Sanctura® (trospium chloride) is a quaternary ammonium compound with the chemical name of spiro[8-azoniabicyclo[3,2,1]octane-8,1'-pyrrolidinium]-3-[(hydroxydiphenyl-acetyl)-oxy]chloride(1α, 3β, 5α)- (9Cl). The empirical formula of trospium chloride is C₂₅H₃₀ClNO₃ and its molecular weight is 427.97. The structural formula of trospium chloride is represented below:

Trospium chloride is a fine, colorless to slightly yellow, crystalline solid. The compound's solubility in water is approximately 1 g/2 mL.

Each Sanctura tablet contains 20 mg of trospium chloride and is to be given orally. Each tablet also contains the following inactive ingredients: sucrose, wheat starch, microcrystalline cellulose, talc, lactose monohydrate, calcium carbonate, titanium dioxide, stearic acid, croscarmellose sodium, povidone, polyethylene glycol 8000, colloidal silicon dioxide, ferric oxide, carboxymethylcellulose sodium, white wax, magnesium stearate, and carnauba wax.

Sanctura is indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency.

The recommended dose is 20 mg twice daily. Sanctura should be dosed at least one hour before meals or given on an empty stomach.

Dosage modification is recommended in the following patient populations:

• For patients with severe renal impairment (CLcr < 30 mL/min), the recommended dose is 20 mg once daily at bedtime (See PRECAUTIONS: General).
• In geriatric patients ≥ 75 years of age, dose may be titrated down to 20 mg once daily based upon tolerability (See PRECAUTIONS: Geriatric Use).

Sanctura tablets 20 mg (brownish yellow, biconvex, glossy coated tablets printed with black ink) are supplied as follows:

60 count HDPE bottle - NDC 15456-980-04

14 count blister (PVC/Paper backed foil) - NDC 15456-980-70

14 count blister (PVC-Aclar/Paper backed foil) - NDC 15456-980-71

Store at controlled room temperature 20° to 25°C (68° to 77°F) (see USP).

Manufactured for: Esprit Pharmaceuticals, East Brunswick, NJ 08816, USA and Indevus Pharmaceuticals, Inc. Lexington, MA 02421, USA. Manufactured by: Madaus GmbH, Troisdorf, Germany. Address Medical Inquiries to: 866-230-0375. December 2006. FDA Rev date: 12/7/2006

The safety of Sanctura was evaluated in Phase 2 and 3 controlled clinical trials in a total of 2975 patients, who were treated with Sanctura (N=1673), placebo (N=1056) or active control medications (N=246). Of this total, 1181 patients participated in two, 12-week, Phase 3, U.S., efficacy and safety studies and a 9-month open-label extension. Of this total, 591 patients received Sanctura 20 mg twice daily. In all controlled trials combined, 232 and 208 patients received treatment with Sanctura 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 Sanctura 20 mg BID and 1.5% among patients receiving placebo. Of these, 0.2% and 0.3% were judged to be at least possibly related to treatment with Sanctura or placebo, respectively, by the investigator.

Table 4 lists treatment emergent adverse events from the combined 12-week U.S. safety and efficacy trials that were judged to be at least possibly related to treatment with Sanctura by the investigator, were reported by at least 1% of patients, and were reported more frequently in the Sanctura group than in the placebo group.

The two most common adverse events reported by patients receiving Sanctura 20 mg BID were dry mouth and constipation. The single most frequently reported adverse event for Sanctura, dry mouth, occurred in 20.1% of Sanctura treated patients and 5.8% of patients receiving placebo. In the two Phase 3 U.S. studies, dry mouth led to discontinuation in 1.9% of patients treated with Sanctura 20 mg BID. For the patients who reported dry mouth, most had their first occurrence of the event within the first month of treatment.

Table 4. Incidence (%) of adverse events judged at least possibly related to treatment with Sanctura, reported in ≥ 1% of all patients treated with Sanctura and more frequent with Sanctura (20 mg BID) than placebo in Studies 1 and 2 combined.

Other adverse events from the Phase 3, U.S., placebo-controlled trials judged possibly related to treatment with Sanctura by the investigator, occurring in ≥ 0.5% of Sanctura-treated patients, and more common with Sanctura than placebo are: tachycardia NOS, vision blurred, abdominal distension, vomiting NOS, dysgeusia, dry throat, and dry skin.

During controlled clinical studies, one event of angioneurotic edema was reported.

Postmarketing Surveillance

Additional spontaneous adverse events, regardless of relationship to drug, reported from marketing experience with trospium chloride include: Gastrointestinal – gastritis; Cardiovascular – palpitations, supraventricular tachycardia, chest pain, syncope, "hypertensive crisis"; Immunological – Stevens-Johnson syndrome, anaphylactic reaction; Nervous System – vision abnormal, hallucinations and delirium; Musculoskeletal – rhabdomyolysis; General – rash.

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

Drugs Eliminated by Active Tubular Secretion: Although demonstrated in a drug-drug interaction study not to affect the pharmacokinetics of digoxin, Sanctura has the potential for pharmacokinetic interactions with other drugs that are eliminated by active tubular secretion (e.g. procainamide, pancuronium, morphine, vancomycin, metformin and tenofovir). Coadministration of Sanctura with these drugs may increase the serum concentration of Sanctura 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: Excretion, and CLINICAL PHARMACOLOGY: Drug-Drug Interactions).

Drug-Laboratory-Test Interactions

Interactions between Sanctura and laboratory tests have not been studied.

No information provided.

General

Risk of Urinary Retention: Sanctura should be administered with caution to patients with clinically significant bladder outflow obstruction because of the risk of urinary retention.

Decreased Gastrointestinal Motility: Sanctura should be administered with caution to patients with gastrointestinal obstructive disorders because of the risk of gastric retention (See CONTRAINDICATIONS). Sanctura, like other anticholinergic drugs, may decrease gastrointestinal motility and should be used with caution in patients with conditions such as ulcerative colitis, intestinal atony and myasthenia gravis.

Controlled Narrow-angle Glaucoma: In patients being treated for narrow-angle glaucoma, Sanctura should only be used if the potential benefits outweigh the risks and in that circumstance only with careful monitoring.

Patients with Renal Insufficiency: Dose modification is recommended in patients with severe renal insufficiency (CLcr < 30 mL/min). In such patients, Sanctura should be administered as 20 mg once a day at bedtime (See DOSAGE AND ADMINISTRATION).

Patients with Hepatic Impairment: Caution should be used when administering Sanctura in patients with moderate or severe hepatic dysfunction (See CLINICAL PHARMACOLOGY: Pharmacokinetics in Special Populations).

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity studies with trospium chloride were conducted in mice and rats. A 78-week carcinogenicity study in mice and a 104-week carcinogenicity study in rats were conducted at doses of 2, 20, and 200 mg/kg/day. No evidence of a carcinogenic effect was found in either mice or rats. The 200 mg/kg/day dose in the mouse and rat represents approximately 25 and 60 times, respectively, the human dose based on body surface area. At 200 mg/kg/day in the mouse and rat after 4 weeks the AUC was 34 and 753 ng•h/mL, respectively. The exposure in the rat is 8.6-fold higher than the AUC following 40 mg daily exposure in healthy young or elderly subjects (88 ng•h/mL).

Trospium chloride was not mutagenic in tests for detection of gene mutations in bacteria (Ames test) and mammalian cells (L5178Y mouse lymphoma and CHO cells) or in vivo in the rat micronucleus test.

No evidence of impaired fertility was observed in rats administered doses up to 200 mg/kg/day (about 10 multiples of the expected clinical exposure via AUC).

Pregnancy: Teratogenic Effects

Pregnancy Category C: Trospium chloride has been shown to cause maternal toxicity in rats and a decrease in fetal survival in rats administered approximately 10 times the expected clinical exposure (AUC). The no-effect levels for maternal and fetal toxicity were approximately equivalent to the expected clinical exposure in rats, and about 5-6 times the expected clinical exposure in rabbits. No malformations or developmental delays were observed. There are no adequate and well controlled studies in pregnant women. Sanctura should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

Trospium chloride (2 mg/kg PO and 50 µg/kg IV) was excreted, to a limited extent ( < 1%), into the milk of lactating rats. The activity observed in the milk was primarily from the parent compound. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Sanctura is administered to a nursing woman. Sanctura should be used during lactation only if the potential benefit justifies the potential risk to the newborn.

Pediatric Use

The safety and effectiveness of Sanctura in pediatric patients have not been established.

Geriatric Use

Of the 591 patients with overactive bladder who received treatment with Sanctura in the two U.S., placebo-controlled, efficacy and safety studies, 249 patients (42%) were 65 years of age and older. Eighty-eight Sanctura-treated patients (15%) were ≥ 75 years of age.

In these 2 studies, the incidence of commonly reported anticholinergic adverse events in patients treated with Sanctura (including dry mouth, constipation, dyspepsia, UTI, 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: Pharmacokinetics in Special Populations and DOSAGE AND ADMINISTRATION). Therefore, based upon tolerability, the dose frequency of Sanctura may be reduced to 20 mg once daily in patients 75 years of age and older.

Management of Overdosage

Overdosage with Sanctura may result in severe anticholinergic effects. Treatment should be provided according to symptoms and supportive. In the event of overdosage, ECG 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 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 bpm. Therapeutic intervention was not deemed necessary. The baby was discharged as completely recovered the following day.

Sanctura is contraindicated in patients with urinary retention, gastric retention, or uncontrolled narrow-angle glaucoma and in patients who are at risk for these conditions. Sanctura is also contraindicated in patients who have demonstrated hypersensitivity to the drug or its ingredients.

Sanctura is an antispasmodic, antimuscarinic agent.

Trospium chloride antagonizes the effect of acetylcholine on muscarinic receptors in cholinergically innervated organs. Its parasympatholytic action reduces the tonus of smooth muscle in the bladder. Receptor assays showed that trospium chloride has negligible affinity for nicotinic receptors as compared to muscarinic receptors at concentrations obtained from therapeutic doses.

Pharmacodynamics

Placebo-controlled studies employing urodynamic variables were conducted in patients with conditions characterized by involuntary detrusor contractions. The results demonstrate that Sanctura increases maximum cystometric bladder capacity and volume at first detrusor contraction.

Pharmacokinetics

Absorption: After oral administration, less than 10% of the dose is absorbed. Mean absolute bioavailability of a 20 mg dose is 9.6% (range: 4.0-16.1%). 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. Sanctura 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 fat meal resulted in reduced absorption, with AUC and Cmax values 70-80% lower than those obtained when Sanctura was administered while fasting. Therefore, it is recommended that Sanctura should be taken at least one hour prior to meals or on an empty stomach. (See DOSAGE AND ADMINISTRATION and PRECAUTIONS: PATIENT INFORMATION).

Distribution: Protein binding ranged from 50 to 85% when therapeutic concentration levels (0.5-50 ng/mL) were incubated with human serumin 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.

Metabolism: 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 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 cytochrome P450 isoenzyme substrates (CYP1A2, 2A6, 2C9, 2C19, 2D6, 2E1, and 3A4) suggest a lack of inhibition at clinically relevant concentrations of trospium.

Excretion: The plasma half-life for Sanctura following oral administration is approximately 20 hours. After administration of oral ¹⁴C-trospium chloride, the majority of the dose (85.2%) 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 PRECAUTIONS: DRUG INTERACTIONS).

A summary of mean for A summary of mean (± standard deviation) pharmacokinetic parameters for a single 20 mg dose of Sanctura is provided in Table 1.

Table 1. Mean (± SD) Pharmacokinetic Parameter Estimates for a Single 20 mg Sanctura Dose in Healthy Volunteers.

The mean plasma concentration-time (+ SD) profile for Sanctura is shown in Figure 1.

Figure 1. Mean (+ SD) Concentration-Time Profile for a Single 20 mg Oral Dose of Sanctura in Healthy Volunteers.

Pharmacokinetics in Special Populations

Age: Age did not appear to significantly affect the pharmacokinetics of Sanctura, however, increased anticholinergic side effects unrelated to drug exposure were observed in patients ≥ 75 years of age. (See PRECAUTIONS: Geriatric Use and DOSAGE AND ADMINISTRATION).

Pediatric: The pharmacokinetics of Sanctura were not evaluated in pediatric patients.

Gender: Studies comparing the pharmacokinetics in different genders had conflicting results. When a single 40 mg Sanctura dose was administered to 16 elderly subjects, exposure was 45% lower in elderly females compared to elderly males. When 20 mg Sanctura was dosed BID 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.

Race: Pharmacokinetic differences due to race have not been studied.

Renal Insufficiency: Severe renal impairment significantly altered the disposition of Sanctura. A 4.5-fold and 2-fold increase in mean AUC_0-∞ and Cmax, respectively, and the appearance of an additional elimination phase with a long half-life (~33 hr) was detected in patients with severe renal insufficiency (CLcr < 30 mL/min) compared with healthy, nearly age-matched subjects. The different pharmacokinetic behavior of Sanctura in patients with severe renal insufficiency necessitates adjustment of dosage frequency. The pharmacokinetics of Sanctura have not been studied in people with moderate or mild renal impairment (CLcr ranging from 30-80 mL/min). (See PRECAUTIONS: General and DOSAGE AND ADMINISTRATION).

Hepatic Insufficiency: There is no information regarding the effect of severe hepatic impairment on exposure to Sanctura. Maximum trospium concentration (Cmax) increased 12% and 63% in subjects with mild and moderate hepatic impairment, respectively, compared to healthy subjects. Mean area under the plasma concentration-time curve (AUC) was similar. Caution should be used when administering Sanctura to patients with moderate and severe hepatic dysfunction. (See PRECAUTIONS: General).

Drug-Drug Interactions

Sanctura is metabolized by ester hydrolysis and excreted by the kidneys by a combination of tubular secretion and glomerular filtration. Based on in vitro data, no clinically relevant interactions with the metabolism of trospium are expected. However, some drugs which are actively secreted may interact with trospium by competing for renal tubular secretion. (See PRECAUTIONS: DRUG INTERACTIONS).

Concomitant use of Sanctura and digoxin did not affect the pharmacokinetics of either drug.

Electrophysiology

The effect of 20 mg BID and up to 100 mg BID Sanctura on QT interval was evaluated in a single-blind, randomized, placebo and active (moxifloxacin 400 mg QD) controlled 5-day parallel trial in 170 male and female healthy140) liters. volunteer subjects aged 18 to 45 years. The QT interval was measured over a 24-hour period at steady state. The 100 mg BID dose of Sanctura was chosen because this achieves the Cmax expected in severe renal impairment. Sanctura 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 Sanctura 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 Sanctura-treated overactive bladder patients (See Clinical Studies). The clinical significance of T wave inversion in this study is unknown. Sanctura is associated with an increase in heart rate that correlates with increasing plasma concentrations. In the study described above, Sanctura demonstrated a mean increase in heart rate compared to placebo of 9.1 bpm for the 20 mg dose and of 18.0 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 3.0 bpm and in Study 2 was 4.0 bpm.

Clinical Studies

Sanctura was evaluated for the treatment of patients with overactive bladder who had symptoms of urinary frequency, urgency, and urge deviation) pharmacokinetic parameters 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- SD) Pharmacokinetic Parameter Estimates for a group study in 523 patients. A total of 262 patients received Sanctura 20 mg twice daily and 261 patients received placebo. The majority of patients were Caucasian (85%) and female (74%) with a mean age of (hr)(hr) 61 years (range: 21 to 90 years). Entry criteria required that patients 4.0 36.4 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 Sanctura treatment groups are summarized in Table 2 and Figures 2 and 3.

Table 2. 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

b>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 Sanctura 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 Sanctura treatment groups are summarized in Table 3 and Figures 4 and 5.

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 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

Patients should be informed that anticholinergic agents, such as Sanctura, may produce clinically significant adverse effects related to anticholinergic pharmacological activity. For example, heat prostration (fever and heat stroke due to decreased sweating) can occur when anticholinergics such as Sanctura are used in a hot environment. Because anticholinergics such as Sanctura may also produce dizziness or blurred vision, patients should be advised to exercise caution. Patients should be informed that alcohol may enhance the drowsiness caused by anticholinergic agents.

Sanctura should be taken 1 hour prior to meals or on an empty stomach. If a dose is skipped, patients are advised to take their next dose 1 hour prior to their next meal.

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

TROSPIUM - ORAL

(TROW-spee-um)

COMMON BRAND NAME(S): Sanctura

USES: This medication is used to treat an overactive bladder. By relaxing the muscles in the bladder, trospium improves your ability to control your urination. It helps to reduce leaking of urine, feelings of needing to urinate right away, and frequent trips to the bathroom. Trospium belongs to a class of drugs known as antispasmodics. It is also known as an antimuscarinic.

HOW TO USE: Take this medication by mouth, usually twice daily, 1 hour before a meal or on an empty stomach.

Use this medication regularly in order to get the most benefit from it. Remember to use it at the same time(s) each day. Dosage is based on your medical condition and response to therapy.

Tell your doctor if your condition does not improve or if it worsens.

SIDE EFFECTS: Dry mouth, constipation, stomach upset, headache, dry eyes, dizziness, blurred vision, or drowsiness may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

To relieve dry mouth, suck on (sugarless) hard candy or ice chips, chew (sugarless) gum, drink water or use a saliva substitute.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: eye pain, difficulty urinating, fast heartbeat.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking trospium, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: a certain type of glaucoma (uncontrolled narrow-angle type), inability to urinate (urinary retention), delayed or slow emptying of your stomach.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney disease, liver disease, constipation, other stomach conditions (such as ulcerative colitis, intestinal atony), myasthenia gravis.

This drug may make you dizzy or drowsy or cause blurred vision. Use caution while driving, using machinery, or doing any activity that requires alertness or clear vision. Limit alcoholic beverages.

This medication can reduce sweating, making you more likely to develop a serious condition called heat stroke. Avoid strenuous work or exercise in hot weather.

Caution is advised when using this drug in the elderly because they may be more sensitive to its effects, especially dry mouth, constipation, and difficulty urinating.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

It is not known whether this drug passes into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with them first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: other drugs that are also removed by the kidneys (such as metformin, morphine, procainamide, tenofovir, vancomycin), certain anti-Parkinson's drugs (such as benztropine, trihexyphenidyl), other antimuscarinic drugs (such as dicyclomine, oxybutynin, scopolamine, tolterodine), potassium tablets/capsules, pramlintide.

Tell your doctor or pharmacist if you are taking other products that cause drowsiness, including alcohol, certain antihistamines (such as cetirizine, diphenhydramine), anti-seizure drugs (such as carbamazepine), drugs for sleep or anxiety (such as alprazolam, diazepam, zolpidem), muscle relaxants, and narcotic pain relievers (such as codeine).

Check the labels on all your medicines (such as allergy or cough-and-cold products) because they may contain ingredients that cause drowsiness. Ask your pharmacist about using those products safely.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: fast heartbeat, widened pupils.

NOTES: Do not share this medication with others.

MISSED DOSE: If you miss a dose, use it as soon as you remember. Take the missed dose at least 2 hours after a meal or 1 hour before your next meal. If it is near the time of your next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature between 68-77 degrees F (20-25 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised August 2008 Copyright(c) 2008 First DataBank, Inc.