Oxybutynin
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| Trade names | Ditropan, Gelnique, others |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a682141 |
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| Routes of administration | Oral,transdermal |
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| Protein binding | 91–93% |
| Eliminationhalf-life | 12.4–13.2 hours |
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| ECHA InfoCard | 100.158.590 |
| Chemical and physical data | |
| Formula | C22H31NO3 |
| Molar mass | 357.494g·mol−1 |
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Oxybutynin,sold under the brand nameDitropanamong others, is ananticholinergicmedication primarily used to treatoveractive bladder.It is widely considered afirst-line therapyfor overactive bladder due to its well-studied side effect profile, broad applicability, and continued efficacy over long periods of time. It works similar totolterodine,darifenacin,andsolifenacin,although it is usually preferred over these medications. It is sometimes usedoff-labelfor treatment ofhyperhidrosis,or excessive sweating. It has also been used off-label to treatbed wettingin children, but this use has declined, as it is most likely ineffective in this role. It is takenby mouthorapplied to the skin.
Common side effects includedry mouth,constipation,dizziness,trouble sleeping,andurinary tract infections.[6]Serious side effects may includeurinary retentionand an increased risk ofheat stroke.[6]Use inpregnancyappears safe but has not been well studied while use inbreastfeedingis of unclear safety.[7]It is anantimuscarinicand works by blocking the effects ofacetylcholineonsmooth muscle.[6]
Oxybutynin was approved for medical use in the US in 1975.[6]It is available as ageneric medication.[8]In 2022, it was the 110th most commonly prescribed medication in the United States, with more than 5million prescriptions.[9][10]
Medical use
[edit]Oxybutynin is used in the form of standard-release capsules,extended-releasecapsules, or transdermal (topical) products. All of these are considered safe and effective options for treatment ofdetrusor muscle-mediatedoveractive bladder.[6]Extended-release formulations decrease the number of weekly incontinence episodes by an average of 90% compared to an untreated state.[11]Some studies have identified advantages of transdermal oxybutynin over capsules, finding decreased frequency of incontinence episodes and increased average voided volume of urine.[12]
Oxybutynin has been established through head-to-head trials as a more effective for overactive bladder thantolterodine,another anticholinergic medication. Specifically, the extended release form of oxybutynin was found to have greater effect in both the short- and long-term.[11]However, oxybutynin is notselectivefor the bladder like tolterodine, and thus has a wider range of side effects. Tolterodine and other anticholinergics are primarily used when clinicians and patients want to reduce the side effect profile.[13]
Because both drugs have been studied extensively and shown relatively high efficacy, both oxybutynin and tolterodine are considered first-line treatments for overactive bladder. They are thus the typical choices for initial treatment of the condition. The choice of initial therapy often comes down to whether a patient prefers somewhat higher efficacy (oxybutynin) or somewhat reduced side effects (tolterodine).[14]
Hyperhidrosis
[edit]Since the 2010s, oxybutynin has increasingly been used to treathyperhidrosis(excessive sweating).[15][16]Numerous studies have identified concrete benefits of the drug in treating this condition, but have not identified appropriatedosingor the full spectrum of possibleside effects,althoughdry mouthis seemingly infrequent in patients with hyperhidrosis. Until further clinical trials can be conducted, oxybutynin is only used as anoff-label medicationfor hyperhidrosis (as of 2024).[16]
Adverse effects
[edit]Common adverse effects that are associated with oxybutynin and otheranticholinergicsinclude: dry mouth, difficulty inurination,constipation, blurred vision, drowsiness, and dizziness.[17]Anticholinergics have also been known to inducedelirium.[18]
Oxybutynin's tendency to reduce sweating can be dangerous. Reduced sweating increases the risk of heat exhaustion and heat stroke in apparently safe situations where normal sweating keeps others safe and comfortable.[19]Adverse effects of elevated body temperature are more likely for the elderly and for those with health issues, especially multiple sclerosis.[20]
N-Desethyloxybutynin is anactive metaboliteof oxybutynin that is thought responsible for much of the adverse effects associated with the use of oxybutynin.[21]N-Desethyloxybutynin plasma levels may reach as much as six times that of the parent drug after administration of the immediate-release oral formulation.[22]Alternative dosage forms have been developed in an effort to reduce blood levels ofN-desethyloxybutynin and achieve a steadier concentration of oxybutynin than is possible with the immediate release form. The long-acting formulations also allow once-daily administration instead of the twice-daily dosage required with the immediate-release form. The transdermal patch, in addition to the benefits of the extended-release oral formulations, bypasses thefirst-pass hepatic effectthat the oral formulations are subject to.[23]
Contraindications
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Oxybutynin chloride is contraindicated in patients with untreated narrow angleglaucoma,and in patients with untreated narrow anterior chamber angles—sinceanticholinergic drugsmay aggravate these conditions. It is also contraindicated in partial or complete obstruction of the gastrointestinal tract, hiatal hernia,gastroesophageal reflux disease,paralytic ileus, intestinal atony of the elderly or debilitated patient,megacolon,toxic megacoloncomplicatingulcerative colitis,severe colitis, andmyasthenia gravis.It is contraindicated in patients withobstructive uropathyand in patients with unstable cardiovascular status in acute hemorrhage. Oxybutynin chloride is contraindicated in patients who have demonstrated hypersensitivity to the product.
Pharmacology
[edit]Sources[which?]say the drug is absorbed within one hour and has an elimination half-life of 2 to 5 hours.[24][25]There is a wide variation among individuals in the drug's concentration in blood. This, and its low concentration in urine, suggest that it is eliminated through the liver.[25]
Chemistry
[edit]Oxybutynin contains onestereocenter.Commercial formulations are sold as theracemate.The(R)-enantiomeris a more potent anticholinergic than either the racemate or the (S)-enantiomer, which is essentially without anticholinergic activity at doses used in clinical practice.[26][27]However, (R)-oxybutynin administered alone offers little or no clinical benefit above and beyond the racemic mixture. The other actions (calcium antagonism, local anesthesia) of oxybutynin are not stereospecific. (S)-Oxybutynin has not been clinically tested for its spasmolytic effects, but may be clinically useful for the same indications as the racemate, without the unpleasant anticholinergic side effects.
| Enantiomers of oxybutynin | |
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 CAS-Number: 119618-21-2 |
 CAS-Number: 119618-22-3 |
Society and culture
[edit]Brand names
[edit]Oxybutynin is available by mouth in generic formulation and under the brand names Ditropan,[28]Lyrinel XL, Ditrospam, Kentera,[29]and Aquiette,[30]as a transdermal patch under the brand name Oxytrol, and as atopical gelunder the brand name Gelnique.
Research
[edit]A large study linked the development of dementia in those over 65 to the use of oxybutynin, due to itsanticholinergicproperties.[31]
References
[edit]- ^"Ditropan XL (oxybutynin chloride) Extended Release Tablets for oral use Initial U.S. Approval: 1975".DailyMed.RetrievedJune 17,2024.
- ^"Gelnique- oxybutynin chloride gel".DailyMed.March 1, 2019.RetrievedJune 17,2024.
- ^"Oxytrol- oxybutynin patch".DailyMed.May 29, 2024.RetrievedJune 17,2024.
- ^"Oxytrol for Women- oxybutynin patch".DailyMed.August 13, 2016.RetrievedJune 17,2024.
- ^"Kentera EPAR".European Medicines Agency (EMA).June 15, 2004.RetrievedOctober 12,2024.
- ^abcde"Oxybutynin Chloride Monograph for Professionals".Drugs.com.American Society of Health-System Pharmacists.RetrievedMarch 3,2019.
- ^"Oxybutynin Pregnancy and Breastfeeding Warnings".Drugs.com.RetrievedMarch 3,2019.
- ^British National Formulary: BNF 76(76th ed.). Pharmaceutical Press. 2018.ISBN978-0-85711-338-2.
- ^"The Top 300 of 2022".ClinCalc.Archivedfrom the original on August 30, 2024.RetrievedAugust 30,2024.
- ^"Oxybutynin Drug Usage Statistics, United States, 2013 - 2022".ClinCalc.RetrievedAugust 30,2024.
- ^abDiokno A, Ingber M (November 2006). "Oxybutynin in detrusor overactivity".The Urologic Clinics of North America.Overactive Bladder.33(4): 439–45, vii.doi:10.1016/j.ucl.2006.06.003.PMID17011379.
- ^Baldwin CM, Keating GM (2009). "Transdermal oxybutynin".Drugs.69(3): 327–337.doi:10.2165/00003495-200969030-00008.PMID19275276.S2CID33534909.
- ^Loloi J, Clearwater W, Schulz A, Suadicani SO, Abraham N (May 2022). "Medical Treatment of Overactive Bladder".The Urologic Clinics of North America.Urologic Pharmacology.49(2): 249–261.doi:10.1016/j.ucl.2021.12.005.PMID35428431.
- ^White N, Iglesia CB (March 2016). "Overactive Bladder".Obstetrics and Gynecology Clinics of North America.Medical and Advanced Surgical Management of Pelvic Floor Disorders.43(1): 59–68.doi:10.1016/j.ogc.2015.10.002.PMID26880508.
- ^Cruddas L, Baker DM (June 2017). "Treatment of primary hyperhidrosis with oral anticholinergic medications: a systematic review".Journal of the European Academy of Dermatology and Venereology.31(6): 952–963.doi:10.1111/jdv.14081.PMID27976476.S2CID4535312.
- ^abEl-Samahy M, Mouffokes A, Badawy MM, Amro S, Fayad T, Abdelwahab OA (October 2023)."Safety and efficacy of oxybutynin in patients with hyperhidrosis: systematic review and meta-analysis of randomized controlled trials".Archives of Dermatological Research.315(8): 2215–2226.doi:10.1007/s00403-023-02587-5.PMC10462517.PMID36869926.
- ^Mehta D, ed. (2006).British National Formulary.Vol. 51. Pharmaceutical Press.ISBN0-85369-668-3.
- ^Andreasen NC, Black DW (2006).Introductory Textbook of Psychiatry.American Psychiatric Publishing Inc.
- ^"Oxybutynin (By mouth)".PubMed Health.U.S. National Library of Medicine. mmdn/DNX0064.
- ^White AT, Vanhaitsma TA, Vener J, Davis SL (June 2013)."Effect of passive whole body heating on central conduction and cortical excitability in multiple sclerosis patients and healthy controls".Journal of Applied Physiology.114(12): 1697–1704.doi:10.1152/japplphysiol.01119.2012.PMC3680823.PMID23599395.
- ^Reitz AB, Gupta SK, Huang Y, Parker MH, Ryan RR (November 2007). "The preparation and human muscarinic receptor profiling of oxybutynin and N-desethyloxybutynin enantiomers".Medicinal Chemistry.3(6): 543–545.doi:10.2174/157340607782360353.PMID18045203.
- ^Zobrist RH, Schmid B, Feick A, Quan D, Sanders SW (July 2001). "Pharmacokinetics of the R- and S-enantiomers of oxybutynin and N-desethyloxybutynin following oral and transdermal administration of the racemate in healthy volunteers".Pharmaceutical Research.18(7): 1029–1034.doi:10.1023/a:1010956832113.PMID11496941.S2CID8004795.
- ^Oki T, Toma-Okura A, Yamada S (March 2006). "Advantages for transdermal over oral oxybutynin to treat overactive bladder: Muscarinic receptor binding, plasma drug concentration, and salivary secretion".The Journal of Pharmacology and Experimental Therapeutics.316(3): 1137–1145.doi:10.1124/jpet.105.094508.PMID16282521.S2CID30397079.
- ^"Oxybutynin".drugs.com.RetrievedAugust 30,2012.
- ^abDouchamps J, Derenne F, Stockis A, Gangji D, Juvent M, Herchuelz A (1988). "The pharmacokinetics of oxybutynin in man".European Journal of Clinical Pharmacology.35(5): 515–520.doi:10.1007/bf00558247.PMID3234461.S2CID33628778.
- ^Kachur JF, Peterson JS, Carter JP, Rzeszotarski WJ, Hanson RC, Noronha-Blob L (December 1988). "R and S enantiomers of oxybutynin: pharmacological effects in guinea pig bladder and intestine".The Journal of Pharmacology and Experimental Therapeutics.247(3): 867–872.PMID2849672.
- ^Noronha-Blob L, Kachur JF (February 1991). "Enantiomers of oxybutynin: in vitro pharmacological characterization at M1, M2 and M3 muscarinic receptors and in vivo effects on urinary bladder contraction, mydriasis and salivary secretion in guinea pigs".The Journal of Pharmacology and Experimental Therapeutics.256(2): 562–567.PMID1993995.
- ^"DITROPAN®(oxybutynin chloride) Tablets and Syrup"(PDF).FDA. February 2008.RetrievedJune 18,2020.
- ^"Oxybutynin – Brand names: Ditropan, Lyrinel, Kentera".NHS UK.June 15, 2021.
- ^Robinson J (April 26, 2022)."Pharmacists express concerns over proposed reclassification of overactive bladder drug".The Pharmaceutical Journal.
- ^Gray SL, Anderson ML, Dublin S, Hanlon JT, Hubbard R, Walker R, et al. (March 2015)."Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study".JAMA Internal Medicine.175(3): 401–407.doi:10.1001/jamainternmed.2014.7663.PMC4358759.PMID25621434.
