Clinical data | |
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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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Pharmacokinetic data | |
Protein binding | 91–93% |
Elimination half-life | 12.4–13.2 hours |
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ECHA InfoCard | 100.158.590 |
Chemical and physical data | |
Formula | C22H31NO3 |
Molar mass | 357.494 g·mol−1 |
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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.
Common side effects include dry mouth, constipation, dizziness, trouble sleeping, and urinary tract infections. [1] Serious side effects may include urinary retention and an increased risk of heat stroke. [1] Use in pregnancy appears safe but has not been well studied while use in breastfeeding is of unclear safety. [2] It is an antimuscarinic and works by blocking the effects of acetylcholine on smooth muscle. [1]
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 6 million prescriptions. [4] [5]
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]
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]
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.
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]
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 | |
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CAS-Number: 119618-21-2 | CAS-Number: 119618-22-3 |
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.
Urinary incontinence (UI), also known as involuntary urination, is any uncontrolled leakage of urine. It is a common and distressing problem, which may have a large impact on quality of life. It has been identified as an important issue in geriatric health care. The term enuresis is often used to refer to urinary incontinence primarily in children, such as nocturnal enuresis. UI is an example of a stigmatized medical condition, which creates barriers to successful management and makes the problem worse. People may be too embarrassed to seek medical help, and attempt to self-manage the symptom in secrecy from others.
Anticholinergics are substances that block the action of the acetylcholine (ACh) neurotransmitter at synapses in the central and peripheral nervous system.
Flavoxate is an anticholinergic with antimuscarinic effects. Its muscle relaxant properties may be due to a direct action on the smooth muscle rather than by antagonizing muscarinic receptors.
Ipratropium bromide, sold under the trade name Atrovent among others, is a type of anticholinergic medication which is applied by different routes: inhaler, nebulizer, or nasal spray, for different reasons.
Glycopyrronium bromide is a medication of the muscarinic anticholinergic group. It does not cross the blood–brain barrier and consequently has few to no central effects. It is given by mouth, via intravenous injection, on the skin, and via inhalation. It is a synthetic quaternary ammonium compound. The cation, which is the active moiety, is called glycopyrronium (INN) or glycopyrrolate (USAN).
Tolterodine, sold under the brand name Detrol among others, is a medication used to treat frequent urination, urinary incontinence, or urinary urgency. Effects are seen within an hour. It is taken by mouth.
Orphenadrine is an anticholinergic drug of the ethanolamine antihistamine class; it is closely related to diphenhydramine. It is a muscle relaxant that is used to treat muscle pain and to help with motor control in Parkinson's disease, but has largely been superseded by newer drugs. It is considered a dirty drug due to its multiple mechanisms of action in different pathways. It was discovered and developed in the 1940s.
Percutaneous tibial nerve stimulation (PTNS), also referred to as posterior tibial nerve stimulation, is the least invasive form of neuromodulation used to treat overactive bladder (OAB) and the associated symptoms of urinary urgency, urinary frequency and urge incontinence. These urinary symptoms may also occur with interstitial cystitis and following a radical prostatectomy. Outside the United States, PTNS is also used to treat fecal incontinence.
Darifenacin is a medication used to treat urinary incontinence due to an overactive bladder. It was discovered by scientists at the Pfizer research site in Sandwich, UK under the identifier UK-88,525 and used to be marketed by Novartis. In 2010, the US rights were sold to Warner Chilcott for US$400 million.
Solifenacin, sold as the brand name Vesicare among others, is a medicine used to treat overactive bladder and neurogenic detrusor overactivity (NDO). It may help with incontinence, urinary frequency, and urinary urgency.
Trospium chloride is a muscarinic antagonist used to treat overactive bladder. It has side effects typical of this class of drugs, namely dry mouth, stomach upset, and constipation; these side effects cause problems with people taking their medicine as directed. However it doesn't cause central nervous system side effects like some other muscarinic antagonists. It is in pregnancy category C and is excreted in breast milk.
Neurogenic bladder dysfunction, often called by the shortened term neurogenic bladder, refers to urinary bladder problems due to disease or injury of the central nervous system or peripheral nerves involved in the control of urination. There are multiple types of neurogenic bladder depending on the underlying cause and the symptoms. Symptoms include overactive bladder, urinary urgency, frequency, incontinence or difficulty passing urine. A range of diseases or conditions can cause neurogenic bladder including spinal cord injury, multiple sclerosis, stroke, brain injury, spina bifida, peripheral nerve damage, Parkinson's disease, multiple system atrophy or other neurodegenerative diseases. Neurogenic bladder can be diagnosed through a history and physical as well as imaging and more specialized testing. In addition to symptomatic treatment, treatment depends on the nature of the underlying disease and can be managed with behavioral changes, medications, surgeries, or other procedures. The symptoms of neurogenic bladder, especially incontinence, can severely degrade a person's quality of life.
Overactive bladder (OAB) is a common condition where there is a frequent feeling of needing to urinate to a degree that it negatively affects a person's life. The frequent need to urinate may occur during the day, at night, or both. Loss of bladder control may occur with this condition. This condition is also sometimes characterized by a sudden and involuntary contraction of the bladder muscles, in response to excitement or anticipation. This in turn leads to a frequent and urgent need to urinate.
Pentoxyverine (rINN) or carbetapentane is an antitussive commonly used for cough associated with illnesses like common cold. It is sold over-the-counter as Solotuss, or in combination with other medications, especially decongestants. One such product is Certuss, a combination of guaifenesin and pentoxyverine. The drug has been available in the form of drops, suspensions and suppositories.
Bornaprine is a synthetic anticholinergic medication that is primarily used to treat Parkinson's disease. Additionally, bornaprine has been used to treat other disorders, including hyperhidrosis.
Mirabegron, sold under the brand name Myrbetriq among others, is a medication used to treat overactive bladder. Its benefits are similar to antimuscarinic medication such as solifenacin or tolterodine. It is taken by mouth.
Methoctramine is a polymethylene tetraamine that acts as a muscarinic antagonist. It preferentially binds to the pre-synaptic receptor M2, a muscarinic acetylcholine ganglionic protein complex present basically in heart cells. In normal conditions -absence of methoctramine-, the activation of M2 receptors diminishes the speed of conduction of the sinoatrial and atrioventricular nodes thus reducing the heart rate. Thanks to its apparently high cardioselectivity, it has been studied as a potential parasymphatolitic drug, particularly against bradycardia. However, currently it is only addressed for research purposes, since the administration to humans is still unavailable.
Vibegron, sold under the brand name Gemtesa, is a medication for the treatment of overactive bladder. Vibegron is a selective beta-3 adrenergic receptor agonist.
Cholinergic blocking drugs are a group of drugs that block the action of acetylcholine (ACh), a neurotransmitter, in synapses of the cholinergic nervous system. They block acetylcholine from binding to cholinergic receptors, namely the nicotinic and muscarinic receptors.
Sofpironium bromide is a drug used to treat hyperhidrosis. It was approved in Japan in 2020 as a 5% gel for the treatment of primary axillary hyperhidrosis (PAH).