Oxybutynin, sold as under the brand name Ditropan among others, is an
anticholinergic drug primarily used to treat
overactive bladder. It is widely considered a
first-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 to
tolterodine,
darifenacin, and
solifenacin, although it is usually preferred over these medications. It is sometimes used
off-label for treatment of
hyperhidrosis, or excessive sweating. It has also been used off-label to treat
bed wetting in children, but this use has declined, as it is most likely ineffective in this role. It is
taken by mouth or
applied to the skin.
Oxybutynin was approved for medical use in the US in 1975.[1] It is available as a
generic medication.[3] In 2021, it was the 102nd most commonly prescribed medication in the US, with more than 6million prescriptions.[4][5]
Medical use
Oxybutynin is used in the form of standard-release capsules,
extended-release capsules, or transdermal (
topical) products. All of these are considered safe and effective options for treatment of
detrusor muscle-mediated
overactive bladder.[1] Extended-release formulations decrease the number of weekly incontinence episodes by an average of 90% compared to an untreated state.[6] Some studies have identified advantages of transdermal oxybutynin over capsules, finding decreased frequency of incontinence episodes and increased average voided volume of urine.[7]
Oxybutynin has been established through head-to-head trials as a more effective for overactive bladder than
tolterodine, another anticholinergic medication. Specifically, the extended release form of oxybutynin was found to have greater effect in both the short- and long-term.[6] However, oxybutynin is not
selective 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.[8]
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).[9]
Hyperhidrosis
Since the 2010s, oxybutynin has increasingly been used to treat
hyperhidrosis (excessive sweating).[10][11] Numerous studies have identified concrete benefits of the drug in treating this condition, but have not identified appropriate
dosing or the full spectrum of possible
side effects, although
dry mouth is seemingly infrequent in patients with hyperhidrosis. Until further clinical trials can be conducted, oxybutynin is only used as an
off-label medication for hyperhidrosis (as of 2024).[11]
Adverse effects
Common adverse effects that are associated with oxybutynin and other
anticholinergics include: dry mouth, difficulty in
urination, constipation, blurred vision, drowsiness, and dizziness.[12] Anticholinergics have also been known to induce
delirium.[13]
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.[14] Adverse effects of elevated body temperature are more likely for the elderly and for those with health issues, especially multiple sclerosis.[15]
N-Desethyloxybutynin is an
active metabolite of oxybutynin that is thought responsible for much of the adverse effects associated with the use of oxybutynin.[16]N-Desethyloxybutynin plasma levels may reach as much as six times that of the parent drug after administration of the immediate-release oral formulation.[17] Alternative dosage forms have been developed in an effort to reduce blood levels of N-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 the
first-pass hepatic effect that the oral formulations are subject to.[18] In those with overflow incontinence because of diabetes or neurological diseases like multiple sclerosis or spinal cord trauma, oxybutynin can worsen overflow incontinence since the fundamental problem is that the bladder is not contracting.
A large study linked the development of dementia in those over 65 to the use of oxybutynin, due to its
anticholinergic properties.[19]
Oxybutynin chloride is contraindicated in patients with untreated narrow angle
glaucoma, and in patients with untreated narrow anterior chamber angles—since
anticholinergic 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 complicating
ulcerative colitis, severe colitis, and
myasthenia gravis. It is contraindicated in patients with
obstructive uropathy and in patients with unstable cardiovascular status in acute hemorrhage. Oxybutynin chloride is contraindicated in patients who have demonstrated hypersensitivity to the product.
Pharmacology
Sources say the drug is absorbed within one hour and has an elimination half-life of 2 to 5 hours.[20][21] 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.[21]
Chemistry
Oxybutynin contains one
stereocenter. Commercial formulations are sold as the
racemate. 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.[22][23] 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
CAS-Number: 119618-21-2
CAS-Number: 119618-22-3
Brand names
is available by mouth in generic formulation and under the brand names Ditropan,[24] Lyrinel XL, Ditrospam, Kentera,[25] and Aquiette,[26] as a transdermal patch under the brand name Oxytrol, and as a
topical 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.
^"Oxybutynin". drugs.com. Retrieved August 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.