Oxybutynin

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Oxybutynin
Clinical data
Trade namesDitropan, Gelnique, others
AHFS/Drugs.comMonograph
MedlinePlusa682141
License data
Pregnancy
category
  • AU: B1
Routes of
administration
Oral, transdermal
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding91–93%
Elimination half-life12.4–13.2 hours
Identifiers
  • 4-Diethylaminobut-2-ynyl 2-cyclohexyl-2-hydroxy-2-phenylethanoate
JSmol)
  • O=C(OCC#CCN(CC)CC)C(O)(c1ccccc1)C2CCCCC2
  • 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 checkY
  • Key:XIQVNETUBQGFHX-UHFFFAOYSA-N checkY
  (verify)

Oxybutynin, sold as under the brand name Ditropan among others, is an

applied to the skin
.

Common side effects include

antimuscarinic and works by blocking the effects of acetylcholine on smooth muscle.[1]

Oxybutynin was approved for medical use in the United States in 1975.

generic medication.[3] In 2021, it was the 102nd most commonly prescribed medication in the United States, with more than 6 million 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 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 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

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]

Contraindications

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

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

Oxybutynin 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.

References

  1. ^ a b c d e "Oxybutynin Chloride Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved March 3, 2019.
  2. ^ "Oxybutynin Pregnancy and Breastfeeding Warnings". Drugs.com. Retrieved March 3, 2019.
  3. .
  4. ^ "The Top 300 of 2021". ClinCalc. Archived from the original on January 15, 2024. Retrieved January 14, 2024.
  5. ^ "Oxybutynin - Drug Usage Statistics". ClinCalc. Retrieved January 14, 2024.
  6. ^
    PMID 17011379
    .
  7. .
  8. .
  9. .
  10. .
  11. ^ .
  12. .
  13. ^ Andreasen NC, Black DW (2006). Introductory Textbook of Psychiatry. American Psychiatric Publishing Inc.
  14. ^ "Oxybutynin (By mouth)". PubMed Health. U.S. National Library of Medicine. mmdn/DNX0064.
  15. PMID 23599395
    .
  16. .
  17. .
  18. .
  19. .
  20. ^ "Oxybutynin". drugs.com. Retrieved August 30, 2012.
  21. ^
    S2CID 33628778
    .
  22. .
  23. .
  24. ^ "DITROPAN®(oxybutynin chloride) Tablets and Syrup" (PDF). FDA. February 2008. Retrieved June 18, 2020.
  25. ^ "Oxybutynin – Brand names: Ditropan, Lyrinel, Kentera". NHS UK. June 15, 2021.
  26. ^ Robinson J (April 26, 2022). "Pharmacists express concerns over proposed reclassification of overactive bladder drug". The Pharmaceutical Journal.