DRUGS & SUPPLEMENTS
1 INDICATIONS AND USAGE
Spasmoplex tablets USP are a muscarinic antagonist indicated for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency.
Spasmoplex tablets USP are a muscarinic antagonist indicated for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency. (1)
2 DOSAGE AND ADMINISTRATION
The recommended dose is 20 mg twice daily. Spasmoplex tablets USP should be dosed at least one hour before meals or given on an empty stomach.
Dosage modification is recommended in the following patient populations:
3 DOSAGE FORMS AND STRENGTHS
Spasmoplex tablets USP are supplied as 20 mg tablets (brownish yellow, round, biconvex film-coated tablets, debossed with ‘L’ on one side and ‘1’ on other side).
Spasmoplexis contraindicated in patients with:
Spasmoplex is contraindicated in
5 WARNINGS AND PRECAUTIONS
5.1 Risk of Urinary Retention
Spasmoplex should be administered with caution to patients with clinically significant bladder outflow obstruction because of the risk of urinary retention [see Contraindications (4)].
Angioedema of the face, lips, tongue, and/or larynx has been reported with Spasmoplex, the active ingredient in Spasmoplex. In one case, angioedema occurred after the first dose of Spasmoplex. Angioedema associated with upper airway swelling may be life threatening. If involvement of the tongue, hypopharynx, or larynx occurs, Spasmoplex should be promptly discontinued and appropriate therapy and/or measures necessary to ensure a patent airway should be promptly provided.
5.3 Decreased Gastrointestinal Motility
Spasmoplex should be administered with caution to patients with gastrointestinal obstructive disorders because of the risk of gastric retention [see Contraindications ]. Spasmoplex, like other antimuscarinic agents, may decrease gastrointestinal motility and should be used with caution in patients with conditions such as ulcerative colitis, intestinal atony and myasthenia gravis.
5.4 Controlled Narrow-angle Glaucoma
In patients being treated for narrow-angle glaucoma, Spasmoplexshould only be used if the potential benefits outweigh the risks and in that circumstance only with careful monitoring [see Contraindications (4)].
5.5 Central Nervous System Effects
Spasmoplex is associated with anticholinergic central nervous system effects . A variety of CNS anticholinergic effects have been reported, including dizziness, confusion, hallucinations and somnolence. Patients should be monitored for signs of anticholinergic CNS effects, particularly after beginning treatment or increasing the dose. Advise patients not to drive or operate heavy machinery until they know how Spasmoplex affects them. If a patient experiences anticholinergic CNS effects, dose reduction or drug discontinuation should be considered.
5.6 Anticholinergic Adverse Reactions in Patients with Moderate Renal Impairment
Trospium is substantially excreted by the kidney. The effects of moderate renal impairment on systemic exposure are not known but systemic exposure is likely increased. Therefore, anticholinergic adverse reactions (including dry mouth, constipation, dyspepsia, urinary tract infection, and urinary retention) are expected to be greater in patients with moderate renal impairment [see Dosage and Administration (2), and Use in Specific Populations (8.6)].
6 ADVERSE REACTIONS
The most common adverse reactions with Spasmoplex are dry mouth (20.1%), constipation (9.6%), and headache (4.2%). (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Glenmark Pharmaceuticals Inc., USA at 1(888) 721-7115 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trials Experience
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 of Spasmoplex was evaluated in controlled clinical trials in a total of 2975 patients, who were treated with Spasmoplex (N=1673), placebo (N=1056) or active control medications (N=246). Of this total, 1181 patients participated in two, 12-week, U.S., efficacy and safety studies and a 9-month open-label extension. Of this total, 591 patients received Spasmoplex tablets 20 mg twice daily. In all controlled trials combined, 232 and 208 patients received treatment with Spasmoplex for at least 24 and 52 weeks, respectively.
In all placebo-controlled trials combined, the incidence of serious adverse events was 2.9% among patients receiving Spasmoplex tablets 20 mg twice daily and 1.5% among patients receiving placebo. Table 1 lists adverse reactions from the combined 12-week U.S. safety and efficacy trials were reported by at least 1% of patients, and were reported more frequently in the Spasmoplex group than in the placebo group.
The two most common adverse reactions reported by patients receiving Spasmoplex tablets 20 mg twice daily were dry mouth and constipation. The single most frequently reported adverse reaction for Spasmoplex, dry mouth, occurred in 20.1% of Spasmoplex treated patients and 5.8% of patients receiving placebo. In the two U.S. studies, dry mouth led to discontinuation in 1.9% of patients treated with Spasmoplex tablets 20 mg twice daily. For the patients who reported dry mouth, most had their first occurrence of the event within the first month of treatment.
Table 1. Incidence (%) of adverse reactions with Spasmoplex, reported in greater than or equal to 1% of all patients treated with Spasmoplex and more frequent with Spasmoplex tablets (20 mg twice daily) than placebo in Studies 1 and 2 combined
Other adverse reactions from the U.S., placebo-controlled trials, occurring in greater than or equal to 0.5% and less than 1.0% of Spasmoplex treated patients, and more common with Spasmoplex than placebo are: tachycardia, vision blurred, abdominal distension, vomiting, dysgeusia, dry throat, and dry skin.
During controlled clinical studies, one adverse reaction of angioneurotic edema was reported.
6.2 Post-marketing Experience
The following adverse reactions have been identified during post-approval use of Spasmoplex. 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.
Gastrointestinal – gastritis; Cardiovascular – palpitations, supraventricular tachycardia, chest pain, syncope, “hypertensive crisis”; Immunological – Stevens-Johnson syndrome, anaphylactic reaction, angioedema; Nervous System – dizziness, confusion, vision abnormal, hallucinations, somnolence and delirium; Musculoskeletal – rhabdomyolysis; General – rash.
7 DRUG INTERACTIONS
Concomitant use of Spasmoplex and digoxin did not affect the pharmacokinetics of either drug [see Clinical Pharmacology (12.3)].
7.2 Drugs Eliminated by Active Tubular Secretion
Although demonstrated in a drug-drug interaction study not to affect the pharmacokinetics of digoxin, Spasmoplex has the potential for pharmacokinetic interactions with other drugs that are eliminated by active tubular secretion. Coadministration of Spasmoplex with these drugs may increase the serum concentration of Spasmoplex and/or the coadministered drug due to competition for this elimination pathway. Careful patient monitoring is recommended in patients receiving such drugs [see Clinical Pharmacology (12.3)].
7.3 Antimuscarinic Agents
The concomitant use of Spasmoplex with other antimuscarinic agents that produce dry mouth, constipation, and other anticholinergic pharmacological effects may increase the frequency and/or severity of such effects. Spasmoplex may potentially alter the absorption of some concomitantly administered drugs due to anticholinergic effects on gastrointestinal motility.
Co-administration of 500 mg metformin immediate release tablets twice daily with Spasmoplex 60 mg extended release reduced the steady-state systemic exposure of trospium by approximately 29% for mean AUC0-24 and by 34% for mean Cmax [see Clinical Pharmacology (12.3)].
8 USE IN SPECIFIC POPULATIONS
Pregnancy Category C: There are no adequate and well-controlled studies of Spasmoplex in pregnant women. Spasmoplex 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 Spasmoplex treatment are encouraged to contact their physician.
Based on animal data, Spasmoplex is predicted to have a low probability of increased risk of adverse developmental outcomes, above background risk. Adverse developmental findings were not observed to correlate with dose in rats or in rabbits. No increased risk above background was observed in rats and rabbits treated at an exposure approximately equivalent to the maximal recommended human dose of 40 mg.
In a rat embryo/fetal development study, pregnant rats received doses of Spasmoplex up to 200 mg/kg/day, from implantation to closure of the fetal hard palate, with maternal systemic exposures corresponding to approximately nine times the exposure of women treated at the MRHD of 40 mg, based on AUC. No malformations or fetal toxicity were observed.
The offspring of female rats exposed orally, pre-and post-natally, to Spasmoplex up to 200 mg/kg/day showed no increased developmental toxicity over background in surviving pups. However, maternal toxicity (death, irregular breathing, increased excitability) was observed at 200 mg/kg/day. A no-effect level for maternal and pup toxicity (survival to Day 4) was 20 mg/kg/day, an exposure approximately equivalent to the maximal recommended human dose (MRHD) of 40 mg.
In a rabbit embryo/fetal development study, pregnant rabbits received doses of Spasmoplex up to 200 mg/kg/day, from implantation to closure of the fetal hard palate. At 200 mg/kg/day, maternal systemic exposures corresponded to approximately 16 times the exposure of women treated at the MRHD of 40 mg, based on AUC. However, one fetus in each of the three treated dose groups (0.3 to 16 times exposures at the MRHD) demonstrated multiple malformations, including umbilical hernia and skeletal malformations. A maternal no-effect level was set at 20 mg/kg/day, at an exposure approximately equivalent to the maximal recommended human dose (MRHD) of 40 mg, due to clinical signs (reduced feces, hunched posture, diarrhea) observed in a pharmacokinetic study at 200 mg/kg/day.
8.2 Labor and Delivery
The effect of Spasmoplex tablets on labor and delivery is unknown.
8.3 Nursing Mothers
Spasmoplex was excreted, to a limited extent (less than 1%), into the milk of lactating rats (primarily as parent compound). It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, Spasmoplex should be used during lactation only if the potential benefit justifies the potential risk to the newborn.
8.4 Pediatric Use
The safety and effectiveness of Spasmoplex in pediatric patients have not been established.
8.5 Geriatric Use
Of the 591 patients with overactive bladder who received treatment with Spasmoplex in the two U.S., placebo-controlled, efficacy and safety studies, 249 patients were 65 years of age and older. Eighty-eight Spasmoplex treated patients (15%) were greater than or equal to 75 years of age.
In these 2 studies, the incidence of commonly reported anticholinergic adverse reactions in patients treated with Spasmoplex (including dry mouth, constipation, dyspepsia, urinary tract infection, and urinary retention) was higher in patients 75 years of age and older as compared to younger patients. This effect may be related to an enhanced sensitivity to anticholinergic agents in this patient population [see Clinical Pharmacology (12.3)]. Therefore, based upon tolerability, the dose frequency of Spasmoplex may be reduced to 20 mg once daily in patients 75 years of age and older.
8.6 Renal Impairment
Severe renal impairment (creatinine clearance less than 30 mL/minute) significantly altered the disposition of Spasmoplex. A 4.2-fold and 1.8-fold increase in mean AUC(0-∞) and Cmax, respectively, and the appearance of an additional elimination phase with a long half-life (~33 hr) were detected in patients with severe renal impairment compared with nearly age-matched subjects with creatinine clearance equal to or higher than 80 mL/min. The different pharmacokinetic behavior of Spasmoplex in patients with severe renal impairment necessitates adjustment of dosage frequency [see Dosage and Administration (2)]. The pharmacokinetics of trospium have not been studied in patients with creatinine clearance ranging from 30-80 mL/min.
Trospium is known to be substantially excreted by the kidney, and the risk of adverse reactions may be greater in patients with impaired renal function.
8.7 Hepatic Impairment
There is no information regarding the effect of severe hepatic impairment on exposure to Spasmoplex. In a study of patients with mild and with moderate hepatic impairment, given 40 mg of immediate-release Spasmoplex, mean Cmax increased 12% and 63%, respectively, and mean AUC(0-∞) decreased 5% and 15%, respectively, compared to healthy subjects. The clinical significance of these findings is unknown. Caution should be used when administering Spasmoplex to patients with moderate and severe hepatic impairment.
Overdosage with antimuscarinic agents, including Spasmoplex, can result in severe antimuscarinic effects. Supportive treatment should be provided according to symptoms. In the event of overdosage, electrocardiographic monitoring is recommended.
A 7-month-old baby experienced tachycardia and mydriasis after administration of a single dose of trospium 10 mg given by a sibling. The baby’s weight was reported as 5 kg. Following admission into the hospital and about 1 hour after ingestion of the trospium, medicinal charcoal was administered for detoxification. While hospitalized, the baby experienced mydriasis and tachycardia up to 230 beats per minute. Therapeutic intervention was not deemed necessary. The baby was discharged as completely recovered the following day.
Spasmoplex USP is a quaternary ammonium compound with the chemical name of Spiro[8-azoniabicyclo[3.2.1]octane-8,1'-pyrrolidinium], 3-[(hydroxydiphenylacetyl)oxy]-, chloride, (1α, 3β, 5α). The empirical formula of Spasmoplex USP is C25H30ClNO3 and its molecular weight is 427.97. The structural formula of Spasmoplex USP is represented below:
Spasmoplex USP is a white or almost white, crystalline powder. It is soluble in water, freely soluble in methanol, practically insoluble in methylene chloride.
Each Spasmoplextablet USP contains 20 mg of Spasmoplex USP, a muscarinic antagonist, for oral administration. Each tablet also contains the following inactive ingredients: microcrystalline cellulose, lactose monohydrate, corn starch, povidone, croscarmellose sodium, colloidal silicon dioxide, magnesium stearate, sucrose, copovidone, titanium dioxide, polyethylene glycol 6000, talc, hypromellose, macrogol, yellow iron oxide, red iron oxide.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Spasmoplex is a muscarinic antagonist.
Spasmoplex antagonizes the effect of acetylcholine on muscarinic receptors in cholinergically innervated organs including the bladder. Its parasympatholytic action reduces the tonus of smooth muscle in the bladder.
Receptor assays showed that Spasmoplex has negligible affinity for nicotinic receptors as compared to muscarinic receptors at concentrations obtained from therapeutic doses.
Placebo-controlled studies employing urodynamic variables were conducted in patients with conditions characterized by involuntary detrusor contractions. The results demonstrate that Spasmoplexincreases maximum cystometric bladder capacity and volume at first detrusor contraction.
The effect of 20 mg twice daily and up to 100 mg twice daily Spasmoplex on QT interval was evaluated in a single-blind, randomized, placebo and active controlled 5 day parallel trial in 170 male and female healthy volunteer subjects aged 18 to 45 years. The QT interval was measured over a 24-hour period at steady state. The 100 mg twice daily dose of Spasmoplex was chosen because this achieves the Cmax expected in severe renal impairment. Spasmoplex was not associated with an increase in individual corrected (QTcI) or Fridericia corrected (QTcF) QT interval at any time during steady state measurement, while moxifloxacin was associated with a 6.4 msec increase in QTcF.
In this study, asymptomatic, non-specific T wave inversions were observed more often in subjects receiving Spasmoplex than in subjects receiving moxifloxacin or placebo following five days of treatment. This finding was not observed during routine safety monitoring in 2 other placebo-controlled clinical trials in 591 Spasmoplex treated overactive bladder patients [see Clinical Studies (14)]. The clinical significance of T wave inversion in this study is unknown. Spasmoplex is associated with an increase in heart rate that correlates with increasing plasma concentrations. In the study described above, Spasmoplex demonstrated a mean increase in heart rate compared to placebo of 9.1 bpm for the 20 mg dose and of 18 bpm for the 100 mg dose. In the two U.S. placebo-controlled trials in patients with overactive bladder, the mean increase in heart rate compared to placebo in Study 1 was observed to be 3 bpm and in Study 2 was 4 bpm.
After oral administration, less than 10% of the dose is absorbed. Mean absolute bioavailability of a 20 mg dose is 9.6%. Peak plasma concentrations (Cmax) occur between 5 to 6 hours post-dose. Mean Cmax increases greater than dose-proportionally; a 3-fold and 4-fold increase in Cmax was observed for dose increases from 20 mg to 40 mg and from 20 mg to 60 mg, respectively. AUC exhibits dose linearity for single doses up to 60 mg. Spasmoplex exhibits diurnal variability in exposure with a decrease in Cmax and AUC of up to 59% and 33%, respectively, for evening relative to morning doses.
Effect of Food:
Administration with a high (50%) fat-content meal resulted in reduced absorption, with AUC and Cmax values 70-80% lower than those obtained when Spasmoplex was administered while fasting. Therefore, it is recommended that Spasmoplexshould be taken at least one hour prior to meals or on an empty stomach [see Dosage and Administration (2)].
A summary of mean (± standard deviation) pharmacokinetic parameters for a single 20 mg dose of Spasmoplex tablets is provided in Table 2.
Table 2. Mean (± SD) Pharmacokinetic Parameter Estimates for a Single 20 mg Spasmoplex Tablet Dose in Healthy Volunteers
The mean plasma concentration-time (+ SD) profile for Spasmoplex is shown in Figure 1.
Figure 1 -Mean (+ SD) Concentration-Time Profile for a Single 20 mg Oral Dose of Spasmoplex Tablets in Healthy Volunteers
Figure 1 -Mean (+ SD) Concentration-Time Profile for a Single 20 mg Oral Dose of Spasmoplex Tablets in Healthy Volunteers
Protein binding ranged from 50 to 85% when concentration levels of Spasmoplex were incubated with human serum in vitro.
The 3H-trospium chloride ratio of plasma to whole blood was 1.6:1. This ratio indicates that the majority of 3H-trospium chloride is distributed in plasma.
The apparent volume of distribution for a 20 mg oral dose is 395 (± 140) liters.
The metabolic pathway of trospium in humans has not been fully defined. Of the 10% of the dose absorbed, metabolites account for approximately 40% of the excreted dose following oral administration. The major metabolic pathway is hypothesized as ester hydrolysis with subsequent conjugation of benzylic acid to form azoniaspironortropanol with glucuronic acid. Cytochrome P450 (CYP) is not expected to contribute significantly to the elimination of trospium. Data taken from in vitro human liver microsomes investigating the inhibitory effect of trospium on seven CYP isoenzyme substrates (CYP1A2, 2A6, 2C9, 2C19, 2D6, 2E1, and 3A4) suggest a lack of inhibition at clinically relevant concentrations.
The plasma half-life for Spasmoplex following oral administration is approximately 20 hours. After oral administration of an immediate-release formulation of 14C-trospium chloride, the majority of the dose was recovered in feces and a smaller amount (5.8% of the dose) was recovered in urine; 60% of the radioactivity excreted in urine was unchanged trospium.
The mean renal clearance for trospium (29.07 L/hour) is 4-fold higher than average glomerular filtration rate, indicating that active tubular secretion is a major route of elimination for trospium. There may be competition for elimination with other compounds that are also renally eliminated [see Drug Interactions (7.2)].
Digoxin: Concomitant use of 20 mg Spasmoplex immediate release twice daily at steady state and a single dose of 0.5 mg digoxin in a crossover study with 40 male and female subjects did not affect the pharmacokinetics of either drug.
Metformin: A drug interaction study was conducted in which Spasmoplex extended release 60 mg once daily was coadministered with Glucophage ® (metformin hydrochloride) 500 mg twice daily under steady-state conditions in 44 healthy subjects. Co-administration of 500 mg metformin immediate release tablets twice daily reduced the steady-state systemic exposure of trospium by approximately 29% for mean AUC0-24 and by 34% for mean Cmax. The effect of decrease in trospium exposure on the efficacy of Spasmoplex extended release is unknown. The steady-state pharmacokinetics of metformin were comparable when administered with or without 60 mg Spasmoplex extended release once daily under fasted condition. The effect of metformin at higher doses on trospium PK is unknown.
Age : Age did not appear to significantly affect the pharmacokinetics of Spasmoplex, however, increased anticholinergic side effects unrelated to drug exposure were observed in patients greater than or equal to 75 years of age [see Use in Specific Populations (8.5)].
Pediatric : The pharmacokinetics of Spasmoplex were not evaluated in pediatric patients.
Race : Pharmacokinetic differences due to race have not been studied.
Gender : Studies comparing the pharmacokinetics in different genders had conflicting results. When a single 40 mg Spasmoplex tablets dose was administered to 16 elderly subjects, exposure was 45% lower in elderly females compared to elderly males. When 20 mg Spasmoplex tablets was dosed twice daily for 4 days to 6 elderly males and 6 elderly females (60 to 75 years), AUC and Cmax were 26% and 68% higher, respectively, in females without hormone replacement therapy than in males.
Renal Impairment: In a clinical pharmacokinetic study where a single dose of 40 mg immediate release Spasmoplex was administered to 12 healthy males and 12 males with severe renal impairment, severe renal impairment (creatinine clearance less than 30 mL/minute) significantly altered the disposition of Spasmoplex. A 4.2-fold and 1.8-fold increase in mean AUC(0-∞) and Cmax, respectively, and the appearance of an additional elimination phase with a long half-life (~33 hours vs. 18 hours) were detected in patients with severe renal impairment compared with nearly age-matched subjects with creatinine clearance equal to or higher than 80 mL/min. The different pharmacokinetic behavior of Spasmoplexin patients with severe renal impairment necessitates adjustment of dosage frequency [see Dosage and Administration (2)]. The pharmacokinetics of trospium have not been studied in patients with creatinine clearance ranging from 30-80 mL/min.
Hepatic Impairment: In a clinical pharmacokinetic study in patients with mild (Child-Pugh score 5-6) and with moderate (Child-Pugh score 7-8) hepatic impairment, given a single dose of 40 mg immediate-release Spasmoplex, mean Cmax increased 12% and 63%, respectively, and mean AUC(0-∞) decreased 5% and 15%, respectively, compared to healthy subjects. There is no information regarding the effect of severe hepatic impairment on exposure to Spasmoplex.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis: Carcinogenicity studies with Spasmoplex were conducted in mice and rats for 78 weeks and 104 weeks, respectively, at maximally tolerated doses. No evidence of a carcinogenic effect was found in either mice or rats administered up to 200 mg/kg/day, approximately 9 times the expected clinical exposure levels at the maximum recommended human dose (MRHD) of 40 mg.
Mutagenesis: Spasmoplex was not mutagenic nor genotoxic in tests in vitro in bacteria (Ames test) and mammalian cells (L5178Y mouse lymphoma and CHO cells) or in vivo in the rat micronucleus test.
Impairment of Fertility: No evidence of impaired fertility was observed in rats administered doses up to 200 mg/kg/day (about 16 times the expected clinical exposure at the MRHD, based on AUC).
14 CLINICAL STUDIES
Spasmoplex was evaluated for the treatment of patients with overactive bladder who had symptoms of urinary frequency, urgency, and urge incontinence in two U.S. 12-week, placebo-controlled studies and one 9-month open label extension.
Study 1 was a randomized, double-blind, placebo-controlled, parallel-group study in 523 patients. A total of 262 patients received Spasmoplex tablets 20 mg twice daily and 261 patients received placebo. The majority of patients were Caucasian (85%) and female (74%) with a mean age of 61 years (range: 21 to 90 years). Entry criteria required that patients have urge or mixed incontinence (with a predominance of urge), urge incontinence episodes of at least 7 per week, and greater than 70 micturitions per week. The patient’s medical history and urinary diary during the treatment-free baseline confirmed the diagnosis. Reductions in urinary frequency, urge incontinence episodes and urinary void volume for placebo and Spasmoplex treatment groups are summarized in Table 3 and Figures 2 and 3.
Table 3. Mean (SE) change from baseline to end of treatment (Week 12 or last observation carried forward) for urinary frequency, urge incontinence episodes, and void volume in Study 1
Figure 2 – Mean Change from Baseline in Urinary Frequency/24 Hours, by Visit: Study 1
Figure 3 – Mean Change from Baseline in Urge Incontinence/Week, by Visit: Study 1
Study 2 was nearly identical in design to Study 1. A total of 329 patients received Spasmoplex tablets 20 mg twice daily and 329 patients received placebo. The majority of patients were Caucasian (88%) and female (82%) with a mean age of 61 years (range: 19 to 94 years). Entry criteria were identical to Study 1. Reductions in urinary frequency, urge incontinence episodes, and urinary void volume for placebo and Spasmoplex treatment groups are summarized in Table 4 and Figures 4 and 5.
Table 4. Mean (SE) change from baseline to end of treatment (Week 12 or last observation carried forward) for urinary frequency, urge incontinence episodes, and void volume in Study 2
Figure 4 – Mean Change from Baseline in Urinary Frequency/24 Hours, by Visit: Study 2
Figure 5 – Mean Change from Baseline in Urge Incontinence/Week, by Visit: Study 2
Figure 2 – Mean Change from Baseline in Urinary Frequency/24 Hours, by Visit: Study 1 Figure 3 – Mean Change from Baseline in Urge Incontinence/Week, by Visit: Study 1 Figure 4 – Mean Change from Baseline in Urinary Frequency/24 Hours, by Visit: Study 2 Figure 5 – Mean Change from Baseline in Urge Incontinence/Week, by Visit: Study 2
16 HOW SUPPLIED/STORAGE AND HANDLING
Spasmoplex tablets USP 20 mg (brownish yellow, round, biconvex film-coated tablets, debossed with ‘L’ on one side and ‘1’ on other side) are supplied as follows:
Bottles of 30 NDC 68462-461-30
Bottles of 60 NDC 68462-461-60
Bottles of 500 NDC 68462-461-05
Bottles of 1000 NDC 68462-461-10
Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F).
Protect from light.
17 PATIENT COUNSELING INFORMATION
“See FDA-approved Patient Labeling ”
Patients should be informed that Spasmoplex, the active ingredient in Spasmoplex tablets, may produce angioedema which could result in life-threatening airway obstruction. Patients should be advised to promptly discontinue Spasmoplex tablets and seek immediate medical attention if they experience edema of the tongue, edema of the laryngopharynx, or difficulty breathing.
17.2 When Not to Use
Prior to treatment, patients should fully understand the risks and benefits of Spasmoplex. In particular, patients should be informed not to take Spasmoplex tablets if they:
Patients should be instructed regarding the recommended dosing and administration of Spasmoplex tablets:
17.4 Adverse Reactions
Patients should be informed that the most common side effects with Spasmoplex are dry mouth and constipation and that other less common side effects include trouble emptying the bladder, blurred vision, and heat prostration. Because anticholinergics, such as Spasmoplex, may produce dizziness or blurred vision, patients should be advised to exercise caution in decisions to engage in potentially dangerous activities until the drug’s effects have been determined. Patients should be informed that alcohol may enhance the drowsiness caused by anticholinergic agents.
Spasmoplex Tablets USP
Read the Patient Information that comes with Spasmoplex tablets before you start taking it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your doctor about your medical condition or your treatment.
What are Spasmoplex tablets?
Spasmoplex tablets are a prescription medicine used to treat adults with overactive bladder who have the following symptoms:
Who should not take Spasmoplex tablets?
Do not take Spasmoplex tablets if you:
Spasmoplex tablets have not been studied in children under the age of 18 years.
What should I tell my doctor before starting Spasmoplex tablets?
Tell your doctor about all of your medical conditions including if you:
Tell your doctor about all the medicines you take including prescription and nonprescription medicines, vitamins and herbal supplements. Spasmoplex tablets and certain other medicines can interact and make some side effects worse. Spasmoplex tablets can affect how other medicines are handled by the body.
Know all the medicines you take. Keep a list of them with you to show your doctor and pharmacist each time you get a new medicine.
How should I take Spasmoplex tablets?
Take Spasmoplex tablets exactly as prescribed.
What are the possible side effects of Spasmoplex tablets?
Spasmoplex tablets may cause allergic reactions that may be serious. Symptoms of a serious allergic reaction may include swelling of the face, lips, throat or tongue. If you experience these symptoms, you should stop taking Spasmoplex tablets and get emergency medical help right away.
The most common side effects with Spasmoplex tablets are:
Spasmoplex tablets may cause other less common side effects, including:
Tell your doctor if you have any side effects that bother you or that do not go away.
These are not all possible side effects of Spasmoplex tablets. For more information, ask your doctor, healthcare professional or pharmacist.
How should I store Spasmoplex tablets?
General information about Spasmoplex tablets
Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not use Spasmoplex tabletsfor a condition for which they were not prescribed. Do not give Spasmoplex tablets to other people, even if they have the same symptoms you have. It may harm them.
This leaflet summarizes the most important information about Spasmoplex tablets. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about Spasmoplex tablets that is written for health professionals. You can also call Glenmark Pharmaceuticals Inc., USA at 1 (888)721-7115.
What are the ingredients in Spasmoplex tablets?
Active Ingredient: Spasmoplex USP.
Inactive Ingredients: microcrystalline cellulose, lactose monohydrate, corn starch, povidone, croscarmellose sodium, colloidal silicon dioxide, magnesium stearate, sucrose, copovidone, titanium dioxide, polyethylene glycol 6000, talc, hypromellose, macrogol, yellow iron oxide, red iron oxide.
Glenmark Pharmaceuticals Ltd.
Glenmark Pharmaceuticals Inc., USA
Mahwah, NJ 07430
Questions? 1 (888)721-7115
Spasmoplex TABLETS USP
Pharmacist: Dispense the patient information sheet provided separately to each patient.
Spasmoplex pharmaceutical active ingredients containing related brand and generic drugs:
Active ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.
Spasmoplex available forms, composition, doses:
Form of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.
Spasmoplex destination | category:
Destination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.
Spasmoplex Anatomical Therapeutic Chemical codes:
A medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.
Spasmoplex pharmaceutical companies:
Pharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.
Frequently asked QuestionsCan i drive or operate heavy machine after consuming Spasmoplex?
Depending on the reaction of the Spasmoplex after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Spasmoplex 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 Spasmoplex 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.
ReviewsDrugs.com conducted a study on Spasmoplex, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Spasmoplex consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.
Three visitors reported frequency of useHow often in a day do you take the medicine?
Are you taking the Spasmoplex drug as prescribed by the doctor?
Few medications can be taken Twice in a day more than prescribed when the doctor's advice mentions the medicine can be taken according to frequency or severity of symptoms. Most times, be very careful and clear about the number of times you are taking the medication. The report of sDrugs.com website users about the frequency of taking the drug Spasmoplex is mentioned below.
Two visitors reported dosesWhat is the dose of Spasmoplex drug you are taking?
According to the survey conducted among sDrugs.com website users, the maximum number of people are using the following dose 11-50mg. Few medications come in only one or two doses. Few are specific for adult dose and child dose. The dose of the medicine given to the patient depends on the severity of the symptom/disease. There can be dose adjustments made by the doctor, based on the progression of the disease. Follow-up is important.
One visitor reported age
The information was verified by Dr. Arunabha Ray, MD Pharmacology