Anturol information, interactions and side effects, Oxybutynin is an antispasmodic, antimuscarinic agent. ANTUROL (oxybutynin) gel 3% is a topical, homogeneous, very lightly to moderately opalescent, translucent colorless to slightly colored gel, without particles hydroalcoholic gel containing 30 mg oxybutynin per gram of gel. ANTUROL 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, 1 (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 ANTUROL are diethylene glycol monoethyl ether, NF; alcohol, USP; hydroxypropyl cellulose, NF; propylene glycol, NF; butylated hydroxytoluene, NF; HC1 0.1 M, NF; and purified water, USP.
ANTUROL (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].
DOSAGE AND ADMINISTRATION
The recommended dosage is three pumps of ANTUROL (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]. ANTUROL 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].
Dosage Forms and Strengths
ANTUROL is a homogeneous, colorless to slightly colored gel 3%.
ANTUROL (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.
55948-301-01 2 x 45 mL (2 x 42g) metered pump dispensers each containing 30 metered 0.92 g (1.0 mL) pumps delivering 28 mg oxybutynin per pump actuation.
55948-301-02 100 mL (92g) 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.
Clinical Trials Experience
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 ANTUROL was evaluated in 626 patients (210 randomized to ANTUROL 56 mg/day, 214 randomized to ANTUROL 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 ANTUROL. 364 patients received at least 12 weeks of ANTUROL treatment and 66 patients received an additional 24 weeks of ANTUROL 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 ANTUROL.
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 ANTUROL 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.
Table 1: Commonly Reported Adverse Reactions that were reported In greater than 3% of patients treated with ANTUROL and at an incidence greater than placebo.
|Application site erythema
|Application site rash
|1 Each patient is counted only once within each treatment, body system and preferred term. All percentages are based on number of patients in the ITT population within each treatment group as denominator.
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 ANTUROL.
The concomitant use of ANTUROL with other anticholinergic (antimuscarinic) agents may increase the frequency and/or severity of dry mouth, blurred vision, and other anticholinergic pharmacological effects.
Use ANTUROL with caution in patients with clinically significant bladder outflow obstruction because of the risk of urinary retention.
Use In Patients with Gastrointestinal Disorders
Use ANTUROL with caution in patients with gastrointestinal obstructive disorders because of the risk of gastric retention. ANTUROL, 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. ANTUROL 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 ANTUROL -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]. Patients should wash their hands immediately after application of ANTUROL.
ANTUROL is an alcohol-based gel and is therefore flammable. Avoid open fire or smoking until gel has dried.
Administer ANTUROL 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.
Controlled Narrow-Angle Glaucoma
Administer ANTUROL with caution in patients being treated for narrow-angle glaucoma.
Patient Counseling Information
“See FDA-approved patient labeling (PATIENT INFORMATION)”
Instructions for Use
Inform patients of the following:
- ANTUROL is for topical application only and should not be ingested. Keep out of reach of children.
- ANTUROL should be applied once daily to clean, dry, intact skin on the abdomen, or upper arms/shoulders, or thighs.
- Do not use any ANTUROL that came out while priming.
- Apply immediately after actuating the dose.
- Application sites may be rotated to reduce the potential for local site reactions
- ANTUROL should not be applied to recently shaved skin surfaces. Avoid skin with open sores, wounds, irritation, scars, and tattoos.
- Do not apply the gel to the breasts or genital area.
- Discard used pump dispensers in household trash in a manner that prevents accidental application or ingestion by children, pets, or others.
- Wash hands immediately after product application.
- Do not shower or immerse the application site in water for 1 hour after product application.
- Cover the application sites with clothing if skin-to-skin contact at the application site is anticipated.
- Alcohol based gels are flammable. Avoid open fire or smoking until the gel has dried.
- If you get ANTUROL in your eyes, thoroughly rinse your eyes right away with warm, clean water to flush out any ANTUROL. Seek medical attention if needed.
Important Anticholinergic Adverse Reactions
Patients should be informed that anticholinergic (antimuscarinic) agents, such as ANTUROL, may produce clinically significant adverse reactions related to anticholinergic pharmacological activity. Heat prostration (due to decreased sweating) can occur when anticholinergics such as ANTUROL are used in a hot environment. Because anticholinergic (antimuscarinic) agents, such as ANTUROL, may produce dizziness or blurred vision, patients should be advised to exercise caution in decisions to engage in potentially dangerous activities until ANTUROL’s effects have been determined. Patients should be informed that alcohol may enhance the drowsiness caused by anticholinergic (antimuscarinic) agents such as ANTUROL.
Carcinogenesis, Mutagenesis, Impairment of Fertility
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 evidence of impaired fertility.
Use In Specific Populations
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 ANTUROL administration to women who are or who may become pregnant has not been established. Therefore, ANTUROL should not be given to pregnant women unless, in the judgment of the physician, the probable clinical benefits outweigh the possible hazards.
Labor and Delivery
ANTUROL 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 ANTUROL is administered to a nursing woman.
This drug product should not be used in children because the safety and effectiveness of ANTUROL has not been established in pediatric patients.
Of the 424 patients exposed to ANTUROL 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 ANTUROL 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.
Patients with hepatic impairment received ANTUROL during clinical trials. These trials were not designed to determine whether there were differences in safety or effectiveness in patients with or without impaired hepatic 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.
The use of ANTUROL is contraindicated in patients with the following conditions:
- Urinary retention [see WARNINGS AND PRECAUTIONS].
- Gastric retention [see WARNINGS AND PRECAUTIONS].
- Uncontrolled narrow-angle glaucoma [see WARNINGS AND PRECAUTIONS].