GELNIQUE- oxybutynin gel
Watson Pharma, Inc.
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use GELNIQUE 3%® safely and effectively. See full prescribing information for GELNIQUE 3%.
GELNIQUE 3% (oxybutynin) gel 3%, for topical use
Initial U.S. Approval: 1975
RECENT MAJOR CHANGES
WARNINGS AND PRECAUTIONS, Central Nervous System Effects (5.5) 1/2013
INDICATIONS AND USAGE
GELNIQUE 3% is a muscarinic receptor antagonist indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency. (1)
DOSAGE AND ADMINISTRATION
DOSAGE FORMS AND STRENGTHS
Gel; 3% (3)
WARNINGS AND PRECAUTIONS
Most common adverse reactions (≥ 3%) are dry mouth, and application site reactions. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Watson Pharmaceuticals, Inc. at 1-800-272-5525 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
USE IN SPECIFIC POPULATIONS
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.
FULL PRESCRIBING INFORMATION: CONTENTS*
GELNIQUE 3% (oxybutynin) gel 3% is a muscarinic receptor antagonist indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency [see Clinical Studies (14)].
The recommended dosage is three pumps of GELNIQUE 3% (84 mg/day) applied once daily to clean, dry, intact skin on the abdomen, or upper arms/shoulders, or thighs. Apply immediately after actuating the dose. Application sites may be rotated to reduce the potential for local site reactions [see Adverse Reactions (6.1)]. GELNIQUE 3% is for topical application only and should not be ingested.
Wash hands immediately after product application. Patients should cover the application site with clothing after the gel has dried if direct skin-to-skin contact at the application site is anticipated [see Warnings and Precautions (5.3)].
The use of GELNIQUE 3% is contraindicated in patients with the following conditions:
Use GELNIQUE 3% with caution in patients with clinically significant bladder outflow obstruction because of the risk of urinary retention.
Use GELNIQUE 3% with caution in patients with gastrointestinal obstructive disorders because of the risk of gastric retention.
GELNIQUE 3%, like other anticholinergic drugs, may decrease gastrointestinal motility and should be used with caution in patients with conditions such as ulcerative colitis or intestinal atony.
GELNIQUE 3% 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.
Transfer of oxybutynin to another person can occur when vigorous bare skin-to-skin contact is made with the application site. To minimize the potential transfer of oxybutynin from treated skin to another person, patients should cover the application site with clothing after the gel has dried if direct skin-to-skin contact at the application site is anticipated [see Clinical Pharmacology (12.3)]. Patients should wash their hands immediately after application of GELNIQUE 3%.
GELNIQUE 3% is an alcohol-based gel and is therefore flammable. Avoid open fire or smoking until gel has dried.
Administer GELNIQUE 3% with caution in patients with myasthenia gravis, a disease characterized by decreased cholinergic activity at the neuromuscular junction.
Angioedema requiring hospitalization and emergency medical treatment has occurred with the first or subsequent doses of oral oxybutynin. In the event of angioedema, oxybutynin containing product should be discontinued and appropriate therapy promptly provided.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trial of another drug and may not reflect the rates observed in practice.
The safety of GELNIQUE 3% was evaluated in 626 patients (210 randomized to GELNIQUE 3% 56 mg/day, 214 randomized to GELNIQUE 3% 84 mg/day and 202 randomized to placebo) during a randomized, placebo-controlled, double-blind, 12-week clinical efficacy and safety study. A subset of these 626 patients (N = 77) participated in the 24-week open-label safety extension that followed the placebo-controlled study. Of the 77 patients in the safety extension, 24 were randomized to placebo gel during the double-blind, placebo-controlled 12-week study. In the combined double-blind, placebo-controlled study and the open-label safety extension, a total of 441 patients were exposed to at least one dose of GELNIQUE 3%. 364 patients received at least 12 weeks of GELNIQUE 3% treatment and 66 patients received an additional 24 weeks of GELNIQUE 3% treatment during the open-label safety extension. The study population primarily consisted of women (87%) of Caucasian descent (87%) with an average age of 59 years who had overactive bladder with urge urinary incontinence.
Table 1 lists adverse reactions (ARs), regardless of causality, that were reported in the randomized, double-blind, placebo-controlled 12-week study at an incidence greater than placebo and in greater than 3% of patients treated with GELNIQUE 3%.
Overall, 672 ARs were experienced by 51.9% of patients. Majority of the ARs were mild to moderate in intensity. The AR most commonly reported was dry mouth which was experienced by a greater proportion of patients in the oxybutynin group than the placebo group (26 patients [12.1%] in the oxybutynin 84 mg group, 10 patients [5.0%] in the placebo group). Application site erythema was the next most commonly reported AR (8 patients [3.7%] in the oxybutynin 84 mg group and 2 patients [1.0%] in the placebo group). Other commonly reported ARs experienced by more patients in the oxybutynin groups compared with placebo were application site rash (7 patients [3.3%] in the oxybutynin 84 mg group and 1 patient [0.5%] in the placebo group); application site pruritus (6 patients [2.8%] in the oxybutynin 84 mg group and 1 patient [0.5%] in the placebo group). The overall rate of application site adverse reactions of any kind was 14.2% in patients receiving GELNIQUE 3% as compared to 3.7% in patients receiving placebo. Other cholinergic AEs < 2% in occurrence include dry eyes and blurred vision.
There were no deaths during the study. There were no clinically meaningful changes in vital signs, laboratory values, or ECG examinations over the course of the study.
|Preferred Term*||Treatment Group|
(N = 214)
(N = 202)
|n (%)||n (%)|
|Dry mouth||26 (12.1)||10 (5.0)|
|Application site erythema||8 (3.7)||2 (1.0)|
|Application site rash||7 (3.3)||1 (0.5)|
During the 24-week open-label safety extension, the most commonly reported ARs were urinary tract infection and nasopharyngitis reported in 4 patients each (5.2%), followed by conjunctivitis and application site erythema (both occurred in 3 patients [3.9%]). One patient prematurely discontinued due to the application site erythema and pruritus (both considered to be of mild severity).
No specific drug-drug interaction studies have been performed with GELNIQUE 3%.
Pregnancy Category B.
There are no adequate and well-controlled studies of topical or oral oxybutynin use in pregnant women. Reproduction studies using oxybutynin chloride in the hamster, rabbit, rat, and mouse have shown no evidence of impaired fertility or harm to the fetus. The safety of GELNIQUE 3% administration to women who are or who may become pregnant has not been established. Therefore, GELNIQUE 3% should not be given to pregnant women unless, in the judgment of the physician, the probable clinical benefits outweigh the possible hazards.
GELNIQUE 3% has not been studied for use during labor and delivery. Treatment should only be given if clearly needed.
It is not known whether oxybutynin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when GELNIQUE 3% is administered to a nursing woman.
This drug product should not be used in children because the safety and effectiveness of GELNIQUE 3% have not been established in pediatric patients.
Of the 424 patients exposed to GELNIQUE 3% in the randomized, double-blind, placebo-controlled 12-week study, 182 patients (34%) were 65 years of age and older. No overall differences in safety or effectiveness were observed between these patients and younger patients.
Patients with renal impairment received GELNIQUE 3% during clinical trials. These trials were not designed to determine whether there were differences in safety or effectiveness in patients with or without impaired renal function.
Overdosage with oxybutynin has been associated with anticholinergic effects including central nervous system excitation, flushing, fever, dehydration, cardiac arrhythmia, vomiting, exhaustion, heat sensitivity, and urinary retention. Oral ingestion of 100 mg oxybutynin chloride in association with alcohol has been reported in a 13-year-old who experienced memory loss, and in a 34-year-old who developed stupor, followed by disorientation and agitation on awakening, dilated pupils, dry skin, cardiac arrhythmia, and retention of urine. Both patients recovered fully with symptomatic treatment. If overexposure occurs, monitor patients until symptoms resolve.
Oxybutynin is an antispasmodic, antimuscarinic agent. GELNIQUE 3% is a topical, homogeneous, very lightly to moderately opalescent, translucent colorless to slightly colored gel, without particles. The product is a hydroalcoholic gel containing 30 mg oxybutynin per gram of gel. GELNIQUE 3% is available in a 0.92 gram (1 mL) unit dose that contains 28 mg oxybutynin. Oxybutynin is delivered as a racemate of R- and S-isomers. Chemically, oxybutynin base is d, l (racemic) 4-(Diethylamino)-2-butynyl (±)-α-phenylcyclohexaneglycolate.
The empirical formula of oxybutynin base is C22H31NO3. Its structural formula is:
Oxybutynin is a white powder with a molecular weight of 357.
Inactive ingredients in GELNIQUE 3% are diethylene glycol monoethyl ether, NF; alcohol, USP; hydroxypropyl cellulose, NF; propylene glycol, NF; butylated hydroxytoluene, NF; HCl 0.1 M, NF; and purified water, USP.
Oxybutynin is a racemic (50:50) mixture of R- and S- isomers. Antimuscarinic activity resides predominantly with the R-isomer.
Oxybutynin acts as a competitive antagonist of acetylcholine at postganglionic muscarinic receptors, resulting in relaxation of bladder smooth muscle. The active metabolite, N-desethyloxybutynin, has pharmacological activity on the human detrusor muscle that is similar to that of oxybutynin in in vitro studies. 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 transported across intact skin and into the systemic circulation by passive diffusion across the stratum corneum. Steady-state concentrations are achieved within 3 days of continuous dosing.
Absorption of oxybutynin is similar when GELNIQUE 3% is applied to the abdomen, upper arm/shoulders or thighs. The pharmacokinetic parameters and mean plasma concentrations during a randomized, crossover study of the three recommended application sites in 25 healthy men and women are shown in Table 2 and Figure 1, respectively.
|Application Site||AUC0-t |
|Cmax (ng/mL)||T max (h)|
Figure 1: Mean (including SD) plasma oxybutynin concentrations versus time after application of GELNIQUE 3% to the abdomen (Site A), thigh (Site B), and upper arm/shoulder (Site C) (N = 25).
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.
Oxybutynin is metabolized primarily by the cytochrome P450 enzyme systems, particularly CYP3A4, found mostly in the liver and gut wall. Metabolites include N-desethyloxybutynin (DEO), which is pharmacologically active and phenylcyclohexylglycolic acid, which is pharmacologically inactive.
Transdermal administration of oxybutynin bypasses the first-pass gastrointestinal and hepatic metabolism, reducing the formation of the N-desethyloxybutynin metabolite. Only small amounts of CYP3A4 are found in skin, limiting pre-systemic metabolism during transdermal absorption. The AUC ratio of N-desethyloxybutynin metabolite to parent compound following multiple transdermal applications is approximately 1:1 for GELNIQUE 3%. The apparent half-life was approximately 30 hours.
Oxybutynin undergoes extensive hepatic metabolism, with less than 0.1% of the administered dose excreted unchanged in the urine. Less than 0.1% of the administered dose is excreted as the metabolite N-desethyloxybutynin.
The potential for dermal transfer of oxybutynin from a treated person to an untreated person was evaluated in a single-dose study where subjects dosed with GELNIQUE 3% engaged in vigorous contact with an untreated partner for 15 minutes, either with (N = 14 couples) or without (N = 14 couples) clothing covering the application area. The untreated partners not protected by clothing demonstrated low detectable plasma concentrations of oxybutynin (mean Cmax = 0.65 ng/mL). Only one of the 14 untreated subjects participating in the clothing-to-skin contact regimen had very low measurable oxybutynin plasma concentrations (Cmax = 0.06 ng/mL) during the 24 hours following contact with treated subjects; oxybutynin was not detectable with the remaining 13 untreated subjects. Regardless of the low exposure observed in this study, patients should avoid skin-to-skin contact with partners after applying the gel.
Use of Sunscreen
The effect of sunscreen on the absorption of oxybutynin when applied 30 minutes before or 30 minutes after GELNIQUE 3% application was evaluated in a single-dose randomized crossover study (N = 20). Concomitant application of sunscreen, either before or after GELNIQUE 3% application, had no effect on the systemic exposure of oxybutynin.
The effect of showering on the absorption of oxybutynin was evaluated in a randomized, steady-state crossover study under conditions of no shower, or showering 1, 2 or 6 hours after GELNIQUE 3% application (N = 22). The results of the study indicate that showering one hour after administration does not affect the overall systemic exposure to oxybutynin.
The effect of race on the pharmacokinetics of GELNIQUE 3% has not been studied.
Available data suggest that there are no significant differences in the pharmacokinetics of oxybutynin based on geriatric status in patients following administration of GELNIQUE 3% [see Use in Specific Populations (8.5)].
The pharmacokinetics of oxybutynin and N-desethyloxybutynin following application of GELNIQUE 3% has not been evaluated in individuals younger than 18 years of age [see Use in Specific Populations (8.4)].
Available data suggest that there are no significant differences in the pharmacokinetics of oxybutynin based on gender in healthy volunteers following administration of GELNIQUE 3%.
A 24-month study in rats at dosages of oxybutynin chloride of 20, 80, and 60 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 evidence of impaired fertility.
The efficacy and safety of GELNIQUE 3% were evaluated in a single randomized, double-blind, placebo-controlled, multicenter 12-week study in patients with urinary frequency and urge and mixed urinary incontinence with a predominance of urge incontinence episodes. This was followed by an open-label safety extension. Key entry criteria included adults with overactive bladder (OAB) symptoms for at least 3 months who were either treatment-naïve or had demonstrated a beneficial response to anticholinergic treatment for OAB. Subjects were randomly assigned to receive 84 mg/day oxybutynin, 56 mg/day oxybutynin, or placebo. A total of 214 patients received 84 mg/day oxybutynin, 210 patients received 56 mg/day oxybutynin, and 202 patients received placebo gel. The majority of patients were Caucasian (87%) and female (87%), with a mean age of 59 years (range: 19 to 89 years). The primary efficacy endpoint was the change from baseline to week 12 in the number of urinary incontinence episodes (UIE) per week, as determined from a 3‑day patient daily diary.
Patients treated with GELNIQUE 3% (84 mg) experienced a statistically significant decrease in the number of urinary incontinence episodes per week from baseline to endpoint (the primary efficacy endpoint) compared with placebo (p = 0.0445) and patients treated with the 56 mg dose did not show statistically significant efficacy. Statistically significant improvements in daily urinary frequency (p = 0.0010) and urinary void volume (p < 0.0001) were also seen with GELNIQUE 3% (84 mg) relative to placebo. The mean difference from placebo for GELNIQUE 3% (84 mg) was -2.3 for urinary incontinence episodes per week in a group of patients with a mean of greater than 40 incontinence episodes per week at baseline. Mean and median change from baseline in weekly incontinence episodes (primary endpoint), daily urinary frequency, and urinary void volume (secondary endpoints) between placebo and GELNIQUE 3% are summarized in Table 3.
(N = 202)
| GELNIQUE 3% (84 mg/day)
(N = 214)
|Mean (SD)||Median||Mean (SD)||Median|
|Weekly Urinary Incontinence Episodes|
|Baseline||45.8 (31.87)||40.9||43.6 (27.90)||37.3|
|Reduction||-18.1 (28.81)||-14.0||-20.4 (24.39)||-16.4|
|Mean difference [GELNIQUE 3% – placebo] (SE)||-2.3 (2.65)|
|Daily Urinary Frequency|
|Baseline||11.5 (3.34)||11.0||11.3 (2.87)||10.7|
|Reduction||-1.9 (3.34)||- 1.7||- 2.6 (2.66)||- 2.3|
|Mean difference [GELNIQUE 3% - placebo] (SE)||- 0.7 (0.30)|
|Urinary Void Volume (mL)|
|Baseline||184.5 (85.71)||173.4||196.9 (88.11)||189.2|
|Increase||9.8 (64.98)||5.7||32.7 (77.25)||26.6|
|Mean difference [GELNIQUE 3% – placebo] (SE)||23.0 (7.24)|
|P-value†vs. placebo||< 0.0001§|
GELNIQUE 3% (oxybutynin) gel 3% is supplied in a metered-dose pump dispenser composed of an inner aluminum laminated foil liner encased in a rigid plastic bottle with a plastic cap. The nozzle of the pump dispenser is sealed by a removable cap attached to the actuator by a plastic string.
NDC 52544-041-54 100 mL (92 g) metered pump dispenser containing 90 metered 0.92 g (1 mL) pumps delivering 28 mg oxybutynin per pump actuation.
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.
“See FDA-approved patient labeling (Patient Information)”
Inform patients of the following:
Patients should be informed that anticholinergic (antimuscarinic) agents, such as GELNIQUE 3%, may produce clinically significant adverse reactions related to anticholinergic pharmacological activity. Heat prostration (due to decreased sweating) can occur when anticholinergics such as GELNIQUE 3% are used in a hot environment. Because anticholinergic (antimuscarinic) agents, such as GELNIQUE 3%, may produce dizziness or blurred vision, patients should be advised to exercise caution in decisions to engage in potentially dangerous activities until this product's effects have been determined. Patients should be informed that alcohol may enhance the drowsiness caused by anticholinergic (antimuscarinic) agents such as GELNIQUE 3%.
[see attached Patient Information leaflet]
For all medical inquiries contact:
Parsippany, NJ 07054
Watson Pharma, Inc.
Parsippany, NJ 07054 USA
Revised: January 2013
Important: For use on the skin only (topical). Do not get GELNIQUE 3% in or near your eyes, nose, or mouth.
Read this Patient Information carefully before you use GELNIQUE 3% and each time you get a refill. There may be new information. This information does not take the place of talking with your doctor about your medical condition or your treatment.
What is GELNIQUE 3%?
GELNIQUE 3% is a prescription medicine used to treat the symptoms of overactive bladder including:
It is not known if GELNIQUE 3% is safe or effective in children.
Who should not use GELNIQUE 3%?
Do not use GELNIQUE 3% if:
Talk to your healthcare provider before taking this medicine if you have any of these conditions.
What should I tell my doctor before using GELNIQUE 3%?
Before you use GELNIQUE 3%, tell your doctor if you:
Tell your doctor about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements.
GELNIQUE 3% may affect the way other medicines work, and other medicines may affect how GELNIQUE 3% works.
Especially tell your doctor if you take:
Ask your doctor if you are not sure if your medicine is one listed above.
Know the medicines you take. Keep a list of them to show your doctor or pharmacist when you get a new medicine.
How should I use GELNIQUE 3%?
GELNIQUE 3% is for skin use only.
How to use the GELNIQUE 3% pump:
You must prime the pump before you use it for the first time.
To prime the pump:
Applying GELNIQUE 3%:
1. Selecting your application site:
Apply GELNIQUE 3% only to 1 of the shaded areas shown in the figure below: (See Figure A).
2. Dispensing your dose of GELNIQUE 3%:
What should I avoid while using GELNIQUE 3%?
What are the possible side effects of GELNIQUE 3%?
The most common side effects of GELNIQUE 3% include:
Tell your doctor if you have any side effect that bothers you or that does not go away.
These are not all the possible side effects of GELNIQUE 3%. For more information, ask your doctor or pharmacist.
Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.
How should I store GELNIQUE 3%?
Keep GELNIQUE 3% and all medicines out of the reach of children.
General information about the safe and effective use of GELNIQUE 3%.
Medicines are sometimes prescribed for conditions that are not mentioned in the patient information leaflet. Do not use GELNIQUE 3% for a condition for which it was not prescribed. Do not give GELNIQUE 3% to other people, even if they have the same symptoms you have. It may harm them.
This Patient Information leaflet summarizes the most important information about GELNIQUE 3%. If you would like more information about GELNIQUE 3%, talk with your doctor. You can ask your pharmacist or doctor for information about GELNIQUE 3% that is written for health professionals.
For more information go to www.gelnique.com or call 1-800-272-5525.
What are the ingredients in GELNIQUE 3%?
Active ingredient: oxybutynin
Inactive ingredients: diethylene glycol monoethyl ether, NF; alcohol, USP; hydroxypropyl cellulose, NF; propylene glycol, NF; butylated hydroxytoluene, NF; HCl 0.1 M, NF; and purified water, USP.
This Patient Information has been approved by the U.S. Food and Drug Administration.
For all medical inquiries contact:
Parsippany, NJ 07054
Watson Pharma, Inc.
Parsippany, NJ 07054 USA
Revised: January 2013
|Labeler - Watson Pharma, Inc. (106931488)|