Editing Ribavirin (section)

==Medical uses==
Ribavirin is primarily used to treat chronic [[hepatitis C]] and [[viral hemorrhagic fever]]s (an orphan indication in most countries).<ref name=MSR>{{cite web|title=Rebetol, Ribasphere (ribavirin) dosing, indications, interactions, adverse effects, and more|work=Medscape Reference|publisher=WebMD|access-date=23 February 2014 |url= http://reference.medscape.com/drug/rebetol-ribasphere-ribavirin-342625#showall|url-status=live|archive-url=https://web.archive.org/web/20140228132755/http://reference.medscape.com/drug/rebetol-ribasphere-ribavirin-342625#showall|archive-date=28 February 2014}}</ref> Its [[efficacy]] for these purposes has been questioned in light of its [[Food and Drug Administration]] [[boxed warning]] against its use as monotherapy for chronic hepatitis C. Thus, it may be prescribed in the United States only as an [[Adjuvant therapy|adjunct]] to one or more other medications. Its efficacy against viruses other than HCV, including those that cause viral hemorrhagic fever, has not been conclusively demonstrated. In effect, it is not approved in the United States for treatment of viruses other than HCV.<ref name="Drugs.com_2023">{{Cite web |date=2023-03-27 |title=Copegus: Package Insert |url=https://www.drugs.com/pro/copegus.html |access-date=2024-01-19 |website=Drugs.com |language=en}}</ref><ref name="Safrin_2024">{{Cite book | vauthors = Safrin S |title=Katzung's Basic & Clinical Pharmacology |publisher=McGraw Hill |year=2024 |edition=16th |at=Other antiviral agents: Ribavirin |chapter=Chapter 49: Antiviral Agents}}</ref>

=== Hepatitis C ===
For [[Chronic condition|chronic]] HCV infection, the oral (capsule or tablet) form of ribavirin is used only in combination with [[Pegylated interferon alpha|pegylated]] [[interferon alfa]].<ref name="Safrin_2024" /><ref>{{cite journal | vauthors = Paeshuyse J, Dallmeier K, Neyts J | title = Ribavirin for the treatment of chronic hepatitis C virus infection: a review of the proposed mechanisms of action | journal = Current Opinion in Virology | volume = 1 | issue = 6 | pages = 590–598 | date = December 2011 | pmid = 22440916 | doi = 10.1016/j.coviro.2011.10.030 }}</ref><ref>{{cite journal | vauthors = Flori N, Funakoshi N, Duny Y, Valats JC, Bismuth M, Christophorou D, Daurès JP, Blanc P | title = Pegylated interferon-α2a and ribavirin versus pegylated interferon-α2b and ribavirin in chronic hepatitis C : a meta-analysis | journal = Drugs | volume = 73 | issue = 3 | pages = 263–277 | date = March 2013 | pmid = 23436591 | doi = 10.1007/s40265-013-0027-1 | s2cid = 46334977 }}</ref><ref name="Druyts 961–7">{{cite journal | vauthors = Druyts E, Thorlund K, Wu P, Kanters S, Yaya S, Cooper CL, Mills EJ | title = Efficacy and safety of pegylated interferon alfa-2a or alfa-2b plus ribavirin for the treatment of chronic hepatitis C in children and adolescents: a systematic review and meta-analysis | journal = Clinical Infectious Diseases | volume = 56 | issue = 7 | pages = 961–967 | date = April 2013 | pmid = 23243171 | doi = 10.1093/cid/cis1031 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Zeuzem S, Poordad F | title = Pegylated-interferon plus ribavirin therapy in the treatment of CHC: individualization of treatment duration according to on-treatment virologic response | journal = Current Medical Research and Opinion | volume = 26 | issue = 7 | pages = 1733–1743 | date = July 2010 | pmid = 20482242 | doi = 10.1185/03007995.2010.487038 | s2cid = 206965239 }}</ref> [[Statin]]s may improve this combination's efficacy in treating hepatitis C.<ref>{{cite journal | vauthors = Zhu Q, Li N, Han Q, Zhang P, Yang C, Zeng X, Chen Y, Lv Y, Liu X, Liu Z | title = Statin therapy improves response to interferon alfa and ribavirin in chronic hepatitis C: a systematic review and meta-analysis | journal = Antiviral Research | volume = 98 | issue = 3 | pages = 373–379 | date = June 2013 | pmid = 23603497 | doi = 10.1016/j.antiviral.2013.04.009 }}</ref> When possible, [[genotyping]] of the specific viral [[Strain (biology)|strain]] is done; and ribavirin is only used as a dose-escalating{{Efn-la|Begins with a low dose, at or near the lowest point of the expected [[therapeutic index]], and then the dose is progressively increased until achieving desired effects.|name=a|group=}} adjuvant to specific combinations of genotypes and other medications.<ref name="Chung_2018">{{cite journal | vauthors = Chung RT, Ghany MG, Kim AY, Marks KM, Naggie S, Vargas HE, Aronsohn AI, Bhattacharya D, Broder T, Falade-Nwulia OO, Fontana RJ, Gordon SC, Heller T, Holmberg SD, Jhaveri R, Jonas MM, Kiser JJ, Linas BP, Lo Re V, Morgan TR, Nahass RG, Peters MG, Reddy KR, Reynolds A, Scott JD, Searson G, Swan T, Terrault NA, Trooskin SB, Wong JB | collaboration = AASLD-IDSA HCV Guidance Panel | title = Hepatitis C Guidance 2018 Update: AASLD-IDSA Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection | journal = Clinical Infectious Diseases | volume = 67 | issue = 10 | pages = 1477–1492 | date = October 2018 | pmid = 30215672 | pmc = 7190892 | doi = 10.1093/cid/ciy585 }}</ref>

Acute hepatitis C infection (within the first 6 months) often does not require immediate treatment, as many infections eventually resolve without treatment.<ref name="Pawlotsky_2018">{{cite journal | title = EASL Recommendations on Treatment of Hepatitis C 2018 | journal = Journal of Hepatology | volume = 69 | issue = 2 | pages = 461–511 | date = August 2018 | pmid = 29650333 | doi = 10.1016/j.jhep.2018.03.026 | vauthors = Pawlotsky J, Negro F, Aghemo A, Berenguer M, Dalgard O, Dusheiko G, Marra F, Puoti M, Wedemeyer H }}</ref> When the decision is made to treat acute hepatitis C, ribavirin may be used as an adjunct to several drug combinations.<ref name="Chung_2018" /> However, other medications are still preferred.<ref name="Chung_2018" /><ref name="Pawlotsky_2018" />

=== Viral hemorrhagic fever ===
Ribavirin is the only known treatment for a variety of [[viral hemorrhagic fever]]s, including [[Lassa fever]], [[Crimean-Congo hemorrhagic fever]], [[Venezuelan hemorrhagic fever]], and [[Hantavirus]] infection, although data regarding these infections are scarce and the drug might be effective only in early stages.<ref>{{cite book|url=http://www.rki.de/cln_091/nn_468470/DE/Content/InfAZ/Steckbriefe/Steckbriefe__120606,templateId=raw,property=publicationFile.pdf/Steckbriefe_120606.pdf|title=Steckbriefe seltener und importierter Infektionskrankheiten|trans-title=Characteristics of rare and imported infectious diseases|publisher=[[Robert Koch Institute]]|isbn=978-3-89606-095-2|location=Berlin|year=2006|url-status=dead|archive-url=https://web.archive.org/web/20110929151854/http://www.rki.de/cln_091/nn_468470/DE/Content/InfAZ/Steckbriefe/Steckbriefe__120606%2CtemplateId%3Draw%2Cproperty%3DpublicationFile.pdf/Steckbriefe_120606.pdf|archive-date=2011-09-29}}</ref><ref>{{cite journal | vauthors = Ascioglu S, Leblebicioglu H, Vahaboglu H, Chan KA | title = Ribavirin for patients with Crimean-Congo haemorrhagic fever: a systematic review and meta-analysis | journal = The Journal of Antimicrobial Chemotherapy | volume = 66 | issue = 6 | pages = 1215–1222 | date = June 2011 | pmid = 21482564 | doi = 10.1093/jac/dkr136 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Bausch DG, Hadi CM, Khan SH, Lertora JJ | title = Review of the literature and proposed guidelines for the use of oral ribavirin as postexposure prophylaxis for Lassa fever | journal = Clinical Infectious Diseases | volume = 51 | issue = 12 | pages = 1435–1441 | date = December 2010 | pmid = 21058912 | pmc = 7107935 | doi = 10.1086/657315 }}</ref><ref>{{cite journal | vauthors = Soares-Weiser K, Thomas S, Thomson G, Garner P | title = Ribavirin for Crimean-Congo hemorrhagic fever: systematic review and meta-analysis | journal = BMC Infectious Diseases | volume = 10 | pages = 207 | date = July 2010 | pmid = 20626907 | pmc = 2912908 | doi = 10.1186/1471-2334-10-207 | doi-access = free }}</ref> It is noted by the [[United States Army Medical Research Institute of Infectious Diseases]] (USAMRIID) that "Ribavirin has poor ''[[in vitro]]'' and ''[[in vivo]]'' activity against the [[filoviruses]] ([[Ebola]]<ref name="Goeijenbier2014">{{cite journal | vauthors = Goeijenbier M, van Kampen JJ, Reusken CB, Koopmans MP, van Gorp EC | title = Ebola virus disease: a review on epidemiology, symptoms, treatment and pathogenesis | journal = The Netherlands Journal of Medicine | volume = 72 | issue = 9 | pages = 442–448 | date = November 2014 | pmid = 25387613 | url = http://www.njmonline.nl/getpdf.php?t=a&id=10001148 | url-status = live | archive-url = https://web.archive.org/web/20141129144852/http://www.njmonline.nl/getpdf.php?t=a&id=10001148 | archive-date = 2014-11-29 }}</ref> and [[Marburg Virus|Marburg]]) and the [[flaviviruses]] ([[dengue]], [[yellow fever]], [[Omsk hemorrhagic fever]], and [[Kyasanur forest disease]])"<ref>{{Cite book|title = Medical Management of Biological Casualties Handbook|publisher = United States Government Printing Office|year = 2011|isbn = 978-0-16-090015-0|pages = 115}}</ref> The aerosol form has been used in the past to treat [[respiratory syncytial virus]]-related diseases in children, although the evidence to support this is rather weak.<ref>{{cite journal | vauthors = Ventre K, Randolph AG | title = Ribavirin for respiratory syncytial virus infection of the lower respiratory tract in infants and young children | journal = The Cochrane Database of Systematic Reviews | issue = 1 | pages = CD000181 | date = January 2007 | pmid = 17253446 | doi = 10.1002/14651858.CD000181.pub3 | veditors = Ventre K }}</ref>

Despite questions surrounding its efficacy, ribavirin remains the only antiviral known to be effective in treating Lassa fever.<ref>{{Cite web |date=2023-09-26 |title=Treatment {{!}} Lassa Fever {{!}} CDC |url=https://www.cdc.gov/vhf/lassa/treatment/index.html |access-date=2024-01-20 |archive-url=https://web.archive.org/web/20230926004520/https://www.cdc.gov/vhf/lassa/treatment/index.html |archive-date=2023-09-26 }}</ref>

It has been used (in combination with [[ketamine]], [[midazolam]], and [[amantadine]]) in treatment of [[rabies]].<ref>{{cite journal | vauthors = Hemachudha T, Ugolini G, Wacharapluesadee S, Sungkarat W, Shuangshoti S, Laothamatas J | title = Human rabies: neuropathogenesis, diagnosis, and management | journal = The Lancet. Neurology | volume = 12 | issue = 5 | pages = 498–513 | date = May 2013 | pmid = 23602163 | doi = 10.1016/S1474-4422(13)70038-3 | s2cid = 1798889 }}</ref>

=== Experimental uses ===
Experimental data indicate that ribavirin may have useful activity against [[canine distemper]] and [[Poxviridae|poxviruses]].<ref name=Elia2008>{{cite journal | vauthors = Elia G, Belloli C, Cirone F, Lucente MS, Caruso M, Martella V, Decaro N, Buonavoglia C, Ormas P | title = In vitro efficacy of ribavirin against canine distemper virus | journal = Antiviral Research | volume = 77 | issue = 2 | pages = 108–113 | date = February 2008 | pmid = 17949825 | doi = 10.1016/j.antiviral.2007.09.004 }}</ref><ref>{{cite journal | vauthors = Baker RO, Bray M, Huggins JW | title = Potential antiviral therapeutics for smallpox, monkeypox and other orthopoxvirus infections | journal = Antiviral Research | volume = 57 | issue = 1–2 | pages = 13–23 | date = January 2003 | pmid = 12615299 | pmc = 9533837 | doi = 10.1016/S0166-3542(02)00196-1 }}</ref> Ribavirin has also been used as a treatment for [[herpes simplex virus]]. One small study found that ribavirin treatment reduced the severity of herpes outbreaks and promoted recovery, as compared with placebo treatment.<ref>{{cite journal | vauthors = Bierman SM, Kirkpatrick W, Fernandez H | title = Clinical efficacy of ribavirin in the treatment of genital herpes simplex virus infection | journal = Chemotherapy | volume = 27 | issue = 2 | pages = 139–145 | year = 1981 | pmid = 7009087 | doi = 10.1159/000237969 }}</ref> Another study found that ribavirin potentiated the antiviral effect of [[acyclovir]].<ref>{{cite journal | vauthors = Pancheva SN | title = Potentiating effect of ribavirin on the anti-herpes activity of acyclovir | journal = Antiviral Research | volume = 16 | issue = 2 | pages = 151–161 | date = September 1991 | pmid = 1665959 | doi = 10.1016/0166-3542(91)90021-I }}</ref>

Some interest has been seen in its possible use as a treatment for cancers with elevated eukaryotic translation initiation factor eIF4E, especially [[acute myeloid leukemia]] (AML) as well as in head and neck cancers.<ref>{{cite journal | vauthors = Kast RE | title = Ribavirin in cancer immunotherapies: controlling nitric oxide helps generate cytotoxic lymphocyte | journal = Cancer Biology & Therapy | volume = 1 | issue = 6 | pages = 626–630 | date = November–December 2002 | pmid = 12642684 | doi = 10.4161/cbt.310 | s2cid = 24010404 | doi-access = free }}</ref><ref name="Ribavirin as an anti-cancer therapy">{{cite journal | vauthors = Borden KL, Culjkovic-Kraljacic B | title = Ribavirin as an anti-cancer therapy: acute myeloid leukemia and beyond? | journal = Leukemia & Lymphoma | volume = 51 | issue = 10 | pages = 1805–1815 | date = October 2010 | pmid = 20629523 | pmc = 2950216 | doi = 10.3109/10428194.2010.496506 }}</ref><ref name="Phase I study of induction chemothe">{{cite journal | vauthors = Dunn LA, Fury MG, Sherman EJ, Ho AA, Katabi N, Haque SS, Pfister DG | title = Phase I study of induction chemotherapy with afatinib, ribavirin, and weekly carboplatin and paclitaxel for stage IVA/IVB human papillomavirus-associated oropharyngeal squamous cell cancer | journal = Head & Neck | volume = 40 | issue = 2 | pages = 233–241 | date = February 2018 | pmid = 28963790 | pmc = 6760238 | doi = 10.1002/hed.24938 }}</ref><ref name="Pharmacodynamic and therapeutic pil">{{cite journal | vauthors = Burman B, Drutman SB, Fury MG, Wong RJ, Katabi N, Ho AL, Pfister DG | title = Pharmacodynamic and therapeutic pilot studies of single-agent ribavirin in patients with human papillomavirus-related malignancies | journal = Oral Oncology | volume = 128 | pages = 105806 | date = May 2022 | pmid = 35339025 | pmc = 9788648 | doi = 10.1016/j.oraloncology.2022.105806 }}</ref> Ribavirin targeted eIF4E in AML patients in monotherapy and combination studies and this corresponded to objective clinical responses including complete remissions.<ref>{{cite journal | vauthors = Assouline S, Culjkovic B, Cocolakis E, Rousseau C, Beslu N, Amri A, Caplan S, Leber B, Roy DC, Miller WH, Borden KL | title = Molecular targeting of the oncogene eIF4E in acute myeloid leukemia (AML): a proof-of-principle clinical trial with ribavirin | journal = Blood | volume = 114 | issue = 2 | pages = 257–260 | date = July 2009 | pmid = 19433856 | doi = 10.1182/blood-2009-02-205153 | s2cid = 28957125 | doi-access = free }}</ref><ref name="Assouline_2015"/><ref name="Assouline_2023"/> Ribavirin resistance in AML patients arose leading to loss of eIF4E targeting and relapse. Resistance was caused by deactivation of ribavirin through its glucuronidation in AML cells or impaired drug entry/retention in the AML cells.<ref name="Zahreddine_2014"/> There may be additional forms of ribavirin resistance displayed by cancer cells. In HPV related oropharyngeal cancers, ribavirin reduced levels of phosphorylated form of eIF4E in some patients.<ref name="Pharmacodynamic and therapeutic pil"/> The best response here was stable disease but another head and neck study had more promising results.<ref name="Phase I study of induction chemothe"/>