OXYTROL is a muscarinic antagonist indicated for the treatment of overactive bladder in men with symptoms of urge urinary incontinence, urgency, and frequency.

{ "type": "p", "children": [], "text": "OXYTROL is a muscarinic antagonist indicated for the treatment of overactive bladder in men with symptoms of urge urinary incontinence, urgency, and frequency." }

OXYTROL 3.9 mg/day should be applied to dry, intact skin on the abdomen, hip, or buttock twice weekly (every 3 or 4 days). A new application site should be selected with each new transdermal system to avoid re-application to the same site within 7 days. Do not divide or cut the transdermal system into pieces. Do not use if the transdermal system is damaged. 

{ "type": "p", "children": [], "text": "\nOXYTROL 3.9 mg/day should be applied to dry, intact skin on the abdomen, hip, or buttock twice weekly (every 3 or 4 days). A new application site should be selected with each new transdermal system to avoid re-application to the same site within 7 days. Do not divide or cut the transdermal system into pieces. Do not use if the transdermal system is damaged. \n" }

Transdermal System: 3.9 mg/day

{ "type": "p", "children": [], "text": "Transdermal System: 3.9 mg/day" }

The use of OXYTROL is contraindicated in the following conditions:

{ "type": "p", "children": [], "text": "The use of OXYTROL is contraindicated in the following conditions:" }

{ "type": "ul", "children": [ "Urinary retention\n", "Gastric retention\n", "Uncontrolled narrow-angle glaucoma\n", "Known serious hypersensitivity reaction to OXYTROL, oxybutynin, or to any of the components of OXYTROL [see Warnings and Precautions (5.5)]." ], "text": "" }

Administer OXYTROL with caution in patients with clinically significant bladder outflow obstruction because of the risk of urinary retention [see Contraindications (4)].

Administer OXYTROL with caution to patients with gastrointestinal obstructive disorders because of the risk of gastric retention [see Contraindications (4)].

OXYTROL, 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.

OXYTROL should be used with caution in patients who have hiatus hernia/gastroesophageal reflux and/or who are concurrently taking drugs (such as bisphosphonates) that can cause or exacerbate esophagitis.

Products containing oxybutynin are associated with anticholinergic central nervous system (CNS) effects. A variety of CNS anticholinergic effects have been reported, including headache, dizziness, somnolence, confusion and hallucinations [see Adverse Events (6.2)]. 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 OXYTROL affects them. If a patient experiences anticholinergic CNS effects, drug discontinuation should be considered.

Angioedema requiring hospitalization and emergency medical treatment has occurred with the first or subsequent doses of oral oxybutynin. In the event of angioedema, OXYTROL should be discontinued and appropriate therapy promptly provided.

Patients who develop skin hypersensitivity to OXYTROL should discontinue drug treatment.

Avoid use of OXYTROL in patients with myasthenia gravis, a disease characterized by decreased cholinergic activity at the neuromuscular junction. If experiencing exacerbation of symptoms of myasthenia gravis, oxybutynin-containing product should be discontinued and appropriate therapy promptly provided.

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 trials of another drug and may not reflect the rates observed in clinical practice.

The safety of OXYTROL was evaluated in a total of 417 patients who participated in two clinical efficacy and safety studies and an open-label extension. Additional safety information was collected in earlier phase trials. In the two pivotal studies, a total of 246 patients received OXYTROL during the 12-week treatment periods. A total of 411 patients entered the open-label extension and of those, 65 patients and 52 patients received OXYTROL for at least 24 weeks and at least 36 weeks, respectively.

No deaths were reported during treatment. No serious adverse events related to treatment were reported.

Adverse reactions reported in the pivotal trials are summarized in Tables 1 and 2 below.

<div class="scrollingtable"><table> <col width="165"/> <col width="45"/> <col width="66"/> <col width="60"/> <col width="114"/> <tbody class="Headless"> <tr class="First"> <td colspan="5"><span class="Bold">Table 1: Number (%) of adverse reactions occurring in ≥ 2% of OXYTROL-treated patients and greater in the OXYTROL group than in the placebo group (Study 1).</span></td> </tr> <tr> <td class="Lrule Rrule Toprule"><span class="Bold">Adverse Reaction  </span></td><td align="center" class="Lrule Rrule Toprule" colspan="2"><span class="Bold">Placebo </span><span class="Bold"> <br/>(N = 132)</span></td><td align="center" class="Lrule Rrule Toprule" colspan="2"><span class="Bold">OXYTROL (3.9 mg/day)</span><span class="Bold"> <br/>(N = 125)</span>  </td> </tr> <tr> <td class="Lrule Rrule"></td><td align="center" class="Lrule Rrule Toprule"><span class="Bold"> N</span></td><td align="center" class="Lrule Rrule Toprule"><span class="Bold"> %</span></td><td align="center" class="Lrule Rrule Toprule"><span class="Bold"> N</span></td><td align="center" class="Lrule Rrule Toprule"><span class="Bold"> %</span></td> </tr> <tr> <td class="Lrule Rrule Toprule"> Application site pruritus</td><td align="center" class="Lrule Rrule Toprule"> 8</td><td align="center" class="Lrule Rrule Toprule"> 6.1%</td><td align="center" class="Lrule Rrule Toprule"> 21</td><td align="center" class="Lrule Rrule Toprule"> 16.8%</td> </tr> <tr> <td class="Lrule Rrule Toprule"> Dry mouth</td><td align="center" class="Lrule Rrule Toprule"> 11</td><td align="center" class="Lrule Rrule Toprule"> 8.3%</td><td align="center" class="Lrule Rrule Toprule"> 12</td><td align="center" class="Lrule Rrule Toprule"> 9.6%</td> </tr> <tr> <td class="Lrule Rrule Toprule"> Application site erythema</td><td align="center" class="Lrule Rrule Toprule"> 3</td><td align="center" class="Lrule Rrule Toprule"> 2.3%</td><td align="center" class="Lrule Rrule Toprule"> 7</td><td align="center" class="Lrule Rrule Toprule"> 5.6%</td> </tr> <tr> <td class="Lrule Rrule Toprule"> Application site vesicles</td><td align="center" class="Lrule Rrule Toprule"> 0</td><td align="center" class="Lrule Rrule Toprule"> 0.0%</td><td align="center" class="Lrule Rrule Toprule"> 4</td><td align="center" class="Lrule Rrule Toprule"> 3.2%</td> </tr> <tr> <td class="Lrule Rrule Toprule"> Diarrhea</td><td align="center" class="Lrule Rrule Toprule"> 3</td><td align="center" class="Lrule Rrule Toprule"> 2.3%</td><td align="center" class="Lrule Rrule Toprule"> 4</td><td align="center" class="Lrule Rrule Toprule"> 3.2%</td> </tr> <tr class="Last"> <td class="Lrule Rrule Toprule"> Dysuria</td><td align="center" class="Lrule Rrule Toprule"> 0</td><td align="center" class="Lrule Rrule Toprule"> 0.0%</td><td align="center" class="Lrule Rrule Toprule"> 3</td><td align="center" class="Lrule Rrule Toprule"> 2.4%</td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table> <col width="165"/> <col width="51"/> <col width="60"/> <col width="66"/> <col width="108"/> <tbody class="Headless"> <tr class="First"> <td colspan="5"><span class="Bold">Table 2: Number (%) of adverse reactions occurring in ≥ 2% of OXYTROL-treated patients and greater in the OXYTROL group than in the placebo group (Study 2).</span></td> </tr> <tr> <td class="Lrule Rrule Toprule"><span class="Bold">Adverse Reaction  </span></td><td align="center" class="Lrule Rrule Toprule" colspan="2"><span class="Bold">Placebo</span><span class="Bold"> <br/>(N = 117)</span></td><td align="center" class="Lrule Rrule Toprule" colspan="2"><span class="Bold">OXYTROL (3.9 mg/day)</span><span class="Bold"> <br/>(N = 121)</span>  </td> </tr> <tr> <td class="Lrule Rrule"></td><td align="center" class="Lrule Rrule Toprule"><span class="Bold"> N</span></td><td align="center" class="Lrule Rrule Toprule"><span class="Bold"> %</span></td><td align="center" class="Lrule Rrule Toprule"><span class="Bold"> N</span></td><td align="center" class="Lrule Rrule Toprule"><span class="Bold"> %</span></td> </tr> <tr> <td class="Lrule Rrule Toprule"> Application site pruritus</td><td align="center" class="Lrule Rrule Toprule"> 5</td><td align="center" class="Lrule Rrule Toprule"> 4.3%</td><td align="center" class="Lrule Rrule Toprule"> 17</td><td align="center" class="Lrule Rrule Toprule"> 14.0%</td> </tr> <tr> <td class="Lrule Rrule Toprule"> Application site erythema</td><td align="center" class="Lrule Rrule Toprule"> 2</td><td align="center" class="Lrule Rrule Toprule"> 1.7%</td><td align="center" class="Lrule Rrule Toprule"> 10</td><td align="center" class="Lrule Rrule Toprule"> 8.3%</td> </tr> <tr> <td class="Lrule Rrule Toprule"> Dry mouth</td><td align="center" class="Lrule Rrule Toprule"> 2</td><td align="center" class="Lrule Rrule Toprule"> 1.7%</td><td align="center" class="Lrule Rrule Toprule"> 5</td><td align="center" class="Lrule Rrule Toprule"> 4.1%</td> </tr> <tr> <td class="Lrule Rrule Toprule"> Constipation</td><td align="center" class="Lrule Rrule Toprule"> 0</td><td align="center" class="Lrule Rrule Toprule"> 0.0%</td><td align="center" class="Lrule Rrule Toprule"> 4</td><td align="center" class="Lrule Rrule Toprule"> 3.3%</td> </tr> <tr> <td class="Lrule Rrule Toprule"> Application site rash</td><td align="center" class="Lrule Rrule Toprule"> 1</td><td align="center" class="Lrule Rrule Toprule"> 0.9%</td><td align="center" class="Lrule Rrule Toprule"> 4</td><td align="center" class="Lrule Rrule Toprule"> 3.3%</td> </tr> <tr> <td class="Lrule Rrule Toprule"> Application site macules</td><td align="center" class="Lrule Rrule Toprule"> 0</td><td align="center" class="Lrule Rrule Toprule"> 0.0%</td><td align="center" class="Lrule Rrule Toprule"> 3</td><td align="center" class="Lrule Rrule Toprule"> 2.5%</td> </tr> <tr class="Last"> <td class="Lrule Rrule Toprule"> Abnormal vision</td><td align="center" class="Lrule Rrule Toprule"> 0</td><td align="center" class="Lrule Rrule Toprule"> 0.0%</td><td align="center" class="Lrule Rrule Toprule"> 3</td><td align="center" class="Lrule Rrule Toprule"> 2.5%</td> </tr> </tbody> </table></div>

Most adverse reactions were described as mild or moderate in intensity. Severe application site reactions were reported by 6.4% of OXYTROL-treated patients in Study 1 and by 5.0% of OXYTROL-treated patients in Study 2.

Adverse reactions that resulted in discontinuation were reported by 11.2% of OXYTROL-treated patients in Study 1 and 10.7% of OXYTROL-treated patients in Study 2. Most of these discontinuations were due to application site reaction. In the two pivotal studies, no patient discontinued OXYTROL treatment due to dry mouth.

In the open-label extension, the most common treatment-related adverse reactions were: application site pruritus, application site erythema, and dry mouth.

The following adverse reactions have been identified during post approval use of OXYTROL. Because these reactions are reported voluntarily from  a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Nervous System Disorders: Memory impairment, dizziness, somnolence, confusion

Psychiatric Disorders: Delirium, hallucinations

The concomitant use of OXYTROL with other anticholinergic drugs, or with other agents that produce dry mouth, constipation, somnolence, and/or other anticholinergic-like effects may increase the frequency and/or severity of such effects. Anticholinergic agents may potentially alter the absorption of some concomitantly administered drugs due to anticholinergic effects on gastrointestinal motility.

Pharmacokinetic studies have not been performed with patients concomitantly receiving cytochrome P450 enzyme inhibitors, such as antimycotic agents (e.g., ketoconazole, itraconazole, and miconazole) or macrolide antibiotics (e.g., erythromycin and clarithromycin).

Risk Summary

There are no studies with topical or oral oxybutynin use in pregnant women to inform a drug associated risk for birth defects or miscarriage. No adverse developmental outcomes were observed in animal reproduction studies when oxybutynin chloride was administered to pregnant rats and rabbits during organogenesis at approximately 50 and 1 times, respectively, the maximum human dose based on body surface area (see Data). 

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20% respectively.

Data            

Animal Data

Subcutaneous administration of oxybutynin chloride 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 based on body surface area) throughout the period of organogenesis revealed no evidence of harm to the fetus.

Risk Summary

There is no information on the presence of oxybutynin in human milk, the effects on the breastfed child, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for OXYTROL and any potential adverse effects on the breastfed child from OXYTROL or from the underlying maternal condition.

The safety and efficacy of OXYTROL in pediatric patients have not been established.

Forty-nine percent of OXYTROL-treated patients in the clinical studies were at least 65 years of age. No overall differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in response between elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out [see Clinical Pharmacology (12.3)].

The plasma concentration of oxybutynin declines within 1 to 2 hours after removal of transdermal system(s). Patients should be monitored until symptoms resolve. Overdosage with oxybutynin has been associated with anticholinergic effects including CNS excitation, flushing, fever, dehydration, cardiac arrhythmia, vomiting, and urinary retention. Ingestion of 100 mg oral 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 treatment directed at their symptoms.

{ "type": "p", "children": [], "text": "The plasma concentration of oxybutynin declines within 1 to 2 hours after removal of transdermal system(s). Patients should be monitored until symptoms resolve. Overdosage with oxybutynin has been associated with anticholinergic effects including CNS excitation, flushing, fever, dehydration, cardiac arrhythmia, vomiting, and urinary retention. Ingestion of 100 mg oral 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 treatment directed at their symptoms." }

OXYTROL (oxybutynin transdermal system) is designed to deliver oxybutynin over a 3- to 4-day interval after application to intact skin. OXYTROL is available as a 39 cm2 transdermal system containing 36 mg of oxybutynin. OXYTROL has a nominal in vivo delivery rate of 3.9 mg oxybutynin per day through skin of average permeability (inter-individual variation in skin permeability is approximately 20%).

{ "type": "p", "children": [], "text": "OXYTROL (oxybutynin transdermal system) is designed to deliver oxybutynin over a 3- to 4-day interval after application to intact skin. OXYTROL is available as a 39 cm2 transdermal system containing 36 mg of oxybutynin. OXYTROL has a nominal in vivo delivery rate of 3.9 mg oxybutynin per day through skin of average permeability (inter-individual variation in skin permeability is approximately 20%)." }

Oxybutynin is an antispasmodic, anticholinergic agent. Oxybutynin is administered as a racemate of R- and S-isomers. Chemically, oxybutynin is d, l (racemic) 4-diethylamino-2-butynyl phenylcyclohexylglycolate. The empirical formula of oxybutynin is C22H31NO3. Its structural formula is:

{ "type": "p", "children": [], "text": "Oxybutynin is an antispasmodic, anticholinergic agent. Oxybutynin is administered as a racemate of R- and S-isomers. Chemically, oxybutynin is d, l (racemic) 4-diethylamino-2-butynyl phenylcyclohexylglycolate. The empirical formula of oxybutynin is C22H31NO3. Its structural formula is:" }

Oxybutynin is a white powder with a molecular weight of 357. It is soluble in alcohol, but relatively insoluble in water.

{ "type": "p", "children": [], "text": "Oxybutynin is a white powder with a molecular weight of 357. It is soluble in alcohol, but relatively insoluble in water." }

OXYTROL is a matrix-type transdermal system composed of three layers as illustrated in Figure 1. Layer 1 (Backing Film) is a thin flexible polyester/ethylene-vinyl acetate film that provides the matrix transdermal system with occlusivity and physical integrity and protects the adhesive/drug layer. Layer 2 (Adhesive/Drug Layer) is a cast film of acrylic adhesive containing oxybutynin and triacetin, USP. Layer 3 (Release Liner) is two overlapped siliconized polyester strips that are peeled off and discarded by the patient prior to applying the matrix transdermal system.

{ "type": "p", "children": [], "text": "OXYTROL is a matrix-type transdermal system composed of three layers as illustrated in Figure 1. Layer 1 (Backing Film) is a thin flexible polyester/ethylene-vinyl acetate film that provides the matrix transdermal system with occlusivity and physical integrity and protects the adhesive/drug layer. Layer 2 (Adhesive/Drug Layer) is a cast film of acrylic adhesive containing oxybutynin and triacetin, USP. Layer 3 (Release Liner) is two overlapped siliconized polyester strips that are peeled off and discarded by the patient prior to applying the matrix transdermal system." }

Figure 1: Side and top views of the OXYTROL transdermal system. (Not to scale)

{ "type": "p", "children": [], "text": "\nFigure 1: Side and top views of the OXYTROL transdermal system.\n(Not to scale)\n" }

The free base form of oxybutynin is pharmacologically equivalent to oxybutynin hydrochloride. Oxybutynin acts as a competitive antagonist of acetylcholine at postganglionic muscarinic receptors, resulting in relaxation of bladder smooth muscle. In patients with conditions characterized by involuntary detrusor contractions, cystometric studies have demonstrated that oxybutynin increases maximum urinary bladder capacity and increases the volume to first detrusor contraction.

Oxybutynin is a racemic (50:50) mixture of R- and S-isomers. Antimuscarinic activity resides predominantly in 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.

Absorption

Oxybutynin is transported across intact skin and into the systemic circulation by passive diffusion across the stratum corneum. The average daily dose of oxybutynin absorbed from the 39 cm2 OXYTROL transdermal system is 3.9 mg. The average (SD) nominal dose, 0.10 (0.02) mg oxybutynin per cm2 surface area, was obtained from analysis of residual oxybutynin content of transdermal systems worn over a continuous 4-day period during 303 separate occasions in 76 healthy volunteers. Following application of the first OXYTROL 3.9 mg/day transdermal system, oxybutynin plasma concentrations increase for approximately 24 to 48 hours, reaching average maximum concentrations of 3 to 4 ng/mL. Thereafter, steady concentrations are maintained for up to 96 hours. Absorption of oxybutynin is bioequivalent when OXYTROL is applied to the abdomen, buttocks, or hip. Average plasma concentrations measured during a randomized, crossover study of the three recommended application sites in 24 healthy men and women are shown in Figure 2.

Figure 2: Average plasma oxybutynin concentrations (Cp) in 24 healthy male and female volunteers during single-dose application of OXYTROL 3.9 mg/day to the abdomen, buttock, and hip (Transdermal System removal at 96 hours).

Steady-state conditions are reached during the second OXYTROL application. Average steady-state plasma concentrations were 3.1 ng/mL for oxybutynin and 3.8 ng/mL for N-desethyloxybutynin (Figure 3). Table 3 provides a summary of pharmacokinetic parameters of oxybutynin in healthy volunteers after single and multiple applications of OXYTROL.

Figure 3: Average (SEM) steady-state oxybutynin and N-desethyloxybutynin plasma concentrations (Cp) measured in 13 healthy volunteers following the second transdermal system application in a multiple-dose, randomized, crossover study.

<div class="scrollingtable"><table> <col width="78"/> <col width="96"/> <col width="60"/> <col width="90"/> <col width="162"/> <tbody class="Headless"> <tr class="First"> <td class="Rrule" colspan="5"><span class="Bold">Table 3: Mean (SD) oxybutynin pharmacokinetic parameters from single and multiple dose studies in healthy men and women volunteers after application of OXYTROL on the abdomen.</span></td> </tr> <tr> <td class="Lrule Rrule Toprule"> <span class="Bold">Dosing</span></td><td align="center" class="Lrule Rrule Toprule" colspan="4"> <span class="Bold">Oxybutynin</span></td> </tr> <tr> <td class="Lrule Rrule"></td><td align="center" class="Lrule Rrule Toprule"> <span class="Bold">C</span><span class="Bold"><span class="Sub">max </span></span><span class="Bold">(SD)</span><span class="Bold"> <br/>(ng/mL)</span></td><td align="center" class="Lrule Rrule Toprule"><span class="Bold"> T</span><span class="Bold"><span class="Sub">max</span></span><span class="Bold"><span class="Sup">1</span></span> <br/> <span class="Bold">(hr)</span></td><td align="center" class="Lrule Rrule Toprule"><span class="Bold"> C</span><span class="Bold"><span class="Sub">avg</span></span><span class="Bold"> (SD)</span><span class="Bold"> <br/>(ng/mL)</span></td><td align="center" class="Lrule Rrule Toprule"><span class="Bold">AUC (SD)</span><span class="Bold"> <br/>(ng/mLxh)</span> </td> </tr> <tr> <td class="Lrule Rrule Toprule"> <span class="Bold">Single</span></td><td align="center" class="Lrule Rrule Toprule"> 3.0 (0.8)</td><td align="center" class="Lrule Rrule Toprule"> 48</td><td align="center" class="Lrule Rrule Toprule"> -</td><td align="center" class="Lrule Rrule Toprule">245 (59)<span class="Bold"><span class="Sup">2</span></span></td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule"> </td><td align="center" class="Lrule Rrule Toprule"> 3.4 (1.1)</td><td align="center" class="Lrule Rrule Toprule"> 36</td><td align="center" class="Lrule Rrule Toprule"> -</td><td align="center" class="Lrule Rrule Toprule">279 (99)<span class="Bold"><span class="Sup">2</span></span></td> </tr> <tr> <td class="Lrule Rrule Toprule"> <span class="Bold">Multip</span><span class="Bold">le</span></td><td align="center" class="Lrule Rrule Toprule"> 6.6 (2.4)</td><td align="center" class="Lrule Rrule Toprule"> 10</td><td align="center" class="Lrule Rrule Toprule"> 4.2 (1.1)</td><td align="center" class="Lrule Rrule Toprule">408 (108)<span class="Bold"><span class="Sup">3</span></span></td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule"> </td><td align="center" class="Lrule Rrule Toprule"> 4.2 (1.0)</td><td align="center" class="Lrule Rrule Toprule"> 28</td><td align="center" class="Lrule Rrule Toprule"> 3.1 (0.7)</td><td align="center" class="Lrule Rrule Toprule">259 (57)<span class="Bold"><span class="Sup">4</span></span></td> </tr> <tr class="Last"> <td class="Toprule" colspan="5"><span class="Sup">1</span>T<span class="Sub">max</span> given as median<br/> <span class="Sup">2</span>AUC<span class="Sub">inf</span> <br/> <span class="Sup">3</span>AUC<span class="Sub">0-96</span> <br/> <span class="Sup">4</span>AUC<span class="Sub">0-84</span></td> </tr> </tbody> </table></div>

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, which is pharmacologically active.

After oral administration of oxybutynin, pre-systemic first-pass metabolism results in an oral bioavailability of approximately 6% and higher plasma concentration of the N-desethyl metabolite compared to oxybutynin (see Figure 4). The plasma concentration area under the time-concentration curve (AUC) ratio of N-desethyl metabolite to parent compound following a single 5 mg oral dose of oxybutynin chloride was 11.9:1.

Transdermal administration of oxybutynin bypasses first-pass gastrointestinal and hepatic metabolism, reducing the formation of the N-desethyl metabolite (see Figure 4). Only small amounts of CYP3A4 are found in skin, limiting pre-systemic metabolism during transdermal absorption. The resulting plasma concentration AUC ratio of N-desethyl metabolite to parent compound following multiple OXYTROL applications was 1.3:1.

Figure 4: Average plasma concentrations (Cp) measured after a single, 96-hour application of the OXYTROL 3.9 mg/day transdermal system (AUCinf/96) and a single, 5 mg, oral immediate-release dose of oxybutynin chloride (AUCinf/8) in 16 healthy male and female volunteers.

Following intravenous administration, the elimination half-life of oxybutynin is approximately 2 hours. Following removal of OXYTROL, plasma concentrations of oxybutynin and N-desethyloxybutynin decline with an apparent half-life of approximately 7 to 8 hours.

Excretion

Oxybutynin is extensively metabolized by the liver, with less than 0.1% of the administered dose excreted unchanged in the urine. Also, less than 0.1% of the administered dose is excreted as the metabolite N-desethyloxybutynin.

Specific Populations:

Geriatric: The pharmacokinetics of oxybutynin and N-desethyloxybutynin were similar in older and younger patients.

Pediatric: The pharmacokinetics of oxybutynin and N-desethyloxybutynin were not evaluated in individuals younger than 18 years of age.

Gender: There were no significant differences in the pharmacokinetics of oxybutynin in healthy male and female volunteers following application of OXYTROL.

Race: Available data suggest that there are no significant differences in the pharmacokinetics of oxybutynin based on race in healthy volunteers following administration of OXYTROL. Japanese volunteers demonstrated a somewhat lower metabolism of oxybutynin to N-desethyloxybutynin compared to Caucasian volunteers.

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.

The efficacy and safety of OXYTROL were evaluated in patients with urge urinary incontinence in two controlled studies and one open-label extension. Study 1 was a placebo controlled study, comparing the safety and efficacy of OXYTROL at dose levels of 1.3, 2.6, and 3.9 mg/day to placebo in 520 patients. Open-label treatment was available for patients completing the study. Study 2 was a study comparing the safety and efficacy of OXYTROL 3.9 mg/day versus active and placebo controls in 361 patients.

{ "type": "p", "children": [], "text": "The efficacy and safety of OXYTROL were evaluated in patients with urge urinary incontinence in two controlled studies and one open-label extension. Study 1 was a placebo controlled study, comparing the safety and efficacy of OXYTROL at dose levels of 1.3, 2.6, and 3.9 mg/day to placebo in 520 patients. Open-label treatment was available for patients completing the study. Study 2 was a study comparing the safety and efficacy of OXYTROL 3.9 mg/day versus active and placebo controls in 361 patients." }

Study 1 was a randomized, double-blind, placebo-controlled, parallel group study of three dose levels of OXYTROL conducted in 520 patients. The 12-week double-blind treatment included an OXYTROL dose of 3.9 mg/day or matching placebo. An open-label, dose titration treatment extension allowed continued treatment for up to an additional 40 weeks for patients completing the double-blind period. The majority of patients were Caucasian (91%) and female (92%) with a mean age of 61 years (range, 20 to 88 years). Entry criteria required that patients have urge or mixed incontinence (with a predominance of urge), urge incontinence episodes of ≥ 10 per week, and ≥ 8 micturitions per day. The patient’s medical history and a urinary diary during the treatment-free baseline period confirmed the diagnosis of urge incontinence. Approximately 80% of patients had no prior pharmacological treatment for incontinence. Changes in weekly incontinence episodes, urinary frequency, and urinary void volume between placebo and active treatment groups are summarized in Table 4.

{ "type": "p", "children": [], "text": "\nStudy 1 was a randomized, double-blind, placebo-controlled, parallel group study of three dose levels of OXYTROL conducted in 520 patients. The 12-week double-blind treatment included an OXYTROL dose of 3.9 mg/day or matching placebo. An open-label, dose titration treatment extension allowed continued treatment for up to an additional 40 weeks for patients completing the double-blind period. The majority of patients were Caucasian (91%) and female (92%) with a mean age of 61 years (range, 20 to 88 years). Entry criteria required that patients have urge or mixed incontinence (with a predominance of urge), urge incontinence episodes of ≥ 10 per week, and ≥ 8 micturitions per day. The patient’s medical history and a urinary diary during the treatment-free baseline period confirmed the diagnosis of urge incontinence. Approximately 80% of patients had no prior pharmacological treatment for incontinence. Changes in weekly incontinence episodes, urinary frequency, and urinary void volume between placebo and active treatment groups are summarized in Table 4." }

<div class="scrollingtable"><table> <col width="228"/> <col width="86"/> <col width="102"/> <col width="100"/> <col width="132"/> <tbody class="Headless"> <tr class="First"> <td colspan="5"><span class="Bold">Table 4: Mean and median change from baseline to end of treatment (Week 12 or last observation carried forward) in incontinence episodes, urinary frequency, and urinary void volume in patients treated with OXYTROL 3.9 mg/day or placebo for 12 weeks (Study 1).</span></td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule"><span class="Bold">Parameter</span></td><td align="center" class="Lrule Rrule Toprule" colspan="2"><span class="Bold">Placebo</span><span class="Bold"> <br/>(N = 127)</span></td><td align="center" class="Lrule Rrule Toprule" colspan="2"><span class="Bold">OXYTROL </span><span class="Bold">3.9 mg/day</span><span class="Bold"> <br/>(N = 120)</span></td> </tr> <tr> <td align="center" class="Lrule Rrule"><span class="Bold"> </span></td><td align="center" class="Lrule Rrule Toprule"><span class="Bold"> Mean (SD)</span></td><td align="center" class="Lrule Rrule Toprule"><span class="Bold"> Median</span></td><td align="center" class="Lrule Rrule Toprule"><span class="Bold"> Mean (SD)</span></td><td align="center" class="Lrule Rrule Toprule"><span class="Bold">Median</span> </td> </tr> <tr> <td class="Lrule Rrule Toprule" colspan="5"> <span class="Bold Italics">Weekly Incontinence Episodes</span></td> </tr> <tr> <td class="Lrule Rrule Toprule">     Baseline</td><td align="center" class="Lrule Rrule Toprule"> 37.7 (24.0)</td><td align="center" class="Lrule Rrule Toprule"> 30</td><td align="center" class="Lrule Rrule Toprule"> 34.3 (18.2)</td><td align="center" class="Lrule Rrule Toprule"> 31</td> </tr> <tr> <td class="Lrule Rrule Toprule">     Reduction</td><td align="center" class="Lrule Rrule Toprule"> 19.2 (21.4)</td><td align="center" class="Lrule Rrule Toprule"> 15</td><td align="center" class="Lrule Rrule Toprule"> 21.0 (17.1)</td><td align="center" class="Lrule Rrule Toprule"> 19</td> </tr> <tr> <td class="Lrule Rrule Toprule">     p value vs. placebo</td><td align="center" class="Lrule Rrule Toprule" colspan="2"> -</td><td align="center" class="Lrule Rrule Toprule" colspan="2"> 0.0265<span class="Bold"><span class="Sup">*</span></span></td> </tr> <tr> <td class="Lrule Rrule Toprule" colspan="5"> <span class="Bold Italics">Daily Urinary Frequency</span></td> </tr> <tr> <td class="Lrule Rrule Toprule">     Baseline</td><td align="center" class="Lrule Rrule Toprule"> 12.3 (3.5)</td><td align="center" class="Lrule Rrule Toprule"> 11</td><td align="center" class="Lrule Rrule Toprule"> 11.8 (3.1)</td><td align="center" class="Lrule Rrule Toprule"> 11</td> </tr> <tr> <td class="Lrule Rrule Toprule">     Reduction</td><td align="center" class="Lrule Rrule Toprule"> 1.6 (3.0)</td><td align="center" class="Lrule Rrule Toprule"> 1</td><td align="center" class="Lrule Rrule Toprule"> 2.2 (2.5)</td><td align="center" class="Lrule Rrule Toprule"> 2</td> </tr> <tr> <td class="Lrule Rrule Toprule">     p value vs. placebo</td><td align="center" class="Lrule Rrule Toprule" colspan="2"> -</td><td align="center" class="Lrule Rrule Toprule" colspan="2"> 0.0313<span class="Bold"><span class="Sup">*</span></span></td> </tr> <tr> <td class="Lrule Rrule Toprule"><span class="Bold Italics">Urinary Void Volume (mL)</span></td><td align="center" class="Lrule Rrule Toprule"> </td><td align="center" class="Lrule Rrule Toprule"> </td><td align="center" class="Lrule Rrule Toprule"> </td><td align="center" class="Lrule Rrule Toprule"> </td> </tr> <tr> <td class="Lrule Rrule Toprule">     Baseline</td><td align="center" class="Lrule Rrule Toprule"> 175.9 (69.5)</td><td align="center" class="Lrule Rrule Toprule"> 166.5</td><td align="center" class="Lrule Rrule Toprule"> 171.6 (65.1)</td><td align="center" class="Lrule Rrule Toprule"> 168</td> </tr> <tr> <td class="Lrule Rrule Toprule">     Increase</td><td align="center" class="Lrule Rrule Toprule"> 10.5 (56.9)</td><td align="center" class="Lrule Rrule Toprule"> 5.5</td><td align="center" class="Lrule Rrule Toprule"> 31.6 (65.6)</td><td align="center" class="Lrule Rrule Toprule"> 26</td> </tr> <tr> <td class="Lrule Rrule Toprule">     p value vs. placebo</td><td align="center" class="Lrule Rrule Toprule" colspan="2"> -</td><td align="center" class="Lrule Rrule Toprule" colspan="2"> 0.0009<span class="Sup">**</span><span class="Sup"> </span> </td> </tr> <tr class="Last"> <td class="Toprule" colspan="5"> *Comparison significant if p &lt; 0.05<br/> **Comparison significant if p ≤ 0.0167</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table>\n<col width=\"228\"/>\n<col width=\"86\"/>\n<col width=\"102\"/>\n<col width=\"100\"/>\n<col width=\"132\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td colspan=\"5\"><span class=\"Bold\">Table 4: Mean and median change from baseline to end of treatment (Week 12 or last observation carried forward) in incontinence episodes, urinary frequency, and urinary void volume in patients treated with OXYTROL 3.9 mg/day or placebo for 12 weeks (Study 1).</span></td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Lrule Rrule Toprule\"><span class=\"Bold\">Parameter</span></td><td align=\"center\" class=\"Lrule Rrule Toprule\" colspan=\"2\"><span class=\"Bold\">Placebo</span><span class=\"Bold\">\n<br/>(N = 127)</span></td><td align=\"center\" class=\"Lrule Rrule Toprule\" colspan=\"2\"><span class=\"Bold\">OXYTROL </span><span class=\"Bold\">3.9 mg/day</span><span class=\"Bold\">\n<br/>(N = 120)</span></td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Lrule Rrule\"><span class=\"Bold\"> </span></td><td align=\"center\" class=\"Lrule Rrule Toprule\"><span class=\"Bold\"> Mean (SD)</span></td><td align=\"center\" class=\"Lrule Rrule Toprule\"><span class=\"Bold\"> Median</span></td><td align=\"center\" class=\"Lrule Rrule Toprule\"><span class=\"Bold\"> Mean (SD)</span></td><td align=\"center\" class=\"Lrule Rrule Toprule\"><span class=\"Bold\">Median</span> </td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\" colspan=\"5\"> <span class=\"Bold Italics\">Weekly Incontinence Episodes</span></td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\">     Baseline</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 37.7 (24.0)</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 30</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 34.3 (18.2)</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 31</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\">     Reduction</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 19.2 (21.4)</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 15</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 21.0 (17.1)</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 19</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\">     p value vs. placebo</td><td align=\"center\" class=\"Lrule Rrule Toprule\" colspan=\"2\"> -</td><td align=\"center\" class=\"Lrule Rrule Toprule\" colspan=\"2\"> 0.0265<span class=\"Bold\"><span class=\"Sup\">*</span></span></td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\" colspan=\"5\"> <span class=\"Bold Italics\">Daily Urinary Frequency</span></td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\">     Baseline</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 12.3 (3.5)</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 11</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 11.8 (3.1)</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 11</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\">     Reduction</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 1.6 (3.0)</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 1</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 2.2 (2.5)</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 2</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\">     p value vs. placebo</td><td align=\"center\" class=\"Lrule Rrule Toprule\" colspan=\"2\"> -</td><td align=\"center\" class=\"Lrule Rrule Toprule\" colspan=\"2\"> 0.0313<span class=\"Bold\"><span class=\"Sup\">*</span></span></td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\"><span class=\"Bold Italics\">Urinary Void Volume (mL)</span></td><td align=\"center\" class=\"Lrule Rrule Toprule\"> </td><td align=\"center\" class=\"Lrule Rrule Toprule\"> </td><td align=\"center\" class=\"Lrule Rrule Toprule\"> </td><td align=\"center\" class=\"Lrule Rrule Toprule\"> </td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\">     Baseline</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 175.9 (69.5)</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 166.5</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 171.6 (65.1)</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 168</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\">     Increase</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 10.5 (56.9)</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 5.5</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 31.6 (65.6)</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 26</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\">     p value vs. placebo</td><td align=\"center\" class=\"Lrule Rrule Toprule\" colspan=\"2\"> -</td><td align=\"center\" class=\"Lrule Rrule Toprule\" colspan=\"2\"> 0.0009<span class=\"Sup\">**</span><span class=\"Sup\"> </span> </td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Toprule\" colspan=\"5\"> *Comparison significant if p &lt; 0.05<br/> **Comparison significant if p ≤ 0.0167</td>\n</tr>\n</tbody>\n</table></div>" }

Study 2 was a randomized, double-blind, study of OXYTROL 3.9 mg/day versus active and placebo controls conducted in 361 patients. The 12-week double-blind treatment included an OXYTROL dose of 3.9 mg/day, an active comparator, and placebo. The majority of patients were Caucasian (95%) and female (93%) with a mean age of 64 years (range, 18 to 89 years). Entry criteria required that all patients have urge or mixed incontinence (with a predominance of urge) and had achieved a beneficial response from the anticholinergic treatment they were using at the time of study entry. The average duration of prior pharmacological treatment was greater than 2 years. The patient’s medical history and a urinary diary during the treatment-free baseline period confirmed the diagnosis of urge incontinence. Changes in daily incontinence episodes, urinary frequency, and urinary void volume between placebo and active treatment groups are summarized in Table 5.

{ "type": "p", "children": [], "text": "\nStudy 2 was a randomized, double-blind, study of OXYTROL 3.9 mg/day versus active and placebo controls conducted in 361 patients. The 12-week double-blind treatment included an OXYTROL dose of 3.9 mg/day, an active comparator, and placebo. The majority of patients were Caucasian (95%) and female (93%) with a mean age of 64 years (range, 18 to 89 years). Entry criteria required that all patients have urge or mixed incontinence (with a predominance of urge) and had achieved a beneficial response from the anticholinergic treatment they were using at the time of study entry. The average duration of prior pharmacological treatment was greater than 2 years. The patient’s medical history and a urinary diary during the treatment-free baseline period confirmed the diagnosis of urge incontinence. Changes in daily incontinence episodes, urinary frequency, and urinary void volume between placebo and active treatment groups are summarized in Table 5." }

<div class="scrollingtable"><table> <col width="192"/> <col width="108"/> <col width="96"/> <col width="132"/> <col width="114"/> <tbody class="Headless"> <tr class="First"> <td colspan="5"><span class="Bold">Table 5: Mean and median change from baseline to end of treatment (Week 12 or last observation carried forward) in incontinence episodes, urinary frequency, and urinary void volume in patients treated with OXYTROL 3.9 mg/day or placebo for 12 weeks (Study 2).</span></td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule"><span class="Bold"> Parameter</span></td><td align="center" class="Lrule Rrule Toprule" colspan="2"><span class="Bold"> Placebo</span><span class="Bold"> <br/>(N = 117)</span></td><td align="center" class="Lrule Rrule Toprule" colspan="2"><span class="Bold">OXYTROL 3.9 mg/day</span><span class="Bold"> <br/>(N = 121) </span></td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule"></td><td align="center" class="Lrule Rrule Toprule" colspan="2"><span class="Bold"> </span></td><td align="center" class="Lrule Rrule Toprule" colspan="2"><span class="Bold"> </span></td> </tr> <tr> <td align="center" class="Lrule Rrule"><span class="Bold"> </span></td><td align="center" class="Lrule Rrule Toprule"><span class="Bold"> Mean (SD)</span></td><td align="center" class="Lrule Rrule Toprule"><span class="Bold"> Median</span></td><td align="center" class="Lrule Rrule Toprule"><span class="Bold"> Mean (SD)</span></td><td align="center" class="Lrule Rrule Toprule"><span class="Bold">Median </span></td> </tr> <tr> <td class="Lrule Rrule Toprule" colspan="5"><span class="Bold"> </span><span class="Bold Italics">Daily Incontinence Episodes</span></td> </tr> <tr> <td class="Lrule Rrule Toprule">     Baseline</td><td align="center" class="Lrule Rrule Toprule"> 5.0 (3.2)</td><td align="center" class="Lrule Rrule Toprule"> 4</td><td align="center" class="Lrule Rrule Toprule"> 4.7 (2.9)</td><td align="center" class="Lrule Rrule Toprule"> 4</td> </tr> <tr> <td class="Lrule Rrule Toprule">     Reduction</td><td align="center" class="Lrule Rrule Toprule"> 2.1 (3.0)</td><td align="center" class="Lrule Rrule Toprule"> 2</td><td align="center" class="Lrule Rrule Toprule"> 2.9 (3.0)</td><td align="center" class="Lrule Rrule Toprule"> 3</td> </tr> <tr> <td class="Lrule Rrule Toprule">     p value vs. placebo</td><td align="center" class="Lrule Rrule Toprule" colspan="2"> -</td><td align="center" class="Lrule Rrule Toprule" colspan="2"> 0.0137*</td> </tr> <tr> <td class="Lrule Rrule Toprule" colspan="5"> <span class="Bold Italics">Daily Urinary Frequency</span></td> </tr> <tr> <td class="Lrule Rrule Toprule">     Baseline</td><td align="center" class="Lrule Rrule Toprule"> 12.3 (3.3)</td><td align="center" class="Lrule Rrule Toprule"> 12</td><td align="center" class="Lrule Rrule Toprule"> 12.4 (2.9)</td><td align="center" class="Lrule Rrule Toprule"> 12</td> </tr> <tr> <td class="Lrule Rrule Toprule">     Reduction</td><td align="center" class="Lrule Rrule Toprule"> 1.4 (2.7)</td><td align="center" class="Lrule Rrule Toprule"> 1</td><td align="center" class="Lrule Rrule Toprule"> 1.9 (2.7)</td><td align="center" class="Lrule Rrule Toprule"> 2</td> </tr> <tr> <td class="Lrule Rrule Toprule">     p value vs. placebo</td><td align="center" class="Lrule Rrule Toprule" colspan="2"> -</td><td align="center" class="Lrule Rrule Toprule" colspan="2"> 0.1010*</td> </tr> <tr> <td class="Lrule Rrule Toprule" colspan="5"> <span class="Bold Italics">Urinary Void Volume (mL)</span></td> </tr> <tr> <td class="Lrule Rrule Toprule">     Baseline</td><td align="center" class="Lrule Rrule Toprule"> 175.0 (68.0)</td><td align="center" class="Lrule Rrule Toprule"> 171.0</td><td align="center" class="Lrule Rrule Toprule"> 164.8 (62.3)</td><td align="center" class="Lrule Rrule Toprule"> 160</td> </tr> <tr> <td class="Lrule Rrule Toprule">     Increase</td><td align="center" class="Lrule Rrule Toprule"> 9.3 (63.1)</td><td align="center" class="Lrule Rrule Toprule"> 5.5</td><td align="center" class="Lrule Rrule Toprule"> 32.0 (55.2)</td><td align="center" class="Lrule Rrule Toprule"> 24</td> </tr> <tr> <td class="Lrule Rrule Toprule">     P value vs placebo</td><td align="center" class="Lrule Rrule Toprule" colspan="2"> -</td><td align="center" class="Lrule Rrule Toprule" colspan="2"> 0.0010*</td> </tr> <tr class="Last"> <td class="Toprule" colspan="5">*Comparison significant if p &lt; 0.05</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table>\n<col width=\"192\"/>\n<col width=\"108\"/>\n<col width=\"96\"/>\n<col width=\"132\"/>\n<col width=\"114\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td colspan=\"5\"><span class=\"Bold\">Table 5: Mean and median change from baseline to end of treatment (Week 12 or last observation carried forward) in incontinence episodes, urinary frequency, and urinary void volume in patients treated with OXYTROL 3.9 mg/day or placebo for 12 weeks (Study 2).</span></td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Lrule Rrule Toprule\"><span class=\"Bold\"> Parameter</span></td><td align=\"center\" class=\"Lrule Rrule Toprule\" colspan=\"2\"><span class=\"Bold\"> Placebo</span><span class=\"Bold\">\n<br/>(N = 117)</span></td><td align=\"center\" class=\"Lrule Rrule Toprule\" colspan=\"2\"><span class=\"Bold\">OXYTROL 3.9 mg/day</span><span class=\"Bold\">\n<br/>(N = 121) </span></td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Lrule Rrule Toprule\"></td><td align=\"center\" class=\"Lrule Rrule Toprule\" colspan=\"2\"><span class=\"Bold\"> </span></td><td align=\"center\" class=\"Lrule Rrule Toprule\" colspan=\"2\"><span class=\"Bold\"> </span></td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Lrule Rrule\"><span class=\"Bold\"> </span></td><td align=\"center\" class=\"Lrule Rrule Toprule\"><span class=\"Bold\"> Mean (SD)</span></td><td align=\"center\" class=\"Lrule Rrule Toprule\"><span class=\"Bold\"> Median</span></td><td align=\"center\" class=\"Lrule Rrule Toprule\"><span class=\"Bold\"> Mean (SD)</span></td><td align=\"center\" class=\"Lrule Rrule Toprule\"><span class=\"Bold\">Median </span></td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\" colspan=\"5\"><span class=\"Bold\"> </span><span class=\"Bold Italics\">Daily Incontinence Episodes</span></td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\">     Baseline</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 5.0 (3.2)</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 4</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 4.7 (2.9)</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 4</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\">     Reduction</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 2.1 (3.0)</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 2</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 2.9 (3.0)</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 3</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\">     p value vs. placebo</td><td align=\"center\" class=\"Lrule Rrule Toprule\" colspan=\"2\"> -</td><td align=\"center\" class=\"Lrule Rrule Toprule\" colspan=\"2\"> 0.0137*</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\" colspan=\"5\"> <span class=\"Bold Italics\">Daily Urinary Frequency</span></td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\">     Baseline</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 12.3 (3.3)</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 12</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 12.4 (2.9)</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 12</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\">     Reduction</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 1.4 (2.7)</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 1</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 1.9 (2.7)</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 2</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\">     p value vs. placebo</td><td align=\"center\" class=\"Lrule Rrule Toprule\" colspan=\"2\"> -</td><td align=\"center\" class=\"Lrule Rrule Toprule\" colspan=\"2\"> 0.1010*</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\" colspan=\"5\"> <span class=\"Bold Italics\">Urinary Void Volume (mL)</span></td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\">     Baseline</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 175.0 (68.0)</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 171.0</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 164.8 (62.3)</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 160</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\">     Increase</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 9.3 (63.1)</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 5.5</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 32.0 (55.2)</td><td align=\"center\" class=\"Lrule Rrule Toprule\"> 24</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\">     P value vs placebo</td><td align=\"center\" class=\"Lrule Rrule Toprule\" colspan=\"2\"> -</td><td align=\"center\" class=\"Lrule Rrule Toprule\" colspan=\"2\"> 0.0010*</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Toprule\" colspan=\"5\">*Comparison significant if p &lt; 0.05</td>\n</tr>\n</tbody>\n</table></div>" }

In a controlled clinical trial of skin sensitization, none of the 103 test subjects demonstrated skin hypersensitivity to OXYTROL.

{ "type": "p", "children": [], "text": "In a controlled clinical trial of skin sensitization, none of the 103 test subjects demonstrated skin hypersensitivity to OXYTROL." }

Adhesion

{ "type": "p", "children": [], "text": "\nAdhesion\n" }

Adhesion was periodically evaluated during the pivotal studies. Of the 4,746 OXYTROL evaluations in the trials, 20 (0.4%) were observed at clinic visits to have become completely detached and 35 (0.7%) became partially detached during routine clinic use. Similar to the pharmacokinetic studies, > 98% of the transdermal systems evaluated in the pivotal studies were assessed as being ≥ 75% attached and thus would be expected to perform as anticipated. 

{ "type": "p", "children": [], "text": "Adhesion was periodically evaluated during the pivotal studies. Of the 4,746 OXYTROL evaluations in the trials, 20 (0.4%) were observed at clinic visits to have become completely detached and 35 (0.7%) became partially detached during routine clinic use. Similar to the pharmacokinetic studies, > 98% of the transdermal systems evaluated in the pivotal studies were assessed as being ≥ 75% attached and thus would be expected to perform as anticipated. " }

How Supplied

{ "type": "p", "children": [], "text": "\nHow Supplied\n" }

Unit Dose: Heat sealed pouch containing 1 OXYTROL (oxybutynin transdermal system).

{ "type": "p", "children": [], "text": "Unit Dose: Heat sealed pouch containing 1 OXYTROL (oxybutynin transdermal system)." }

Each 39 cm2 transdermal system imprinted with “OXYTROL 3.9 mg/day” contains 36 mg of oxybutynin for nominal delivery of 3.9 mg oxybutynin per day when dosed in a twice weekly regimen.

{ "type": "p", "children": [], "text": "Each 39 cm2 transdermal system imprinted with “OXYTROL 3.9 mg/day” contains 36 mg of oxybutynin for nominal delivery of 3.9 mg oxybutynin per day when dosed in a twice weekly regimen." }

Patient Calendar Box of 8 Transdermal Systems (NDC 0023-6153-08) 

{ "type": "p", "children": [], "text": "Patient Calendar Box of 8 Transdermal Systems (NDC 0023-6153-08) " }

Storage

{ "type": "p", "children": [], "text": "\nStorage\n" }

Store at 20-25°C (68-77°F). [See USP controlled room temperature.] Protect from moisture and humidity. Do not store outside the sealed pouch. Apply immediately after removal from the protective pouch. Discard used OXYTROL in household trash in a manner that prevents accidental application or ingestion by children, pets, or others.

{ "type": "p", "children": [], "text": "Store at 20-25°C (68-77°F). [See USP controlled room temperature.] Protect from moisture and humidity. Do not store outside the sealed pouch. Apply immediately after removal from the protective pouch. Discard used OXYTROL in household trash in a manner that prevents accidental application or ingestion by children, pets, or others." }

Keep out of reach of children.

{ "type": "p", "children": [], "text": "\nKeep out of reach of children.\n" }

 See FDA-Approved Patient Labeling (Patient Information and Instructions for Use)

{ "type": "p", "children": [], "text": " See FDA-Approved Patient Labeling (Patient Information and Instructions for Use)" }

Administration Instructions

{ "type": "p", "children": [], "text": "\nAdministration Instructions \n" }

Inform patients that OXYTROL should be applied to dry, intact skin on the abdomen, hip, or buttock and not be applied to areas that have been treated with oils, lotions or powders. OXYTROL should not be exposed to sunlight. Contact with water while bathing, swimming, showering or exercising will not change the effect of OXYTROL.

{ "type": "p", "children": [], "text": "Inform patients that OXYTROL should be applied to dry, intact skin on the abdomen, hip, or buttock and not be applied to areas that have been treated with oils, lotions or powders. OXYTROL should not be exposed to sunlight. Contact with water while bathing, swimming, showering or exercising will not change the effect of OXYTROL." }

Do not divide or cut the transdermal system into pieces. Do not use if the transdermal system is damaged.

{ "type": "p", "children": [], "text": "Do not divide or cut the transdermal system into pieces. Do not use if the transdermal system is damaged." }

A new application site should be selected with each new transdermal system to avoid re-application to the same site within 7 days. Inform patients to try to change OXYTROL on the same 2 days each week and that the package of OXYTROL has a calendar checklist printed on the back to remind patients of their schedule. Inform patients to avoid rubbing the area of the transdermal system during bathing, swimming, showering or exercising. Inform patients that details on use of the transdermal system are explained in the Patient Information Leaflet.

{ "type": "p", "children": [], "text": "A new application site should be selected with each new transdermal system to avoid re-application to the same site within 7 days. Inform patients to try to change OXYTROL on the same 2 days each week and that the package of OXYTROL has a calendar checklist printed on the back to remind patients of their schedule. Inform patients to avoid rubbing the area of the transdermal system during bathing, swimming, showering or exercising. Inform patients that details on use of the transdermal system are explained in the Patient Information Leaflet." }

Inform patients to discard used OXYTROL in household trash in a manner that prevents accidental application or ingestion by children, pets, or others. Inform patients to keep out of reach of children.

{ "type": "p", "children": [], "text": "Inform patients to discard used OXYTROL in household trash in a manner that prevents accidental application or ingestion by children, pets, or others. Inform patients to keep out of reach of children." }

Important Anticholinergic Adverse Reactions

{ "type": "p", "children": [], "text": "\nImportant Anticholinergic Adverse Reactions\n" }

Inform patients that anticholinergic (antimuscarinic) agents, such as OXYTROL, may produce adverse reactions related to anticholinergic pharmacological activity including:

{ "type": "p", "children": [], "text": "Inform patients that anticholinergic (antimuscarinic) agents, such as OXYTROL, may produce adverse reactions related to anticholinergic pharmacological activity including:" }

{ "type": "ul", "children": [ "Urinary retention and constipation.\n", "Heat prostration (due to decreased sweating) when anticholinergics such as OXYTROL are used in a hot environment.\n", "Dizziness or blurred vision. Patients should be advised to avoid driving or operating heavy machinery until OXYTROL’s effects have been determined.\n", "Drowsiness that may be worsened by alcohol.\n", "Angioedema has been reported with oral oxybutynin use. Patients should be advised to promptly discontinue OXYTROL and seek immediate medical attention if they experience symptoms consistent with angioedema." ], "text": "" }

Distributed By:AbbVie, Inc.North Chicago, IL 60064

{ "type": "p", "children": [], "text": "Distributed By:AbbVie, Inc.North Chicago, IL 60064" }

© 2024 AbbVie. All rights reserved.

{ "type": "p", "children": [], "text": "© 2024 AbbVie. All rights reserved." }

OXYTROL and its design are trademarks of Allergan Sales, LLC, an AbbVie company.

{ "type": "p", "children": [], "text": "OXYTROL and its design are trademarks of Allergan Sales, LLC, an AbbVie company." }

<div class="scrollingtable"><table> <col width="641"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Lrule Rrule Toprule"><span class="Bold">PATIENT INFORMATION</span> <br/> <span class="Bold">OXYTROL (OKSEE TROLE)</span> <br/> <span class="Bold">(oxybutynin transdermal system)</span></td> </tr> <tr> <td class="Lrule Rrule Toprule"><span class="Bold">What is OXYTROL?</span> <br/>OXYTROL is a prescription medicine used to treat overactive bladder in men with symptoms of sudden need to urinate with leaking or wetting accidents (urge urinary incontinence), need to urinate right away (urgency), and a need to urinate often (frequency). OXYTROL is a transdermal system (patch) you apply to your skin.<br/>It is not known if OXYTROL is safe and effective in children.</td> </tr> <tr> <td class="Lrule Rrule Toprule"><span class="Bold">Do not use OXYTROL if:</span> <br/>• your bladder does not empty or does not empty completely when you urinate (urinary retention).<br/>• your stomach empties slowly or incompletely after a meal (gastric retention).<br/>• you have uncontrolled narrow-angle glaucoma (high pressure in your eye). Tell your doctor if you have glaucoma or a family history of glaucoma.<br/>• you are allergic to oxybutynin or any of the ingredients in OXYTROL<span class="Bold">. </span>See the end of this Patient Information leaflet for a complete list of ingredients in OXYTROL. If you have allergies to medical tape products or other skin patches, tell your doctor.</td> </tr> <tr> <td class="Lrule Rrule Toprule"><span class="Bold">Before using OXYTROL, tell your doctor about all of your medical conditions, including if you:</span> <br/>• have problems emptying your bladder completely.<br/>• have a gastrointestinal obstruction (blockage in the digestive system).<br/>• have ulcerative colitis (inflamed bowels).<br/>• have gastroesophageal reflux disease (GERD) or esophagitis (inflamed esophagus, the tube between your mouth and stomach).<br/>• have myasthenia gravis (condition that causes muscle weakness).<br/> <br/> <span class="Bold">Tell your doctor about all the medicines you take, </span>including prescription and over-the-counter medicines, vitamins, and herbal supplements.<br/>Using OXYTROL with certain other medicines may affect each other. Using OXYTROL with other medicines can cause serious side effects.<br/> <span class="Bold">Especially tell your doctor if you take</span>:<br/>• medicines called “bisphosphonates” to treat osteoporosis<br/>• medicines called “anticholinergics”<br/>Ask your doctor or pharmacist for a list of these medicines if you are not sure you take any of these medicines.<br/>Know the medicines you take. Keep a list of them and show it to your doctor and pharmacist when you get a new medicine.</td> </tr> <tr> <td class="Lrule Rrule Toprule"><span class="Bold">How should I use OXYTROL?</span> <br/>• Read the Instructions for Use at the end of this Patient Information leaflet for information on the right way to use OXYTROL.<br/>• Use OXYTROL exactly as your doctor tells you to use it.<br/>• Put on a new patch of OXYTROL 2 times a week (every 3 to 4 days) according to your doctor’s instructions.<br/>• Choose a new skin site for each new patch application. You should not use the same skin site within 7 days.<br/>• Wear the patch all the time until it is time to apply a new one.<br/>• Wear only 1 patch of OXYTROL at a time.<br/>• Try to change the patch on the same 2 days each week.<br/>• Your package of OXYTROL has a calendar checklist printed on the back to help you remember your schedule. Mark the schedule you plan to follow. Always change OXYTROL on the 2 days of the week you mark on the calendar.<br/>• Contact with water when you are bathing, swimming, showering or exercising will not change the way that OXYTROL works.<br/>• Do not divide or cut the patch into pieces. Damaged patches should not be used.<br/> </td> </tr> <tr> <td class="Lrule Rrule Toprule"><span class="Bold">What should I avoid while using OXYTROL?</span> <br/>• You should not drink alcohol while using OXYTROL. Drinking alcohol can increase drowsiness that results from OXYTROL use.<br/>• OXYTROL can cause dizziness or blurred vision. <span class="Bold">Do not </span>drive, operate machinery, or do other dangerous activities until you know how OXYTROL affects you.<br/>• <span class="Bold">Do not </span>put OXYTROL on areas that have been treated with oils, lotions, or powders that could keep the patch from sticking well to your skin. <span class="Bold">Do not </span>expose the patch to sunlight. Wear your patch under clothing.<br/>• Avoid rubbing the patch area during bathing, swimming, showering or exercising.</td> </tr> <tr> <td class="Lrule Rrule Toprule"><span class="Bold">What are the possible side effects of OXYTROL?</span> <br/> <span class="Bold">OXYTROL may cause serious side effects, including:</span> <br/>• <span class="Bold">inability to empty your bladder (urinary retention). </span>OXYTROL may increase your chances of not being able to empty your bladder if you have a blockage at the base of your bladder that decreases or stops the flow of urine into the urethra, the tube that carries urine out of the body (bladder outlet obstruction). Tell your doctor right away if you are unable to empty your bladder. <br/>• <span class="Bold">increased risk of stomach and esophagus problems in certain </span><span class="Bold">p</span><span class="Bold">eople</span><span class="Bold">. </span>OXYTROL may cause stomach and esophagus problems in people who have a history of stomach or intestinal blockage, ulcerative colitis, intestinal atony, hiatal hernia, gastroesophageal reflux disease, or who are taking certain medicines called bisphosphonates.<br/>• <span class="Bold">central nervous system effects. </span>OXYTROL can cause central nervous system side effects including headache, dizziness, sleepiness, confusion, and seeing or hearing things that are not really there (hallucinations). Your doctor should monitor you for these effects after starting OXYTROL. See “What should I avoid while using OXYTROL.”<br/>• <span class="Bold">swelling (angioedema). </span>The active ingredient in OXYTROL, oxybutynin, can cause swelling around the eyes, lips, genitals, hands or feet. Some people who have taken oxybutynin medicines by mouth have had to be hospitalized. Stop using OXYTROL immediately and get emergency medical treatment right away if you have any of these symptoms.<br/>• <span class="Bold">skin hypersensitivity. </span>You may have skin changes where the patch was placed such as itching, rash, or redness. Tell your doctor if these changes do not go away or bother you.<br/>• <span class="Bold">worsening of myasthenia gravis (condition that causes muscle weakness). </span>OXYTROL may cause worsening of myasthenia gravis symptoms, including muscle weakness and breathing problems. Call your doctor right away if you have any worsening muscle weakness or breathing problems. <br/>The most common side effects of OXYTROL include skin reactions where the patch is placed and dry mouth.<br/>OXYTROL may cause you to sweat less and may increase your chances of being overheated, having a fever or heat stroke if you are in hot temperatures.<br/>Tell your doctor if you have any side effect that bothers you or that does not go away or if you have constipation.<br/>These are not all the possible side effects of OXYTROL. For a complete list, ask your doctor or pharmacist. <br/>Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA- 1088.</td> </tr> <tr> <td class="Lrule Rrule Toprule"><span class="Bold">How should I store OXYTROL?</span> <br/>• Store OXYTROL at room temperature between 68°F to 77°F (20°C to 25°C).<br/>• Do not store OXYTROL outside the sealed pouch.<br/>• Keep OXYTROL patches in a dry place.<br/>• Safely throw away used OXYTROL patches in the household trash. Be careful to prevent accidental exposure of OXYTROL to children or pets.<br/> <span class="Bold">Keep OXYTROL and all medicines out of the reach of children.</span></td> </tr> <tr> <td class="Lrule Rrule Toprule"><span class="Bold">General information about the safe and effective use of OXYTROL.</span> <br/>Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use OXYTROL for a condition for which it was not prescribed. Do not give OXYTROL to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or doctor for information about OXYTROL that is written for health professionals.</td> </tr> <tr class="Last"> <td class="Lrule Rrule Toprule"><span class="Bold">What are the ingredients of OXYTROL?</span> <br/> <span class="Bold">Active Ingredient: </span>oxybutynin<br/> <span class="Bold">Inactive Ingredients: </span>flexible polyester/ethylene-vinyl acetate film, acrylic adhesive, triacetin, siliconized polyester film.<br/>For more information, go to www.OXYTROL.com or call 1-800-678-1605</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table>\n<col width=\"641\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td align=\"center\" class=\"Lrule Rrule Toprule\"><span class=\"Bold\">PATIENT INFORMATION</span>\n<br/>\n<span class=\"Bold\">OXYTROL (OKSEE TROLE)</span>\n<br/>\n<span class=\"Bold\">(oxybutynin transdermal system)</span></td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\"><span class=\"Bold\">What is OXYTROL?</span>\n<br/>OXYTROL is a prescription medicine used to treat overactive bladder in men with symptoms of sudden need to urinate with leaking or wetting accidents (urge urinary incontinence), need to urinate right away (urgency), and a need to urinate often (frequency). OXYTROL is a transdermal system (patch) you apply to your skin.<br/>It is not known if OXYTROL is safe and effective in children.</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\"><span class=\"Bold\">Do not use OXYTROL if:</span>\n<br/>• your bladder does not empty or does not empty completely when you urinate (urinary retention).<br/>• your stomach empties slowly or incompletely after a meal (gastric retention).<br/>• you have uncontrolled narrow-angle glaucoma (high pressure in your eye). Tell your doctor if you have glaucoma or a family history of glaucoma.<br/>• you are allergic to oxybutynin or any of the ingredients in OXYTROL<span class=\"Bold\">. </span>See the end of this Patient Information leaflet for a complete list of ingredients in OXYTROL. If you have allergies to medical tape products or other skin patches, tell your doctor.</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\"><span class=\"Bold\">Before using OXYTROL, tell your doctor about all of your medical conditions, including if you:</span>\n<br/>• have problems emptying your bladder completely.<br/>• have a gastrointestinal obstruction (blockage in the digestive system).<br/>• have ulcerative colitis (inflamed bowels).<br/>• have gastroesophageal reflux disease (GERD) or esophagitis (inflamed esophagus, the tube between your mouth and stomach).<br/>• have myasthenia gravis (condition that causes muscle weakness).<br/> <br/>\n<span class=\"Bold\">Tell your doctor about all the medicines you take, </span>including prescription and over-the-counter medicines, vitamins, and herbal supplements.<br/>Using OXYTROL with certain other medicines may affect each other. Using OXYTROL with other medicines can cause serious side effects.<br/>\n<span class=\"Bold\">Especially tell your doctor if you take</span>:<br/>• medicines called “bisphosphonates” to treat osteoporosis<br/>• medicines called “anticholinergics”<br/>Ask your doctor or pharmacist for a list of these medicines if you are not sure you take any of these medicines.<br/>Know the medicines you take. Keep a list of them and show it to your doctor and pharmacist when you get a new medicine.</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\"><span class=\"Bold\">How should I use OXYTROL?</span>\n<br/>• Read the Instructions for Use at the end of this Patient Information leaflet for information on the right way to use OXYTROL.<br/>• Use OXYTROL exactly as your doctor tells you to use it.<br/>• Put on a new patch of OXYTROL 2 times a week (every 3 to 4 days) according to your doctor’s instructions.<br/>• Choose a new skin site for each new patch application. You should not use the same skin site within 7 days.<br/>• Wear the patch all the time until it is time to apply a new one.<br/>• Wear only 1 patch of OXYTROL at a time.<br/>• Try to change the patch on the same 2 days each week.<br/>• Your package of OXYTROL has a calendar checklist printed on the back to help you remember your schedule. Mark the schedule you plan to follow. Always change OXYTROL on the 2 days of the week you mark on the calendar.<br/>• Contact with water when you are bathing, swimming, showering or exercising will not change the way that OXYTROL works.<br/>• Do not divide or cut the patch into pieces. Damaged patches should not be used.<br/>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\"><span class=\"Bold\">What should I avoid while using OXYTROL?</span>\n<br/>• You should not drink alcohol while using OXYTROL. Drinking alcohol can increase drowsiness that results from OXYTROL use.<br/>• OXYTROL can cause dizziness or blurred vision. <span class=\"Bold\">Do not </span>drive, operate machinery, or do other dangerous activities until you know how OXYTROL affects you.<br/>• <span class=\"Bold\">Do not </span>put OXYTROL on areas that have been treated with oils, lotions, or powders that could keep the patch from sticking well to your skin. <span class=\"Bold\">Do not </span>expose the patch to sunlight. Wear your patch under clothing.<br/>• Avoid rubbing the patch area during bathing, swimming, showering or exercising.</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\"><span class=\"Bold\">What are the possible side effects of OXYTROL?</span>\n<br/>\n<span class=\"Bold\">OXYTROL may cause serious side effects, including:</span>\n<br/>• <span class=\"Bold\">inability to empty your bladder (urinary retention). </span>OXYTROL may increase your chances of not being able to empty your bladder if you have a blockage at the base of your bladder that decreases or stops the flow of urine into the urethra, the tube that carries urine out of the body (bladder outlet obstruction). Tell your doctor right away if you are unable to empty your bladder. <br/>• <span class=\"Bold\">increased risk of stomach and esophagus problems in certain </span><span class=\"Bold\">p</span><span class=\"Bold\">eople</span><span class=\"Bold\">. </span>OXYTROL may cause stomach and esophagus problems in people who have a history of stomach or intestinal blockage, ulcerative colitis, intestinal atony, hiatal hernia, gastroesophageal reflux disease, or who are taking certain medicines called bisphosphonates.<br/>• <span class=\"Bold\">central nervous system effects. </span>OXYTROL can cause central nervous system side effects including headache, dizziness, sleepiness, confusion, and seeing or hearing things that are not really there (hallucinations). Your doctor should monitor you for these effects after starting OXYTROL. See “What should I avoid while using OXYTROL.”<br/>• <span class=\"Bold\">swelling (angioedema). </span>The active ingredient in OXYTROL, oxybutynin, can cause swelling around the eyes, lips, genitals, hands or feet. Some people who have taken oxybutynin medicines by mouth have had to be hospitalized. Stop using OXYTROL immediately and get emergency medical treatment right away if you have any of these symptoms.<br/>• <span class=\"Bold\">skin hypersensitivity. </span>You may have skin changes where the patch was placed such as itching, rash, or redness. Tell your doctor if these changes do not go away or bother you.<br/>• <span class=\"Bold\">worsening of myasthenia gravis (condition that causes muscle weakness). </span>OXYTROL may cause worsening of myasthenia gravis symptoms, including muscle weakness and breathing problems. Call your doctor right away if you have any worsening muscle weakness or breathing problems. <br/>The most common side effects of OXYTROL include skin reactions where the patch is placed and dry mouth.<br/>OXYTROL may cause you to sweat less and may increase your chances of being overheated, having a fever or heat stroke if you are in hot temperatures.<br/>Tell your doctor if you have any side effect that bothers you or that does not go away or if you have constipation.<br/>These are not all the possible side effects of OXYTROL. For a complete list, ask your doctor or pharmacist. <br/>Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA- 1088.</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\"><span class=\"Bold\">How should I store OXYTROL?</span>\n<br/>• Store OXYTROL at room temperature between 68°F to 77°F (20°C to 25°C).<br/>• Do not store OXYTROL outside the sealed pouch.<br/>• Keep OXYTROL patches in a dry place.<br/>• Safely throw away used OXYTROL patches in the household trash. Be careful to prevent accidental exposure of OXYTROL to children or pets.<br/>\n<span class=\"Bold\">Keep OXYTROL and all medicines out of the reach of children.</span></td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\"><span class=\"Bold\">General information about the safe and effective use of OXYTROL.</span>\n<br/>Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use OXYTROL for a condition for which it was not prescribed. Do not give OXYTROL to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or doctor for information about OXYTROL that is written for health professionals.</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Lrule Rrule Toprule\"><span class=\"Bold\">What are the ingredients of OXYTROL?</span>\n<br/>\n<span class=\"Bold\">Active Ingredient: </span>oxybutynin<br/>\n<span class=\"Bold\">Inactive Ingredients: </span>flexible polyester/ethylene-vinyl acetate film, acrylic adhesive, triacetin, siliconized polyester film.<br/>For more information, go to www.OXYTROL.com or call 1-800-678-1605</td>\n</tr>\n</tbody>\n</table></div>" }

Instructions for Use

{ "type": "p", "children": [], "text": "\nInstructions for Use\n" }

OXYTROL (OKSEE TROLE)

{ "type": "p", "children": [], "text": "\nOXYTROL (OKSEE TROLE)\n" }

(oxybutynin transdermal system)

{ "type": "p", "children": [], "text": "\n(oxybutynin transdermal system)\n" }

Read this Instructions for Use that comes with your OXYTROL before you start using it and each time you get a refill.  There may be new information.  This information does not take the place of talking to your doctor about your medical condition or treatment.

{ "type": "p", "children": [], "text": "Read this Instructions for Use that comes with your OXYTROL before you start using it and each time you get a refill.  There may be new information.  This information does not take the place of talking to your doctor about your medical condition or treatment." }

Where to apply OXYTROL:

{ "type": "p", "children": [], "text": "\nWhere to apply OXYTROL: \n" }

{ "type": "ul", "children": [ "Put the patch on a clean, dry, and smooth (fold-free) area of skin on your abdomen (stomach area), hips or buttocks. See Figure A.\n\n", "Avoid your waistline area, since tight clothing may rub against the patch.\n", "The areas you choose should not be oily, damaged (cut or scraped), irritated (rashes) or have any other skin problems.\n", "\nDo not put OXYTROL on areas that have been treated with oils, lotions, or powders that could keep the patch from sticking well to your skin.\n", "When you put on a new patch, use a different area of skin from the most recent patch site. You may find it useful to change the site from one side of your body to the other.\n", "\nDo not use the same area for the patch for at least 7 days. You may choose to try different sites when using OXYTROL to find the sites that are most comfortable for you and where clothing will not rub against it. \n", "\nDo not divide or cut the patch into pieces. Damaged patches should not be used." ], "text": "" }

How to apply OXYTROL:

{ "type": "p", "children": [], "text": "\nHow to apply OXYTROL:\n" }

Step 1.

{ "type": "p", "children": [], "text": "\nStep 1.\n" }

{ "type": "ul", "children": [ "Each patch is sealed in its own protective pouch. See Figure B.\n\n", "When you are ready to put on your OXYTROL patch, tear open the pouch and remove the patch. See Figure C.\n" ], "text": "" }

Step 2.

{ "type": "p", "children": [], "text": "\nStep 2.\n" }

{ "type": "ul", "children": [ "The sticky adhesive side of the patch is covered by 2 strips of overlapping protective liner. See Figure D.\n\n", "Remove the first piece of the protective liner and place the patch, adhesive face down, firmly onto the skin. See Figure E.\n" ], "text": "" }

Step 3.

{ "type": "p", "children": [], "text": "\nStep 3.\n" }

{ "type": "ul", "children": [ "Bend the patch in half and gently roll the remaining part onto your skin using the tips of your fingers. As you roll the patch in place, the second piece of the protective liner should come off the patch. See Figure F.\n\n", "Apply firm pressure over the surface of the patch with your fingers to make sure the patch stays on. See Figure G.\n\n", "When putting on the patch, avoid touching the sticky adhesive side.\n", "Touching the adhesive may cause the patch to fall off early.\n", "Throw away the protective liners.\n", "If the patch partly or completely falls off, press it back in place and continue to follow your application schedule.\n", "If the patch does not stay on, throw it away.  Put on a new patch on a different area of skin, and continue to follow your original application schedule.\n", "If you forget to change your patch after 3 or 4 days, remove the old patch, put on a new patch in a different area of skin and continue to follow your original application schedule." ], "text": "" }

How to remove OXYTROL:

{ "type": "p", "children": [], "text": "\nHow to remove OXYTROL:\n" }

{ "type": "ul", "children": [ "When changing your OXYTROL patch, remove the old patch slowly and carefully to avoid damaging your skin.\n", "After the old patch is removed, fold it in half with the sticky sides together.\n", "\nThe patch will still contain some oxybutynin. Throw the patch away so that it cannot be worn or swallowed by another person, child, or pet.\n\n", "Gently wash the application site with warm water and a mild soap to remove any adhesive that stays on your skin after removing the patch.\n", "A small amount of baby oil may also be used to remove any adhesive remaining on your skin. Rings of adhesive that become dirty may need a medical adhesive removal pad that you can get from your pharmacist.\n", "Alcohol or other dissolving liquids (nail polish remover or other solvents) may cause skin irritation and should not be used." ], "text": "" }

This Patient Information and Instructions for Use has been approved by the U.S. Food and Drug Administration.

{ "type": "p", "children": [], "text": "\nThis Patient Information and Instructions for Use has been approved by the U.S. Food and Drug Administration.\n" }

Distributed By:AbbVie, Inc. North Chicago, IL 60064

{ "type": "p", "children": [], "text": "Distributed By:AbbVie, Inc. North Chicago, IL 60064" }

© 2024 AbbVie. All rights reserved.

{ "type": "p", "children": [], "text": "© 2024 AbbVie. All rights reserved." }

OXYTROL and its design are trademarks of Allergan Sales, LLC, an AbbVie company.

{ "type": "p", "children": [], "text": "OXYTROL and its design are trademarks of Allergan Sales, LLC, an AbbVie company. " }

Revised: 05/2024

{ "type": "p", "children": [], "text": "Revised: 05/2024" }

NDC 0023-6153-08OXYTROL® Oxybutynin Transdermal System3.9 mg/dayNominal delivery of 3.9 mg/day.Continuous delivery for twice weekly dosing.Each 39 cm2 system contains 36 mg oxybutynin.Inactive Components: triacetin, USP; acrylic adhesive;polyester/ethylene-vinyl acetate film, and siliconized polyester film.Contains 8 transdermal systems Keep out of reach of children. Do not divide or cut the transdermal system into pieces. Do not use If the transdermal system is damaged, cut, or altered in any way. Rx only abbvie

{ "type": "p", "children": [], "text": "NDC 0023-6153-08OXYTROL® Oxybutynin Transdermal System3.9 mg/dayNominal delivery of 3.9 mg/day.Continuous delivery for twice weekly dosing.Each 39 cm2 system contains 36 mg oxybutynin.Inactive Components: triacetin, USP; acrylic adhesive;polyester/ethylene-vinyl acetate film, and siliconized polyester film.Contains 8 transdermal systems\nKeep out of reach of children.\n\nDo not divide or cut the transdermal system into pieces. Do not use\n\nIf the transdermal system is damaged, cut, or altered in any way.\n\nRx only\n\nabbvie\n" }

Oxybutynin chloride extended-release tablets are a muscarinic antagonist indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency.

{ "type": "p", "children": [], "text": "Oxybutynin chloride extended-release tablets are a muscarinic antagonist indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency." }

Oxybutynin chloride extended-release tablets are also indicated for the treatment of pediatric patients aged 6 years and older with symptoms of detrusor overactivity associated with a neurological condition (e.g., spina bifida).

{ "type": "p", "children": [], "text": "Oxybutynin chloride extended-release tablets are also indicated for the treatment of pediatric patients aged 6 years and older with symptoms of detrusor overactivity associated with a neurological condition (e.g., spina bifida)." }

The recommended starting dose of Oxybutynin chloride extended-release tablets is 5 or 10 mg once daily at approximately the same time each day. Dosage may be adjusted in 5-mg increments to achieve a balance of efficacy and tolerability (up to a maximum of 30 mg/day). In general, dosage adjustment may proceed at approximately weekly intervals.

The recommended starting dose of Oxybutynin chloride extended-release tablets is 5 mg once daily at approximately the same time each day. Dosage may be adjusted in 5-mg increments to achieve a balance of efficacy and tolerability (up to a maximum of 20 mg/day).

Oxybutynin chloride extended-release tablets are available as 5, 10 and 15 mg tablets for oral use:

{ "type": "p", "children": [], "text": "Oxybutynin chloride extended-release tablets are available as 5, 10 and 15 mg tablets for oral use:" }

5 mg: White, round, biconvex tablet with "270" printed on one side and "KU" printed on the other side with black ink.

{ "type": "p", "children": [], "text": "5 mg: White, round, biconvex tablet with \"270\" printed on one side and \"KU\" printed on the other side with black ink." }

10 mg: White, round, biconvex tablet with "271" printed on one side and "KU" printed on the other side with black ink.

{ "type": "p", "children": [], "text": "10 mg: White, round, biconvex tablet with \"271\" printed on one side and \"KU\" printed on the other side with black ink." }

15 mg: White, round, biconvex tablet with "272" printed on one side and "KU" printed on the other side with black ink.

{ "type": "p", "children": [], "text": "15 mg: White, round, biconvex tablet with \"272\" printed on one side and \"KU\" printed on the other side with black ink." }

Oxybutynin chloride extended-release tablets are contraindicated in patients with urinary retention, gastric retention and other severe decreased gastrointestinal motility conditions, uncontrolled narrow-angle glaucoma.

{ "type": "p", "children": [], "text": "Oxybutynin chloride extended-release tablets are contraindicated in patients with urinary retention, gastric retention and other severe decreased gastrointestinal motility conditions, uncontrolled narrow-angle glaucoma." }

Oxybutynin chloride extended-release tablets are also contraindicated in patients who have demonstrated hypersensitivity to the drug substance or other components of the product. There have been reports of hypersensitivity reactions, including anaphylaxis and angiodema.

{ "type": "p", "children": [], "text": "Oxybutynin chloride extended-release tablets are also contraindicated in patients who have demonstrated hypersensitivity to the drug substance or other components of the product. There have been reports of hypersensitivity reactions, including anaphylaxis and angiodema." }

Angioedema of the face, lips, tongue and/or larynx has been reported with oxybutynin. In some cases, angioedema occurred after the first dose. Angioedema associated with upper airway swelling may be life-threatening. If involvement of the tongue, hypopharynx, or larynx occurs, oxybutynin should be promptly discontinued and appropriate therapy and/or measures necessary to ensure a patent airway should be promptly provided.

Oxybutynin is associated with anticholinergic central nervous system (CNS) effects [see Adverse Reactions (6)].  A variety of CNS anticholinergic effects have been reported, including hallucinations, agitation, confusion and somnolence. Patients should be monitored for signs of anticholinergic CNS effects, particularly in the first few months after beginning treatment or increasing the dose. Advise patients not to drive or operate heavy machinery until they know how Oxybutynin chloride extended-release tablets affect them. If a patient experiences anticholinergic CNS effects, dose reduction or drug discontinuation should be considered.

Oxybutynin chloride extended-release tablets should be used with caution in patients with preexisting dementia treated with cholinesterase inhibitors due to the risk of aggravation of symptoms.

Oxybutynin chloride extended-release tablets should be used with caution in patients with Parkinson's disease due to the risk of aggravation of symptoms.

Oxybutynin chloride extended-release tablets should be used with caution in patients with myasthenia gravis due to the risk of symptom aggravation.

Oxybutynin chloride extended-release tablets should be used with caution in patients with autonomic neuropathy due to the risk of aggravation of symptoms of decreased gastrointestinal motility.

Oxybutynin chloride extended-release tablets should be administered with caution to patients with clinically significant bladder outflow obstruction because of the risk of urinary retention [see Contraindications (4)].

Oxybutynin chloride extended-release tablets should be administered with caution to patients with gastrointestinal obstructive disorders because of the risk of gastric retention [see Contraindications (4)].

Oxybutynin chloride extended-release tablets, like other anticholinergic drugs, may decrease gastrointestinal motility and should be used with caution in patients with conditions such as ulcerative colitis and intestinal atony.

Oxybutynin chloride extended-release tablets 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.

As with any other nondeformable material, caution should be used when administering Oxybutynin chloride extended-release tablets to patients with preexisting severe gastrointestinal narrowing (pathologic or iatrogenic). There have been rare reports of obstructive symptoms in patients with known strictures in association with the ingestion of other drugs in nondeformable controlled-release formulations.

Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The safety and efficacy of Oxybutynin chloride extended-release tablets (5 to 30 mg/day) was evaluated in 774 adult subjects who participated in five double-blind, controlled clinical trials. In four of the five studies, Oxybutynin chloride IR (5 to 20 mg/day in 199 subjects) was an active comparator. Adverse reactions reported by ≥ 1% of subjects are shown in Table 1.

<div class="scrollingtable"><table> <caption> <span>Table 1: Adverse Drug Reactions Reported by ≥ 1% of Oxybutynin chloride extended-release tablets-treated Adult Subjects in Five Double-blind, Controlled Clinical Trials of Oxybutynin chloride extended-release tablets</span> </caption> <thead> <tr class="First Last"> <th class="Lrule Rrule">System/Organ Class <br/> <br/> Preferred Term </th><th align="center" class="Rrule">Oxybutynin chloride extended-release tablets <br/> <br/> 5 to 30 mg/day <br/> <br/> n = 774 <br/> <br/> % </th><th align="center" class="Rrule">Oxybutynin chloride IR <a class="Sup" href="#footnote-1" name="footnote-reference-1">*</a> <br/> <br/> 5 to 20 mg/day <br/> <br/> n = 199 <br/> <br/> % </th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="0"> <dl class="Footnote"> <dt> <a href="#footnote-reference-1" name="footnote-1">*</a> </dt> <dd>IR = immediate release</dd> <dt> <a href="#footnote-reference-2" name="footnote-2">†</a> </dt> <dd>The bundled term residual urine volume consists of the preferred terms residual urine volume and residual urine volume increased.</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="First"> <td class="Lrule Rrule" colspan="3"><span class="Bold">Psychiatric Disorders</span></td> </tr> <tr> <td class="Lrule Rrule"> Insomnia</td><td align="center" class="Rrule"> 3.0</td><td align="center" class="Rrule"> 5.5</td> </tr> <tr> <td class="Lrule Rrule" colspan="3"><span class="Bold">Nervous System Disorders</span></td> </tr> <tr> <td class="Lrule Rrule"> Headache</td><td align="center" class="Rrule"> 7.5</td><td align="center" class="Rrule"> 8.0</td> </tr> <tr> <td class="Lrule Rrule"> Somnolence</td><td align="center" class="Rrule"> 5.6</td><td align="center" class="Rrule"> 14.1</td> </tr> <tr> <td class="Lrule Rrule"> Dizziness</td><td align="center" class="Rrule"> 5.0</td><td align="center" class="Rrule"> 16.6</td> </tr> <tr> <td class="Lrule Rrule"> Dysgeusia</td><td align="center" class="Rrule"> 1.6</td><td align="center" class="Rrule"> 1.5</td> </tr> <tr> <td class="Lrule Rrule" colspan="3"><span class="Bold">Eye Disorders</span></td> </tr> <tr> <td class="Lrule Rrule"> Vision blurred</td><td align="center" class="Rrule"> 4.3</td><td align="center" class="Rrule"> 9.6</td> </tr> <tr> <td class="Lrule Rrule"> Dry eye</td><td align="center" class="Rrule"> 3.1</td><td align="center" class="Rrule"> 2.5</td> </tr> <tr> <td class="Lrule Rrule" colspan="3"><span class="Bold">Respiratory, Thoracic and Mediastinal Disorders</span></td> </tr> <tr> <td class="Lrule Rrule"> Cough</td><td align="center" class="Rrule"> 1.9</td><td align="center" class="Rrule"> 3.0</td> </tr> <tr> <td class="Lrule Rrule"> Oropharyngeal pain</td><td align="center" class="Rrule"> 1.9</td><td align="center" class="Rrule"> 1.5</td> </tr> <tr> <td class="Lrule Rrule"> Dry throat</td><td align="center" class="Rrule"> 1.7</td><td align="center" class="Rrule"> 2.5</td> </tr> <tr> <td class="Lrule Rrule"> Nasal dryness</td><td align="center" class="Rrule"> 1.7</td><td align="center" class="Rrule"> 4.5</td> </tr> <tr> <td class="Lrule Rrule" colspan="3"><span class="Bold">Gastrointestinal Disorders</span></td> </tr> <tr> <td class="Lrule Rrule"> Dry mouth</td><td align="center" class="Rrule"> 34.9</td><td align="center" class="Rrule"> 72.4</td> </tr> <tr> <td class="Lrule Rrule"> Constipation</td><td align="center" class="Rrule"> 8.7</td><td align="center" class="Rrule"> 15.1</td> </tr> <tr> <td class="Lrule Rrule"> Diarrhea</td><td align="center" class="Rrule"> 7.9</td><td align="center" class="Rrule"> 6.5</td> </tr> <tr> <td class="Lrule Rrule"> Dyspepsia</td><td align="center" class="Rrule"> 4.5</td><td align="center" class="Rrule"> 6.0</td> </tr> <tr> <td class="Lrule Rrule"> Nausea</td><td align="center" class="Rrule"> 4.5</td><td align="center" class="Rrule"> 11.6</td> </tr> <tr> <td class="Lrule Rrule"> Abdominal pain</td><td align="center" class="Rrule"> 1.6</td><td align="center" class="Rrule"> 2.0</td> </tr> <tr> <td class="Lrule Rrule"> Vomiting</td><td align="center" class="Rrule"> 1.3</td><td align="center" class="Rrule"> 1.5</td> </tr> <tr> <td class="Lrule Rrule"> Flatulence</td><td align="center" class="Rrule"> 1.2</td><td align="center" class="Rrule"> 2.5</td> </tr> <tr> <td class="Lrule Rrule"> Gastro-esophageal reflux disease</td><td align="center" class="Rrule"> 1.0</td><td align="center" class="Rrule"> 0.5</td> </tr> <tr> <td class="Lrule Rrule" colspan="3"><span class="Bold">Skin and Subcutaneous Tissue Disorders</span></td> </tr> <tr> <td class="Lrule Rrule"> Dry skin</td><td align="center" class="Rrule"> 1.8</td><td align="center" class="Rrule"> 2.5</td> </tr> <tr> <td class="Lrule Rrule"> Pruritus</td><td align="center" class="Rrule"> 1.3</td><td align="center" class="Rrule"> 1.5</td> </tr> <tr> <td class="Lrule Rrule" colspan="3"><span class="Bold">Renal and Urinary Disorders</span></td> </tr> <tr> <td class="Lrule Rrule"> Dysuria</td><td align="center" class="Rrule"> 1.9</td><td align="center" class="Rrule"> 2.0</td> </tr> <tr> <td class="Lrule Rrule"> Urinary hesitation</td><td align="center" class="Rrule"> 1.9</td><td align="center" class="Rrule"> 8.5</td> </tr> <tr> <td class="Lrule Rrule"> Urinary retention</td><td align="center" class="Rrule"> 1.2</td><td align="center" class="Rrule"> 3.0</td> </tr> <tr> <td class="Lrule Rrule" colspan="3"><span class="Bold">General Disorders and Administration Site Conditions</span></td> </tr> <tr> <td class="Lrule Rrule"> Fatigue</td><td align="center" class="Rrule"> 2.6</td><td align="center" class="Rrule"> 3.0</td> </tr> <tr> <td class="Lrule Rrule" colspan="3"><span class="Bold">Investigations</span></td> </tr> <tr class="Last"> <td class="Lrule Rrule"> Residual urine volume <a class="Sup" href="#footnote-2" name="footnote-reference-2">†</a></td><td align="center" class="Rrule"> 2.3</td><td align="center" class="Rrule"> 3.5</td> </tr> </tbody> </table></div>

The discontinuation rate due to adverse reactions was 4.4% with Oxybutynin chloride extended-release tablets compared to 0% with Oxybutynin chloride IR. The most frequent adverse reaction causing discontinuation of study medication was dry mouth (0.7% ).

The following adverse reactions were reported by <1% of Oxybutynin chloride extended-release tablets-treated patients and at a higher incidence than placebo in clinical trials: Metabolism and Nutrition Disorders: anorexia, fluid retention; Vascular disorders: hot flush; Respiratory, thoracic and mediastinal disorders: dysphonia; Gastrointestinal Disorders: dysphagia, frequent bowel movements; General disorders and administration site conditions: chest discomfort, thirst.

The following additional adverse reactions have been reported from worldwide postmarketing experience with Oxybutynin chloride extended-release tablets. Because postmarketing reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Infections and Infestations: Urinary tract infection; Psychiatric Disorders: psychotic disorder, agitation, confusional state, hallucinations, memory impairment; Nervous System Disorders: convulsions; Eye Disorders: glaucoma; Respiratory, Thoracic and Mediastinal Disorders: nasal congestion; Cardiac Disorders: arrhythmia, tachycardia, palpitations; QT interval prolongation; Vascular Disorders: flushing, hypertension; Skin and Subcutaneous Tissue Disorders: rash; Renal and Urinary Disorders: impotence; General Disorders and Administration Site Conditions: hypersensitivity reactions, including angioedema with airway obstruction, urticaria, and face edema; anaphylactic reactions requiring hospitalization for emergency treatment; Injury, poisoning and procedural complications: fall.

Additional adverse events reported with some other oxybutynin chloride formulations include: cycloplegia, mydriasis, and suppression of lactation.

To report SUSPECTED ADVERSE REACTIONS, contact AvKARE at 1-855-361-3993; email drugsafety@avkare.com; or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

The concomitant use of oxybutynin with other anticholinergic drugs or with other agents which produce dry mouth, constipation, somnolence (drowsiness), and/or other anticholinergic-like effects may increase the frequency and/or severity of such effects.

{ "type": "p", "children": [], "text": "The concomitant use of oxybutynin with other anticholinergic drugs or with other agents which produce dry mouth, constipation, somnolence (drowsiness), and/or other anticholinergic-like effects may increase the frequency and/or severity of such effects." }

Anticholinergic agents may potentially alter the absorption of some concomitantly administered drugs due to anticholinergic effects on gastrointestinal motility. This may be of concern for drugs with a narrow therapeutic index. Anticholinergic agents may also antagonize the effects of prokinetic agents, such as metoclopramide.

{ "type": "p", "children": [], "text": "Anticholinergic agents may potentially alter the absorption of some concomitantly administered drugs due to anticholinergic effects on gastrointestinal motility. This may be of concern for drugs with a narrow therapeutic index. Anticholinergic agents may also antagonize the effects of prokinetic agents, such as metoclopramide." }

Mean oxybutynin chloride plasma concentrations were approximately 2 fold higher when Oxybutynin chloride extended-release tablets were administered with ketoconazole, a potent CYP3A4 inhibitor. Other inhibitors of the cytochrome P450 3A4 enzyme system, such as antimycotic agents (e.g., itraconazole and miconazole) or macrolide antibiotics (e.g., erythromycin and clarithromycin), may alter oxybutynin mean pharmacokinetic parameters (i.e., C max and AUC). The clinical relevance of such potential interactions is not known. Caution should be used when such drugs are co-administered.

{ "type": "p", "children": [], "text": "Mean oxybutynin chloride plasma concentrations were approximately 2 fold higher when Oxybutynin chloride extended-release tablets were administered with ketoconazole, a potent CYP3A4 inhibitor. Other inhibitors of the cytochrome P450 3A4 enzyme system, such as antimycotic agents (e.g., itraconazole and miconazole) or macrolide antibiotics (e.g., erythromycin and clarithromycin), may alter oxybutynin mean pharmacokinetic parameters (i.e., C\n \n \n \n \n \n max and AUC). The clinical relevance of such potential interactions is not known. Caution should be used when such drugs are co-administered.\n \n\n \n \n\n " }

Pregnancy Category B. There are no adequate and well-controlled studies using Oxybutynin chloride extended-release tablets in pregnant women. Oxybutynin chloride extended-release tablets should be used during pregnancy only if the potential benefit to the patient outweighs the risk to the patient and fetus. Women who become pregnant during Oxybutynin chloride extended-release tablets treatment are encouraged to contact their physician.

Risk Summary

Based on animal data, oxybutynin is predicted to have a low probability of increasing the risk of adverse developmental effects above background risk.

Animal Data

Reproduction studies with oxybutynin chloride in the mouse, rat, hamster, and rabbit showed no evidence of impaired fertility or harm to the animal fetus.

It is not known whether oxybutynin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Oxybutynin chloride extended-release tablets are administered to a nursing woman.

The safety and efficacy of Oxybutynin chloride extended-release tablets were studied in 60 children in a 24-week, open-label, non-randomized trial. Patients were aged 6–15 years, all had symptoms of detrusor overactivity in association with a neurological condition (e.g., spina bifida), all used clean intermittent catheterization, and all were current users of oxybutynin chloride. Study results demonstrated that administration of Oxybutynin chloride extended-release tablets 5 to 20 mg/day was associated with an increase from baseline in mean urine volume per catheterization from 108 mL to 136 mL, an increase from baseline in mean urine volume after morning awakening from 148 mL to 189 mL, and an increase from baseline in the mean percentage of catheterizations without a leaking episode from 34% to 51%.

Urodynamic results were consistent with clinical results. Administration of Oxybutynin chloride extended-release tablets resulted in an increase from baseline in mean maximum cystometric capacity from 185 mL to 254 mL, a decrease from baseline in mean detrusor pressure at maximum cystometric capacity from 44 cm H 2O to 33 cm H 2O, and a reduction in the percentage of patients demonstrating uninhibited detrusor contractions (of at least 15 cm H 2O) from 60% to 28%.

The pharmacokinetics of Oxybutynin chloride extended-release tablets in these patients were consistent with those reported for adults [see Clinical Pharmacology (12.3)].

Oxybutynin chloride extended-release tablets are not recommended in pediatric patients who cannot swallow the tablet whole without chewing, dividing, or crushing, or in children under the age of 6.

The rate and severity of anticholinergic effects reported by patients less than 65 years old and those 65 years and older were similar. The pharmacokinetics of Oxybutynin chloride extended-release tablets were similar in all patients studied (up to 78 years of age).

There were no studies conducted with Oxybutynin chloride extended-release tablets in patients with renal impairment.

There were no studies conducted with Oxybutynin chloride extended-release tablets in patients with hepatic impairment.

The continuous release of oxybutynin from Oxybutynin chloride extended-release tablets should be considered in the treatment of overdosage. Patients should be monitored for at least 24 hours. Treatment should be symptomatic and supportive. Activated charcoal as well as a cathartic may be administered.

{ "type": "p", "children": [], "text": "The continuous release of oxybutynin from Oxybutynin chloride extended-release tablets should be considered in the treatment of overdosage. Patients should be monitored for at least 24 hours. Treatment should be symptomatic and supportive. Activated charcoal as well as a cathartic may be administered." }

Overdosage with oxybutynin chloride has been associated with anticholinergic effects including central nervous system excitation, flushing, fever, dehydration, cardiac arrhythmia, vomiting, and urinary retention.

{ "type": "p", "children": [], "text": "Overdosage with oxybutynin chloride has been associated with anticholinergic effects including central nervous system excitation, flushing, fever, dehydration, cardiac arrhythmia, vomiting, and urinary retention." }

Ingestion of 100 mg oxybutynin chloride in association with alcohol has been reported in a 13-year-old boy who experienced memory loss, and 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 fully recovered with symptomatic treatment.

{ "type": "p", "children": [], "text": "Ingestion of 100 mg oxybutynin chloride in association with alcohol has been reported in a 13-year-old boy who experienced memory loss, and 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 fully recovered with symptomatic treatment." }

System Components and Performance

Oxybutynin chloride extended-release tablets uses osmotic pressure to deliver oxybutynin chloride at a controlled rate over approximately 24 hours.  The system, which resembles a conventional tablet in appearance, comprises an osmotically active core surrounded by a semipermeable membrane.  The unitary tablet core is composed of the drug and excipients (including the osmotically active components).  There is a precision-laser drilled orifice in the semipermeable membrane on the side of the tablet.  In an aqueous environment, such as the gastrointestinal tract, water permeates through the membrane into the tablet core, causing the drug to go into suspension and the osmotic components to expand.  This expansion pushes the drug out through the orifice.  The semipermeable membrane controls the rate at which water permeates into the tablet core, which in turn controls the rate of drug delivery.  The controlled rate of drug delivery into the gastrointestinal lumen is thus independent of pH or gastrointestinal motility.  The function of Oxybutynin chloride extended-release tablets depends on the existence of an osmotic gradient between the contents of the core and the fluid in the gastrointestinal tract.  Since the osmotic gradient remains constant, drug delivery remains essentially constant.  The biologically inert components of the tablet remain intact during gastrointestinal transit and are eliminated in the feces as an insoluble shell.

USP Drug Release Test 3.

Oxybutynin relaxes bladder smooth muscle. Oxybutynin chloride exerts a direct antispasmodic effect on smooth muscle and inhibits the muscarinic action of acetylcholine on smooth muscle. No blocking effects occur at skeletal neuromuscular junctions or autonomic ganglia (antinicotinic effects).

Antimuscarinic activity resides predominantly in the R-isomer. A metabolite, desethyloxybutynin, has pharmacological activity similar to that of oxybutynin in in vitro studies.

In patients with conditions characterized by involuntary bladder contractions, cystometric studies have demonstrated that oxybutynin increases bladder (vesical) capacity, diminishes the frequency of uninhibited contractions of the detrusor muscle, and delays the initial desire to void.

Absorption

Following the first dose of Oxybutynin chloride extended-release tablets, oxybutynin plasma concentrations rise for 4 to 6 hours; thereafter steady concentrations are maintained for up to 24 hours, minimizing fluctuations between peak and trough concentrations associated with oxybutynin.

The relative bioavailabilities of R- and S-oxybutynin from Oxybutynin chloride extended-release tablets are 156% and 187%, respectively, compared with oxybutynin. The mean pharmacokinetic parameters for R- and S-oxybutynin are summarized in Table 2. The plasma concentration-time profiles for R- and S-oxybutynin are similar in shape; Figure 1 shows the profile for R-oxybutynin.

<div class="scrollingtable"><table> <caption> <span>Table 2: Mean (SD) R- and S-Oxybutynin Pharmacokinetic Parameters Following a Single Dose of Oxybutynin chloride extended-release tablets 10 mg (n=43)</span> </caption> <thead> <tr class="First Last"> <th class="Lrule">Parameters (units)</th><th class="Rrule" colspan="2">R-Oxybutynin</th><th class="Rrule" colspan="2">S-Oxybutynin</th> </tr> </thead> <tbody> <tr class="First"> <td class="Lrule"> C <span class="Sub">max</span> (ng/mL) </td><td> 1.0</td><td class="Rrule"> (0.6)</td><td> 1.8</td><td class="Rrule"> (1.0)</td> </tr> <tr> <td class="Lrule"> T <span class="Sub">max</span> (h) </td><td> 12.7</td><td class="Rrule"> (5.4)</td><td> 11.8</td><td class="Rrule"> (5.3)</td> </tr> <tr> <td class="Lrule"> t <span class="Sub">1/2</span> (h) </td><td> 13.2</td><td class="Rrule"> (6.2)</td><td> 12.4</td><td class="Rrule"> (6.1)</td> </tr> <tr> <td class="Lrule"> AUC <span class="Sub">(0–48)</span> (ng∙h/mL) </td><td> 18.4</td><td class="Rrule"> (10.3)</td><td> 34.2</td><td class="Rrule"> (16.9)</td> </tr> <tr class="Last"> <td class="Lrule"> AUC <span class="Sub">inf</span> (ng∙h/mL) </td><td> 21.3</td><td class="Rrule"> (12.2)</td><td> 39.5</td><td class="Rrule"> (21.2)</td> </tr> </tbody> </table></div>

Figure 1: Mean R-oxybutynin plasma concentrations following a single dose of Oxybutynin chloride extended-release tablets 10 mg and oxybutynin 5 mg administered every 8 hours (n=23 for each treatment).

Steady state oxybutynin plasma concentrations are achieved by Day 3 of repeated Oxybutynin chloride extended-release tablets dosing, with no observed drug accumulation or change in oxybutynin and desethyloxybutynin pharmacokinetic parameters.

Oxybutynin chloride extended-release tablets steady state pharmacokinetics were studied in 19 children aged 5–15 years with detrusor overactivity associated with a neurological condition (e.g., spina bifida). The children were on Oxybutynin chloride extended-release tablets total daily dose ranging from 5 to 20 mg (0.10 to 0.77 mg/kg). Sparse sampling technique was used to obtain serum samples. When all available data are normalized to an equivalent of 5 mg per day of Oxybutynin chloride extended-release tablets, the mean pharmacokinetic parameters derived for R- and S-oxybutynin and R- and S-desethyloxybutynin are summarized in Table 3. The plasma-time concentration profiles for R- and S-oxybutynin are similar in shape; Figure 2 shows the profile for R-oxybutynin when all available data are normalized to an equivalent of 5 mg per day.

<div class="scrollingtable"><table> <caption> <span>Table 3: Mean ± SD R- and S-Oxybutynin and R- and S-Desethyloxybutynin Pharmacokinetic Parameters in Children Aged 5–15 Following Administration of 5 to 20 mg Oxybutynin chloride extended-release tablets Once Daily (n=19), All Available Data Normalized to an Equivalent of Oxybutynin chloride extended-release tablets 5 mg Once Daily</span> </caption> <thead> <tr class="First Last"> <th class="Lrule Rrule"></th><th>R-Oxybutynin</th><th class="Rrule">S-Oxybutynin</th><th class="Rrule">R- Desethyloxybutynin</th><th class="Rrule">S- Desethyloxybutynin</th> </tr> </thead> <tbody> <tr class="First"> <td class="Lrule"> C <span class="Sub">max</span> (ng/mL) </td><td class="Lrule"> 0.7 ± 0.4</td><td class="Lrule"> 1.3 ± 0.8</td><td class="Lrule"> 7.8 ± 3.7</td><td class="Lrule Rrule"> 4.2 ± 2.3</td> </tr> <tr> <td class="Lrule"> T <span class="Sub">max</span> (h) </td><td class="Lrule"> 5.0</td><td class="Lrule"> 5.0</td><td class="Lrule"> 5.0</td><td class="Lrule Rrule"> 5.0</td> </tr> <tr class="Last"> <td class="Lrule"> AUC (ng∙h/mL)</td><td class="Lrule"> 12.8 ± 7.0</td><td class="Lrule"> 23.7 ± 14.4</td><td class="Lrule"> 125.1 ± 66.7</td><td class="Lrule Rrule"> 73.6 ± 47.7</td> </tr> </tbody> </table></div>

Figure 2: Mean steady state (± SD) R-oxybutynin plasma concentrations following administration of 5 to 20 mg Oxybutynin chloride extended-release tablets once daily in children aged 5–15. Plot represents all available data normalized to an equivalent of Oxybutynin chloride extended-release tablets 5 mg once daily.

Food Effects

The rate and extent of absorption and metabolism of oxybutynin are similar under fed and fasted conditions.

Distribution

Oxybutynin is widely distributed in body tissues following systemic absorption. The volume of distribution is 193 L after intravenous administration of 5 mg oxybutynin chloride. Both enantiomers of oxybutynin are highly bound (>99%) to plasma proteins. Both enantiomers of N-desethyloxybutynin are also highly bound (>97%) to plasma proteins. The major binding protein is alpha-1 acid glycoprotein.

Metabolism

Oxybutynin is metabolized primarily by the cytochrome P450 enzyme systems, particularly CYP3A4 found mostly in the liver and gut wall. Its metabolic products include phenylcyclohexylglycolic acid, which is pharmacologically inactive, and desethyloxybutynin, which is pharmacologically active. Following Oxybutynin chloride extended-release tablets administration, plasma concentrations of R- and S-desethyloxybutynin are 73% and 92%, respectively, of concentrations observed with oxybutynin.

Excretion

Oxybutynin is extensively metabolized by the liver, with less than 0.1% of the administered dose excreted unchanged in the urine. Also, less than 0.1% of the administered dose is excreted as the metabolite desethyloxybutynin.

Dose Proportionality

Pharmacokinetic parameters of oxybutynin and desethyloxybutynin (C max and AUC) following administration of 5–20 mg of Oxybutynin chloride extended-release tablets are dose proportional.

Use in Specific Populations

Pediatric

The pharmacokinetics of Oxybutynin chloride extended-release tablets were evaluated in 19 children aged 5–15 years with detrusor overactivity associated with a neurological condition (e.g., spina bifida). The pharmacokinetics of Oxybutynin chloride extended-release tablets in these pediatric patients were consistent with those reported for adults (see Tables 2 and 3, and Figures 1 and 2 above).

Gender

There are no significant differences in the pharmacokinetics of oxybutynin in healthy male and female volunteers following administration of Oxybutynin chloride extended-release tablets.

Race

Available data suggest that there are no significant differences in the pharmacokinetics of oxybutynin based on race in healthy volunteers following administration of Oxybutynin chloride extended-release tablets.

A 24-month study in rats at dosages of oxybutynin chloride of 20, 80, and 160 mg/kg/day showed no evidence of carcinogenicity. These doses are approximately 6, 25, and 50 times the maximum human exposure, based on a human equivalent dose taking into account normalization of 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 evidence of impaired fertility.

Oxybutynin chloride extended-release tablets were evaluated for the treatment of patients with overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency in three controlled efficacy studies. The majority of patients were Caucasian (89.0%) and female (91.9%) with a mean age of 59 years (range, 18 to 98 years). Entry criteria required that patients have urge or mixed incontinence (with a predominance of urge) as evidenced by ≥ 6 urge incontinence episodes per week and ≥ 10 micturitions per day. Study 1 was a fixed-dose escalation design, whereas the other two studies used a dose-adjustment design in which each patient's final dose was adjusted to a balance between improvement of incontinence symptoms and tolerability of side effects. All three studies included patients known to be responsive to oxybutynin or other anticholinergic medications, and these patients were maintained on a final dose for up to 2 weeks.

{ "type": "p", "children": [], "text": "Oxybutynin chloride extended-release tablets were evaluated for the treatment of patients with overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency in three controlled efficacy studies. The majority of patients were Caucasian (89.0%) and female (91.9%) with a mean age of 59 years (range, 18 to 98 years). Entry criteria required that patients have urge or mixed incontinence (with a predominance of urge) as evidenced by ≥ 6 urge incontinence episodes per week and ≥ 10 micturitions per day. Study 1 was a fixed-dose escalation design, whereas the other two studies used a dose-adjustment design in which each patient's final dose was adjusted to a balance between improvement of incontinence symptoms and tolerability of side effects. All three studies included patients known to be responsive to oxybutynin or other anticholinergic medications, and these patients were maintained on a final dose for up to 2 weeks." }

The efficacy results for the three controlled trials are presented in the following tables and figures.

{ "type": "p", "children": [], "text": "The efficacy results for the three controlled trials are presented in the following tables and figures." }

<div class="scrollingtable"><table> <caption> <span>Number of Urge Urinary Incontinence Episodes Per Week</span> </caption> <thead> <tr class="First Last"> <th class="Lrule" valign="top">Study 1</th><th align="center">n</th><th align="center">Oxybutynin chloride extended-release tablets</th><th align="center">n</th><th align="center" class="Rrule">Placebo</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="0"> <dl class="Footnote"> <dt> <a href="#footnote-reference-3" name="footnote-3">*</a> </dt> <dd>Covariate adjusted mean with missing observations set to baseline values</dd> <dt> <a href="#footnote-reference-4" name="footnote-4">†</a> </dt> <dd>The difference between Oxybutynin chloride extended-release tabletsand placebo was statistically significant.</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="First"> <td class="Lrule" valign="top"> Mean Baseline</td><td align="center"> 34</td><td align="center"> 15.9</td><td align="center"> 16</td><td align="center" class="Rrule"> 20.9</td> </tr> <tr> <td class="Lrule" valign="top"> Mean (SD) Change from Baseline <a class="Sup" href="#footnote-3" name="footnote-reference-3">*</a></td><td align="center"> 34</td><td align="center"> -15.8 (8.9)</td><td align="center"> 16</td><td align="center" class="Rrule"> -7.6 (8.6)</td> </tr> <tr> <td class="Lrule" valign="top"> 95% Confidence Interval for Difference</td><td align="center" class="Rrule" colspan="4"> (-13.6, -2.8) <a class="Sup" href="#footnote-4" name="footnote-reference-4">†</a></td> </tr> <tr class="Last"> <td class="Lrule Rrule" colspan="5" valign="top"> (Oxybutynin chloride extended-release tablets- Placebo)</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table>\n<caption>\n<span>Number of Urge Urinary Incontinence Episodes Per Week</span>\n</caption>\n<thead>\n<tr class=\"First Last\">\n<th class=\"Lrule\" valign=\"top\">Study 1</th><th align=\"center\">n</th><th align=\"center\">Oxybutynin chloride extended-release tablets</th><th align=\"center\">n</th><th align=\"center\" class=\"Rrule\">Placebo</th>\n</tr>\n</thead>\n<tfoot>\n<tr>\n<td align=\"left\" colspan=\"0\">\n<dl class=\"Footnote\">\n<dt>\n<a href=\"#footnote-reference-3\" name=\"footnote-3\">*</a>\n</dt>\n<dd>Covariate adjusted mean with missing observations set to baseline values</dd>\n<dt>\n<a href=\"#footnote-reference-4\" name=\"footnote-4\">†</a>\n</dt>\n<dd>The difference between Oxybutynin chloride extended-release tabletsand placebo was statistically significant.</dd>\n</dl>\n</td>\n</tr>\n</tfoot>\n<tbody>\n<tr class=\"First\">\n<td class=\"Lrule\" valign=\"top\"> Mean Baseline</td><td align=\"center\"> 34</td><td align=\"center\"> 15.9</td><td align=\"center\"> 16</td><td align=\"center\" class=\"Rrule\"> 20.9</td>\n</tr>\n<tr>\n<td class=\"Lrule\" valign=\"top\"> Mean (SD) Change from Baseline \n <a class=\"Sup\" href=\"#footnote-3\" name=\"footnote-reference-3\">*</a></td><td align=\"center\"> 34</td><td align=\"center\"> -15.8 (8.9)</td><td align=\"center\"> 16</td><td align=\"center\" class=\"Rrule\"> -7.6 (8.6)</td>\n</tr>\n<tr>\n<td class=\"Lrule\" valign=\"top\"> 95% Confidence Interval for Difference</td><td align=\"center\" class=\"Rrule\" colspan=\"4\"> (-13.6, -2.8) \n <a class=\"Sup\" href=\"#footnote-4\" name=\"footnote-reference-4\">†</a></td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Lrule Rrule\" colspan=\"5\" valign=\"top\"> (Oxybutynin chloride extended-release tablets- Placebo)</td>\n</tr>\n</tbody>\n</table></div>" }

<div class="scrollingtable"><table> <thead> <tr class="First Last"> <th class="Lrule" valign="top">Study 2</th><th align="center">n</th><th align="center">Oxybutynin chloride extended-release tablets</th><th align="center">n</th><th align="center" class="Rrule">oxybutynin</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="0"> <dl class="Footnote"> <dt> <a href="#footnote-reference-5" name="footnote-5">*</a> </dt> <dd>Covariate adjusted mean with missing observations set to baseline values</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="First"> <td class="Lrule" valign="top"> Mean Baseline</td><td align="center"> 53</td><td align="center"> 27.6</td><td align="center"> 52</td><td align="center" class="Rrule"> 23.0</td> </tr> <tr> <td class="Lrule" valign="top"> Mean (SD) Change from Baseline <a class="Sup" href="#footnote-5" name="footnote-reference-5">*</a></td><td align="center"> 53</td><td align="center"> -17.6 (11.9)</td><td align="center"> 52</td><td align="center" class="Rrule"> -19.4 (11.9)</td> </tr> <tr> <td class="Lrule" valign="top"> 95% Confidence Interval for Difference</td><td align="center" class="Rrule" colspan="4"> (-2.8, 6.5)</td> </tr> <tr class="Last"> <td class="Lrule Rrule" colspan="5" valign="top"> (Oxybutynin chloride extended-release tablets- oxybutynin)</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table>\n<thead>\n<tr class=\"First Last\">\n<th class=\"Lrule\" valign=\"top\">Study 2</th><th align=\"center\">n</th><th align=\"center\">Oxybutynin chloride extended-release tablets</th><th align=\"center\">n</th><th align=\"center\" class=\"Rrule\">oxybutynin</th>\n</tr>\n</thead>\n<tfoot>\n<tr>\n<td align=\"left\" colspan=\"0\">\n<dl class=\"Footnote\">\n<dt>\n<a href=\"#footnote-reference-5\" name=\"footnote-5\">*</a>\n</dt>\n<dd>Covariate adjusted mean with missing observations set to baseline values</dd>\n</dl>\n</td>\n</tr>\n</tfoot>\n<tbody>\n<tr class=\"First\">\n<td class=\"Lrule\" valign=\"top\"> Mean Baseline</td><td align=\"center\"> 53</td><td align=\"center\"> 27.6</td><td align=\"center\"> 52</td><td align=\"center\" class=\"Rrule\"> 23.0</td>\n</tr>\n<tr>\n<td class=\"Lrule\" valign=\"top\"> Mean (SD) Change from Baseline \n <a class=\"Sup\" href=\"#footnote-5\" name=\"footnote-reference-5\">*</a></td><td align=\"center\"> 53</td><td align=\"center\"> -17.6 (11.9)</td><td align=\"center\"> 52</td><td align=\"center\" class=\"Rrule\"> -19.4 (11.9)</td>\n</tr>\n<tr>\n<td class=\"Lrule\" valign=\"top\"> 95% Confidence Interval for Difference</td><td align=\"center\" class=\"Rrule\" colspan=\"4\"> (-2.8, 6.5)</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Lrule Rrule\" colspan=\"5\" valign=\"top\"> (Oxybutynin chloride extended-release tablets- oxybutynin)</td>\n</tr>\n</tbody>\n</table></div>" }

<div class="scrollingtable"><table> <thead> <tr class="First Last"> <th class="Lrule" valign="top">Study 3</th><th align="center">n</th><th align="center">Oxybutynin chloride extended-release tablets</th><th align="center">n</th><th align="center" class="Rrule">oxybutynin</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="0"> <dl class="Footnote"> <dt> <a href="#footnote-reference-6" name="footnote-6">*</a> </dt> <dd>Covariate adjusted mean with missing observations set to baseline values</dd> <dt> <a href="#footnote-reference-7" name="footnote-7">†</a> </dt> <dd>The difference between Oxybutynin chloride extended-release tabletsand oxybutynin fulfilled the criteria for comparable efficacy.</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="First"> <td class="Lrule" valign="top"> Mean Baseline</td><td align="center"> 111</td><td align="center"> 18.9</td><td align="center"> 115</td><td align="center" class="Rrule"> 19.5</td> </tr> <tr> <td class="Lrule" valign="top"> Mean (SD) Change from Baseline <a class="Sup" href="#footnote-6" name="footnote-reference-6">*</a></td><td align="center"> 111</td><td align="center"> -14.5 (8.7)</td><td align="center"> 115</td><td align="center" class="Rrule"> -13.8 (8.6)</td> </tr> <tr> <td class="Lrule" valign="top"> 95% Confidence Interval for Difference</td><td align="center" class="Rrule" colspan="4"> (-3.0, 1.6) <a class="Sup" href="#footnote-7" name="footnote-reference-7">†</a></td> </tr> <tr class="Last"> <td class="Lrule Rrule" colspan="5" valign="top"> (Oxybutynin chloride extended-release tablets- oxybutynin)</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table>\n<thead>\n<tr class=\"First Last\">\n<th class=\"Lrule\" valign=\"top\">Study 3</th><th align=\"center\">n</th><th align=\"center\">Oxybutynin chloride extended-release tablets</th><th align=\"center\">n</th><th align=\"center\" class=\"Rrule\">oxybutynin</th>\n</tr>\n</thead>\n<tfoot>\n<tr>\n<td align=\"left\" colspan=\"0\">\n<dl class=\"Footnote\">\n<dt>\n<a href=\"#footnote-reference-6\" name=\"footnote-6\">*</a>\n</dt>\n<dd>Covariate adjusted mean with missing observations set to baseline values</dd>\n<dt>\n<a href=\"#footnote-reference-7\" name=\"footnote-7\">†</a>\n</dt>\n<dd>The difference between Oxybutynin chloride extended-release tabletsand oxybutynin fulfilled the criteria for comparable efficacy.</dd>\n</dl>\n</td>\n</tr>\n</tfoot>\n<tbody>\n<tr class=\"First\">\n<td class=\"Lrule\" valign=\"top\"> Mean Baseline</td><td align=\"center\"> 111</td><td align=\"center\"> 18.9</td><td align=\"center\"> 115</td><td align=\"center\" class=\"Rrule\"> 19.5</td>\n</tr>\n<tr>\n<td class=\"Lrule\" valign=\"top\"> Mean (SD) Change from Baseline \n <a class=\"Sup\" href=\"#footnote-6\" name=\"footnote-reference-6\">*</a></td><td align=\"center\"> 111</td><td align=\"center\"> -14.5 (8.7)</td><td align=\"center\"> 115</td><td align=\"center\" class=\"Rrule\"> -13.8 (8.6)</td>\n</tr>\n<tr>\n<td class=\"Lrule\" valign=\"top\"> 95% Confidence Interval for Difference</td><td align=\"center\" class=\"Rrule\" colspan=\"4\"> (-3.0, 1.6) \n <a class=\"Sup\" href=\"#footnote-7\" name=\"footnote-reference-7\">†</a></td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Lrule Rrule\" colspan=\"5\" valign=\"top\"> (Oxybutynin chloride extended-release tablets- oxybutynin)</td>\n</tr>\n</tbody>\n</table></div>" }

Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F) [see USP Controlled Room Temperature]. Protect from moisture and humidity.

Keep out of reach of children.

{ "type": "ul", "children": [ "Patients should be informed that oxybutynin may produce angioedema that could result in life threatening airway obstruction. Patients should be advised to promptly discontinue oxybutynin therapy and seek immediate medical attention if they experience swelling of the tongue, edema of the laryngopharynx, or difficulty breathing.", "Patients should be informed that anticholinergic (antimuscarinic) agents such as Oxybutynin chloride extended-release tablets, may produce clinically significant adverse reactions related to anticholinergic activity such as:\n\t\n \nUrinary retention and constipation\nHeat prostration due to decreased sweating. Heat prostration can occur when anticholinergic medicines are administered in the presence of high environmental temperature.\n\n", "Patients should be informed that anticholinergic medicines such as Oxybutynin chloride extended-release tablets may produce drowsiness (somnolence), dizziness or blurred vision. Patients should be advised to exercise caution in decisions to engage in potentially dangerous activities until Oxybutynin chloride extended-release tablets effects have been determined.", "Patients should be informed that alcohol may enhance the drowsiness caused by anticholinergic agents such as Oxybutynin chloride extended-release tablets.", "Patients should be informed that Oxybutynin chloride extended-release tablets should be swallowed whole with the aid of liquids. Patients should not chew, divide, or crush tablets. The medication is contained within a nonabsorbable shell designed to release the drug at a controlled rate. The tablet shell is eliminated from the body; patients should not be concerned if they occasionally notice in their stool something that looks like a tablet.", "Oxybutynin chloride extended-release tablets should be taken at approximately the same time each day." ], "text": "" }

For more information call 1-855-361-3993.

{ "type": "p", "children": [], "text": "For more information call 1-855-361-3993." }

Manufactured for:

{ "type": "p", "children": [], "text": "Manufactured for:" }

AvKARE Pulaski, TN 38478

{ "type": "p", "children": [], "text": "AvKARE Pulaski, TN 38478" }

Mfg. Rev. 05/23

{ "type": "p", "children": [], "text": "Mfg. Rev. 05/23 " }

AV Rev. 03/25(M)

{ "type": "p", "children": [], "text": "AV Rev. 03/25(M) " }

AvPAK

{ "type": "p", "children": [], "text": "AvPAK" }