Editing Botulinum toxin (section)

==Medical uses==
Botulinum toxin is used to treat a number of therapeutic indications, many of which are not part of the approved drug label.<ref name="Al-Ghamdi">{{Cite journal |vauthors=Al-Ghamdi AS, Alghanemy N, Joharji H, Al-Qahtani D, Alghamdi H |date=January 2015 |title=Botulinum toxin: Non cosmetic and off-label dermatological uses |journal=Journal of Dermatology & Dermatologic Surgery |volume=19 |issue=1 |pages=1–8 |doi=10.1016/j.jdds.2014.06.002 |doi-access=free |title-link=doi }}</ref>

===Muscle spasticity===
Botulinum toxin is used to treat a number of disorders characterized by overactive muscle movement, including [[cerebral palsy]],<ref name=Farag2020/><ref name=Blumetti2019/> post-stroke [[spasticity]],<ref>{{cite journal |vauthors = Ozcakir S, Sivrioglu K |title = Botulinum toxin in poststroke spasticity |journal = Clinical Medicine & Research |volume = 5 |issue = 2 |pages = 132–138 |date = June 2007 |pmid = 17607049 |pmc = 1905930 |doi = 10.3121/cmr.2007.716 }}</ref> post-spinal cord injury spasticity,<ref>{{cite journal |vauthors = Yan X, Lan J, Liu Y, Miao J |title = Efficacy and Safety of Botulinum Toxin Type A in Spasticity Caused by Spinal Cord Injury: A Randomized, Controlled Trial |journal = Medical Science Monitor |volume = 24 |pages = 8160–8171 |date = November 2018 |pmid = 30423587 |pmc = 6243868 |doi = 10.12659/MSM.911296 }}</ref> [[dystonia|spasms]] of the head and neck,<ref>{{cite web |url=https://www.mayoclinic.org/diseases-conditions/cervical-dystonia/symptoms-causes/syc-20354123 |title=Cervical dystonia - Symptoms and causes |publisher=Mayo Clinic |date=28 January 2014 |access-date=14 October 2015 |archive-date=12 December 2018 |archive-url=https://web.archive.org/web/20181212142423/https://www.mayoclinic.org/diseases-conditions/cervical-dystonia/symptoms-causes/syc-20354123 |url-status=live }}</ref> [[blepharospasm|eyelid]],<ref name=Shukla2004>{{cite journal |vauthors = Shukla HD, Sharma SK |title = Clostridium botulinum: a bug with beauty and weapon |journal = Critical Reviews in Microbiology |volume = 31 |issue = 1 |pages = 11–18 |year = 2005 |pmid = 15839401 |doi = 10.1080/10408410590912952 |s2cid = 2855356 }}</ref> [[vaginismus|vagina]],<ref>{{cite journal |vauthors = Pacik PT |title = Botox treatment for vaginismus |journal = Plastic and Reconstructive Surgery |volume = 124 |issue = 6 |pages = 455e–456e |date = December 2009 |pmid = 19952618 |doi = 10.1097/PRS.0b013e3181bf7f11 |doi-access = free }}</ref> limbs, jaw, and [[vocal cords]].<ref name="Primary">{{cite journal |vauthors = Felber ES |title = Botulinum toxin in primary care medicine |journal = The Journal of the American Osteopathic Association |volume = 106 |issue = 10 |pages = 609–614 |date = October 2006 |pmid = 17122031 |doi = |s2cid = 245177279 }}</ref> Similarly, botulinum toxin is used to relax the clenching of muscles, including those of the [[achalasia|esophagus]],<ref name=achalasia>{{cite journal |vauthors = Stavropoulos SN, Friedel D, Modayil R, Iqbal S, Grendell JH |title = Endoscopic approaches to treatment of achalasia |journal = Therapeutic Advances in Gastroenterology |volume = 6 |issue = 2 |pages = 115–135 |date = March 2013 |pmid = 23503707 |pmc = 3589133 |doi = 10.1177/1756283X12468039 }}</ref> [[bruxism|jaw]],<ref name=Bruxism>{{cite journal |vauthors = Long H, Liao Z, Wang Y, Liao L, Lai W |title = Efficacy of botulinum toxins on bruxism: an evidence-based review |journal = International Dental Journal |volume = 62 |issue = 1 |pages = 1–5 |date = February 2012 |pmid = 22251031 |doi = 10.1111/j.1875-595X.2011.00085.x |pmc = 9374973 |doi-access = free |title-link = doi }}</ref> [[detrusor|lower urinary tract]] and [[urinary bladder|bladder]],<ref name="multiple">{{cite journal |vauthors = Mangera A, Andersson KE, Apostolidis A, Chapple C, Dasgupta P, Giannantoni A, Gravas S, Madersbacher S |title = Contemporary management of lower urinary tract disease with botulinum toxin A: a systematic review of botox (onabotulinumtoxinA) and dysport (abobotulinumtoxinA) |journal = European Urology |volume = 60 |issue = 4 |pages = 784–795 |date = October 2011 |pmid = 21782318 |doi = 10.1016/j.eururo.2011.07.001 }}</ref> or clenching of the anus which can exacerbate [[anal fissure]].<ref>{{cite journal |vauthors = Villalba H, Villalba S, Abbas MA |title = Anal fissure: a common cause of anal pain |journal = The Permanente Journal |volume = 11 |issue = 4 |pages = 62–65 |date = 2007 |pmid = 21412485 |pmc = 3048443 |doi = 10.7812/tpp/07-072 }}</ref> Botulinum toxin appears to be effective for [[disease#Stages|refractory]] [[overactive bladder]].<ref>{{cite journal |vauthors = Duthie JB, Vincent M, Herbison GP, Wilson DI, Wilson D |title = Botulinum toxin injections for adults with overactive bladder syndrome |journal = The Cochrane Database of Systematic Reviews |issue = 12 |pages = CD005493 |date = December 2011 |pmid = 22161392 |doi = 10.1002/14651858.CD005493.pub3 |veditors = Duthie JB }}</ref>

===Other muscle disorders===
[[Strabismus]], otherwise known as improper eye alignment, is caused by imbalances in the actions of muscles that rotate the eyes. This condition can sometimes be relieved by weakening a muscle that pulls too strongly, or pulls against one that has been weakened by disease or trauma. Muscles weakened by toxin injection recover from paralysis after several months, so injection might seem to need to be repeated, but muscles adapt to the lengths at which they are chronically held,<ref>{{cite journal |vauthors = Scott AB |title = Change of eye muscle sarcomeres according to eye position |journal = Journal of Pediatric Ophthalmology and Strabismus |volume = 31 |issue = 2 |pages = 85–88 |year = 1994 |pmid = 8014792 |doi = 10.3928/0191-3913-19940301-05 }}</ref> so that if a paralyzed muscle is stretched by its antagonist, it grows longer, while the antagonist shortens, yielding a permanent effect.<ref>{{cite book |vauthors=Simpson L |url=https://books.google.com/books?id=fIwBX6oBDCMC&q=strabismus%20paralyzed%20muscle%20is%20stretched%20the%20antagonist%20shortens%20permanent&pg=PA400 |title=Botulinum Neurotoxin and Tetanus Toxin |date=2 December 2012 |publisher=Elsevier |isbn=978-0-323-14160-4 |access-date=1 October 2020 |archive-date=28 August 2021 |archive-url=https://web.archive.org/web/20210828010046/https://books.google.com/books?id=fIwBX6oBDCMC&q=strabismus+paralyzed+muscle+is+stretched+the+antagonist+shortens+permanent&pg=PA400 |url-status=live }}</ref>

In January 2014, botulinum toxin was approved by UK's [[Medicines and Healthcare products Regulatory Agency]] for treatment of restricted ankle motion due to lower-limb spasticity associated with stroke in adults.<ref name="DDD" /><ref>{{cite web |url=https://www.thepharmaletter.com/article/uk-s-mhra-approves-botox-for-treatment-of-ankle-disability-in-stroke-survivors |title=UK's MHRA approves Botox for treatment of ankle disability in stroke survivors |website=The Pharma Letter |access-date=16 March 2020 |archive-date=27 July 2020 |archive-url=https://web.archive.org/web/20200727033634/https://www.thepharmaletter.com/article/uk-s-mhra-approves-botox-for-treatment-of-ankle-disability-in-stroke-survivors |url-status=live }}</ref>

In July 2016, the US [[Food and Drug Administration]] (FDA) approved abobotulinumtoxinA (Dysport) for injection for the treatment of lower-limb spasticity in pediatric patients two years of age and older.<ref>{{cite web |title=FDA Approved Drug Products – Dysport |publisher=U.S. [[Food and Drug Administration]] (FDA) |url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=125274 |archive-url=https://web.archive.org/web/20161108054053/https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=125274 |archive-date=8 November 2016 |url-status=dead |access-date=7 November 2016}} {{PD-notice}}</ref><ref>{{cite journal |vauthors = Pavone V, Testa G, Restivo DA, Cannavò L, Condorelli G, Portinaro NM, Sessa G |title = Botulinum Toxin Treatment for Limb Spasticity in Childhood Cerebral Palsy |journal = Frontiers in Pharmacology |volume = 7 |pages = 29 |date = 19 February 2016 |pmid = 26924985 |pmc = 4759702 |doi = 10.3389/fphar.2016.00029 |doi-access = free |title-link = doi }}</ref> AbobotulinumtoxinA is the first and only FDA-approved botulinum toxin for the treatment of pediatric lower limb spasticity.<ref>{{cite journal |vauthors = Syed YY |title = AbobotulinumtoxinA: A Review in Pediatric Lower Limb Spasticity |journal = Paediatric Drugs |volume = 19 |issue = 4 |pages = 367–373 |date = August 2017 |pmid = 28623614 |doi = 10.1007/s40272-017-0242-4 |s2cid = 24857218 }}</ref> In the US, the [[prescription drug#Regulation in the United States|FDA approves]] the text of the labels of prescription medicines and for which medical conditions the drug manufacturer may sell the drug. However, prescribers may freely prescribe them for any condition they wish, also known as [[off-label use]].<ref>{{cite journal |vauthors = Wittich CM, Burkle CM, Lanier WL |title = Ten common questions (and their answers) about off-label drug use |journal = Mayo Clinic Proceedings |volume = 87 |issue = 10 |pages = 982–990 |date = October 2012 |pmid = 22877654 |pmc = 3538391 |doi = 10.1016/j.mayocp.2012.04.017 }}</ref> Botulinum toxins have been used off-label for several pediatric conditions, including [[infantile esotropia]].<ref name="Ocampo_2012" />

===Excessive sweating===
Botulinum toxin (BTO) injections are a modern clinical trend to treat hyperhidrosis, of which palmar hyperhidrosis is a frequent symptom.<ref>{{cite journal | vauthors = Önder Ö |title=Iatrogenic Botulism Following Botulinum Toxin Injection in Palmar Hyperhidrosis: A Case Report |journal=Cyprus Journal of Medical Sciences |date=14 March 2025 |volume=10 |issue=1 |pages=83–85 |doi=10.4274/cjms.2024.2024-51|doi-access=free }}</ref> For example, AbobotulinumtoxinA has been approved for the treatment of axillary [[hyperhidrosis]], which cannot be managed by topical agents.<ref name="Primary"/><ref name="Eisenach JH, Atkinson JL, Fealey RD. 657–666">{{cite journal | vauthors = Eisenach JH, Atkinson JL, Fealey RD | title = Hyperhidrosis: evolving therapies for a well-established phenomenon | journal = Mayo Clinic Proceedings | volume = 80 | issue = 5 | pages = 657–666 | date = May 2005 | pmid = 15887434 | doi = 10.4065/80.5.657 | title-link = doi | doi-access = free }}</ref> But Doctors and patients must stay away from the risks of the illegal use of unlicensed and unverified products.<ref>{{cite journal | vauthors = Chimienti S, Di Spirito M, Molinari F, Rozov O, Lista F, D'Amelio R, Salemi S, Fillo S | title = Botulinum Neurotoxins as Two-Faced Janus Proteins | journal = Biomedicines | volume = 13 | issue = 2 | pages = 411 | date = February 2025 | pmid = 40002825 | pmc = 11853235 | doi = 10.3390/biomedicines13020411 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Wright G, Lax A, Mehta SB | title = A review of the longevity of effect of botulinum toxin in wrinkle treatments | journal = British Dental Journal | volume = 224 | issue = 4 | pages = 255–260 | date = February 2018 | pmid = 29472686 | doi = 10.1038/SJ.BDJ.2018.126 | url = https://kclpure.kcl.ac.uk/portal/en/publications/f263e110-9501-4304-a263-a359a5516a13 }}</ref>

===Migraine===
In 2010, the FDA approved [[intramuscular]] botulinum toxin injections for [[prophylactic]] [[management of chronic headaches|treatment]] of [[chronic condition|chronic]] [[migraine]] [[headache]].<ref>{{cite news |title=FDA Approves Botox to Treat Chronic Migraines |url=http://www.webmd.com/migraines-headaches/news/20101018/fda-approves-botox-to-treat-chronic-migraines#1 |access-date=12 May 2017 |work=WebMD |archive-date=5 May 2017 |archive-url=https://web.archive.org/web/20170505183032/http://www.webmd.com/migraines-headaches/news/20101018/fda-approves-botox-to-treat-chronic-migraines#1 |url-status=live }}</ref> However, the use of botulinum toxin injections for episodic migraine has not been approved by the FDA.<ref>{{Cite journal |date=2011 |title=HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use BOTOX® safely and effectively. See full prescribing information for BOTOX. |url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/103000s5236lbl.pdf |journal=Accessdata.fda.gov |access-date=27 April 2024 |archive-date=16 February 2024 |archive-url=https://web.archive.org/web/20240216083806/https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/103000s5236lbl.pdf |url-status=dead }}</ref>

===Cosmetic uses===
[[File:Dr Braun Performs a Botox Injection (4035273577).jpg|thumb|Botulinum toxin being injected in the human face]]
In cosmetic applications, botulinum toxin is considered relatively safe and effective<ref>{{cite journal |vauthors = Satriyasa BK |title = Botulinum toxin (Botox) A for reducing the appearance of facial wrinkles: a literature review of clinical use and pharmacological aspect |journal = Clinical, Cosmetic and Investigational Dermatology |volume = 12 |pages = 223–228 |date = 10 April 2019 |pmid = 31114283 |pmc = 6489637 |doi = 10.2147/CCID.S202919 |doi-access = free }}</ref> for reduction of facial [[wrinkles]], especially in the uppermost third of the face.<ref name=Small2014>{{cite journal |vauthors = Small R |title = Botulinum toxin injection for facial wrinkles |journal = American Family Physician |volume = 90 |issue = 3 |pages = 168–175 |date = August 2014 |pmid = 25077722 }}</ref> Commercial forms are marketed under the brand names Botox Cosmetic/Vistabel from [[Allergan]], Dysport/Azzalure from [[Galderma]] and [[Ipsen]], Xeomin/Bocouture from Merz, Jeuveau/Nuceiva from Evolus, manufactured by [[Daewoong Pharmaceutical|Daewoong]] in South Korea.<ref name="Krause_2019" /> The effects of botulinum toxin injections for [[glabella]]r lines ('11's lines' between the eyes) typically last two to four months and in some cases, product-dependent, with some patients experiencing a longer duration of effect of up to six months or longer.<ref name="Small2014" /> Injection of botulinum toxin into the muscles under facial wrinkles causes relaxation of those muscles, resulting in the smoothing of the overlying skin.<ref name=Small2014/> Smoothing of wrinkles is usually visible three to five days after injection, with maximum effect typically a week following injection.<ref name=Small2014/> Muscles can be treated repeatedly to maintain the smoothed appearance.<ref name=Small2014/>

DaxibotulinumtoxinA (Daxxify) was approved for medical use in the United States in September 2022.<ref name="Daxxify FDA label" /><ref name="Daxxify FDA snapshot" /> It is indicated for the temporary improvement in the appearance of moderate to severe glabellar lines (wrinkles between the eyebrows).<ref name="Daxxify FDA label" /><ref name="Daxxify FDA snapshot">{{cite web |title=Drug Trials Snapshot: Daxxify |website=U.S. [[Food and Drug Administration]] (FDA) |date=7 September 2022 |url=https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshot-daxxify |access-date=23 March 2024 |archive-date=1 February 2024 |archive-url=https://web.archive.org/web/20240201162717/https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshot-daxxify |url-status=dead }} {{PD-notice}}</ref><ref>{{cite press release |title=Revance Announces FDA Approval of Daxxify (DaxibotulinumtoxinA-lanm) for Injection, the First and Only Peptide-Formulated Neuromodulator With Long-Lasting Results |publisher=Revance |via=Business Wire |date=8 September 2022 |url=https://www.businesswire.com/news/home/20220908005320/en/Revance-Announces-FDA-Approval-of-DAXXIFY%E2%84%A2-DaxibotulinumtoxinA-lanm-for-Injection-the-First-and-Only-Peptide-Formulated-Neuromodulator-With-Long-Lasting-Results |access-date=24 September 2022 |archive-date=10 September 2022 |archive-url=https://web.archive.org/web/20220910163940/https://www.businesswire.com/news/home/20220908005320/en/Revance-Announces-FDA-Approval-of-DAXXIFY%E2%84%A2-DaxibotulinumtoxinA-lanm-for-Injection-the-First-and-Only-Peptide-Formulated-Neuromodulator-With-Long-Lasting-Results/ |url-status=live }}</ref> DaxibotulinumtoxinA is an acetylcholine release inhibitor and neuromuscular blocking agent.<ref name="Daxxify FDA label" /> The FDA approved daxibotulinumtoxinA based on evidence from two clinical trials (Studies GL-1 and GL-2), of 609 adults with moderate to severe glabellar lines.<ref name="Daxxify FDA snapshot" /> The trials were conducted at 30 sites in the United States and Canada.<ref name="Daxxify FDA snapshot" /> Both trials enrolled participants 18 to 75 years old with moderate to severe glabellar lines.<ref name="Daxxify FDA snapshot" /> Participants received a single intramuscular injection of daxibotulinumtoxinA or placebo at five sites within the muscles between the eyebrows.<ref name="Daxxify FDA snapshot" /> The most common side effects of daxibotulinumtoxinA are headache, drooping eyelids, and weakness of facial muscles.<ref name="Daxxify FDA snapshot" />

LetibotulinumtoxinA (Letybo) was approved for medical use in the United States in February 2024.<ref name="Letybo FDA label" /><ref name="Letybo FDA snapshot">{{cite web |title=Drug Trials Snapshots: Letybo |website=U.S. [[Food and Drug Administration]] (FDA) |date=29 February 2024 |url=https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshots-letybo |access-date=23 March 2024 |archive-date=23 March 2024 |archive-url=https://web.archive.org/web/20240323195046/https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshots-letybo |url-status=dead }} {{PD-notice}}</ref><ref>{{cite report |title=New Drug Therapy Approvals 2024 |website=U.S. [[Food and Drug Administration]] (FDA) |date=January 2025 |url=https://www.fda.gov/media/184967/download |format=PDF |access-date=21 January 2025 |archive-url=https://web.archive.org/web/20250121045744/https://www.fda.gov/media/184967/download |archive-date=21 January 2025 |url-status=dead }}</ref> It is indicated to temporarily improve the appearance of moderate-to-severe glabellar lines.<ref name="Letybo FDA label" /><ref>{{cite web |title=Novel Drug Approvals for 2024 |website=U.S. [[Food and Drug Administration]] (FDA) |date=29 April 2024 |url=https://www.fda.gov/drugs/novel-drug-approvals-fda/novel-drug-approvals-2024 |access-date=30 April 2024 |archive-date=30 April 2024 |archive-url=https://web.archive.org/web/20240430031024/https://www.fda.gov/drugs/novel-drug-approvals-fda/novel-drug-approvals-2024 |url-status=dead }}</ref> The FDA approved letibotulinumtoxinA based on evidence from three clinical trials (BLESS I [NCT02677298], BLESS II [NCT02677805], and BLESS III [NCT03985982]) of 1,271 participants with moderate to severe wrinkles between the eyebrows for efficacy and safety assessment.<ref name="Letybo FDA snapshot" /> These trials were conducted at 31 sites in the United States and the European Union.<ref name="Letybo FDA snapshot" /> All three trials enrolled participants 18 to 75 years old with moderate to severe glabellar lines (wrinkles between the eyebrows).<ref name="Letybo FDA snapshot" /> Participants received a single intramuscular injection of letibotulinumtoxinA or placebo at five sites within the muscles between the eyebrows.<ref name="Letybo FDA snapshot" /> The most common side effects of letibotulinumtoxinA are headache, drooping of eyelid and brow, and twitching of eyelid.<ref name="Letybo FDA snapshot" />

===Others===
Botulinum toxin is also used to treat disorders of hyperactive nerves including excessive sweating,<ref name="Eisenach JH, Atkinson JL, Fealey RD. 657–666"/> [[neuropathic pain]],<ref>{{cite journal |vauthors = Mittal SO, Safarpour D, Jabbari B |title = Botulinum Toxin Treatment of Neuropathic Pain |journal = Seminars in Neurology |volume = 36 |issue = 1 |pages = 73–83 |date = February 2016 |pmid = 26866499 |doi = 10.1055/s-0036-1571953 |s2cid = 41120474 }}</ref> and some [[allergic rhinitis|allergy]] symptoms.<ref name="Primary"/> In addition to these uses, botulinum toxin is being evaluated for use in treating [[chronic pain]].<ref>{{cite journal |vauthors = Charles PD |title = Botulinum neurotoxin serotype A: a clinical update on non-cosmetic uses |journal = American Journal of Health-System Pharmacy |volume = 61 |issue = 22 Suppl 6 |pages = S11–S23 |date = November 2004 |pmid = 15598005 |doi = 10.1093/ajhp/61.suppl_6.S11 |doi-access = free }}</ref> Studies show that botulinum toxin may be injected into arthritic shoulder joints to reduce chronic pain and improve range of motion.<ref>{{cite journal |vauthors = Singh JA, Fitzgerald PM |title = Botulinum toxin for shoulder pain |journal = The Cochrane Database of Systematic Reviews |issue = 9 |pages = CD008271 |date = September 2010 |pmid = 20824874 |doi = 10.1002/14651858.cd008271.pub2 }}</ref> The use of botulinum toxin A in children with [[cerebral palsy]] is safe in the upper and lower limb muscles.<ref name="Farag2020" /><ref name="Blumetti2019" />