key: cord-0693651-zh9krbyu
authors: Vora, Agam; Arora, V.K.; Behera, D.; Tripathy, Suryakant
title: White paper on Ivermectin as a potential therapy for COVID-19
date: 2020-08-18
journal: Indian J Tuberc
DOI: 10.1016/j.ijtb.2020.07.031
sha: 5d6e401c9ea8bcc201962ae0511ace10416996c8
doc_id: 693651
cord_uid: zh9krbyu

A group of senior doctors with vast clinical experience met on 19th July’20 under the aegis of Academy of Advanced Medical Education. The panel looked at Ivermectin, one of the old molecule and evaluated it's use in COVID 19 (Novel Coronavirus Disease 2019) management. After critical panel discussion, all the attending doctors came to a conclusion that Ivermectin can be a potential molecule for prophylaxis and treatment of people infected with Coronavirus, owing to its anti-viral properties coupled with effective cost, availability and good tolerability and safety.

Executive summary SARS-CoV-2, a small 100 nm virus has emerged as an elusive foe, threatening mankind. Currently India is placed 3rd in terms of number of reported cases which warrants newer therapeutic treatment options that are widely available, affordable, effective and safe. There are newer drugs on the horizon which have been recommended though with very limited experience & devoid of enough data about safety and efficacy. 1 These newer options are neither easily available nor affordable.

We have revisited some of the old molecules & have found Ivermectin, originally introduced as an anthelmintic to be an effective, safe and affordable therapeutic option in Indian settings for prevention and treatment of COVID-19. 2 Recent research has shown that Ivermectin possesses strong anti-viral properties. 3 It has potential to convert RT-PCR negative quickly. 4 It can be used across the severity of COVID-19 especially in early viremic phase. 5 It can be combined with other molecules of interest, like Hydroxychloroquine, azithromycin, doxycycline. 6 Ivermectin is affordable, easily available, and safe without any major side effects. 5 This white paper is an attempt to propose Ivermectin, a strong antiviral drug as a therapeutic option in the prevention and treatment of mild, moderate and severe cases of COVID-19.

A group of senior doctors with vast experience in the management of COVID-19 got together on 19th July ' 

COVID-19 pandemic has affected more than 14 million people worldwide and number is going up daily. 7 There is no definite therapy available and repurposing of the older molecules is being studied vigorously. 8 The earlier touted molecules like hydroxychloroquine have little efficacy and that too in early Available online at www.sciencedirect.com ScienceDirect jo urnal homepage: http://www.journals.elsevier.co m/ indian-journal-of-tuberculosis/ stage of the disease cycle. 9,10 On the other-hand, with the limited clinical evidence available till date, Ivermectin has shown its promise in all phases of the disease and is being used both prophylactically and for treatment of all phases of disease from mild to severe. 5 

It has been proposed that COVID-19 infection in the lungs encompasses three main phases: an initial phase involving viral replication and relatively mild symptoms (early infection phase); a second phase characterized by adaptive immunity stimulation and predominance of respiratory symptoms (pulmonary phase); and, in some cases, a third and last phase with progress to a hyper inflammatory condition (hyper inflammation phase). According to phase of infection, clinical features ranges from mild symptoms (fever, cough, myalgia or fatigue, sore throat, headache) to acute respiratory distress syndrome (hypoxemia, shortness of breath) to ARDS, shock, multi-organ failure respectively. 11

Ivermectin is an old molecule with proven safety 5

Ivermectin is a well-known anthelmintic agent from the late-1970s. In recent times, the antiviral function of ivermectin has been discovered. Already its effectiveness against certain flavivirus (dengue fever, Japanese encephalitis and tick-borne encephalitis virus) and chikungunya virus has been demonstrated in vitro. Since then the same activity has been assessed in numerous other viral infections. Off lately its potency has been recognized in eliminating coronavirus in vitro. 12 It reduces the SARS-CoV-2 viral load by a factor of 5000 in 48 hours. 4 Current clinical trials have used Ivermectin in a dose ranging from 200 to 1200 mcg/kg body weight, for a duration of 3e7 days, showing promising results both in terms of symptomatology as well as viral load reduction. 13 

Ivermectin mechanism of action Sequestration of the SARS-CoV-2 viral nucleocapsid protein (NCP) into the host nucleus through the nuclear-pore-complex is a vital step in viral pathogenesis and defense against host immune response. 5 Ivermectin selectively inhibits host importin a/b transporter protein which decreases translocation (shuttling) of SARS CoV nucleocapsid protein (NCP) from the cytoplasm to the nucleus, altered NCP distribution disrupts viral propagation & survival. 4 

Ivermectin was found to selectively concentrate in the pulmonary tissue, around 3 times the plasma concentration and is sequestrated in the pulmonary tissue with a long residence time. 5 

Ivermectin has been demonstrated to be generally well tolerated. For the most part side effects have been mild and transient in nature. 14 

Special populations

Pregnancy Category C. Ivermectin has been shown to be teratogenic in mice, rats, and rabbits. There are, however, no adequate and well-controlled studies in pregnant women. Ivermectin should not be used during pregnancy since safety in pregnancy has not been established. 15 

Ivermectin is excreted in human milk in low concentrations. Treatment of mothers who intend to breastfeed should only be undertaken when the risk of delayed treatment to the mother outweighs the possible risk to the neonates. 15 

Safety and effectiveness in pediatric patients weighing less than 15 kg have not been established. 15 

Clinical studies of ivermectin did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. 15 

Ivermectin is easily available and highly affordable 5

Ivermectin therapy costs less than Rs. 1000 for the complete course (at a dose of 12mg BID for 7 days). Ivermectin is easily available at retail stores throughout India.

The Australian team that conducted the breakthrough lab study recently received funds from the Helmsley Charitable Trust to advance Ivermectin targeting COVID-19. 4

Ivermectin is now approved for at least mild cases of COVID-19. 16 

Ivermectin is approved in the north-eastern Beni region. 16 i n d i a n j o u r n a l o f t u b e r c u l o s i s 6 7 ( 2 0 2 0 ) 4 4 8 e4 5 1 

There is urgent need of well-designed randomized controlled trial to assess its efficacy for validating the use of Ivermectin against SARS-CoV-2. 23 Nearly 40 clinical trials are ongoing world over for measuring the outcome of COVID-19 treatment with Ivermectin.

All authors provided critical feedback and contributed to the final manuscript.

The authors have none to declare.

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Authors thank other doctors who shared their personal experience of using Ivermectin during panel discussion. r e f e r e n c e s