Seguridad y eficacia de ivermectina en tiempos de COVID-19

Autores/as

DOI:

https://doi.org/10.24265/horizmed.2021.v20n1.10

Palabras clave:

SARS-CoV-2, COVID-19, infección, Ivermectina, Tratamiento

Resumen

Desde su aparición en diciembre de 2019, la infección por SARS-CoV-2 se expandió rápidamente a todo el mundo. Aproximadamente, el 80 % de pacientes con COVID-19 presentan síntomas leves a moderados, el 20 % desarrolla cuadros respiratorios graves, y alrededor del 6 % pueden requerir ventilación mecánica. En ausencia de pautas terapéuticas comprobadas, varios medicamentos ya conocidos empezaron a ser evaluados por sus probables beneficios en el tratamiento de COVID-19. Entre ellos, está el fármaco antiparasitario ivermectina, una de las avermactinas producidas por la bacteria
Streptomyces avermitilis, que fue descubierta en los años setenta por el grupo del profesor Omura, en colaboración con la industria farmacéutica. Se ha demostrado que la ivermectina inhibe la interacción entre la proteína viral y el heterodímero de importina α/β1, lo que provoca la inhibición de la replicación del virus. Recientemente, este mecanismo de acción de la ivermectina frente al SARS-CoV-2 fue demostrado en células Vero/hSLAM. A la fecha, se conocen los resultados de un ensayo clínico en Argentina que comprueba la utilidad de la ivermectina en las etapas tempranas de la
enfermedad; asimismo, en el mundo se registran alrededor de 40 estudios clínicos que buscan confirmar su importancia
como un tratamiento costo-efectivo para COVID-19. Respecto a la seguridad, en estos años la ivermectina ha demostrado
ser un fármaco bien tolerado.

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Wang C, Horby PW, Hayden FG, Gao GF. A novel coronavirus outbreak of global health concern. Lancet Lond Engl. 2020; 395(10223): 470-3.

Johns Hopkins Coronavirus Resource Center. COVID-19 Map [Internet]. 2020. Disponible en: https://coronavirus.jhu.edu/map.html

Roma Paumgarteen FJ, Amado Xavier de Oliveira AC. Off label, compassionate and irrational use of medicines in Covid-19 pandemic, health consequences and ethical issues. Cienc Saude Coletiva. 2020; 25(9): 3413-9.

Samaddar A, Grover M, Nag VL. Pathophysiology and potential therapeutic candidates for COVID-19: a poorly understood arena. Front Pharmacol. 2020; 11: 585888.

Callaway E, Cyranoski D. Anti-parasite drugs sweep Nobel prize in medicine 2015. Nature. 2015; 526(7572): 174-5.

Rocha Formiga F, Leblanc R, de Souza Reboucas J, Paiva Farias L, Nascimento de Oliveira R, Pena L. Ivermectin: an award-winning drug with expected antiviral activity against COVID-19. J Control Release. 2020; S0168-3659(20): 30580.

González Canga A, Sahagún Prieto AM, Diez Liébana MJ, Fernández Martínez N, Sierra Vega M, García Vieitez JJ. The pharmacokinetics and interactions of ivermectin in human - a mini-review. AAPS J. 2008; 10(1): 42-6.

Sajid MS, Iqbal Z, Muhammad G, Iqbal MU. Immunomodulatory effect of various anti-parasitics: a review. Parasitology. 2006; 132(Pt. 3): 301-13.

Heidary F, Gharebaghi R. Ivermectin: a systematic review from antiviral effects to COVID-19 complementary regimen. J Antibiot (Tokyo). 2020: 1-10.

Pandey S, Pathak SK, Pandey A, Salunke AA, Chawla J, Sharma A, et al. Ivermectin in COVID-19: What do we know?. Diabetes Metab Syndr. 2020; 14(6): 1921-2.

Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM. The FDAapproved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res. 2020; 178: 104787.

Hossen S, Barek A, Jahan N, Safiqul Islam M. A review on current repurposing drugs for the treatment of COVID-19: reality and challenges. SN Compr Clin Med. 2020: 1-13.

Omura S, Crump A. The life and times of ivermectin - a success story. Nat Rev Microbiol. 2004; 2(12): 984-9.

Victoria Ch J. Ivermectina: sus múltiple usos, seguridad y toxicidad. Rev Chil Dermatol. 2010; 26(4): 358-68.

Turab Naqvi AA, Kisa F, Mohammad T, Urooj F, Singh IK, Singh A, et al. Insights into SARS-CoV-2 genome, structure, evolution, pathogenesis and therapies: structural genomics approach. Biochim Biophys Acta Mol Basis Dis. 2020; 1866(10): 165878.

Romano M, Ruggiero A, Squeglia F, Maga G, Berisio R. A structural view of SARS-CoV-2 RNA replication machinery: ARN synthesis, proofreading and final capping. Cells. 2020; 9(5): 1267.

Astuti I, Ysrafil. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): an overview of viral structure and host response. Diabetes Metab Syndr. 2020; 14(4): 407-12.

Tang T, Bidon M, Jaimes JA, Whittaker GR, Daniel S. Coronavirus membrane fusion mechanism offers a potential target for antiviral development. Antiviral Res. 2020; 178: 104792.

Pedersen SF, Ho Y-C. SARS-CoV-2: a storm is raging. J Clin Invest. 2020; 130(5): 2202-5.

Zhou P, Yang X-L, Wang X-G, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020; 579(7798): 270-3.

Panoutsopoulos AA. Known drugs and small molecules in the battle for COVID-19 treatment. Genes Dis. 2020.

Vora A, Arora VK, Behera D, Tripathy SK. White paper on Ivermectin as a potential therapy for COVID-19. Indian J Tuberc. 2020; 67(3): 448-51.

Banerjee K, Nandy M, Dalai CK, Ahmed SN. The Battle against COVID 19 pandemic: what we need to know before we «test fire» ivermectin. Drug Res. 2020; 70(8): 337-40.

Dixit A, Yadav R, Singh AV. Ivermectin: potential role as repurposed drug for COVID-19. Malays J Med Sci. 2020; 27(4): 154-8.

Perišić O. Recognition of potential COVID-19 drug treatments through the study of existing protein-drug and proteinprotein structures: an analysis of kinetically active residues. biomolecules. 2020; 10(9): 1346.

Khan Z, Ghafoor D, Khan A, Ualiyeva D, Khan SA, Bilal H, et al. Diagnostic approaches and potential therapeutic options for coronavirus disease (COVID-19). New Microbes New Infect. 2020; 100770

Li N, Zhao L, Zhan X. Quantitative proteomics reveals a broadspectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2020.

Parvez MSA, Karim MA, Hasan M, Jaman J, Karim Z, Tahsin T, et al. Prediction of potential inhibitors for RNA-dependent RNA polymerase of SARS-CoV-2 using comprehensive drug repurposing and molecular docking approach. Int J Biol Macromol. 2020; 163: 1787-97.

Jans DA, Wagstaff KM. Ivermectin as a broad-spectrum hostdirected antiviral: the real deal?. Cells. 2020.

Jans DA, Martin AJ, Wagstaff KM. Inhibitors of nuclear transport. Curr Opin Cell Biol. 2019; 58: 50-60.

Yang SNY, Atkinson SC, Wang C, Lee A, Bogoyevitch MA, Borg NA, et al. The broad spectrum antiviral ivermectin targets the host nuclear transport importin α/β1 heterodimer. Antiviral Res. 2020; 177: 104760.

Lehrer S, Rheinstein PH. Ivermectin docks to the SARS-CoV-2 spike receptor-binding domain attached to ACE2. Vivo Athens Greece. 2020; 34(5): 3023-6.

Rajter JC, Sherman MS, Fatteh N, Vogel F, Sacks J, Rajter J-J. Use of ivermectin is associated with lower mortality in hospitalized patients with COVID-19 (ICON study). Chest. 2020.

Marchese V, Crosato V, Gulletta M, Castelnuovo F, Cristini G, Matteelli A, et al. Strongyloides infection manifested during immunosuppressive therapy for SARS-CoV-2 pneumonia. Infection. 2020.

Argentina.gob.ar. Un estudio demuestra la respuesta antiviral de la ivermectina en pacientes con COVID-19 [Internet]. 2020. Disponible en: https://www.argentina.gob.ar/noticias/unestudio-demuestra-la-respuesta-antiviral-de-la-ivermectina-enpacientes-con-covid-19

ClinicalTrials.gov. Prophylactic ivermectin in COVID-19 contacts - Full text view [Internet]. 2020. Disponible en: https:// clinicaltrials.gov/ct2/show/NCT04422561

ClinicalTrials.gov. Home [Internet]. 2020. Disponible en: https:// clinicaltrials.gov/

ClinicalTrials.gov. A pilot study for COVID-19 outpatient treatment with the combination of ivermectin-azithromycin-cholecalciferol [Internet]. 2020. Disponible en: https://clinicaltrials.gov/ct2/ show/NCT04399746

ClinicalTrials.gov. Efficacy of ivermectin in Covid-19: a randomized controlled trial [Internet]. 2020. Disponible en: https://clinicaltrials.gov/ct2/show/NCT04392713

ClinicalTrials.gov. Effectiveness of ivermectin as add-on therapy in COVID-19 management (An externally controlled pilot trial) [Internet]. 2020. Disponible en: https://clinicaltrials.gov/ct2/ show/NCT04343092

ClinicalTrials.gov. To study the effectiveness of ivermectin with standard of care treatment versus standard of care treatment for COVID 19 cases. A pilot study [Internet]. 2020. Disponible en: https://clinicaltrials.gov/ct2/show/NCT04373824

ClinicalTrials.gov. Clinical trial evaluating safety and efficacy of ivermectin and nitazoxanide combination as adjuvant therapy in COVID-19 newly diagnosed egyptian patients: a Tanta University Hope [Internet]. 2020. Disponible en: https://clinicaltrials.gov/ ct2/show/NCT04360356

ClinicalTrials.gov. Evaluation of ivermectin, aspirin, dexamethasone and enoxaparin as treatment of Covid-19 [Internet]. 2020. Disponible en: https://clinicaltrials.gov/ct2/ show/NCT04425863

ClinicalTrials.gov. Randomized, multi-arm phase II trial of novel agents for treatment of high-risk COVID-19 positive patients [Internet]. 2020. Disponible en: https://clinicaltrials.gov/ct2/ show/NCT04374019

ClinicalTrials.gov. A comparative observational study on ivermectin and hydroxychloroquine on the COVID19 patients in Bangladesh [Internet]. 2020. Disponible en: https://clinicaltrials. gov/ct2/show/NCT04434144

ClinicalTrials.gov. Efficacy and safety of hydroxychloroquine and ivermectin in hospitalized no critical patients secondary to COVID-19 infection: randomized controlled trial [Internet]. 2020. Disponible en: https://clinicaltrials.gov/ct2/show/NCT04391127

ClinicalTrials.gov. Novel treatment regimens in treatment of COVID-19 [Internet]. 2020. Disponible en: https://clinicaltrials. gov/ct2/show/NCT04382846

ClinicalTrials.gov. Ivermectin vs. Placebo for the treatment of patients with mild to moderate COVID-19 to prevent progression to severe infection and to decrease viral shedding - a double blind, randomized controlled trial [Internet]. 2020. Disponible en: https://clinicaltrials.gov/ct2/show/NCT04429711

ClinicalTrials.gov. A randomized open-label prophylaxis trial among migrant workers at high-risk of COVID-19 (DORM Trial) [Internet]. 2020. Disponible en: https://clinicaltrials.gov/ct2/ show/NCT04446104

ClinicalTrials.gov. A pilot, proof of concept trial to prove ivermectin efficacy in the reduction of SARS-CoV-2 replication at early stages of COVID-19 [Internet]. 2020. Disponible en: https://clinicaltrials.gov/ct2/show/NCT04381884

ClinicalTrials.gov. Use of ivermectin as a therapeutic option for patients with COVID-19 [Internet]. 2020. Disponible en: https:// clinicaltrials.gov/ct2/show/NCT04445311

ClinicalTrials.gov. Multicenter, double-blind, randomized, placebo-controlled study to assess the efficacy, safety and tolerability of ivermectin in mild virus-positive subjects SARSCoV-2 with or without symptoms [Internet]. 2020. Disponible en: https://clinicaltrials.gov/ct2/show/NCT04407507

ClinicalTrials.gov. USEFULNESS of topic ivermectin and carrageenan to prevent contagion of Covid among healthy people and health personnel [Internet]. 2020. Disponible en: https:// clinicaltrials.gov/ct2/show/NCT04425850

ClinicalTrials.gov. The efficacy of ivermectin and doxycycline in cOVID-19 treatment [Internet]. 2020. Disponible en: https:// clinicaltrials.gov/ct2/show/NCT04403555

ClinicalTrials.gov. A phase III trial to promote recovery from Covid 19 with combined doxycycline and ivermectin along standard care [Internet]. 2020. Disponible en: https://clinicaltrials.gov/ ct2/show/NCT04523831

ClinicalTrials.gov. The use of ivermectin in the treatment of COVID 19 patients [Internet]. 2020. Disponible en: https:// clinicaltrials.gov/ct2/show/NCT04425707

ClinicalTrials.gov. Clinical study evaluating the efficacy of ivermectin and nitazoxanide in COVID-19 treatment [Internet]. 2020. Disponible en: https://clinicaltrials.gov/ct2/show/ NCT04351347

ClinicalTrials.gov. Ivermectin and doxycycline in combination or ivermectin alone for the treatment of adult bangladeshi patients hospitalized for COVID-19: a randomised, double-blind, placebocontrolled trial. [Internet]. 2020. Disponible en: https:// clinicaltrials.gov/ct2/show/NCT04407130

ClinicalTrials.gov. Controlled randomized clinical trial on using ivermectin with doxycycline for treating COVID-19 patients in Baghdad, Iraq [Internet]. 2020. Disponible en: https:// clinicaltrials.gov/ct2/show/NCT04591600

ClinicalTrials.gov. Comparative efficacy of ivermectin versus combination of hydroxychloroquine plus Darunavir/Ritonavir for shortening duration of SARS-CoV2 detection from respiratory secretion among asymptomatic or afebrile COVID-19 infection [Internet]. 2020. Disponible en: https://clinicaltrials.gov/ct2/ show/NCT04435587

ClinicalTrials.gov. Phase 2 clinical trial to compare the efficacy and safety of different doses of ivermectin in patients diagnosed with the New Coronavirus Infection (SARS-CoV-2) [Internet]. 2020. Disponible en: https://clinicaltrials.gov/ct2/show/NCT04431466

ClinicalTrials.gov. Anti-Androgen treatment for COVID-19 [Internet]. 2020. Disponible en: https://clinicaltrials.gov/ct2/ show/NCT04446429

ClinicalTrials.gov. Sub-cutaneous ivermectin in combination with and without oral zinc and nigella sativa: a placebo randomized control trial on mild to moderate COVID-19 patients [Internet]. 2020. Disponible en: https://clinicaltrials.gov/ct2/show/ NCT04472585

ClinicalTrials.gov. Randomized, placebo controlled, double blind clinical trial to evaluate the efficacy of molecule D11AX22 in adults patients from Valle Del Cauca, Colombia with early stages of SARS COV2/COVID-19 [Internet]. 2020. Disponible en: https:// clinicaltrials.gov/ct2/show/NCT04405843

ClinicalTrials.gov. Comparative study of hydroxychloroquine and ivermectin in COVID-19 prophylaxis [Internet]. 2020. Disponible en: https://clinicaltrials.gov/ct2/show/NCT04384458

ClinicalTrials.gov. Randomized, doubled-blind phase II trial evaluating the use of ivermectin plus losartan for prophylaxis of severe events in cancer patients with recent diagnosis of COVID-19 [Internet]. 2020. Disponible en: https://clinicaltrials. gov/ct2/show/NCT04447235

ClinicalTrials.gov. Worldwide Trends on COVID-19 research after the declaration of COVID-19 pandemic: an observational study [Internet]. 2020. Disponible en: https://clinicaltrials.gov/ct2/ show/NCT04460547

ClinicalTrials.gov. Sars-CoV-2/COVID-19 Ivermectin NavarraISGlobal Trial - Full text view [Internet]. 2020. Disponible en: https://clinicaltrials.gov/ct2/show/NCT04390022

ClinicalTrials.gov. COVidIVERmectin: ivermectin for treatment of covid-19 - Full text view [Internet]. 2020. Disponible en: https:// clinicaltrials.gov/ct2/show/NCT04438850

ClinicalTrials.gov. Ivermectin to prevent hospitalizations in COVID-19: randomized, double-blind, placebo-controlled [Internet]. 2020. Disponible en: https://clinicaltrials.gov/ct2/ show/NCT04529525

ClinicalTrials.gov. Ivermectin inhalation forms in the management of COVID-19 egyptian patients [Internet]. 2020. Disponible en: https://clinicaltrials.gov/ct2/show/NCT04510233

ClinicalTrials.gov. The safety and efficacy outcome of ivermectin plus doxycycline in treatment of RT-PCR positive adult mild Covid-19 cases: a randomized double blind placebo controlled trial [Internet]. 2020. Disponible en: https://clinicaltrials.gov/ ct2/show/NCT04551755

ClinicalTrials.gov. Trial of combination therapy to treat COVID-19 infection - Full text view [Internet]. 2020. Disponible en: https:// clinicaltrials.gov/ct2/show/NCT04482686

ClinicalTrials.gov. Effectiveness and safety of ivermectin for the prevention of Covid-19 infection in colombian health personnel at all levels of care, during the 2020 pandemic: a randomized clinical controled trial [Internet]. 2020. Disponible en: https:// clinicaltrials.gov/ct2/show/NCT04527211

ClinicalTrials.gov. Outpatient use of ivermectin in COVID-19 [Internet]. 2020. Disponible en: https://clinicaltrials.gov/ct2/ show/NCT04530474

ClinicalTrials.gov. Effect of a combination of nitazoxanide, ribavirin and ivermectin plus zinc supplement on the clearance of COVID-19: a Pilot Sequential Clinical Trial [Internet]. 2020. Disponible en: https://clinicaltrials.gov/ct2/show/NCT04392427

Momekov G, Momekova D. Ivermectin as a potential COVID-19 treatment from the pharmacokinetic point of view: antiviral levels are not likely attainable with known dosing regimens. medRxiv. 2020.

Guzzo CA, Furtek CI, Porras AG, Chen C, Tipping R, Clineschmidt CM, et al. Safety, tolerability, and pharmacokinetics of escalating high doses of ivermectin in healthy adult subjects. J Clin Pharmacol. 2002; 42(10): 1122-33.

Liu Q, Guan J, Qin L, Zhang X, Mao S. Physicochemical properties affecting the fate of nanoparticles in pulmonary drug delivery. Drug Discov Today. 2020; 25(1): 150-9.

Ho D-K, Nichols BLB, Edgar KJ, Murgia X, Loretz B, Lehr C-M. Challenges and strategies in drug delivery systems for treatment of pulmonary infections. Eur J Pharm Biopharm. 2019; 144: 110-24.

Peña-Silva R, Duffull SB, Steer AC, Jaramillo-Rincon SX, Gwee A, Zhu X. Pharmacokinetic considerations on the repurposing of ivermectin for treatment of COVID-19. Br J Clin Pharmacol. 2020.

Elkholy KO, Hegazy O, Erdinc B, Abowali H. Ivermectin: a closer look at a potential remedy. Cureus. 2020; 12(9): e10378.

Ji L, Cen J, Lin S, Hu C, Fang H, Xu J, et al. Study on the subacute inhalation toxicity of ivermectin TC in rats. Chin J Comp Med. 2016; 26(3): 70-4.

Chaccour C, Abizanda G, Irigoyen-Barrio Á, Casellas A, Aldaz A, Martínez-Galán F, et al. Nebulized ivermectin for COVID-19 and other respiratory diseases, a proof of concept, dose-ranging study in rats. Sci Rep. 2020; 10(1): 17073.

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Publicado

2020-12-30

Cómo citar

Pareja Cruz , A. ., & Luque Espino, J. C. . (2020). Seguridad y eficacia de ivermectina en tiempos de COVID-19. Horizonte Médico (Lima), 21(1), e1331. https://doi.org/10.24265/horizmed.2021.v20n1.10

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