:*GELNIQUE is a muscarinic antagonist indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency and frequency.
:*The contents of one sachet of GELNIQUE should be applied once daily to dry, intact skin on the abdomen, upper arms/shoulders, or thighs. Application sites should be rotated. Application of GELNIQUE should not be made to the same site on consecutive days.
:*GELNIQUE is for topical application only and should not be ingested.
<!--Off-Label Use and Dosage (Adult)-->
<!--Guideline-Supported Use (Adult)-->
|offLabelAdultGuideSupport=
=====Condition1=====
* Developed by:
* Class of Recommendation:
* Strength of Evidence:
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
<!--Non–Guideline-Supported Use (Adult)-->
|offLabelAdultNoGuideSupport=
=====Condition1=====
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
<!--Pediatric Indications and Dosage-->
<!--FDA-Labeled Indications and Dosage (Pediatric)-->
|fdaLIADPed=
=====Condition1=====
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>FDA-Labeled Use</i> of {{PAGENAME}} in pediatric patients.
<!--Off-Label Use and Dosage (Pediatric)-->
<!--Guideline-Supported Use (Pediatric)-->
|offLabelPedGuideSupport=
=====Condition1=====
* Developed by:
* Class of Recommendation:
* Strength of Evidence:
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
<!--Non–Guideline-Supported Use (Pediatric)-->
|offLabelPedNoGuideSupport=
=====Condition1=====
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
<!--Contraindications-->
|contraindications=
*Urinary retention
*[[Gastric retention]]
*Uncontrolled [[narrow-angle glaucoma]]
*Known serious [[hypersensitivity]] reaction to GELNIQUE, oxybutynin, or to any of the components of GELNIQUE
<!--Warnings-->
|warnings=
====Precautions====
*Urinary Retention
:*Administer GELNIQUE with caution in patients with clinically significant [[bladder outflow obstruction]] because of the risk of [[urinary retention]].
*Use in Patients with Gastrointestinal Disorders
:*Administer GELNIQUE with caution to patients with gastrointestinal obstructive disorders because of the risk of [[gastric retention]].
:*GELNIQUE, like other [[anticholinergic drugs]], may decrease gastrointestinal motility and should be used with caution in patients with conditions such as [[ulcerative colitis]] or intestinal atony. GELNIQUE should be used with caution in patients who have [[gastroesophageal reflux]] and/or who are concurrently taking drugs (such as [[bisphosphonates]]) that can cause or exacerbate [[esophagitis]].
*Angioedema
:*[[Angioedema]] requiring hospitalization and emergency medical treatment has occurred with the first or subsequent doses of oral oxybutynin. In the event of [[angioedema]], oxybutynin-containing product should be discontinued and appropriate therapy promptly provided.
*Skin Hypersensitivity
:*In a controlled clinical trial of skin sensitization, 1 of 200 patients (0.5%) demonstrated skin [[hypersensitivity]] to GELNIQUE. Patients who develop skin hypersensitivity to GELNIQUE should discontinue drug treatment.
*Central Nervous System Effects
:*GELNIQUE is associated with anticholinergic [[central nervous system]] (CNS) effects. A variety of CNS [[anticholinergic]] effects have been reported, including [[headache]], [[dizziness]], and [[somnolence]]. Patients should be monitored for signs of [[anticholinergic]] CNS effects, particularly after beginning treatment. Advise patients not to drive or operate heavy machinery until they know how GELNIQUE affects them. If a patient experiences anticholinergic CNS effects, drug discontinuation should be considered.
*Skin Transference
:*Transfer of oxybutynin to another person can occur when vigorous skin-to-skin contact is made with the application site. To minimize the potential transfer of oxybutynin from GELNIQUE-treated skin to another person, patients should cover the application site with clothing after the gel has dried if direct skin-to-skin contact at the application site is anticipated. Patients should wash their hands immediately after application of GELNIQUE.
*Flammable Gel
:*GELNIQUE is an alcohol-based gel and is therefore flammable. Avoid open fire or smoking until gel has dried.
*Myasthenia Gravis
:*Administer GELNIQUE with caution in patients with [[myasthenia gravis]], a disease characterized by decreased [[cholinergic]] activity at the [[neuromuscular junction]].
<!--Adverse Reactions-->
<!--Clinical Trials Experience-->
|clinicalTrials=
*Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trial of another drug and may not reflect the rates observed in practice.
*Clinical Studies Experience
:*The safety of GELNIQUE was evaluated in 789 patients (389 randomized to GELNIQUE 1 g and 400 randomized to placebo) during a randomized, placebo-controlled, double-blind, 12-week clinical efficacy and safety study. A subset of these 789 patients (N = 216) participated in the 14-week open-label safety extension that followed the placebo-controlled study. Of 216 patients in the safety extension, 107 were randomized to placebo gel during the double-blind, placebo-controlled 12-week study. In the combined double-blind, placebo-controlled study and the open-label safety extension, a total of 496 patients were exposed to at least one dose of GELNIQUE. Four hundred thirty-one (431) patients received at least 12 weeks of GELNIQUE treatment and 85 patients received 26 weeks of GELNIQUE treatment. The study population primarily consisted of Caucasian women (approximately 90%) with an average age of 59 years who had [[overactive bladder]] with urge [[urinary incontinence]].
:*Table 1 lists adverse reactions that were reported in the randomized, double-blind, placebo-controlled 12-week study in greater than 2% of patients treated with GELNIQUE and at an incidence greater than placebo.
: [[File:{{PAGENAME}}01.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
*Other common adverse reactions that were reported in ≥ 1% of GELNIQUE-treated patients were [[headache]] (1.5%), [[constipation]] (1.3%), and [[pruritus]] (1.3%). Application site [[pruritus]] (2.1%) and application site [[dermatitis]] (1.8%) were the most commonly reported application site reactions. A majority of adverse reactions were described as mild or moderate in intensity, except for two patients reporting severe [[headache]].
*The most common adverse reaction leading to drug discontinuation was application site reaction (0.8% with GELNIQUE versus 0.3% with placebo).
*The most common adverse reactions reported during the 14-week open-label extension study were application site reactions (6.0%) and [[dry mouth]] (1.9%). The most common reason for premature discontinuation was application site reactions (9 patients or 4.2%). Two of these 9 patients experienced application site reactions of severe intensity ([[dermatitis]], [[urticaria]], and [[erythema]]).
<!--Postmarketing Experience-->
|postmarketing=
There is limited information regarding <i>Postmarketing Experience</i> of {{PAGENAME}} in the drug label.
<!--Drug Interactions-->
|drugInteractions=
*No specific drug-drug interaction studies have been performed with GELNIQUE.
*Other Anticholinergics
:*The concomitant use of GELNIQUE with other [[anticholinergic]] ([[antimuscarinic]]) agents may increase the frequency and/or severity of [[dry mouth]], [[constipation]], blurred vision, [[somnolence]] and other [[anticholinergic]] pharmacological effects.
<!--Use in Specific Populations-->
|useInPregnancyFDA=
* '''Pregnancy Category B'''
*There are no adequate and well-controlled studies of topical or oral oxybutynin use in pregnant women. Subcutaneous administration to rats at doses up to 25 mg/kg (approximately 50 times the human exposure based on surface area) and to rabbits at doses up to 0.4 mg/kg (approximately 1 times the human exposure) revealed no evidence of harm to the fetus due to oxybutynin chloride. The safety of GELNIQUE administration to women who are or who may become pregnant has not been established. Therefore, GELNIQUE should not be given to pregnant women unless, in the judgment of the physician, the probable clinical benefits outweigh the possible hazards.
|useInPregnancyAUS=
* '''Australian Drug Evaluation Committee (ADEC) Pregnancy Category'''
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of {{PAGENAME}} in women who are pregnant.
|useInLaborDelivery=
There is no FDA guidance on use of {{PAGENAME}} during labor and delivery.
|useInNursing=
*It is not known whether oxybutynin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when GELNIQUE is administered to a nursing woman.
|useInPed=
*Safety and effectiveness of GELNIQUE in pediatric patients have not been established.
|useInGeri=
*Of the 496 patients exposed to GELNIQUE in the randomized, double-blind, placebo-controlled 12-week study and the 14-week safety extension study, 188 patients (38%) were 65 years of age and older. No overall differences in safety or effectiveness were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
|useInGender=
There is no FDA guidance on the use of {{PAGENAME}} with respect to specific gender populations.
|useInRace=
There is no FDA guidance on the use of {{PAGENAME}} with respect to specific racial populations.
|useInRenalImpair=
There is no FDA guidance on the use of {{PAGENAME}} in patients with renal impairment.
|useInHepaticImpair=
There is no FDA guidance on the use of {{PAGENAME}} in patients with hepatic impairment.
|useInReproPotential=
There is no FDA guidance on the use of {{PAGENAME}} in women of reproductive potentials and males.
|useInImmunocomp=
There is no FDA guidance one the use of {{PAGENAME}} in patients who are immunocompromised.
<!--Administration and Monitoring-->
|administration=
* Topical
|monitoring=
There is limited information regarding <i>Monitoring</i> of {{PAGENAME}} in the drug label.
<!--IV Compatibility-->
|IVCompat=
There is limited information regarding <i>IV Compatibility</i> of {{PAGENAME}} in the drug label.
<!--Overdosage-->
|overdose=
===Acute Overdose===
====Signs and Symptoms====
*Overdosage with oxybutynin has been associated with [[anticholinergic]] effects including [[central nervous system]] excitation, [[flushing]], [[fever]], [[dehydration]], [[cardiac arrhythmia]], [[vomiting]], and [[urinary retention]]. Oral ingestion of 100 mg oxybutynin chloride in association with alcohol has been reported in a 13-year-old boy who experienced [[memory loss]], and in a 34-year-old woman who developed stupor, followed by [[disorientation]] and [[agitation]] on awakening, [[dilated pupils]], [[dry skin]], cardiac [[arrhythmia]], and [[retention of urine]]. Both patients recovered fully with symptomatic treatment.
"*"Plasma concentrations of oxybutynin begin to decline 24 hours after GELNIQUE application.
====Management====
* If overexposure occurs, monitor patients until symptoms resolve.
===Chronic Overdose===
There is limited information regarding <i>Chronic Overdose</i> of {{PAGENAME}} in the drug label.
* Oxybutynin acts as a competitive antagonist of acetylcholine at postganglionic muscarinic receptors, resulting in relaxation of bladder smooth muscle. Oxybutynin is a racemic (50:50) mixture of R- and S- isomers. Antimuscarinic activity resides predominantly with the R- isomer. The active metabolite, N-desethyloxybutynin, has pharmacological activity on the human detrusor muscle that is similar to that of oxybutynin in in vitro studies.
==Overview==
<!--Structure-->
'''Oxybutynin''' is an [[anticholinergic]] medication used to relieve urinary and bladder difficulties, including frequent urination and inability to control urination ([[Urinary incontinence#Urge incontinence|urge incontinence]]), by decreasing muscle spasms of the bladder.<ref>Chapple CR. "Muscarinic receptor antagonists in the treatment of overactive bladder". ''Urology'' (55)5, Supp. 1:33-46, 2000.</ref> It [[Competitive antagonist|competitively]] [[receptor antagonist|antagonizes]] the [[Muscarinic acetylcholine receptor M1|M1]], [[Muscarinic acetylcholine receptor M2|M2]], and [[Muscarinic acetylcholine receptor M1|M3]] subtypes of the [[muscarinic acetylcholine receptor]]. It also has direct [[spasmolytic]] effects on bladder smooth muscle as a [[Voltage-gated calcium channel|calcium antagonist]] and local anesthetic, but at concentrations far above those used clinically. It is available orally in generic formulation and as the brand-names Ditropan and Lyrinel XL, and as a transdermal patch under the brand-name Oxytrol. Also Ditrospam by Avenzor Syria
Oxybutynin is also a possible treatment of [[hyperhidrosis]], or hyper-active sweating.<ref>{{cite journal | author =Tupker RA, Harmsze AM, Deneer VH | title = Oxybutynin therapy for generalized hyperhidrosis. | journal = Arch Dermatol | volume = 142| issue = 8 | pages = 1065–6| year = 2006 | pmid = 16924061 | doi = 10.1001/archderm.142.8.1065 }}</ref><ref>{{cite journal | author =Mijnhout GS, Kloosterman H, Simsek S, Strack van Schijndel RJ, Netelenbos JC. | title = Oxybutynin: dry days for patients with hyperhidrosis. | journal = Neth J Med | volume = 64 | issue = 9 | pages = 326–8| year = 2006 | pmid = 17057269 }}</ref><ref>{{cite journal | author =Schollhammer M, Misery L. | title = Treatment of hyperhidrosis with oxybutynin. | journal = Arch Dermatol. | volume = 143 | issue = 4 | pages = 544–5| year = 2007 | pmid = 17438194 | doi = 10.1001/archderm.143.4.544 }}</ref>
|structure=
==Chemistry==
* Oxybutynin is an antispasmodic, antimuscarinic agent. GELNIQUE (oxybutynin chloride) is a clear and colorless hydroalcoholic gel containing 100 mg oxybutynin chloride per gram of gel. GELNIQUE is available in a 1 gram (1.14 mL) unit dose. Each dose contains 100 mg oxybutynin chloride. Oxybutynin is delivered as a racemate of R- and S- isomers. Chemically, oxybutynin chloride is d, l (racemic) 4-(Diethylamino)-2-butynyl (±)-α-phenylcyclohexaneglycolate hydrochloride.
Oxybutynin contains one [[Chirality (chemistry)|stereocenter]]. Commercial formulations are sold as the [[Racemic|racemate]]. The [[Enantiomer|(''R'')-enantiomer]] is a more potent anticholinergic than either the racemate or the (''S'')-enantiomer, which is essentially without anticholinergic activity at the doses used in clinical practice.<ref>Kachur JF, et al. "R and S enantiomers of oxybutynin: pharmacological effects in guinea pig bladder and intestine." ''Journal of Pharmacology and Experimental Therapeutics'' 247:867-72, 1988.</ref><ref>Noronha-Blob L, Kachur JF. "Enantiomers of oxybutynin: in vitro pharmacological characterization at M<sub>1</sub>, M<sub>2</sub> and M<sub>3</sub> muscarinic receptors and in vivo effects on urinary bladder contraction, mydriasis and salivary secretion in guinea pigs." ''Journal of Pharmacology and Experimental Therapeutics'' 256:562-7, 1991.</ref> 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.
*The empirical formula of oxybutynin is C22H31NO3•HCl. Its structural formula is:
==Adverse effects==
: [[File:{{PAGENAME}}08.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
Common adverse effects associated with oxybutynin and other [[anticholinergics]] include: dry mouth, difficulty in [[micturition]], constipation, blurred vision, drowsiness and dizziness.<ref>Mehta D (Ed.) 2006. [[British National Formulary]] 51. Pharmaceutical Press. ISBN 0-85369-668-3</ref> Anticholinergics have also been known to induce [[delirium]].<ref>Andreasen NC and Black DW, "Introductory Textbook of Psychiatry." American Psychiatric Publishing Inc. 2006</ref> These are dose-related and sometimes severe; in one population studied, after six months more than half of the patients had stopped taking the medication due to side effects.{{Fact|date=May 2008}} Dry mouth may be particularly severe; one estimate is that over a quarter of patients who begin oxybutynin treatment may have to stop because of dry mouth.{{Fact|date=May 2008}}
''N''-Desethyloxybutynin is an active metabolite of oxybutynin that is thought to be responsible for much of the adverse effects associated with the use of oxybutynin.<ref>{{cite journal |author=Reitz AB, Gupta SK, Huang Y, Parker MH, Ryan RR |title=The preparation and human muscarinic receptor profiling of oxybutynin and N-desethyloxybutynin enantiomers |journal=Med Chem |volume=3 |issue=6 |pages=543–5 |year=2007 |pmid=18045203 |doi=}}</ref> ''N''-Desethyloxybutynin plasma levels may reach as much as six times that of the parent drug after administration of the immediate-release oral formulation.<ref>Zobrist RH, et al. "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'' 18:1029-1034, 2001.</ref> Alternative dosage forms have been developed in an effort to reduce blood levels of ''N''-desethyloxybutynin and allow for a more steady concentration of oxybutynin to be achieved than is possible with the immediate release form. The long-acting formulations also allow once-daily administration instead of the twice-daily doseage required with the immediate-release form. The transdermal patch, in addition to the benefits of the extended-release oral formulations, bypasses the [[First pass effect|first-pass hepatic effect]] that the oral formulations are subject to.<ref>Oki T, et al. "Advantages for Transdermal over Oral Oxybutynin to Treat Overactive Bladder: Muscarinic Receptor Binding, Plasma Drug Concentration, and Salivary Secretion". ''Journal of Pharmacology and Experimental Therapeutics'' Fast Forward 316:1137-1145, 2006.</ref>
*Oxybutynin chloride is a white powder with a molecular weight of 393.95.
==Clinical pharmacology==
*Inactive ingredients in GELNIQUE are alcohol, USP; glycerin, USP; hydroxypropyl cellulose, NF; sodium hydroxide, NF; and purified water, USP.
Oxybutynin chloride exerts direct antispasmodic effect on smooth muscle and inhibits the muscarinic action of acetylcholine on smooth muscle. It exhibits on one-fifth of the [[anticholinergic]] activity of [[atropine]] on the rabbit detrusor muscle, but four to ten times the antispasmodic activity. No blocking effects occur at skeletal neuromuscular junctions or autonomic ganglia (antinicotinic effects).
<!--Pharmacodynamics-->
==Contraindications==
|PD=
{{Unreferencedsection|date=December 2007}}
Oxybutynin chloride is contraindicated in patients with untreated angle closure 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, 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.
==References==
{{reflist|2}}
==External links==
There is limited information regarding <i>Pharmacodynamics</i> of {{PAGENAME}} in the drug label.
:*Oxybutynin is transported across intact skin and into the systemic circulation by passive diffusion across the stratum corneum. Steady-state concentrations are achieved within 7 days of continuous dosing. Absorption of oxybutynin is similar when GELNIQUE is applied to the abdomen, upper arm/shoulders or thighs. Mean plasma concentrations during a randomized, crossover study of the three recommended application sites in 39 healthy men and women are shown in Figure 1.
: [[File:{{PAGENAME}}04.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
*Average steady-state plasma oxybutynin concentrations were 4.7, 5.2, and 5.5 ng/mL for the abdomen, upper arm/shoulder and thigh application sites, respectively (Table 2).
: [[File:{{PAGENAME}}02.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
*Distribution
:*Oxybutynin is widely distributed in body tissues following systemic absorption. The volume of distribution was estimated to be 193 L after intravenous administration of 5 mg oxybutynin chloride.
*Metabolism
:*Oxybutynin is metabolized primarily by the cytochrome P450 enzyme systems, particularly CYP3A4, found mostly in the liver and gut wall. Metabolites include phenylcyclohexylglycolic acid, which is pharmacologically inactive, and N-desethyloxybutynin (DEO), which is pharmacologically active.
:*Transdermal administration of oxybutynin bypasses the first-pass gastrointestinal and hepatic metabolism, reducing the formation of the N-desethyloxybutynin metabolite. Only small amounts of CYP3A4 are found in skin, limiting pre-systemic metabolism during transdermal absorption. The AUC ratio of N-desethyloxybutynin metabolite to parent compound following multiple transdermal applications is approximately 1:1 for GELNIQUE.
:*Following intravenous administration, the elimination half-life of oxybutynin is approximately 2 hours. After the final steady-state dose of GELNIQUE, oxybutynin and N-desethyloxybutynin demonstrated biphasic elimination with plasma concentrations beginning to decrease 24 hours after dosing. Elimination was more rapid between 24 and 48 hours after dosing, during which time plasma concentrations of oxybutynin and N-desethyloxybutynin declined by about one-half. This rapid elimination phase was followed by a more prolonged terminal elimination phase. The apparent elimination half-lives including the terminal elimination phase were 64 hours and 82 hours for oxybutynin and DEO, respectively.
*Excretion
:*Oxybutynin is extensively metabolized by the liver, with less than 0.1% of the administered dose excreted unchanged in the urine. Less than 0.1% of the administered dose is excreted as the metabolite N-desethyloxybutynin.
*Person-to-Person Transference
:*The potential for dermal transfer of oxybutynin from a treated person to an untreated person was evaluated in a single-dose study where subjects dosed with GELNIQUE engaged in vigorous contact with an untreated partner for 15 minutes, either with (N = 14 couples) or without (N = 12 couples) clothing covering the application area. The untreated partners not protected by clothing demonstrated detectable plasma concentrations of oxybutynin (mean Cmax = 0.94 ng/mL). Two of the 14 untreated subjects participating in the clothing-to-skin contact regimen had measurable oxybutynin plasma concentrations (Cmax ≤ 0.1 ng/mL) during the 48 hours following contact with treated subjects; oxybutynin was not detectable with the remaining 12 untreated subjects.
*Use of Sunscreen
:*The effect of sunscreen on the absorption of oxybutynin when applied 30 minutes before or 30 minutes after GELNIQUE application was evaluated in a single-dose randomized crossover study (N = 16). Concomitant application of sunscreen, either before or after GELNIQUE application, had no effect on the systemic exposure of oxybutynin.
*Showering
:*The effect of showering on the absorption of oxybutynin was evaluated in a randomized, steady-state crossover study under conditions of no shower, or showering 1, 2 or 6 hours after GELNIQUE application (N = 20). The results of the study indicate that showering after one hour does not affect the overall systemic exposure to oxybutynin.
*Race
:*The effect of race on the pharmacokinetics of GELNIQUE has not been studied.
*Specific Populations:
:*Geriatric: Available data suggest that there are no significant differences in the pharmacokinetics of oxybutynin based on geriatric status in patients following administration of GELNIQUE .
:*Pediatric: The pharmacokinetics of oxybutynin and N-desethyloxybutynin have not been evaluated in individuals younger than 18 years of age.
:*Gender: Available data suggest that there are no significant differences in the pharmacokinetics of oxybutynin based on gender in healthy volunteers following administration of GELNIQUE.
:*Renal Impairment: The effect of renal impairment on the pharmacokinetics of GELNIQUE has not been studied.
:*Hepatic Impairment: The effect of hepatic impairment on the pharmacokinetics of GELNIQUE has not been studied.
<!--Nonclinical Toxicology-->
|nonClinToxic=
*A 24-month study in rats at dosages of oxybutynin chloride of 20, 80 and 160 mg/kg showed no evidence of carcinogenicity. These doses are approximately 6, 25 and 50 times the maximum exposure in humans taking an oral dose, based on body surface area. Oxybutynin chloride showed no increase of mutagenic activity when tested in Schizosaccharomyces pompholiciformis, Saccharomyces cerevisiae, and Salmonella typhimurium test systems. Reproduction studies with oxybutynin chloride in the mouse, rat, hamster, and rabbit showed no definite evidence of impaired fertility.
<!--Clinical Studies-->
|clinicalStudies=
*The efficacy and safety of GELNIQUE were evaluated in a single randomized, double-blind, placebo-controlled, parallel group 12-week study for the treatment of overactive bladder with symptoms of urge incontinence, urgency and frequency. Key entry criteria included adults with symptomatic overactive bladder with an average of ≥ 4 incontinence episodes in a 3-day period and at least 8 micturitions per day. Patients were randomized to daily applications of GELNIQUE 1 gram or matching placebo gel. A total of 389 patients received GELNIQUE and 400 patients received placebo gel. The majority of patients were Caucasian (86.3%) and female (89.2%), with a mean age of 59.4 years (range: 18 to 88 years). The average duration of urinary incontinence was approximately 8.5 years and approximately 75% of patients had no prior pharmacological treatment for urinary incontinence.
*Patients treated with GELNIQUE experienced a statistically significant decrease in the number of urinary incontinence episodes per day from baseline to endpoint compared with placebo (p < 0.0001) as well as a decrease in the average daily urinary frequency (p = 0.0017) and an increase in the average urine volume per void (p = 0.0018).
*Mean and median change from baseline in daily incontinence episodes (primary endpoint), urinary frequency, and urinary void volume (secondary endpoints) between placebo and GELNIQUE are summarized in Table 3.
: [[File:{{PAGENAME}}03.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
<!--How Supplied-->
|howSupplied=
*Unit Dose: Heat-sealed sachet containing 1 gram (1.14 mL) of GELNIQUE gel for topical use.
*Carton of 30 Sachets (NDC 52544-084-30)
*Storage
:*Store at 20-25°C (68-77°F). Protect from moisture and humidity. Apply immediately after the sachets are opened and contents expelled. Discard used sachets in household trash in a manner that prevents accidental application or ingestion by children, pets, or others.
:*Keep out of reach of children.
<!--Patient Counseling Information-->
|fdaPatientInfo=
=====Instructions for Use=====
*GELNIQUE is for topical application only and should not be ingested.
*GELNIQUE should not be applied to recently shaved skin surfaces. Patients should wash hands immediately after product application. Application sites should not be subject to showering or water immersion for 1 hour after product application. Application sites should be covered with clothing if close skin-to-skin contact at the application site is anticipated.
*Alcohol based gels are flammable. Avoid open fire or smoking until the gel has dried.
*Important Anticholinergic Adverse Reactions
:*Patients should be informed that anticholinergic ([[antimuscarinic]]) agents, such as GELNIQUE, may produce clinically significant adverse reactions related to anticholinergic pharmacological activity including:
:**[[Urinary retention]] and [[constipation]].
:**[[Heat prostration]] (due to decreased [[sweating]]) when anticholinergics such as GELNIQUE are used in a hot environment.
:**[[Dizziness]] or [[blurred vision]]. Patients should be advised to exercise caution in decisions to engage in potentially dangerous activities until GELNIQUE’s effects have been determined.
:**[[Drowsiness]] that may be worsened by alcohol.
: [[File:{{PAGENAME}}05.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
<!--Precautions with Alcohol-->
|alcohol=
* Alcohol-{{PAGENAME}} interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
<!--Brand Names-->
|brandNames=
* ®<ref>{{Cite web | title = | url = }}</ref>
<!--Look-Alike Drug Names-->
|lookAlike=
<!--Drug Shortage Status-->
|drugShortage=
}}
<!--Pill Image-->
{{PillImage
|fileName=No image.jpg|This image is provided by the National Library of Medicine.
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<!--Label Display Image-->
{{LabelImage
|fileName={{PAGENAME}}06.png|This image is provided by the National Library of Medicine.
}}
{{LabelImage
|fileName={{PAGENAME}}07.png|This image is provided by the National Library of Medicine.
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GELNIQUE is a muscarinic antagonist indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency and frequency.
The contents of one sachet of GELNIQUE should be applied once daily to dry, intact skin on the abdomen, upper arms/shoulders, or thighs. Application sites should be rotated. Application of GELNIQUE should not be made to the same site on consecutive days.
GELNIQUE is for topical application only and should not be ingested.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
Condition1
Developed by:
Class of Recommendation:
Strength of Evidence:
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Guideline-Supported Use of Oxybutynin (topical) in adult patients.
Non–Guideline-Supported Use
Condition1
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Non–Guideline-Supported Use of Oxybutynin (topical) in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
Condition1
Dosing Information
Dosage
Condition2
There is limited information regarding FDA-Labeled Use of Oxybutynin (topical) in pediatric patients.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
Condition1
Developed by:
Class of Recommendation:
Strength of Evidence:
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Guideline-Supported Use of Oxybutynin (topical) in pediatric patients.
Non–Guideline-Supported Use
Condition1
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Non–Guideline-Supported Use of Oxybutynin (topical) in pediatric patients.
Administer GELNIQUE with caution to patients with gastrointestinal obstructive disorders because of the risk of gastric retention.
GELNIQUE, like other anticholinergic drugs, may decrease gastrointestinal motility and should be used with caution in patients with conditions such as ulcerative colitis or intestinal atony. GELNIQUE should be used with caution in patients who have gastroesophageal reflux and/or who are concurrently taking drugs (such as bisphosphonates) that can cause or exacerbate esophagitis.
Angioedema
Angioedema requiring hospitalization and emergency medical treatment has occurred with the first or subsequent doses of oral oxybutynin. In the event of angioedema, oxybutynin-containing product should be discontinued and appropriate therapy promptly provided.
Skin Hypersensitivity
In a controlled clinical trial of skin sensitization, 1 of 200 patients (0.5%) demonstrated skin hypersensitivity to GELNIQUE. Patients who develop skin hypersensitivity to GELNIQUE should discontinue drug treatment.
Central Nervous System Effects
GELNIQUE is associated with anticholinergic central nervous system (CNS) effects. A variety of CNS anticholinergic effects have been reported, including headache, dizziness, and somnolence. Patients should be monitored for signs of anticholinergic CNS effects, particularly after beginning treatment. Advise patients not to drive or operate heavy machinery until they know how GELNIQUE affects them. If a patient experiences anticholinergic CNS effects, drug discontinuation should be considered.
Skin Transference
Transfer of oxybutynin to another person can occur when vigorous skin-to-skin contact is made with the application site. To minimize the potential transfer of oxybutynin from GELNIQUE-treated skin to another person, patients should cover the application site with clothing after the gel has dried if direct skin-to-skin contact at the application site is anticipated. Patients should wash their hands immediately after application of GELNIQUE.
Flammable Gel
GELNIQUE is an alcohol-based gel and is therefore flammable. Avoid open fire or smoking until gel has dried.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trial of another drug and may not reflect the rates observed in practice.
Clinical Studies Experience
The safety of GELNIQUE was evaluated in 789 patients (389 randomized to GELNIQUE 1 g and 400 randomized to placebo) during a randomized, placebo-controlled, double-blind, 12-week clinical efficacy and safety study. A subset of these 789 patients (N = 216) participated in the 14-week open-label safety extension that followed the placebo-controlled study. Of 216 patients in the safety extension, 107 were randomized to placebo gel during the double-blind, placebo-controlled 12-week study. In the combined double-blind, placebo-controlled study and the open-label safety extension, a total of 496 patients were exposed to at least one dose of GELNIQUE. Four hundred thirty-one (431) patients received at least 12 weeks of GELNIQUE treatment and 85 patients received 26 weeks of GELNIQUE treatment. The study population primarily consisted of Caucasian women (approximately 90%) with an average age of 59 years who had overactive bladder with urge urinary incontinence.
Table 1 lists adverse reactions that were reported in the randomized, double-blind, placebo-controlled 12-week study in greater than 2% of patients treated with GELNIQUE and at an incidence greater than placebo.
Other common adverse reactions that were reported in ≥ 1% of GELNIQUE-treated patients were headache (1.5%), constipation (1.3%), and pruritus (1.3%). Application site pruritus (2.1%) and application site dermatitis (1.8%) were the most commonly reported application site reactions. A majority of adverse reactions were described as mild or moderate in intensity, except for two patients reporting severe headache.
The most common adverse reaction leading to drug discontinuation was application site reaction (0.8% with GELNIQUE versus 0.3% with placebo).
The most common adverse reactions reported during the 14-week open-label extension study were application site reactions (6.0%) and dry mouth (1.9%). The most common reason for premature discontinuation was application site reactions (9 patients or 4.2%). Two of these 9 patients experienced application site reactions of severe intensity (dermatitis, urticaria, and erythema).
Postmarketing Experience
There is limited information regarding Postmarketing Experience of Oxybutynin (topical) in the drug label.
Drug Interactions
No specific drug-drug interaction studies have been performed with GELNIQUE.
There are no adequate and well-controlled studies of topical or oral oxybutynin use in pregnant women. Subcutaneous administration to rats at doses up to 25 mg/kg (approximately 50 times the human exposure based on surface area) and to rabbits at doses up to 0.4 mg/kg (approximately 1 times the human exposure) revealed no evidence of harm to the fetus due to oxybutynin chloride. The safety of GELNIQUE administration to women who are or who may become pregnant has not been established. Therefore, GELNIQUE should not be given to pregnant women unless, in the judgment of the physician, the probable clinical benefits outweigh the possible hazards.
Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Oxybutynin (topical) in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Oxybutynin (topical) during labor and delivery.
Nursing Mothers
It is not known whether oxybutynin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when GELNIQUE is administered to a nursing woman.
Pediatric Use
Safety and effectiveness of GELNIQUE in pediatric patients have not been established.
Geriatic Use
Of the 496 patients exposed to GELNIQUE in the randomized, double-blind, placebo-controlled 12-week study and the 14-week safety extension study, 188 patients (38%) were 65 years of age and older. No overall differences in safety or effectiveness were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Gender
There is no FDA guidance on the use of Oxybutynin (topical) with respect to specific gender populations.
Race
There is no FDA guidance on the use of Oxybutynin (topical) with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Oxybutynin (topical) in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Oxybutynin (topical) in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Oxybutynin (topical) in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Oxybutynin (topical) in patients who are immunocompromised.
Administration and Monitoring
Administration
Topical
Monitoring
There is limited information regarding Monitoring of Oxybutynin (topical) in the drug label.
IV Compatibility
There is limited information regarding IV Compatibility of Oxybutynin (topical) in the drug label.
Oxybutynin acts as a competitive antagonist of acetylcholine at postganglionic muscarinic receptors, resulting in relaxation of bladder smooth muscle. Oxybutynin is a racemic (50:50) mixture of R- and S- isomers. Antimuscarinic activity resides predominantly with the R- isomer. The active metabolite, N-desethyloxybutynin, has pharmacological activity on the human detrusor muscle that is similar to that of oxybutynin in in vitro studies.
Structure
Oxybutynin is an antispasmodic, antimuscarinic agent. GELNIQUE (oxybutynin chloride) is a clear and colorless hydroalcoholic gel containing 100 mg oxybutynin chloride per gram of gel. GELNIQUE is available in a 1 gram (1.14 mL) unit dose. Each dose contains 100 mg oxybutynin chloride. Oxybutynin is delivered as a racemate of R- and S- isomers. Chemically, oxybutynin chloride is d, l (racemic) 4-(Diethylamino)-2-butynyl (±)-α-phenylcyclohexaneglycolate hydrochloride.
The empirical formula of oxybutynin is C22H31NO3•HCl. Its structural formula is:
Oxybutynin chloride is a white powder with a molecular weight of 393.95.
Inactive ingredients in GELNIQUE are alcohol, USP; glycerin, USP; hydroxypropyl cellulose, NF; sodium hydroxide, NF; and purified water, USP.
Pharmacodynamics
There is limited information regarding Pharmacodynamics of Oxybutynin (topical) in the drug label.
Pharmacokinetics
Absorption
Oxybutynin is transported across intact skin and into the systemic circulation by passive diffusion across the stratum corneum. Steady-state concentrations are achieved within 7 days of continuous dosing. Absorption of oxybutynin is similar when GELNIQUE is applied to the abdomen, upper arm/shoulders or thighs. Mean plasma concentrations during a randomized, crossover study of the three recommended application sites in 39 healthy men and women are shown in Figure 1.
Average steady-state plasma oxybutynin concentrations were 4.7, 5.2, and 5.5 ng/mL for the abdomen, upper arm/shoulder and thigh application sites, respectively (Table 2).
Oxybutynin is widely distributed in body tissues following systemic absorption. The volume of distribution was estimated to be 193 L after intravenous administration of 5 mg oxybutynin chloride.
Metabolism
Oxybutynin is metabolized primarily by the cytochrome P450 enzyme systems, particularly CYP3A4, found mostly in the liver and gut wall. Metabolites include phenylcyclohexylglycolic acid, which is pharmacologically inactive, and N-desethyloxybutynin (DEO), which is pharmacologically active.
Transdermal administration of oxybutynin bypasses the first-pass gastrointestinal and hepatic metabolism, reducing the formation of the N-desethyloxybutynin metabolite. Only small amounts of CYP3A4 are found in skin, limiting pre-systemic metabolism during transdermal absorption. The AUC ratio of N-desethyloxybutynin metabolite to parent compound following multiple transdermal applications is approximately 1:1 for GELNIQUE.
Following intravenous administration, the elimination half-life of oxybutynin is approximately 2 hours. After the final steady-state dose of GELNIQUE, oxybutynin and N-desethyloxybutynin demonstrated biphasic elimination with plasma concentrations beginning to decrease 24 hours after dosing. Elimination was more rapid between 24 and 48 hours after dosing, during which time plasma concentrations of oxybutynin and N-desethyloxybutynin declined by about one-half. This rapid elimination phase was followed by a more prolonged terminal elimination phase. The apparent elimination half-lives including the terminal elimination phase were 64 hours and 82 hours for oxybutynin and DEO, respectively.
Excretion
Oxybutynin is extensively metabolized by the liver, with less than 0.1% of the administered dose excreted unchanged in the urine. Less than 0.1% of the administered dose is excreted as the metabolite N-desethyloxybutynin.
Person-to-Person Transference
The potential for dermal transfer of oxybutynin from a treated person to an untreated person was evaluated in a single-dose study where subjects dosed with GELNIQUE engaged in vigorous contact with an untreated partner for 15 minutes, either with (N = 14 couples) or without (N = 12 couples) clothing covering the application area. The untreated partners not protected by clothing demonstrated detectable plasma concentrations of oxybutynin (mean Cmax = 0.94 ng/mL). Two of the 14 untreated subjects participating in the clothing-to-skin contact regimen had measurable oxybutynin plasma concentrations (Cmax ≤ 0.1 ng/mL) during the 48 hours following contact with treated subjects; oxybutynin was not detectable with the remaining 12 untreated subjects.
Use of Sunscreen
The effect of sunscreen on the absorption of oxybutynin when applied 30 minutes before or 30 minutes after GELNIQUE application was evaluated in a single-dose randomized crossover study (N = 16). Concomitant application of sunscreen, either before or after GELNIQUE application, had no effect on the systemic exposure of oxybutynin.
Showering
The effect of showering on the absorption of oxybutynin was evaluated in a randomized, steady-state crossover study under conditions of no shower, or showering 1, 2 or 6 hours after GELNIQUE application (N = 20). The results of the study indicate that showering after one hour does not affect the overall systemic exposure to oxybutynin.
Race
The effect of race on the pharmacokinetics of GELNIQUE has not been studied.
Specific Populations:
Geriatric: Available data suggest that there are no significant differences in the pharmacokinetics of oxybutynin based on geriatric status in patients following administration of GELNIQUE .
Pediatric: The pharmacokinetics of oxybutynin and N-desethyloxybutynin have not been evaluated in individuals younger than 18 years of age.
Gender: Available data suggest that there are no significant differences in the pharmacokinetics of oxybutynin based on gender in healthy volunteers following administration of GELNIQUE.
Renal Impairment: The effect of renal impairment on the pharmacokinetics of GELNIQUE has not been studied.
Hepatic Impairment: The effect of hepatic impairment on the pharmacokinetics of GELNIQUE has not been studied.
Nonclinical Toxicology
A 24-month study in rats at dosages of oxybutynin chloride of 20, 80 and 160 mg/kg showed no evidence of carcinogenicity. These doses are approximately 6, 25 and 50 times the maximum exposure in humans taking an oral dose, based on body surface area. Oxybutynin chloride showed no increase of mutagenic activity when tested in Schizosaccharomyces pompholiciformis, Saccharomyces cerevisiae, and Salmonella typhimurium test systems. Reproduction studies with oxybutynin chloride in the mouse, rat, hamster, and rabbit showed no definite evidence of impaired fertility.
Clinical Studies
The efficacy and safety of GELNIQUE were evaluated in a single randomized, double-blind, placebo-controlled, parallel group 12-week study for the treatment of overactive bladder with symptoms of urge incontinence, urgency and frequency. Key entry criteria included adults with symptomatic overactive bladder with an average of ≥ 4 incontinence episodes in a 3-day period and at least 8 micturitions per day. Patients were randomized to daily applications of GELNIQUE 1 gram or matching placebo gel. A total of 389 patients received GELNIQUE and 400 patients received placebo gel. The majority of patients were Caucasian (86.3%) and female (89.2%), with a mean age of 59.4 years (range: 18 to 88 years). The average duration of urinary incontinence was approximately 8.5 years and approximately 75% of patients had no prior pharmacological treatment for urinary incontinence.
Patients treated with GELNIQUE experienced a statistically significant decrease in the number of urinary incontinence episodes per day from baseline to endpoint compared with placebo (p < 0.0001) as well as a decrease in the average daily urinary frequency (p = 0.0017) and an increase in the average urine volume per void (p = 0.0018).
Mean and median change from baseline in daily incontinence episodes (primary endpoint), urinary frequency, and urinary void volume (secondary endpoints) between placebo and GELNIQUE are summarized in Table 3.
Unit Dose: Heat-sealed sachet containing 1 gram (1.14 mL) of GELNIQUE gel for topical use.
Carton of 30 Sachets (NDC 52544-084-30)
Storage
Store at 20-25°C (68-77°F). Protect from moisture and humidity. Apply immediately after the sachets are opened and contents expelled. Discard used sachets in household trash in a manner that prevents accidental application or ingestion by children, pets, or others.
Keep out of reach of children.
Storage
There is limited information regarding Oxybutynin (topical) Storage in the drug label.
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GELNIQUE is for topical application only and should not be ingested.
GELNIQUE should not be applied to recently shaved skin surfaces. Patients should wash hands immediately after product application. Application sites should not be subject to showering or water immersion for 1 hour after product application. Application sites should be covered with clothing if close skin-to-skin contact at the application site is anticipated.
Alcohol based gels are flammable. Avoid open fire or smoking until the gel has dried.
Important Anticholinergic Adverse Reactions
Patients should be informed that anticholinergic (antimuscarinic) agents, such as GELNIQUE, may produce clinically significant adverse reactions related to anticholinergic pharmacological activity including:
Heat prostration (due to decreased sweating) when anticholinergics such as GELNIQUE are used in a hot environment.
Dizziness or blurred vision. Patients should be advised to exercise caution in decisions to engage in potentially dangerous activities until GELNIQUE’s effects have been determined.
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