Delving into the Latest Updates on Benzonatate with Synapse

Overview

Basic Info

SummaryTESSALON® (Benzonatate) is an FDA-approved non-narcotic oral antitussive medication manufactured by Pfizer Inc. It was first approved in the United States in 1958 for the symptomatic relief of cough. TESSALON acts as a sodium channel blocker, anesthetizing the stretch receptors in the respiratory passages, lungs, and pleura to dampen their activity and reduce the cough reflex. Its effect starts within 15-20 minutes and can last between 3-8 hours. TESSALON has no inhibitory effect on the respiratory center when used as recommended. The active ingredient, 2, 5, 8, 11, 14, 17, 20, 23, 26-nonaoxaoctacosan-28-yl p-(butylamino) benzoate, has a molecular weight of 603.7. TESSALON is solely indicated for the relief of cough, but it has no known potential for abuse or addiction, unlike narcotic antitussives.

Drug Type

Small molecule drug

Synonyms

2,5,8,11,14,17,20,23,26-nonaoxaoctacosan-28-yl p-(butylamino)benzoate, 2-[2-[2-[2-[2-[2-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethyl 4-butylaminobenzoate, 3,6,9,12,15,18,21,24,27-nonaoxaoctacosyl 4-butylaminobenzoate

+ [8]

Target

SCNA

Mechanism

SCNA blockers(Sodium channel alpha subunit blockers)

Therapeutic Areas

Respiratory Diseases

Active Indication

Cough

Inactive Indication

Dry cough

Originator Organization

Pfizer Inc.

Active Organization

CSPC NBP Pharmaceutical Co., Ltd.

Pfizer Inc.

Inactive Organization

Biocon Ltd.

Drug Highest PhaseApproved

First Approval Date

US (10 Feb 1958),

Cough

Regulation-

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Structure

Molecular FormulaC30H53NO11

InChIKeyMAFMQEKGGFWBAB-UHFFFAOYSA-N

CAS Registry104-31-4

Among patients with chronic cough (CC) in the 2012-2021 statewide OneFlorida Clinical Research Consortium database, we examined trends in cough medication (CM) prescribing prevalence over time in repeated cross-sectional analyses and identified distinct CM utilization trajectories using group-based trajectory modeling (GBTM) in a retrospective cohort study. Among eligible adults (≥18 years) without cancer/benign respiratory tumor diagnoses, we identified CC patients and non-CC patients with any cough-related diagnosis. In the GBTM analysis, we calculated the number of monthly prescriptions for any CMs (excluding gabapentinoids) during the 12 months from the first qualifying cough event to identify distinct utilization trajectories. From 2012 to 2021, benzonatate (9.6% to 26.1%), dextromethorphan (5.2% to 8.6%), and gabapentinoid (5.3% to 14.4%) use increased among CC patients, while opioid antitussive use increased from 2012 to 2015 and decreased thereafter (8.4% in 2012, 14.7% in 2015, 6.7% in 2021; all p < 0.001). Of 15,566 CC patients and 655,250 non-CC patients identified in the GBTM analysis, CC patients had substantial burdens of respiratory/non-respiratory comorbidities and healthcare service and concomitant medication use compared to non-CC patients. Among CC patients, GBTM identified three distinct CM utilization trajectories: (1) no CM use (n = 11,222; 72.1%); (2) declining CM use (n = 4105; 26.4%); and (3) chronic CM use (n = 239; 1.5%). CC patients in Florida had limited CM use with increasing trends in use of benzonatate, dextromethorphan, and gabapentinoids and a decreasing trend in opioid antitussive use. CC patients, particularly with chronic prescription CM use, experienced substantial disease burden.

01 Jan 2023·PloS one

Benzonatate as a local anesthetic.

Article

Author: Kohane, Daniel S ; McGuire, Anna ; Aizik, Gil ; Ostertag-Hill, Claire A ; Li, Yang

INTRODUCTION:

Benzonatate is an FDA-approved antitussive agent that resembles tetracaine, procaine, and cocaine in its chemical structure. Based on structural similarities to known local anesthetics and recent findings of benzonatate exerting local anesthetic-like effects on voltage-gated sodium channels in vitro, we hypothesized that benzonatate will act as a local anesthetic to yield peripheral nerve blockade.

METHODS:

Benzonatate was injected at the sciatic nerve of Sprague-Dawley rats. Sensory and motor blockade were assessed using a modified hot plate test and a weight-bearing test, respectively. Additionally, the effect of co-injection with tetrodotoxin and Tween 80 (a chemical permeation enhancer) was examined. Myotoxicity of benzonatate was assessed in vivo by histological analysis.

RESULTS:

Benzonatate produced a concentration-dependent sensory and motor nerve blockade with no appreciable systemic effects. Co-injection with tetrodotoxin or Tween 80 produced prolongation of sensory nerve blockade. Histologic assessment showed significant inflammation and myotoxicity from benzonatate injection, even at low concentrations.

CONCLUSION:

This study demonstrates that benzonatate does act as a local anesthetic at the peripheral nerve, with sensory and motor nerve blockade. Benzonatate interacts with tetrodotoxin and Tween 80 to prolong nerve blockade. However, benzonatate causes significant myotoxicity, even at subtherapeutic concentrations.

01 Oct 2022·Journal of medical toxicology : official journal of the American College of Medical Toxicology

Benzonatate Overdose Presenting as Cardiac Arrest with Rapidly Narrowing QRS Interval

Article

Author: Baumgartner, Kevin T ; Filip, Ari B ; Liss, David B ; Stephens, Robert J ; Schwarz, Evan S

INTRODUCTION:

Benzonatate is a local anesthetic-like sodium channel antagonist that is widely prescribed as an antitussive. While it may be reasonable to assume that patients would present with a prolonged QRS interval following benzonatate overdose, the published literature does not support this. We report a case of a patient presenting following a benzonatate overdose with a prolonged QRS on her initial electrocardiograph (ECG) rhythm strip with rapid normalization of QRS duration.

CASE REPORT:

A 14-year-old girl presented in cardiac arrest following a benzonatate overdose. The patient was found in cardiac arrest within minutes of last being known well. Bystanders immediately provided cardiopulmonary resuscitation (CPR), and she was in asystole on emergency medical services (EMS) arrival. Return of spontaneous circulation (ROSC) was obtained following administration of intraosseous epinephrine and naloxone. EMS obtained an ECG rhythm strip following ROSC demonstrating a sinus rhythm with a QRS duration of 160 ms. Over the ensuing 30 minutes, there was progressive narrowing of the QRS. A 12-lead ECG obtained on arrival in the emergency department (ED) 44 minutes later demonstrated a QRS duration of 94 ms. Initially, EMS ECG rhythm strips were unavailable and an isolated benzonatate ingestion was considered less likely as ECG intervals were normal. Benzonatate exposure was later confirmed with a urine benzonatate concentration, which was 8.5 mcg/mL. The patient made a full recovery.

DISCUSSION:

Cases of pediatric benzonatate overdose with rapid development of cardiac arrest and full recovery have been previously reported. In this case, evidence of cardiac sodium channel blockade was demonstrated with a prolonged QRS interval on initial ECG rhythm strip analysis. However, unlike previous cases, rapid resolution of QRS prolongation occurred in this case. While transient QRS prolongation may be observed, finding a normal QRS interval should not discount the possibility of benzonatate overdose.

1

News (Medical) associated with Benzonatate

09 Jan 2020

·alitairpharmaceuticals.com

Onward to 2020, and the decade ahead ...

The Alitair Pharmaceuticals Executive Team would like to wish our shareholders and stakeholders a Happy New Year! To kick off the year, Alitair will be participating in the J.P. Morgan Healthcare Conference in San Francisco, CA from January 11th - 15th. This is one of the preeminent meetings in 2020 for biopharma and it is a great way to start the year. Alitair will be meeting with both potential funders (as we seek capital to drive the product development program forward) and potential partners (as we seek to identify value-creating transactions for our pipeline assets). Specifically, we seek biopharma companies who wish to license, co-develop or co-commercialize our valuable assets. Current efforts are focused on our lead assets benzonatate polacrilex tablets and the Overdose Reduction (ODR) formulation technology. To schedule a meeting at JPM, contact Frank Koos, SVP, Corporate and Business Development at fkoos@alitair.com. Once Alitair gains additional capital, our team plans to immediately re-initiate product development of benzonatate and ODR. The team also plans to conduct 2 small IP programs to further strengthen our intellectual property. We have one of our most exciting assets, ALT-09 (erdosteine), poised to move ahead following the IP work. This is a pipeline asset with an open IND and is a Phase II-ready Orphan Drug focused on bronchiectasis in both the non-Cystic Fibrosis and Cystic Fibrosis patient populations. Our commitment to bring our products to patients remains strong. It is our passion. Likewise, our commitment to shareholders remains very strong. Looking further into 2020 (and beyond), we seek to reach meaningful transaction points that will significant grow our firm's valuation and that may ultimately unlock additional shareholder value. We express our gratitude to our shareholders for their initial investments in Alitair and we deeply appreciate everyone's patience as we work on executing the business plan.

Phase 2Orphan Drug

100 Deals associated with Benzonatate

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