Oxybutynin, sold under the brand nameDitropan among others, is ananticholinergic medication primarily used to treatoveractive bladder. It is widely considered afirst-line therapy for 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-label for treatment ofhyperhidrosis, or excessive sweating. It has also been used off-label to treatbedwetting in children, but this use has declined, as it is most likely ineffective in this role. It is takenby mouth orapplied to the skin.
Oxybutynin was approved for medical use in the US in 1975.[6] It is available as ageneric medication.[8] In 2023, it was the 114th most commonly prescribed medication in the United States, with more than 5million prescriptions.[9][10]
Oxybutynin is used in the form of instant-release capsules,extended-release capsules, or transdermal 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 is superior to other anticholinergics for treatment of overactive bladder.
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 notselective for 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]
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 appropriatedosing or the full spectrum of possibleside effects, althoughdry mouth is seemingly infrequent in patients with hyperhidrosis. Until further clinical trials can be conducted, oxybutynin is only used as anoff-label medication for hyperhidrosis (as of 2024).[16]
Oxybutynin's tendency to reduce sweating can be dangerous. Reduced sweating increases the risk ofheat exhaustion andheat stroke in apparently safe situations where normal sweating keeps others safe and comfortable.[19] Adverse effects ofelevated body temperature are more likely for the elderly and for those with health issues, especiallymultiple sclerosis.[20]
N-Desethyloxybutynin is anactive metabolite of 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 instant-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 effect that the oral formulations are subject to.[23]
Oxybutynin chloride is contraindicated in patients with untreated narrow angleglaucoma, and in patients with untreated narrow anterior chamber angles—sinceanticholinergic drugs may 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 megacolon complicatingulcerative colitis, severe colitis, andmyasthenia gravis. It is contraindicated in patients withobstructive uropathy and in patients with unstable cardiovascular status in acute hemorrhage. Oxybutynin chloride is contraindicated in patients who have demonstrated hypersensitivity to the product.[24][25]
Sources[which?] say the drug is absorbed within one hour and has an elimination half-life of 2 to 5 hours.[26][27] 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.[27]
Oxybutynin contains onestereocenter. Commercial formulations are sold as theracemate. The(R)-enantiomer is a more potent anticholinergic than either the racemate or the (S)-enantiomer, which is essentially without anticholinergic activity at doses used in clinical practice.[28][29] 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.
Oxybutynin is available by mouth in generic formulation and under the brand names Ditropan,[30] Lyrinel XL, Ditrospam, Kentera,[31] and Aquiette,[32] as a transdermal patch under the brand name Oxytrol, and as atopical gel under the brand name Gelnique.
^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.
^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.
^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.
^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.doi:10.1016/S0022-3565(25)13294-1.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.doi:10.1016/S0022-3565(25)23176-7.PMID1993995.
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