Options for Controlling COVID-19 With Off-Patent Medications and Nutraceuticals
Drugs by physician prescription only; observe all contraindications
First Phase Anti-Virals – Administer to high-risk patients as soon as symptoms manifest or infection is diagnosed
Bromhexine – 8-16 mg 3 times daily (1-5)
Hydroxychloroquine – 1st day 400 mg twice; subsequent days 200 mg twice daily (6-10)
Azithromycin 500 mg once daily (6-12)
Doxycycline 100 mg twice daily (alterative to azithromycin for patients with heart issues) (13-16)
Options for Managing Second Phase - Anti-inflammatory/Antithrombotic agents
Ivermectin 8-16 mg, one time only; may repeat after 10 days (17-19)
Pentoxifylline 400 mg 3 times daily (20-24)
Dipyridamole 50 mg 3 times daily (20,25,26)
Zinc Sulfate 220 mg once daily (50 mg zinc;may aid efficacy of hydroxychloroquine) (35-39)
Vitamin D 5,000 IU once daily (40-44)
Quercetin 250 mg twice daily (45,46)
N-Acetylcysteine 600 mg twice daily (47-52)
Lipoic Acid 600 mg twice daily (47,48,53)
Ferulic Acid 250 mg twice daily (48,54,55)
Spirulina 15 g once daily (48,54)
Glucosamine 3,000 mg once daily (48,56)
Berberine 600 mg twice daily (nutraceutical alternative to metformin) (57-60)
Beta Glucan 200 mg once daily (61)
Melatonin 20 mg at bedtime (63)
Selenium 100 mcg once daily (64)
Suggested for Primary Prevention
Bromhexine 8 mg 3 X daily (62)
Hydroxychloroquine 200 mg once daily (62)
Dedicated to our fine friends in the pharmaceutical industry
(1) Maggio R, Corsini GU. Repurposing the mucolytic cough suppressant and TMPRSS2 protease inhibitor bromhexine for the prevention and management of SARS-CoV-2 infection. Pharmacol Res 2020 July;157:104837.
(2) Habtemariam S, Nabavi SF, Ghavami S, Cismaru CA, Berindan-Neagoe I, Nabavi SM. Possible use of the mucolytic drug, bromhexine hydrochloride, as a prophylactic agent against SARS-CoV-2 infection based on its action on the Transmembrane Serine Protease 2. Pharmacol Res 2020 July;157:104853.
(3) Depfenhart M, de VD, Lemperle G, Meyer M, Di SS. Potential new treatment strategies for COVID-19: is there a role for bromhexine as add-on therapy? Intern Emerg Med 2020 August;15(5):801-12.
(4) Ansarin K, Tolouian R, Ardalan M et al. Effect of bromhexine on clinical outcomes and mortality in COVID-19 patients: A randomized clinical trial. BioImpacts 2020;10(4):209-15.
(5) McCarty MF. How to Crush COVID-19 with Early Treatment. Online source: https://threadreaderapp.com/thread/1291918853341999104.html. 2020.
(6) Risch HA. Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients that Should be Ramped-Up Immediately as Key to the Pandemic Crisis. Am J Epidemiol 2020 May 27.
(7) Risch HA. Response to: "Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients" and "Re: Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients that Should be Ramped-Up Immediately as Key to the Pandemic Crisis". Am J Epidemiol 2020 July 20.
(8) Global HCQ studies. PrEP, PEP, and early treatment studies show high effectiveness, while late treatment shows mixed results. Online source: http://c19tudy.com. 2020.
(9) Scherrmann JM. Intracellular ABCB1 as a Possible Mechanism to Explain the Synergistic Effect of Hydroxychloroquine-Azithromycin Combination in COVID-19 Therapy. AAPS J 2020 June 12;22(4):86.
(10) Lagier JC, Million M, Gautret P et al. Outcomes of 3,737 COVID-19 patients treated with hydroxychloroquine/azithromycin and other regimens in Marseille, France: A retrospective analysis. Travel Med Infect Dis 2020 June 25;36:101791.
(11) 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 July;56(1):105949.
(12) Guerin V, Levy P, Thomas J-L et al. Azithromycin and hydroxychloroquine accelerate recovery of outpatients with mild/moderate COVID-19. Asian J Med Health 2020;18(7):45-55.
(13) Conforti C, Giuffrida R, Zalaudek I, Di MN. Doxycycline, a widely used antibiotic in dermatology with a possible anti-inflammatory action against IL-6 in COVID-19 outbreak. Dermatol Ther 2020 April 20;e13437.
(14) Malek AE, Granwehr BP, Kontoyiannis DP. Doxycycline as a potential partner of COVID-19 therapies. IDCases 2020;21:e00864.
(15) Szolnoky G. Further aspects of doxycycline therapy in COVID-19. Dermatol Ther 2020 June 13;e13810.
(16) Francini E, Miano ST, Fiaschi AI, Francini G. Doxycycline or minocycline may be a viable treatment option against SARS-CoV-2. Med Hypotheses 2020 June 27;144:110054.
(17) Portmann-Baracco A, Bryce-Alberti M, Accinelli RA. Antiviral and Anti-Inflammatory Properties of Ivermectin and Its Potential Use in Covid-19. Arch Bronconeumol 2020 July 7.
(18) Rajter JC, Sherman MS, Fatteh N, Vogel F, Sacks J, Rajter J-J. ICON (Ivermectin in COvid Nineteen) study: Use of ivermectin is associated with lower mortality in hospitalized patients with COVID19. medRxiv 2020;https://doi.org/10.1101/2020.06.06.20124461.
(19) Gorial FI, Mashhadani S, Sayaly HM et al. Effectiveness of ivermectin as add-on therapy in COVID-19 management. medRxiv 2020;https://doi.org/10.1101/2020.07.07.20145979.
(20) DiNicolantonio JJ, Barroso-Aranda J. Harnessing adenosine A2A receptors as a strategy for suppressing the lung inflammation and thrombotic complications of COVID-19: Potential of pentoxifylline and dipyridamole. Med Hypotheses 2020 July 2;143:110051.
(21) Hendry BM, Stafford N, Arnold AD et al. Hypothesis: Pentoxifylline is a potential cytokine modulator therapeutic in COVID-19 patients. Pharmacol Res Perspect 2020 August;8(4):e00631.
(22) Feily A, Daneshpay K, Alighadr A. COVID-19: Pentoxifylline as a potential adjuvant treatment. Int J Clin Pharmacol Ther 2020 July;58(7):406-7.
(23) Seirafianpour F, Mozafarpoor S, Fattahi N, Sadeghzadeh-Bazargan A, Hanifiha M, Goodarzi A. Treatment of COVID-19 with pentoxifylline: Could it be a potential adjuvant therapy? Dermatol Ther 2020 May 30;e13733.
(24) Assimakopoulos SF, Seintis F, Marangos M. Pentoxifylline and complicated COVID-19: A pathophysiologically based treatment proposal. Med Hypotheses 2020 May 30;143:109926.
(25) Liu X, Li Z, Liu S et al. Potential therapeutic effects of dipyridamole in the severely ill patients with COVID-19. Acta Pharm Sin B 2020 April 20.
(26) Kanthi Y, Knight JS, Zuo Y, Pinsky DJ. New (re)purpose for an old drug: purinergic modulation may extinguish the COVID-19 thromboinflammatory firestorm. JCI Insight 2020 July 23;5(14).
(27) Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost 2020 May;18(5):1094-9.
(28) Horby P, Lim WS, Emberson JR et al. Dexamethasone in Hospitalized Patients with Covid-19 - Preliminary Report. N Engl J Med 2020 July 17.
(29) Lee KH, Yoon S, Jeong GH et al. Efficacy of Corticosteroids in Patients with SARS, MERS and COVID-19: A Systematic Review and Meta-Analysis. J Clin Med 2020 July 27;9(8).
(30) Wassmann S, Laufs U, MÃ¼ller K et al. Cellular antioxidant effects of atorvastatin in vitro and in vivo. Arterioscler Thromb Vasc Biol 2002 February 1;22(2):300-5.
(31) Delbosc S, Morena M, Djouad F, Ledoucen C, Descomps B, Cristol JP. Statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, are able to reduce superoxide anion production by NADPH oxidase in THP-1-derived monocytes. J Cardiovasc Pharmacol 2002 October;40(4):611-7.
(32) Zhang XJ, Qin JJ, Cheng X et al. In-Hospital Use of Statins Is Associated with a Reduced Risk of Mortality among Individuals with COVID-19. Cell Metab 2020 August 4;32(2):176-87.
(33) De SA, Bronselaer A, Teo JT et al. The Effects of ARBs, ACEis, and Statins on Clinical Outcomes of COVID-19 Infection Among Nursing Home Residents. J Am Med Dir Assoc 2020 July;21(7):909-14.
(34) Teoh N, Farrell G. Statins as early therapy to mitigate COVID-19 (SARS-CoV-2)-associated ARDS and cytokine storm syndrome - time is of the essence. J Clin Transl Res 2020 June 9;5(5):227-9.
(35) Prasad AS, Beck FW, Bao B et al. Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress. Am J Clin Nutr 2007 March;85(3):837-44.
(36) Prasad AS. Zinc is an Antioxidant and Anti-Inflammatory Agent: Its Role in Human Health. Front Nutr 2014;1:14.
(37) Shittu MO, Afolami OI. Improving the efficacy of Chloroquine and Hydroxychloroquine against SARS-CoV-2 may require Zinc additives - A better synergy for future COVID-19 clinical trials. Infez Med 2020;28(2):192-7.
(38) Derwand R, Scholz M. Does zinc supplementation enhance the clinical efficacy of chloroquine/hydroxychloroquine to win today's battle against COVID-19? Med Hypotheses 2020 May 6;142:109815.
(39) Lagier JC, Million M, Gautret P et al. Outcomes of 3,737 COVID-19 patients treated with hydroxychloroquine/azithromycin and other regimens in Marseille, France: A retrospective analysis. Travel Med Infect Dis 2020 June 25;36:101791.
(40) Grant WB, Lahore H, McDonnell SL et al. Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths. Nutrients 2020 April 2;12(4).
(41) D'Avolio A, Avataneo V, Manca A et al. 25-Hydroxyvitamin D Concentrations Are Lower in Patients with Positive PCR for SARS-CoV-2. Nutrients 2020 May 9;12(5).
(42) Panagiotou G, Tee SA, Ihsan Y et al. Low serum 25-hydroxyvitamin D (25[OH]D) levels in patients hospitalized with COVID-19 are associated with greater disease severity. Clin Endocrinol (Oxf) 2020 July 3.
(43) Merzon E, Tworowski D, Gorohovski A et al. Low plasma 25(OH) vitamin D level is associated with increased risk of COVID-19 infection: an Israeli population-based study. FEBS J 2020 July 23.
(44) Carpagnano GE, Di L, V, Quaranta VN et al. Vitamin D deficiency as a predictor of poor prognosis in patients with acute respiratory failure due to COVID-19. J Endocrinol Invest 2020 August 9;1-7.
(45) DiNicolantonio JJ, McCarty MF. Targeting Casein kinase 2 with quercetin or enzymatically modified isoquercitrin as a strategy for boosting the type 1 interferon response to viruses and promoting cardiovascular health. Med Hypotheses 2020 May 4;142:109800.
(46) Colunga Biancatelli RML, Berrill M, Catravas JD, Marik PE. Quercetin and Vitamin C: An Experimental, Synergistic Therapy for the Prevention and Treatment of SARS-CoV-2 Related Disease (COVID-19). Front Immunol 2020;11:1451.
(47) Horowitz RI, Freeman PR, Bruzzese J. Efficacy of glutathione therapy in relieving dyspnea associated with COVID-19 pneumonia: A report of 2 cases. Respir Med Case Rep 2020 April 21;30:101063.
(48) McCarty MF, DiNicolantonio JJ. Nutraceuticals have potential for boosting the type 1 interferon response to RNA viruses including influenza and coronavirus. Prog Cardiovasc Dis 2020 May;63(3):383-5.
(49) De FS, Balansky R, La MS. Rationale for the use of N-acetylcysteine in both prevention and adjuvant therapy of COVID-19. FASEB J 2020 August 11.
(50) Jaiswal N, Bhatnagar M, Shah H. N-acetycysteine: A potential therapeutic agent in COVID-19 infection. Med Hypotheses 2020 July 24;144:110133.
(51) Ibrahim H, Perl A, Smith D et al. Therapeutic blockade of inflammation in severe COVID-19 infection with intravenous N-acetylcysteine. Clin Immunol 2020 July 22;219:108544.
(52) Poe FL, Corn J. N-Acetylcysteine: A potential therapeutic agent for SARS-CoV-2. Med Hypotheses 2020 May 30;143:109862.
(53) Horowitz RI, Freeman PR. Three novel prevention, diagnostic, and treatment options for COVID-19 urgently necessitating controlled randomized trials. Med Hypotheses 2020 May 22;143:109851.
(54) DiNicolantonio JJ, McCarty M. Thrombotic complications of COVID-19 may reflect an upregulation of endothelial tissue factor expression that is contingent on activation of endosomal NADPH oxidase. Open Heart 2020 June;7(1).
(55) Bhowmik D, Nandi R, Jagadeesan R, Kumar N, Prakash A, Kumar D. Identification of potential inhibitors against SARS-CoV-2 by targeting proteins responsible for envelope formation and virion assembly using docking based virtual screening, and pharmacokinetics approaches. Infect Genet Evol 2020 July 5;84:104451.
(56) Song N, Qi Q, Cao R et al. MAVS O-GlcNAcylation Is Essential for Host Antiviral Immunity against Lethal RNA Viruses. Cell Rep 2019 August 27;28(9):2386-96.
(57) Singh AK, Singh R. Is metformin ahead in the race as a repurposed host-directed therapy for patients with diabetes and COVID-19? Diabetes Res Clin Pract 2020 July;165:108268.
(58) Bramante C, Ingraham N, Murray T et al. Observational Study of Metformin and Risk of Mortality in Patients Hospitalized with Covid-19. medRxiv 2020 June 28.
(59) Scheen AJ. Metformin and COVID-19: From cellular mechanisms to reduced mortality. Diabetes Metab 2020 August 1.
(60) Crouse A, Grimes T, Li P, Might M, Ovalle F, Shalev A. METFORMIN USE IS ASSOCIATED WITH REDUCED MORTALITY IN A DIVERSE POPULATION WITH COVID-19 AND DIABETES. medRxiv 2020 July 31.
(61) Geller A, Yan J. Could the Induction of Trained Immunity by Beta-Glucan Serve as a Defense Against COVID-19? Front Immunol 2020;11:1782.
(62) Low-dose Hydroxychloroquine and Bromhexine: a Novel Regimen for COVID-19 Prophylaxis in Healthcare Professionals (ELEVATE). Online source:
(63) Ramlall V, Zucker J, Tatonetti M. Melatonin is significantly associated with survival of intubated COVID-19 patients. MedRxiv. 2020 Oct 18:2020.10.15.20213546/
(64) Heller Sun Q, Hackler J, et al. Prediction of survival odds in COVID-19 by zinc, age and selenoprotein P as composite biomarker. Redox Biology 2020, in press.