022.
  10. ↑ "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 © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.

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