Generic placeholder image



ISSN (Print): 2666-7967
ISSN (Online): 2666-7975

Mini-Review Article

Off Label Medication to Combat COVID-19: Review Results to Date

Author(s): Netra P. Neupane, Aman K. Das, Anuj Kumar Singh and Amita Verma*

Volume 2, Issue 4, 2021

Published on: 29 July, 2020

Page: [496 - 506] Pages: 11

DOI: 10.2174/2666796701999200729145342


Background: Severe viral pneumonia cases were observed in the people of Wuhan, China in December 2019. It has already affected almost every country around the globe and was declared a pandemic by the World Health Organization. We aim to evaluate the therapeutics and safety of various off label COVID-19 drugs.

Methods: PubMed, Research Gate, Science Direct, Google Scholar, Centre for Disease control and prevention (CDC) portal, Chinese Centre for Disease Control and prevention (CCDC) portal, World Health Organization (WHO) portal were searched for obtaining reliable data.

Result: COVID-19 is creating a storm of deaths and active cases globally, which is forcing the pharmaceutical companies and scientists to work day and night to find an effective and safer anti-COVID-19 medication. Various in vitro and clinical trials had been performed as well as are currently ongoing to analyze the mechanisms and therapeutics of off label medications like Chloroquine, Hydroxychloroquine, Amodiaquine, Azithromycin, Remdesivir, Favipiravir, Ritonavir/Lopinavir, Umifenovir, Oseltamivir, Ribavirin, Nafamostat, Camostat, Tocilizumab, Ivermectin, Nitazoxanide, Famotidine, Vitamin D, Corticosteroids and Dexamethasone. In vitro studies were performed by utilizing Vero E6 cells and hSLAM cells while open/closed, randomized/non-randomized, single-centered/multi-centered and retrospective clinical trials and case studies were organized to determine their safety and efficacy.

Conclusion: Although these drugs have shown promising results against COVID-19 patients, it cannot be concluded that these drugs are truly safe and effective because there are no conclusive evidence to support the facts since only limited researches and studies had been investigated.

Keywords: COVID-19, therapeutic, antiviral, hydroxychloroquine, off label, clinical trial, vitamin D.

Graphical Abstract
Liu Y, Gayle AA, Wilder-Smith A, Rocklöv J. The reproductive number of COVID-19 is higher compared to SARS coronavirus. J Travel Med 2020; 27(2): 1-4.
[] [PMID: 32052846]
Remuzzi A, Remuzzi G. COVID-19 and Italy: what next? Lancet 2020; 395(10231): 1225-8.
[] [PMID: 32178769]
James S, Quinton K, Dana BM, et al. Prior and novel coronaviruses, COVID-19, and human reproduction: What is known? Fertil Steril 2020; 113(6): 1140-9.
[PMID: 32482250]
Hamid S, Mir MY, Rohela GK. Novel coronavirus disease (COVID-19): a pandemic (epidemiology, pathogenesis and potential therapeutics). New Microbes New Infect 2020; 35100679
[] [PMID: 32322401]
Qun L, Xuhua G, Peng W, et al. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N Engl J Med 2020 2020; 382(13): 1199-207.
Yifan T, Ying L, Chunhong G, et al. Symptom cluster of ICU nurses treating COVID-19 pneumonia patients in Wuhan, China. J Pain Symptom Manage 2020; 60(1): e48-53.
[] [PMID: 32276095]
Xiaodong Y, Jie Z, Qiang Y, Shangxin Z, Yigao W, Yongxiang L. A case of COVID-19 patient with the diarrhea as initial symptom and literature review. Clin Res Hepatol Gastroenterol 2020; 44(5): e109-12.
Shadi Z, Mehran K. Review of therapeutic agents for treatment of COVID-19. J Cell Mol Anesth Rev 2020; 5(1): 32-6.
CDC. Information for clinicians on investigational therapeutics for patients with COVID-19. Remdesivir hydroxychloroquine and chloroquine. Centre for disease control and prevention. Available from:
WHO. Report of the WHO-China Joint Mission on Coronavirus Disease 2019. (COVID-19) Available from:
Sciencesano. Interim clinical guidance for patients suspected of /confirmed with Covid-19 in Belgium 2020. Available from:
Food and Drug Administration FDA. Coronavirus (COVID-19) Update Daily Roundup 2020. Available from:
WHO. Landscape analysis of COVID therapeutics as 21 March 2020, 2020. Available from:
Christan AD, Jean-Marc R, Philipe C. Didier. New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19? Int J Antimicrob Agents 2020; 55(5)105938
[ ]
Dan Z, Sheng-Ming D, Qiang T. COVID-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression. J Antimicrob Chemother 2020; 75: 1667-70.
Cortegiani A, Ingoglia G, Ippolito M, Giarratano A, Einav S. A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19. J Crit Care 2020; 57: 279-83.
[] [PMID: 32173110]
Chen J, Liu D, Liu L, et al. A pilot study of hydroxychloroquine in treatment of patients with common coronavirus disease-19 (COVID-19). Zhejiang Da Xue Xue Bao Yi Xue Ban 2020; 49(1): 2015-9.
[ ]
Gbinigie K, Frie K. Should chloroquine and hydroxychloroquine be used to treat COVID-19? A rapid review. BJGP Open 2020; 4(2 bjgpopen20X101069)
Xueting Y, Fei Y, Miao Z, et al. In Vitro Antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome main point : Hydroxychloroquine was found to be more potent than chloroquine at inhibiting SARS-CoV-2 in vit. Clin Infect Dis 2020; 2: 1-25.
Awadesh KS, Akriti S, Altamash S, Ritu S, Anoop M. Chloroquine and hydroxychloroquine in the treatment of COVID-19 with or without diabetes: A systematic search and a narrative review with a special reference to India and other developing countries. Diabetes Metab Syndr 2020; 14(3): 241-6.
[ ]
Hagar M, Ahmed HA, Aljohani G, Alhaddad OA. Investigation of some antiviral N-Heterocycles as COVID 19 drug: Molecular docking and DFT calculations. Int J Mol Sci 2020; 21(11): 1-13.
[] [PMID: 32486229]
Olsen M, Cook SE, Huang V, Pedersen N, Murphy BG. Perspectives: potential therapeutic options for SARS-CoV-2 patients based on feline infectious peritonitis strategies: central nervous system invasion and drug coverage. Int J Antimicrob Agents 2020; 55(6)105964
[] [PMID: 32251732]
Ianevski A, Yao R, Fenstad MH, et al. Potential antiviral options against SARS-CoV-2 Infection. Viruses 2020; 12(6): 1-19.
[] [PMID: 32545799]
Gautret P, Lagier JC, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents 2020; 56105949
[] [PMID: 32205204]
Philippe G, Jean-Christophe L, Philippe P, et al. Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: an observational study Running title: Hydroxychloroquine-Azithromycin and COVID-19. Int J Antimicrob Agents 2020; 34101663
[ ]
Molina JM, Delaugerre C, Goff JL, et al. No Evidence of rapid antiviral clearance or clinical benefit with the combination of Hydroxychloroquine and Azithromycin in patients with severe COVID-19. Med Mal Infect 2020; 50(4): 384.
[ ]
Imperi F, Leoni L, Visca P. Antivirulence activity of azithromycin in Pseudomonas aeruginosa. Front Microbiol 2014; 5(178): 178.
[] [PMID: 24795709]
Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 2020; 30(3): 269-71.
[] [PMID: 32020029]
Mehta N, Mazer-Amirshahi M, Alkindi N, Pourmand A. Pharmacotherapy in COVID-19; A narrative review for emergency providers Am J Emerg Med 2020; S0735-6757(20): 30263-1..
[] [PMID: 32336586]
Dong L, Hu S, Gao J. Discovering drugs to treat coronavirus disease 2019 (COVID-19). Drug Discov Ther 2020; 14(1): 58-60.
[] [PMID: 32147628]
Al-Tawfiq JA, Al-Homoud AH, Memish ZA. Remdesivir as a possible therapeutic option for the COVID-19. Travel Med Infect Dis 2020; 34101615
[] [PMID: 32145386]
Furuta Y, Komeno T, Nakamura T. Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase. Proc Jpn Acad, Ser B, Phys Biol Sci 2017; 93(7): 449-63.
[] [PMID: 28769016]
Chang C, Jianying H, Ping Y, et al. Favipiravir versus Arbidol for COVID-19: A Randomized Clinical Trial. MedRxiv 2020.
Zhai P, Ding Y, Wu X, Long J, Zhong Y, Li Y. The epidemiology, diagnosis and treatment of COVID-19. Int J Antimicrob Agents 2020; 55(5)105955
[] [PMID: 32234468]
Lim J, Jeon S, Shin H-Y, et al. Case of the index patient who caused tertiary transmission of COVID-19 infection in Korea: the application of Lopinavir/Ritonavir for the treatment of COVID-19 infected pneumonia monitored by quantitative RT-PCR. J Korean Med Sci 2020; 35(6)e79
[] [PMID: 32056407]
Rismanbaf A. Potential treatments for COVID-19; a Narrative Literature Review. Off J Emerg Dep 2020; 8(1): 1-4.
Cheng CY, Lee YL, Chen CP, et al. Lopinavir/ritonavir did not shorten the duration of SARS CoV-2 shedding in patients with mild pneumonia in Taiwan. J Microbiol Immunol Infect 2020; 53(3): 488-92.
[] [PMID: 32331982]
Leneva IA, Falynskova IN, Makhmudova NR, Poromov AA, Yatsyshina SB, Maleev VV. Umifenovir susceptibility monitoring and characterization of influenza viruses isolated during ARBITR clinical study. J Med Virol 2019; 91(4): 588-97.
[] [PMID: 30431664]
Lu H. Drug treatment options for the 2019-new coronavirus (2019-nCoV). Biosci Trends 2020; 14(1): 69-71.
[] [PMID: 31996494]
Lian N, Xie H, Lin S, Huang J, Zhao J, Lin Q. Umifenovir treatment is not associated with improved outcomes in patients with coronavirus disease 2019: a retrospective study. Clin Microbiol Infect 2020; 26(7): 917-21.
[] [PMID: 32344167]
McClellan K, Perry CM, Oseltamivir A. Oseltamivir: a review of its use in influenza. Drugs 2001; 61(2): 263-83.
[] [PMID: 11270942]
Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020; 395(10223): 507-13.
[] [PMID: 32007143]
Koren G, King S, Knowles S, Phillips E. Ribavirin in the treatment of SARS: A new trick for an old drug? CMAJ 2003; 168(10): 1289-92.
[PMID: 12743076]
Mahamoud K, Mohammed AN. Virtual screening and repurposing of FDA approved drugs against COVID-19 main protease. Life Sci 2020; 251117627
Hoffmann M, Schroeder S, Kleine-Weber H, Müller MA, Drosten C, Pöhlmann S. Nafamostat mesylate blocks activation of SARS-CoV-2: New treatment option for COVID-19. Antimicrob Agents Chemother 2020; 64(6): 1-7.
[] [PMID: 32312781]
Jang S, Rhee JY. Three cases of treatment with Nafamostat in elderly patients with COVID-19 pneumonia who need oxygen therapy. Int J Infect Dis 2020; 96: 500-2.
[] [PMID: 32470602]
Pan L, Yi L. LIn Q, Xiulan L, Dang L, Juan L. Tocilizumab treatment in COVID-19: a single center experience. J Med Virol 2020.
Sangüesa Gómez C, Flores Robles BJ, Jara Chinarro B, Espinosa Malpartida M, Barbadillo Mateos C. Acute pneumonitis in a patient with adult-onset disease after toclizumab treatment with good response to anakinra. Reumatol Clin 2016; 12(6): 345-7.
[] [PMID: 26602361]
Xiaoling X, Mingfeng H, Tiantian L, et al. Effective treatment of severe COVID-19 patients with Tocilizumab. Proc Natl Acad Sci USA 2020; 117(20): 10970-7.
[ ]
Pierre T, Xavier DL, Pascal M, Pierre G, Karine L, Yazdan Y. Collecting and evaluating convalescent plasma for COVID-19 treatment: why and how. Vox Sang 2020; 115(6): 488-94.
[ ]
Casadevall A, Pirofski LA. The convalescent sera option for containing COVID-19. J Clin Invest 2020; 130(4): 1545-8.
[] [PMID: 32167489]
Chenguang S, Zhaoqin W, Fang Z, et al. Treatment of 5 critically Ill patients with COVID-19 with convalescent plasma. JAMA 2020; 323(16): 1582-9.
Chen L, Xiong J, Bao L, Shi Y. Convalescent plasma as a potential therapy for COVID-19. Lancet Infect Dis 2020; 20(4): 398-400.
[] [PMID: 32113510]
Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res 2020; 178104787
[] [PMID: 32251768]
Laing R, Gillan V, Devaney E. Ivermectin - Old drug, new tricks? Trends Parasitol 2017; 33(6): 463-72.
[] [PMID: 28285851]
Wagstaff KM, Sivakumaran H, Heaton SM, Harrich D, Jans DA. Ivermectin is a specific inhibitor of importin α/β-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus. Biochem J 2012; 443(3): 851-6.
[] [PMID: 22417684]
Fox LM, Saravolatz LD. Nitazoxanide: a new thiazolide antiparasitic agent. Clin Infect Dis 2005; 40(8): 1173-80.
[] [PMID: 15791519]
Ghosh R, Chatterjee S, Dubey S, Lavie CJ. Famotidine against SARS-CoV2: A hope or hype? Mayo Clin Proc 2020; 95(8): 1797-9.
Freedberg DE, Conigliaro J, Wang TC, et al. Famotidine research group famotidine research group. Famotidine use is associated with improved clinical outcomes in hospitalized COVID-19 patients: A propensity score matched retrospective cohort study. Gastroenterology 2020; 159: 1129-31.
[] [PMID: 32446698]
Rawat P, Anand J. Immunomodulatory properties of some herbal plants against candida albicans: a review. Biotechnol Int 201 5(2): 52-68.
Price KN, Frew JW, Hsiao JL, Shi VY. COVID-19 and immunomodulator/immunosuppressant use in dermatology. J Am Acad Dermatol 2020; 82(5): e173-5.
[] [PMID: 32224277]
Wimalawansa S. Global epidemic of coronavirus--COVID-19: What we can do to minimze risks? Eur J Biomed Pharm Sci 2020; 7: 432-8.
William BG, Henry LS, Sharon LM, et al. Evidence that vitamin D supplementation could reduce risk of influenza and COVID-19 infections and deaths. Nutrients 2020; 12(4): 1-19.
Fischer WA II, Vetter P, Bausch DG, et al. Ebola virus disease: an update on post-exposure prophylaxis. Lancet Infect Dis 2018; 18(6): e183-92.
[] [PMID: 29153266]
Shang L, Zhao J, Hu Y, Du R, Cao B. On the use of corticosteroids for 2019-nCoV pneumonia. Lancet 2020; 395(10225): 683-4.
[] [PMID: 32122468]
Lei Z, Shirong L, Lingling P, et al. Corticosteroid treatment of patients with coronavirus disease 2019 (COVID-¬ 19) 2020. Med J Aust 2020; 212(9): 416-20.
[ 10.5694/mja2.50577 ]
Egyed B, Kutszegi N, Sági JC, et al. MicroRNA-181a as novel liquid biopsy marker of central nervous system involvement in pediatric acute lymphoblastic leukemia. J Transl Med 2020; 18(1): 250.
[] [PMID: 32571344]
Marinella MA. Routine antiemetic prophylaxis with dexamethasone during COVID-19: Should oncologists reconsider? J Oncol Pharm Pract 2020; 26(6): 1482-5.
[] [PMID: 32507102]
Ledford H. Coronavirus breakthrough: dexamethasone is first drug shown to save lives. Nature 2020; 582(7813): 469.
[] [PMID: 32546811]
Chang D, Saleh M, Gabriels J, et al. Inpatient use of ambulatory telemetry monitors for COVID-19 patients treated with Hydroxychloroquine and/or Azithromycin. J Am Coll Cardiol 2020; 75(23): 2992-3.
[] [PMID: 32330546]
Okasha KM. Ivermectin and Nitazoxanide combination therapy for COVID-19 Available from: Retrieved from
Cortegiani A, Ingoglia G, Ippolito M, Giarratano A, Einav S. A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19. J Crit Care J 2020; 57: 279-83.
Chen Z, Hu J, Zhang Z, et al. Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial medRxiv Prepr 2020.
Beigel JH, Tomashek KM, Dodd LE, et al. ACTT-1 Study group members. Remdesivir for the treatment of Covid-19 - Preliminary report. N Engl J Med 2020; 383: 1813-26.
[] [PMID: 32445440]

© 2022 Bentham Science Publishers | Privacy Policy