Due to the serious problems caused by the COVID-19 pandemic, several publications have proposed prevention protocols for infection by Sars-CoV-2 [11 Ather A, Patel B, Ruparel NB, Diogenes A, Hargreaves KM. Coronavirus disease 19 (COVID-19): implications for clinical dental care. J Endod. 2020;46(5):584-595. http://dx.doi.org/10.1016/j.joen.2020.03.008
https://doi.org/10.1016/j.joen.2020.03.0...
2 Ahmed MA, Jouhar R, Ahmed N, Adnan S, Aftab M, Zafar MS, et al. Fear and practice modifications among dentists to combat novel coronavirus disease (COVID-19) outbreak. Int J Environ Res Public Health. 2020 Apr 19;17(8):2821. http://dx.doi.org/10.3390/ijerph17082821.
https://doi.org/10.3390/ijerph17082821...
3 Baghizadeh Fini M. What dentists need to know about COVID-19. Oral Oncol. 2020 Jun;105:104741. http://dx.doi.org/10.1016/j.oraloncology.2020.104741
https://doi.org/10.1016/j.oraloncology.2...
-44 Alharbi A, Alharbi S, Alqaidi S. Guidelines for dental care provision during the COVID-19 pandemic. Saudi Dent J. 2020;32(4):181-186. http://dx.doi.org/10.1016/j.sdentj.2020.04.001
https://doi.org/10.1016/j.sdentj.2020.04...
]. This has led dentists to seek information on chemoprophylaxis, since dental staff must provide care for patients with urgent need [55 Coulthard P. Dentistry and coronavirus (COVID-19) – moral decision-making. Br Dent J. 2020;228(7):503-505. http://dx.doi.org/10.1038/s41415-020-1482-1
https://doi.org/10.1038/s41415-020-1482-...
].
Ivermectin has antiviral effects on viruses whose genetic material is DNA and those the present RNA, as is the case of the novel coronavirus [66 Heidary F, Gharebaghi R. Ivermectin: a systematic review from antiviral effects to COVID-19 complementary regimen. J Antibiot (Tokyo). 2020;73(9):593-602. http://dx.doi.org/10.1038/s41429-020-0336-z
https://doi.org/10.1038/s41429-020-0336-...
]. The most widely accepted mechanism of action for ivermectin is the inhibition of the nuclear importation of viral proteins mediated by the heterodimer importin a/ß1, which are indispensable to the replication of RNA viruses [77 Wagstaff KM, Sivakumaran H, Heaton SM, Harrich D, Jans DA. Ivermectin is a specific inhibitor of importin ?/?-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus. Biochem J. 2012;443(3):851-856. http://dx.doi.org/10.1042/BJ20120150.
https://doi.org/10.1042/BJ20120150...
].
Caly et al. [88 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 Jun;178:104787. http://dx.doi.org/10.1016/j.antiviral.2020.104787
https://doi.org/10.1016/j.antiviral.2020...
] demonstrated the effect of ivermectin on Sars-CoV-2. The authors found that the continuous use of 5 microM of ivermectin for two days in an isolated culture of Vero/hSLAM cells infected with Sars-CoV-2 killed the novel coronavirus nearly completely [88 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 Jun;178:104787. http://dx.doi.org/10.1016/j.antiviral.2020.104787
https://doi.org/10.1016/j.antiviral.2020...
]. Despite this promising discovery, the activity of ivermectin has not yet been clinically proven in humans.
Regarding pharmacokinetics, in its daily release on evidence related to COVID-19 [99 Brasil. Ministério da Saúde. Informe Diário de Evidên-cias – covid-19. Brasília (DF); [cited 2020 jul 9]. Available from: <http://portalarquivos.saude.gov.br/images/pdf/2020/April/20/InformeDiario-referente-20-04.pdf>
http://portalarquivos.saude.gov.br/image...
], the Brazilian Health Ministry presented a study in which the authors report that doses that produce inhibitory concentrations of SARS-CoV-2 cannot be achieved in humans, as the maximum dose permitted by the US Food and Drug Administration (FDA) is 200 mg/kg [1010 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 Oct;42(10):1122-1133. http://dx.doi.org/10.1177/009127002401382731
https://doi.org/10.1177/0091270024013827...
] and safe therapeutic doses reach blood levels in the range of 20 to 80 ng/ml [1111 Canga AG, Prieto AMS, Liébana MJD, Martínez NF, Vega MS, Vieitez JJG. The pharmacokinetics and interactions of ivermectin in humans--a mini-review. AAPS J. 2008;10(1):42-46. http://dx.doi.org/10.1208/s12248-007-9000-9
https://doi.org/10.1208/s12248-007-9000-...
] Caly et al. [88 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 Jun;178:104787. http://dx.doi.org/10.1016/j.antiviral.2020.104787
https://doi.org/10.1016/j.antiviral.2020...
] report that ivermectin has an in vitro inhibitory concentration (IC50) of SARS-CoV-2 35 fold higher than the maximum plasma concentration (Cmax) reached after the oral administration of the approved dose of ivermectin for administration to humans [88 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 Jun;178:104787. http://dx.doi.org/10.1016/j.antiviral.2020.104787
https://doi.org/10.1016/j.antiviral.2020...
] This observation limits the execution of tests on humans and suggests a low likelihood of success regarding the treatment of COVID-19 [1212 Schmith VD, Zhou JJ, Lohmer LRL. The Approved Dose of Ivermectin Alone is not the Ideal Dose for the Treatment of COVID-19. Clin Pharmacol Ther. 2020;108(4):762-765. http://dx.doi.org/10.1002/cpt.1889
https://doi.org/10.1002/cpt.1889...
,1313 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. Biotechnol Biotec Eq. 2020;34:1, 469-474. http://dx.doi.org/10.1080/13102818.2020.1775118
https://doi.org/10.1080/13102818.2020.17...
].
After noting an increase in the consumption of ivermectin, the FDA warned the population regarding the side effects and to not use veterinary products, not to use products of a dubious origin, not to take the medication without a medical prescription and only take drugs dispensed by pharmacists at regulated pharmacies [1414 Food and Drug Administration. FDA Letter to Stakeholders: Do Not Use Ivermectin Intended for Animals as Treatment for COVID-19 in Humans. Washington (DC), 2020. [cited 2020 Jul 9]. Available from: <https://www.fda.gov/animal-veterinary/product-safety-information/fda-letter-stakeholders-do-not-use-ivermectin-intended-animals-treatment-covid-19-humans>
https://www.fda.gov/animal-veterinary/pr...
]
Ivermectin is considered safe, with few side effects when taken orally [66 Heidary F, Gharebaghi R. Ivermectin: a systematic review from antiviral effects to COVID-19 complementary regimen. J Antibiot (Tokyo). 2020;73(9):593-602. http://dx.doi.org/10.1038/s41429-020-0336-z
https://doi.org/10.1038/s41429-020-0336-...
] However, its concomitant use with another antiviral medication is associated with neurotoxicity [1515 Chandler RE. Serious Neurological Adverse Events after Ivermectin-Do They Occur beyond the Indication of Onchocerciasis? Am J Trop Med Hyg. 2018;98(2):382-388. http://dx.doi.org/10.4269/ajtmh.17-0042
https://doi.org/10.4269/ajtmh.17-0042...
] The Brazilian Society of Pneumology and Phthisiology reports that there is no scientific evidence that ivermectin, chloroquine or hydroxychloroquine, either alone or in combination, is capable of avoiding the installation of the disease in non-infected individuals [1616 Sociedade Brasileira de Pneumologia e Tisiologia. Posiciona-mento da SBPT acerca da profilaxia e tratamento da COVID-19. Brasília (DF), 2020. [cited 2020 Jul 9]. Available from: <https://sbpt.org.br/portal/wp-content/uploads/2020/06/Profilaxia-e-tratamento-COVID-19.pdf>
https://sbpt.org.br/portal/wp-content/up...
] There are four ongoing studies that are expected to be concluded between August and December 2020, the results of which could lead to changes in the recommendations if clinical benefits are demonstrated [1717 Pan American Health Organization. Ongoing Living Update of Potential COVID-19 Therapeutics: summary of rapid systematic reviews. Washington (DC), 2020. [cited 2020 July 09]. Available from: <https://www.paho.org/en/documents/ongoing-living-update-potential-covid-19-therapeutics-summary-rapid-systematic-reviews>
https://www.paho.org/en/documents/ongoin...
]
The administration of ivermectin in hospitalized patients has been associated with a shorter hospital stay and a reduction in the mortality rate [1818 Patel AN, Desai SS, Grainger DW, Mehra MR. Usefulness of Ivermectin in COVID-19 Illness (April 6, 2020). [cited 2020 July 09]. Available from: <http://www.proyectodime.info/documents/219/Utilidad_de_la_ivermectina.pdf>
http://www.proyectodime.info/documents/2...
]. To date, however, there is no robust scientific evidence attesting to the effectiveness and safety of ivermectin as chemoprophylaxis for COVID-19.
How to cite this article
-
Pinheiro MLP, Rocha RL, Guimarães MM. Is chemoprophylaxis with ivermectin in dentistry effective at preventing COVID-19?. RGO, Rev Gaúch Odontol. 2021;69:e20210025. http://dx.doi.org/10.1590/1981-86372021002520200133
REFERENCES
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1Ather A, Patel B, Ruparel NB, Diogenes A, Hargreaves KM. Coronavirus disease 19 (COVID-19): implications for clinical dental care. J Endod. 2020;46(5):584-595. http://dx.doi.org/10.1016/j.joen.2020.03.008
» https://doi.org/10.1016/j.joen.2020.03.008 -
2Ahmed MA, Jouhar R, Ahmed N, Adnan S, Aftab M, Zafar MS, et al. Fear and practice modifications among dentists to combat novel coronavirus disease (COVID-19) outbreak. Int J Environ Res Public Health. 2020 Apr 19;17(8):2821. http://dx.doi.org/10.3390/ijerph17082821.
» https://doi.org/10.3390/ijerph17082821 -
3Baghizadeh Fini M. What dentists need to know about COVID-19. Oral Oncol. 2020 Jun;105:104741. http://dx.doi.org/10.1016/j.oraloncology.2020.104741
» https://doi.org/10.1016/j.oraloncology.2020.104741 -
4Alharbi A, Alharbi S, Alqaidi S. Guidelines for dental care provision during the COVID-19 pandemic. Saudi Dent J. 2020;32(4):181-186. http://dx.doi.org/10.1016/j.sdentj.2020.04.001
» https://doi.org/10.1016/j.sdentj.2020.04.001 -
5Coulthard P. Dentistry and coronavirus (COVID-19) – moral decision-making. Br Dent J. 2020;228(7):503-505. http://dx.doi.org/10.1038/s41415-020-1482-1
» https://doi.org/10.1038/s41415-020-1482-1 -
6Heidary F, Gharebaghi R. Ivermectin: a systematic review from antiviral effects to COVID-19 complementary regimen. J Antibiot (Tokyo). 2020;73(9):593-602. http://dx.doi.org/10.1038/s41429-020-0336-z
» https://doi.org/10.1038/s41429-020-0336-z -
7Wagstaff KM, Sivakumaran H, Heaton SM, Harrich D, Jans DA. Ivermectin is a specific inhibitor of importin ?/?-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus. Biochem J. 2012;443(3):851-856. http://dx.doi.org/10.1042/BJ20120150.
» https://doi.org/10.1042/BJ20120150 -
8Caly 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 Jun;178:104787. http://dx.doi.org/10.1016/j.antiviral.2020.104787
» https://doi.org/10.1016/j.antiviral.2020.104787 -
9Brasil. Ministério da Saúde. Informe Diário de Evidên-cias – covid-19. Brasília (DF); [cited 2020 jul 9]. Available from: <http://portalarquivos.saude.gov.br/images/pdf/2020/April/20/InformeDiario-referente-20-04.pdf>
» http://portalarquivos.saude.gov.br/images/pdf/2020/April/20/InformeDiario-referente-20-04.pdf -
10Guzzo 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 Oct;42(10):1122-1133. http://dx.doi.org/10.1177/009127002401382731
» https://doi.org/10.1177/009127002401382731 -
11Canga AG, Prieto AMS, Liébana MJD, Martínez NF, Vega MS, Vieitez JJG. The pharmacokinetics and interactions of ivermectin in humans--a mini-review. AAPS J. 2008;10(1):42-46. http://dx.doi.org/10.1208/s12248-007-9000-9
» https://doi.org/10.1208/s12248-007-9000-9 -
12Schmith VD, Zhou JJ, Lohmer LRL. The Approved Dose of Ivermectin Alone is not the Ideal Dose for the Treatment of COVID-19. Clin Pharmacol Ther. 2020;108(4):762-765. http://dx.doi.org/10.1002/cpt.1889
» https://doi.org/10.1002/cpt.1889 -
13Momekov 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. Biotechnol Biotec Eq. 2020;34:1, 469-474. http://dx.doi.org/10.1080/13102818.2020.1775118
» https://doi.org/10.1080/13102818.2020.1775118 -
14Food and Drug Administration. FDA Letter to Stakeholders: Do Not Use Ivermectin Intended for Animals as Treatment for COVID-19 in Humans. Washington (DC), 2020. [cited 2020 Jul 9]. Available from: <https://www.fda.gov/animal-veterinary/product-safety-information/fda-letter-stakeholders-do-not-use-ivermectin-intended-animals-treatment-covid-19-humans>
» https://www.fda.gov/animal-veterinary/product-safety-information/fda-letter-stakeholders-do-not-use-ivermectin-intended-animals-treatment-covid-19-humans -
15Chandler RE. Serious Neurological Adverse Events after Ivermectin-Do They Occur beyond the Indication of Onchocerciasis? Am J Trop Med Hyg. 2018;98(2):382-388. http://dx.doi.org/10.4269/ajtmh.17-0042
» https://doi.org/10.4269/ajtmh.17-0042 -
16Sociedade Brasileira de Pneumologia e Tisiologia. Posiciona-mento da SBPT acerca da profilaxia e tratamento da COVID-19. Brasília (DF), 2020. [cited 2020 Jul 9]. Available from: <https://sbpt.org.br/portal/wp-content/uploads/2020/06/Profilaxia-e-tratamento-COVID-19.pdf>
» https://sbpt.org.br/portal/wp-content/uploads/2020/06/Profilaxia-e-tratamento-COVID-19.pdf -
17Pan American Health Organization. Ongoing Living Update of Potential COVID-19 Therapeutics: summary of rapid systematic reviews. Washington (DC), 2020. [cited 2020 July 09]. Available from: <https://www.paho.org/en/documents/ongoing-living-update-potential-covid-19-therapeutics-summary-rapid-systematic-reviews>
» https://www.paho.org/en/documents/ongoing-living-update-potential-covid-19-therapeutics-summary-rapid-systematic-reviews -
18Patel AN, Desai SS, Grainger DW, Mehra MR. Usefulness of Ivermectin in COVID-19 Illness (April 6, 2020). [cited 2020 July 09]. Available from: <http://www.proyectodime.info/documents/219/Utilidad_de_la_ivermectina.pdf>
» http://www.proyectodime.info/documents/219/Utilidad_de_la_ivermectina.pdf -
19Patel AN, Desai SS, Grainger DW, Mehra MR. Ivermectin in COVID-19 Related Critical Illness [retracted] [cited 2020 July 09]. Available from: https://www.isglobal.org/documents/10179/6022921/Patel+et+al.+2020+version+1.pdf
» https://www.isglobal.org/documents/10179/6022921/Patel+et+al.+2020+version+1.pdf
Publication Dates
-
Publication in this collection
19 July 2021 -
Date of issue
2021
History
-
Received
31 July 2020 -
Accepted
15 Oct 2020