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Oxybutynin

Clinical data
Trade names	Ditropan, Gelnique, others
AHFS/Drugs.com	Monograph
MedlinePlus	a682141
License data	US DailyMed: Oxybutynin
Pregnancy category	AU: B1
Routes of administration	By mouth, transdermal
Drug class	Antimuscarinic
ATC code	G04BD04 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) CA: ℞-only UK: POM (Prescription only) US: ℞-only / OTC EU: Rx-only
Pharmacokinetic data
Protein binding	91–93%
Metabolites	N-Desethyloxybutynin
Elimination half-life	12.4–13.2 hours
Identifiers
IUPAC name 4-Diethylaminobut-2-ynyl 2-cyclohexyl-2-hydroxy-2-phenylethanoate
CAS Number	5633-20-5
PubChem CID	4634
IUPHAR/BPS	359
DrugBank	DB01062
ChemSpider	4473
UNII	K9P6MC7092
KEGG	D00465
ChEBI	CHEBI:7856
ChEMBL	ChEMBL1231
CompTox Dashboard (EPA)	DTXSID0023406
ECHA InfoCard	100.158.590
Chemical and physical data
Formula	C22H31NO3
Molar mass	357.494 g·mol
3D model (JSmol)	Interactive image
SMILES O=C(OCC#CCN(CC)CC)C(O)(c1ccccc1)C2CCCCC2
InChI InChI=1S/C22H31NO3/c1-3-23(4-2)17-11-12-18-26-21(24)22(25,19-13-7-5-8-14-19)20-15-9-6-10-16-20/h5,7-8,13-14,20,25H,3-4,6,9-10,15-18H2,1-2H3 Key:XIQVNETUBQGFHX-UHFFFAOYSA-N
(verify)

Oxybutynin, sold under the brand name Ditropan among others, is an anticholinergic medication 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 bedwetting 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.

Common side effects include dry mouth, constipation, dizziness, trouble sleeping, and urinary tract infections. Serious side effects may include urinary retention and an increased risk of heat stroke. Use in pregnancy appears safe but has not been well studied while use in breastfeeding is of unclear safety. It is an antimuscarinic and works by blocking the effects of acetylcholine on smooth muscle.

Oxybutynin was approved for medical use in the US in 1975. It is available as a generic medication. In 2022, it was the 110th most commonly prescribed medication in the United States, with more than 5 million prescriptions.

Medical use

Oxybutynin is used in the form of instant-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. Extended-release formulations decrease the number of weekly incontinence episodes by an average of 90% compared to an untreated state. Some studies have identified advantages of transdermal oxybutynin over capsules, finding decreased frequency of incontinence episodes and increased average voided volume of urine.

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. 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.

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).

Hyperhidrosis

Since the 2010s, oxybutynin has increasingly been used to treat hyperhidrosis (excessive sweating). 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).

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. Anticholinergics have also been known to induce delirium.

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. Adverse effects of elevated body temperature are more likely for the elderly and for those with health issues, especially multiple sclerosis.

N-Desethyloxybutynin is an active metabolite of oxybutynin that is thought responsible for much of the adverse effects associated with the use of oxybutynin. N-Desethyloxybutynin plasma levels may reach as much as six times that of the parent drug after administration of the immediate-release oral formulation. 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 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 the first-pass hepatic effect that the oral formulations are subject to.

Contraindications

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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. 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.

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. 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

Society and culture

Brand names

Oxybutynin is available by mouth in generic formulation and under the brand names Ditropan, Lyrinel XL, Ditrospam, Kentera, and Aquiette, as a transdermal patch under the brand name Oxytrol, and as a topical gel under the brand name Gelnique.

Research

A large study linked the development of dementia in those over 65 to the use of oxybutynin, due to its anticholinergic properties.

References

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