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DRUGS & SUPPLEMENTS
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Warnings and Precautions, Central Nervous System Effects (5.5) 07/2015
Cystran 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) ].
Cystran 3% is a muscarinic receptor antagonist indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency. (1)
The recommended dosage is three pumps of Cystran 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) ]. Cystran 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) ].
Cystran 3% is a homogeneous, colorless to slightly colored gel 3%.
Gel; 3% (3)
The use of Cystran 3% is contraindicated in patients with the following conditions:
Use Cystran 3% with caution in patients with clinically significant bladder outflow obstruction because of the risk of urinary retention.
Use Cystran 3% with caution in patients with gastrointestinal obstructive disorders because of the risk of gastric retention.
Cystran 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.
Cystran 3% should be used with caution in patients who have gastroesophageal reflux and/or who are concurrently taking drugs that can cause or exacerbate esophagitis.
Transfer of Cystran to another person can occur when vigorous bare skin-to-skin contact is made with the application site. To minimize the potential transfer of Cystran 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 Cystran 3%.
Cystran 3% is an alcohol-based gel and is therefore flammable. Avoid open fire or smoking until gel has dried.
Drugs containing Cystran are associated with anticholinergic central nervous system effects. A variety of CNS anticholinergic effects have been reported, including headache, dizziness, somnolence, confusion and hallucinations . 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 Cystran 3% affects them. If a patient experiences anticholinergic CNS effects, drug discontinuation should be considered.
Administer Cystran 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 Cystran. In the event of angioedema, Cystran containing product should be discontinued and appropriate therapy promptly provided.
Administer Cystran 3% with caution in patients being treated for narrow-angle glaucoma.
Most common adverse reactions are dry mouth, and application site reactions. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Actavis at 1-800-272-5525 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
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 Cystran 3% was evaluated in 626 patients (210 randomized to Cystran 3% 56 mg/day, 214 randomized to Cystran 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 Cystran 3%. 364 patients received at least 12 weeks of Cystran 3% treatment and 66 patients received an additional 24 weeks of Cystran 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 Cystran 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 Cystran group than the placebo group (26 patients [12.1%] in the Cystran 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 Cystran 84 mg group and 2 patients [1.0%] in the placebo group). Other commonly reported ARs experienced by more patients in the Cystran groups compared with placebo were application site rash (7 patients [3.3%] in the Cystran 84 mg group and 1 patient [0.5%] in the placebo group); application site pruritus (6 patients [2.8%] in the Cystran 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 Cystran 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.
Treatment Group | ||
Preferred Term* | Cystran 84 mg/day (N = 214) | Placebo (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) |
* 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).
The following adverse reactions have been identified during post approval use of GELNIQUE. 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: dizziness, somnolence, confusion
Psychiatric Disorders: hallucinations
No specific drug-drug interaction studies have been performed with Cystran 3%.
The concomitant use of Cystran 3% with other anticholinergic (antimuscarinic) agents may increase the frequency and/or severity of dry mouth, blurred vision, and other anticholinergic pharmacological effects.
Pregnancy Category B.
There are no adequate and well-controlled studies of topical or oral Cystran use in pregnant women. Reproduction studies using Cystran chloride in the hamster, rabbit, rat, and mouse have shown no evidence of impaired fertility or harm to the fetus. The safety of Cystran 3% administration to women who are or who may become pregnant has not been established. Therefore, Cystran 3% should not be given to pregnant women unless, in the judgment of the physician, the probable clinical benefits outweigh the possible hazards.
Cystran 3% has not been studied for use during labor and delivery. Treatment should only be given if clearly needed.
It is not known whether Cystran is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Cystran 3% is administered to a nursing woman.
The safety and effectiveness of Cystran 3% have not been established in pediatric patients.
Of the 424 patients exposed to Cystran 3% in the randomized, double-blind, placebo-controlled 12-week study, 182 patients 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 Cystran 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.
Patients with hepatic impairment received Cystran 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 hepatic function.
Overdosage with Cystran 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 Cystran 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.
Cystran is an antispasmodic, antimuscarinic agent. Cystran 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 Cystran per gram of gel. Cystran 3% is available in a 0.92 gram (1 mL) unit dose that contains 28 mg Cystran. Cystran is delivered as a racemate of R- and S-isomers. Chemically, Cystran base is d, l (racemic) 4-(Diethylamino)-2-butynyl (±)-α-phenylcyclohexaneglycolate.
The empirical formula of Cystran base is C22H31NO3. Its structural formula is:
Distribution
Cystran 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 Cystran chloride.
Metabolism
Cystran 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 Cystran 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 Cystran 3%. The apparent half-life was approximately 30 hours.
Excretion
Cystran 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.
Person-to-Person Transference
The potential for dermal transfer of Cystran from a treated person to an untreated person was evaluated in a single-dose study where subjects dosed with Cystran 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 Cystran (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 Cystran plasma concentrations (Cmax = 0.06 ng/mL) during the 24 hours following contact with treated subjects; Cystran 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 Cystran when applied 30 minutes before or 30 minutes after Cystran 3% application was evaluated in a single-dose randomized crossover study (N = 20). Concomitant application of sunscreen, either before or after Cystran 3% application, had no effect on the systemic exposure of Cystran.
Showering
The effect of showering on the absorption of Cystran was evaluated in a randomized, steady-state crossover study under conditions of no shower, or showering 1, 2 or 6 hours after Cystran 3% application (N = 22). The results of the study indicate that showering one hour after administration does not affect the overall systemic exposure to Cystran.
Race
The effect of race on the pharmacokinetics of Cystran 3% has not been studied.
Geriatric Patients
Available data suggest that there are no significant differences in the pharmacokinetics of Cystran based on geriatric status in patients following administration of Cystran 3% [see Use in Specific Populations (8.5) ].
Pediatric Patients
The pharmacokinetics of Cystran and N-desethyloxybutynin following application of Cystran 3% has not been evaluated in individuals younger than 18 years of age [see Use in Specific Populations (8.4) ].
Gender
Available data suggest that there are no significant differences in the pharmacokinetics of Cystran based on gender in healthy volunteers following administration of Cystran 3%.
Renal Impairment
There is limited experience with the use of Cystran 3% in patients with renal insufficiency [see Use in Specific Populations (8.6) ].
Hepatic Impairment
There is limited experience with the use of Cystran 3% in patients with hepatic insufficiency [see Use in Specific Populations (8.7) ].
A 24-month study in rats at dosages of Cystran 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. Cystran chloride showed no increase of mutagenic activity when tested in Schizosaccharomyces pompholiciformis, Saccharomyces cerevisiae, and Salmonella typhimurium test systems. Reproduction studies with Cystran chloride in the mouse, rat, hamster, and rabbit showed no evidence of impaired fertility.
The efficacy and safety of Cystran 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 Cystran, 56 mg/day Cystran, or placebo. A total of 214 patients received 84 mg/day Cystran, 210 patients received 56 mg/day Cystran, 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 Cystran 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 Cystran 3% (84 mg) relative to placebo. The mean difference from placebo for Cystran 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 Cystran 3% are summarized in Table 3.
Parameter | Placebo (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) | |||
P-value† vs. placebo | 0.0445‡ | |||
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) | |||
P-value† vs. placebo | 0.0010§ | |||
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§ |
¶ Last-Observation-Carried-Forward imputation for missing data
† P-value is based on ANCOVA analysis on rank-transformed data
‡ Comparison is significant if p ≤ 0.05
§ Comparison is significant if p ≤ 0.0125, adjusting for multiplicity
Cystran 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.
How Supplied
NDC 52544-041-54 100 mL (92 g) metered pump dispenser containing 90 metered 0.92 g (1 mL) pumps delivering 28 mg Cystran per pump actuation.
Storage
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)
Instructions for Use
Inform patients of the following:
Important Anticholinergic Adverse Reactions
Patients should be informed that anticholinergic (antimuscarinic) agents, such as Cystran 3%, may produce clinically significant adverse reactions related to anticholinergic pharmacological activity. Heat prostration (due to decreased sweating) can occur when anticholinergics such as Cystran 3% are used in a hot environment. Because anticholinergic (antimuscarinic) agents, such as Cystran 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 Cystran 3%.
For all medical inquiries contact:
ACTAVIS
Medical Communications
Parsippany, NJ 07054
1-800-272-5525
Distributed By:
Actavis Pharma, Inc.
Parsippany, NJ 07054 USA
Content Updated: July 2015
FDA-approved patient labeling
Patient Information
Cystran [Gel-nēk] 3%
(oxybutynin) gel 3%
Topical
Important: For use on the skin only (topical). Do not get Cystran 3% in or near your eyes, nose, or mouth.
Read this Patient Information carefully before you use Cystran 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 Cystran 3%?
Cystran 3% is a prescription medicine used to treat the symptoms of overactive bladder including:
It is not known if Cystran 3% is safe or effective in children.
Who should not use Cystran 3%?
Do not use Cystran 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 Cystran 3%?
Before you use Cystran 3%, tell your doctor if you:
- constipation or difficulty in emptying your bowels
- inflamed bowels (ulcerative colitis)
- inflammation of the tube between your mouth and stomach (gastric reflux disease or esophagitis)
Tell your doctor about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements.
Cystran 3% may affect the way other medicines work, and other medicines may affect how Cystran 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 Cystran 3%?
Cystran 3% is for skin use only.
How to use the Cystran 3% pump:
You must prime the pump before you use it for the first time.
To prime the pump:
Applying Cystran 3%:
1. Selecting your application site:
Apply Cystran 3% only to 1 of the shaded areas shown in the figure below:.
2. Dispensing your dose of Cystran 3%:
What should I avoid while using Cystran 3%?
What are the possible side effects of Cystran 3%?
The most common side effects of Cystran 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 Cystran 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 Cystran 3%?
Keep Cystran 3% and all medicines out of the reach of children.
General information about the safe and effective use of Cystran 3%.
Medicines are sometimes prescribed for conditions that are not mentioned in the patient information leaflet. Do not use Cystran 3% for a condition for which it was not prescribed. Do not give Cystran 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 Cystran 3%. If you would like more information about Cystran 3%, talk with your doctor. You can ask your pharmacist or doctor for information about Cystran 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 Cystran 3%?
Active ingredient: Cystran
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:
ACTAVIS
Medical Communications
Parsippany, NJ 07054
1-800-272-5525
Distributed By:
Actavis Pharma, Inc.
Parsippany, NJ 07054 USA
Content Updated: January 2013
219404-01
How to use the Cystran 3% pump Figure A Figure B Figure C
Depending on the reaction of the Cystran after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Cystran not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.
Is Cystran addictive or habit forming?Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.
Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.
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The information was verified by Dr. Rachana Salvi, MD Pharmacology