Introduction:

The pandemic, novel (COVID-19) is caused by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,which got it’s spread bifurcated from Wuhan, China, in December 2019, and has spreaded largely worldwide. This Beta-coronavirus bears similar characteristics of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV),  based on its genetic labels, which is originated from bat-derived coronaviruses via the unknown intermediate cause to host humans.

Currently, there is no evidence based monitoring available as  from randomized clinical trials (RCTs) , that may suggest any potential therapy improvising the outcomes in suspected or confimed patients with COVID-19. There are no clinical trial data that can support various prophylactic therapies. The structured proteins are synthesized profiling to aggregation of assembly and release of viral particles.The viral lifecycle somehow provide potential targets for drug therapy.The promising drug targets include nonstructural proteins. Reference: (Daniel S. Streetman, PharmD, MS)

As news about COVID-19 gets modified and updated each and every day and the world awaits the distant promise of a defined marketed vaccine, healthcare workers are now focused on the monotonous realities of treating the disease. Every day there are new whims and ideas, new evidences, old possibilities of disapprovals and clinicians and researchers in trenches sharing the benefit of their experiences.

For those of  who tirelessly and monotonously monitors the work every day , evaluating the studies of different therapies, it is believed, that it is essential that even as the undermined monitoring information and best practices may lead to the most effective and efficacious treatments for COVID-19, it is judgemental to also pay attention in emerging evidences about potential interactions.

Likely they are as follows:

1. Remdesivir:

Remdesivir is a nucleotide analog with a broad-spectrum pharmacological action against several viruses that is being made available for treatment of some patients with COVID-19 infections , as part of a stage one of the clinical trial. The Pharmacokinetic interaction concerns states that a very little information about Remdesivir is available. Consequently, it is impregnated over the predictions whether other medications may impact its concentrations or distribution or bioavailability, or whether Remdesivir itself could alter the pharmacokinetics of other medications being administered. Remdesivir being sensitive to CYP3A4-mediated drug interactions , based on in vitro findings, no clinical interactions with CYP3A4 are expected, as it is primarily metabolized by hydrolase in vivo. Further, in rhesus monkeys, Remdesivir gets rapidly distributed through the peripheral mononucleated cells , where it gets converted to the active nucleotide triphosphate metabolites. These findings strongly support a progressive low risk and grading  of significant pharmacokinetic interactions .

2. Hydroxychloroquine:

In proposed pharmacological manifestations, to its antimalarial and immunomodulating actions, Hydroxychloroquine has been able to show active against SARS-CoV-2. The major drug interaction bothers Hydroxychloroquine  in  prolonging the QT interval, possibly increasing the obligated factors of risk for arrhythmias An arrhythmia describes an irregular heartbeat. A person’s heart may beat too quickly, too slowly, too early, or with an irregular rhythm. Arrhythmias occur when the electrical signals that coordinate heartbeats does not work correctly. An irregular heartbeat may feel like a racing heart or fluttering. Despite the publications available, Hydroxychloroquine labeling recommends avoiding concurrent use of other medications that may prolong the QT interval, based on effects seen when administered in overdose. However, many publications in the past weeks have described the potential cardiac risks of Hydroxychloroquine, when co- administered  combinely with Azithromycin, which itself is categorized as a moderate QT-prolonging drug, where the QT interval is an electrocardiogram representation of ventricular depolarization and repolarization. Another drug interaction concern with Hydroxychloroquine is its potential to lower blood glucose concentrations, which aroused concern in patients who are receiving other blood glucose-lowering medications. This effect has been regulated , observed and reported in both diabetic and non-diabetic patients and Hydroxychloroquine labeling states that patients taking Hydroxychloroquine should be warned about the adverse effects and signs/symptoms of hypoglycemia.

3. Chloroquine:

This antimalarial medication is similar to Hydroxychloroquine. One important area of strengthening the data regarding the QT-prolonging effects of Chloroquine are clear and broader, that is, there is less uncertainty regarding the increased risk for potentially drug interactions between Chloroquine and other QT-prolonging medications. Chloroquine is a moderate QT-prolonging medication and is recommended for contraindicated drug therapy avoided with high-risk QT-prolonging drugs and extra precaution and close monitoring with other moderate-risk QT-prolonging drugs are performed. Chloroquine also has being able to lower blood glucose concentration,  leading to a possiblity with any concurrent use of antidiabetic drugs or other drugs capable of lowering blood glucose concentrations.

India pharma’s global standing: Reference: (James B. Cutrell, MD, Division of Infectious Diseases and Geographic Medicine, Department of Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9113As)

The impact of the coronavirus pandemic and the lockdown triggered worldwide as well as Curfew, clearly  makes visual impact on financial markets , but there is still no clarity on the deeper impact that it is having across businesses , monetary and industrial sectors. Based on assessments made by different analysts and industry bodies, Ficci, an impact analysis on the pharma sector is established. The Indian pharma industry has been a world leader in deliverables of generics drugs both globally and in domestic markets contributing significantly to the global demand for generics in terms of volume.

Risks from India pharma’s China linkages:

India’s large import dependence on China, has pose a pervedent and  significant threat to India’s healthcare manufacturing and global supply chain. While Indian pharma rules over a time period that have steadily immigrated and raised up the chain to focus on value-added formulations with higher margins, but this over dependence on other developed countries  has increased the threat to the nation’s health security as some of these critical Active Pharmaceutical Ingredients are crucial to mitigate or ban the leading growth of  India’s growing disease burden.

Supply chain disruption for India pharma:

Any disruption in the supply chain of Ingredients  results in significant shortages in the supply of essential drugs in India. Some of the critical APIs for high-burden disease categories such as cardiovascular diseases, diabetes enlisted in National List of Essential Medicines, creates an over dependency of low-cost API , which mainly attributes to extensive efforts towards developing economies of scale, easing regulations for bulk manufacturing, availability of low-cost utilities, building efficiencies and manufacturers through regulated subsidy, low taxes and incentives. India has significantly lost out on the API manufacturing owing to the inadequate government support, API focused infrastructure  with  growing complexity , gets approvals for setting up a manufacturing plant, delayed pollution clearances, high cost with low availability of utilities, regulatory and price control regimes.Various multitudes are co-lined  as the  key challenges faced.

Major earnings cuts ahead for pharma firms:

Securities says the novel coronavirus pandemic has caused severe supply-side disruptions in earnings , which has devastated and a profound surge in  cut by 10-15% is observed. Pharma as a sector has emerged as a strong contender and confines to drive the next pull of  rally, whenever it comes. In anticipation, pharma stocks have seen the  huge runs.This is not just true for India, but globally too the various pharma companies have performed.  While in the short term, most companies will bounce back from the last few years of under-mined performance, this time around, the leader will be different.

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