Bladder spasm

Morphine, the major active principle of powdered opium, is responsible for the action of powdered opium although the other alkaloids present also contribute to it. The sedative and analgesic action of morphine, the effect desired by inclusion in belladonna and opium suppositories of powdered opium, are thought to be due to the depressant effect on the cerebral cortex, hypothalamus and medullary centers. In large doses, the opiates and their analogs also exhibit synaptic conduction in the spinothalamic tracts, depress the function of the reticular formation, the lemniscus and the thalamic relays, and inhibit spinal synaptic reflexes: but these inhibitor actions should not be elicited with therapeutic doses of the drug. Moderate doses of powdered opium should not alter the electroencephalogram.

The action of morphine consists mainly of a descending depression of the central nervous system. It exerts its analgesic action by increasing the pain threshold or the magnitude of stimulus required to evoke pain and by dulling the sensibility or reaction to pain. In addition to its action in abolishing pain, morphine induces a sense of well-being (euphoria) facilitating certain mental processes while retarding others. Upon absorption of morphine, oxidative dealkylation to produce nor-compounds appears to be the first step in the reaction sequence which imparts analgesia. Morphine is conjugated in the liver to form the 3-glucuronide which passes into the bile and is reabsorbed and excreted in the urine. The atropine effect of the belladonna extract serves to eliminate morphine induced smooth muscle spasm without affecting the sedative analgesic action of powdered opium.

INDICATIONS AND USAGE
Belladonna and opium suppositories are used for relief of moderate to severe pain associated with ureteral spasm not responsive to non-narcotic analgesics and to space intervals between injections of opiates.

CONTRAINDICATIONS
Do not use belladonna and opium suppositories in patients suffering from glaucoma, severe hepatic or renal disease, bronchial asthma, narcotic idiosyncrasies, respiratory depression, convulsive disorders, acute alcoholism, delirium tremens and premature labor.

WARNINGS
True addiction may result from opium usage. These preparations are not recommended for use in children.

PRECAUTIONS
Administer with caution to persons with a known idiosyncrasy to atropine or to atropinelike compounds; to persons known to be sensitive to or addicted to morphine or morphinelike drugs; to persons with cardiac disease, incipient glaucoma or prostatic hypertrophy. Caution should be used in the administration of this drug to elderly and debilitated patients and patients with increased intracranial pressure, toxic psychosis and myxedema.

Pregnancy Category C
Animal studies have not been conducted with belladonna and opium suppositories. It is also not known whether belladonna and opium suppositories can affect reproductive capacity. The active principles of belladonna and opium suppositories, atropine and morphine, are known to enter the fetal circulation. Regular use of opium alkaloids during pregnancy has resulted in addiction of the fetus leading to withdrawal symptoms in the neonate. Belladonna and opium suppositories therefore should be used by a pregnant woman with caution and only when clearly indicated.

Nursing Mothers
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 belladonna and opium suppositories are administered to a nursing woman.

ADVERSE REACTIONS
Belladonna may cause drowsiness, dry mouth, urinary retention, photophobia, rapid pulse, dizziness and blurred vision. Opium usage may result in constipation, nausea or vomiting. Pruritis and urticaria may occasionally occur.
---------------------------------------------------------------------------
DOSAGE AND ADMINISTRATION
---------------------------------------------------------------------------
Adults:
One belladonna and opium suppository rectally once or twice daily, not to exceed four doses daily or as recommended by the physician. Moisten finger and suppository with water before inserting. Absorption is dependent on body hydration and not on body temperature.

Not recommended for use in children 12 years of age and under.

Store at room temperature. DO NOT REFRIGERATE. PROTECT FROM MOISTURE DURING STORAGE.

HOW SUPPLIED
Belladonna (16.2 mg) and Opium (30 mg) suppositories are easy to open, color-coded and available in cartons of 12's.
12's NDC 0574-7045-12

Belladonna (16.2 mg) and Opium (60 mg) suppositories are easy to open, color coded and available in cartons of 12's.
12's NDC 0574-7040-12

Schedule II controlled substances-DEA order required.

DOSAGE AND ADMINISTRATION
The recommended starting dose of Toviaz is 4 mg once daily. Based upon individual response and tolerability, the dose may be increased to 8 mg once daily.

The daily dose of Toviaz should not exceed 4 mg in the following populations:

--Patients with severe renal impairment (CLCR <30 mL/min)
--Patients taking potent CYP3A4 inhibitors, such as ketoconazole, itraconazole, and clarithromycin.

Toviaz is not recommended for use in patients with severe hepatic impairment (Child-Pugh C).

Toviaz should be taken with liquid and swallowed whole. Toviaz can be administered with or without food, and should not be chewed, divided, or crushed.

HOW SUPPLIED
Toviaz (fesoterodine fumarate) extended-release tablets 4 mg are light blue, oval, biconvex, film-coated, and engraved with "FS" on one side. They are supplied as follows:
Bottles of 30 NDC 0069-0242-30
Bottles of 90 NDC 0069-0242-68
Unit Dose Package of 100 NDC 0069-0242-41

Toviaz (fesoterodine fumarate) extended-release tablets 8 mg are blue, oval, biconvex, film-coated, and engraved with "FT" on one side. They are supplied as follows:
Bottles of 30 NDC 0069-0244-30
Bottles of 90 NDC 0069-0244-68
Unit Dose Package of 100 NDC 0069-0244-41

In a single study of 11 normal male subjects, the time to onset of action was 55 minutes. The peak effect was observed at 112 minutes. 57% of the flavoxate hydrochloride was excreted in the urine within 24 hours.

INDICATIONS AND USAGE:
Flavoxate hydrochloride tablets are indicated for symptomatic relief of dysuria, urgency, nocturia, suprapubic pain, frequency and incontinence as may occur in cystitis, prostatitis, urethritis, urethrocystitis/urethrotrigonitis. Flavoxate hydrochloride tablets are not indicated for definitive treatment, but are compatible with drugs used for the treatment of urinary tract infections.

----------------------------------------------------------------------------------------
DOSAGE AND ADMINISTRATION:
----------------------------------------------------------------------------------------
Adults and children over 12 years of age

One or two 100 mg tablets 3 or 4 times a day. With improvement of symptoms, the dose may be reduced. This drug cannot be recommended for infants and children under 12 years of age because safety and efficacy have not been demonstrated in this age group.

CONTRAINDICATIONS:
Flavoxate hydrochloride is contraindicated in patients who have any of the following obstructive conditions: pyloric or duodenal obstruction, obstructive intestinal lesions or ileus, achalasia, gastrointestinal hemorrhage and obstructive uropathies of the lower urinary tract.

WARNINGS AND PRECAUTIONS:
WARNINGS
Flavoxate hydrochloride should be given cautiously in patients with suspected glaucoma.

PRECAUTIONS-----
Information for Patients

Patients should be informed that if drowsiness and blurred vision occur, they should not operate a motor vehicle or machinery or participate in activities where alertness is required.

Carcinogenesis, Mutagenesis, Impairment of Fertility
Mutagenicity studies and long-term studies in animals to determine the carcinogenic potential of flavoxate hydrochloride have not been performed.

Pregnancy
Teratogenic Effects-Pregnancy Category B.

Reproduction studies have been performed in rats and rabbits at doses up to 34 times the human dose and revealed no evidence of impaired fertility or harm to the fetus due to flavoxate hydrochloride. There are, however, no well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers
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 flavoxate hydrochloride is administered to a nursing woman.

Pediatric Use
Safety and effectiveness in children below the age of 12 years have not been established.

ADVERSE REACTIONS
The following adverse reactions have been observed, but there are not enough data to support an estimate of their frequency.

Gastrointestinal: Nausea, vomiting, dry mouth.

CNS: Vertigo, headache, mental confusion, especially in the elderly, drowsiness, nervousness.

Hematologic: Leukopenia (one case which was reversible upon discontinuation of the drug).

Cardiovascular: Tachycardia and palpitation.

Allergic: Urticaria and other dermatoses, eosinophilia and hyperpyrexia.

Ophthalmic: Increased ocular tension, blurred vision, disturbance in eye accommodation.

Renal: Dysuria.

DOSAGE FORMS AND STRENGTHS:
Flavoxate hydrochloride 100 mg tablets are available as white, round biconvex, film-coated tablets, debossed “? 58” on one side and plain on the other side, and are available in bottles of 100 and 1000.

Store at 20° - 25°C (68° - 77°F) [see USP Controlled Room Temperature]. Dispense contents in a tight, light-resistant container.

SOURCE:
Package insert data:

Levsin® is absorbed totally and completely by sublingual administration as well as oral administration. Once absorbed, Levsin® disappears rapidly from the blood and is distributed throughout the entire body. The half-life of Levsin® is 2 to 3½ hours. Levsin® is partly hydrolyzed to tropic acid and tropine but the majority of the drug is excreted in the urine unchanged within the first 12 hours. Only traces of this drug are found in breast milk. Levsin® passes the blood brain barrier and the placental barrier.

Dosage
Children >12 years and Adults:
Gastrointestinal disorders: 0.125-0.25 mg every 4 hours or as needed (before meals or food); maximum: 1.5 mg/24 hours.
Cystospaz®: 0.15-0.3 mg up to 4 times/day.

Oral (timed release): Children >12 years and Adults: Gastrointestinal disorders: 0.375-0.75 mg every 12 hours; maximum: 1.5 mg/24 hours

 I.M., I.V., SubQ: Children >12 years and Adults: Gastrointestinal disorders: 0.25-0.5 mg; may repeat as needed up to 4 times/day, at 4-hour intervals

 I.V.: Adults: Diagnostic procedures: 0.25-0.5 mg given 5-10 minutes prior to procedure

To reduce drug-induced bradycardia during surgery: 0.125 mg; repeat as needed

To reverse neuromuscular blockade: 0.2 mg for every 1 mg neostigmine (or the physostigmine/pyridostigmine equivalent)

Supplied
Capsule, timed release, as sulfate (Cystospaz-M® [DSC], Levsinex®): 0.375 mg
Elixir, as sulfate: 0.125 mg/5 mL (480 mL)
Hyosine: 0.125 mg/5 mL (480 mL)
Levsin®: 0.125 mg/5 mL (480 mL) [contains alcohol 20%; orange flavor]

Injection, solution, as sulfate (Levsin®): 0.5 mg/mL (1 mL)
Solution, oral drops, as sulfate: 0.125 mg/mL (15 mL)
Hyosine: 0.125 mg/mL (15 mL)
Levsin®: 0.125 mg/mL (15 mL) [contains alcohol 5%; orange flavor]
Tablet (Cystospaz®): 0.15 mg
Tablet, orally-disintegrating, as sulfate (NuLev™): 0.125 mg [contains phenylalanine 1.7 mg/tablet, mint flavor]
Tablet, sublingual, as sulfate: 0.125 mg
Levsin/SL®: 0.125 mg [peppermint flavor]
Symax SL: 0.125 mg

In vitro studies using human recombinant muscarinic receptor subtypes show that darifenacin has greater affinity for the M3 receptor than for the other known muscarinic receptors (9- and 12-fold greater affinity for M3 compared to M1 and M5, respectively, and 59-fold greater affinity for M3 compared to both M2 and M4). M3 receptors are involved in contraction of human bladder and gastrointestinal smooth muscle, saliva production, and iris sphincter function. Adverse drug effects such as dry mouth, constipation and abnormal vision may be mediated through effects on M3 receptors in these organs

INDICATIONS AND USAGE
ENABLEX® (darifenacin) extended-release tablets are indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency and frequency.

CONTRAINDICATIONS
ENABLEX® (darifenacin) extended-release tablets are contraindicated in patients with urinary retention, gastric retention or uncontrolled narrow-angle glaucoma and in patients who are at risk for these conditions. ENABLEX is also contraindicated in patients with known hypersensitivity to the drug or its ingredients.

Dosing (Adults): Symptoms of bladder overactivity - Initial: 7.5 mg orally once daily. If response is not adequate after a minimum of 2 weeks, dosage may be increased to 15 mg once daily. Dosage should not be increased in patients with hepatic impairment or in those receiving potent inhibitors of CYP3A4.

Hepatic dosing: Moderate impairment (Child-Pugh Class B): Daily dosage should not exceed 7.5 mg/day. Severe impairment (Child-Pugh Class C): Use is not recommended.

Supplied: Extended release tablet: 7.5 mg, 15 mg.

Mechanism of Action: Mirabegron is an agonist of the human beta-3 adrenergic receptor (AR) as demonstrated by in vitro laboratory experiments using the cloned human beta-3 AR. Mirabegron relaxes the detrusor smooth muscle during the storage phase of the urinary bladder fill-void cycle by activation of beta-3 AR which increases bladder capacity. Although mirabegron showed very low intrinsic activity for cloned human beta-1 AR and beta-2 AR, results in humans indicate that beta-1 AR stimulation occurred at a mirabegron dose of 200 mg.

INDICATIONS AND USAGE:  MYRBETRIQ® is a beta-3 adrenergic agonist indicated for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency

DOSAGE AND ADMINISTRATION
ABBREVIATED MONOGRAPH - SEE PACKAGE INSERT.
Recommended starting dose is 25 mg once daily, with or without food ( 2.1).

25 mg is effective within 8 weeks. Based on individual efficacy and tolerability, may increase dose to 50 mg once daily ( 2.1, 14).

Swallow whole with water, do not chew, divide or crush ( 2.1).

Patients with Severe Renal Impairment or Patients with Moderate Hepatic Impairment: Maximum dose is 25 mg once daily ( 2.2, 8.6, 8.7, 12.3).

Patients with End Stage Renal Disease (ESRD) or Patients with Severe Hepatic Impairment: Not recommended ( 2.2, 8.6, 8.7, 12.3).

HOW SUPPLIED:
Extended-release tablets: 25 mg and 50 mg
CONTRAINDICATIONS
Hypersensitivity reactions

WARNINGS AND PRECAUTIONS:
Increases in Blood Pressure: Myrbetriq can increase blood pressure. Periodic blood pressure determinations are recommended, especially in hypertensive patients.
Myrbetriq is not recommended for use in severe uncontrolled hypertensive patients.

Urinary Retention in Patients With Bladder Outlet Obstruction and in Patients Taking Antimuscarinic Drugs for Overactive Bladder: Administer with caution in these patients because of risk of urinary retention.

Patients Taking Drugs Metabolized by CYP2D6: Myrbetriq is a moderate inhibitor of CYP2D6. Appropriate monitoring is recommended and dose adjustment may be necessary for narrow therapeutic index CYP2D6 substrates.

Oxybutynin chloride relaxes bladder smooth muscle. In patients with conditions characterized by involuntary bladder contractions, cystometric studies have demonstrated that oxybutynin chloride increases bladder (vesical) capacity, diminishes the frequency of uninhibited contractions of the detrusor muscle, and delays the initial desire to void. Oxybutynin chloride thus decreases urgency and the frequency of both incontinent episodes and voluntary urination.

Antimuscarinic activity resides predominately in the R-isomer. A metabolite, desethyloxybutynin, has pharmacological activity similar to that of oxybutynin in in vitro studies.

Exhibits 20% of the anticholinergic activity of atropine, however, has 4 to 10 times the antispasmodic activity.

INDICATIONS AND USAGE
DITROPAN® (oxybutynin chloride) is indicated for the relief of symptoms of bladder instability associated with voiding in patients with uninhibited neurogenic or reflex neurogenic bladder (i.e., urgency, frequency, urinary leakage, urge incontinence, dysuria).

CONTRAINDICATIONS
DITROPAN® (oxybutynin chloride) is contraindicated in patients with urinary retention, gastric retention and other severe decreased gastrointestinal motility conditions, uncontrolled narrow-angle glaucoma and in patients who are at risk for these conditions.

DITROPAN is also contraindicated in patients who have demonstrated hypersensitivity to the drug substance or other components of the product.

Dosing (Adults): 
Oral: 5 mg 2-3 times/day up to 5 mg 4 times/day maximum.
Extended release: Initial: 5-10 mg once daily, may increase in 5-10 mg increments; maximum: 30 mg daily.
Transdermal: Adults: Apply one 3.9 mg/day patch twice weekly (every 3-4 days).
Note: Should be discontinued periodically to determine whether the patient can manage without the drug and to minimize resistance to the drug

Elderly: 2.5 to 5 mg 2-3 times/day

Administration
Oral: Immediate release tablets and solution should be administered on an empty stomach with water. Extended release tablets may be taken with or without food and must be swallowed whole; do not crush, divide, or chew.
Transdermal: Apply to clean, dry skin on abdomen, hip, or buttock. Select a new site for each new system (avoid re-application to same site within 7 days).

Supplied
Syrup, as chloride (Ditropan®): 5 mg/5 mL (473 mL)
Tablet, as chloride (Ditropan®): 5 mg
Tablet, extended release, as chloride (Ditropan® XL): 5 mg, 10 mg, 15 mg
Transdermal system (Oxytrol™): 3.9 mg/day (8s, 24s) [39 cm 2 ; total oxybutynin 36 mg]

INDICATIONS AND USAGE
VESIcare is indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency.

CONTRAINDICATIONS
VESIcare is contraindicated in patients with urinary retention, gastric retention, uncontrolled narrow-angle glaucoma, and in patients who have demonstrated hypersensitivity to the drug substance or other components of the product.

Dosing (Adults):  Overactive bladder: 5 mg orally once daily. If tolerated, may increase to 10 mg orally once daily.

Renal Dosing: Use with caution in patients with reduced renal function ( Clcr <30 ml/minute: 5 mg/day).

Hepatic impairment: Use with caution in reduced hepatic function: Moderate: 5 mg/day. Severe impairment: Not recommended.

Supplied: 5 mg, 10 mg tablet.

INDICATIONS AND USAGE:
DETROL Tablets are indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency.

----------------------------------------------------------------------------------------
DOSAGE AND ADMINISTRATION:
----------------------------------------------------------------------------------------
The initial recommended dose of DETROL Tablets is 2 mg twice daily. The dose may be lowered to 1 mg twice daily based on individual response and tolerability. For patients with significantly reduced hepatic or renal function or who are currently taking drugs that are potent inhibitors of CYP3A4, the recommended dose of DETROL is 1 mg twice daily

EXTENDED RELEASE:
Dosing Information
The recommended dose of DETROL LA Capsules is 4 mg once daily with water and swallowed whole. The dose may be lowered to 2 mg daily based on individual response and tolerability; however, limited efficacy data are available for DETROL LA 2 mg.

Dosage Adjustment in Specific Populations
For patients with mild to moderate hepatic impairment (Child-Pugh Class A or B) or severe renal impairment (CCr 10-30 mL/min), the recommended dose of DETROL LA is 2 mg once daily. DETROL LA is not recommended for use in patients with severe hepatic impairment (Child-Pugh Class C). Patients with CCr<10 mL/min have not been studied and use of DETROL LA in this population is not recommended [see PACKAGE INSERT - WARNINGS AND PRECAUTIONS (5.6) and USE IN SPECIFIC POPULATIONS (8.6, 8.7)].

Dosage Adjustment in Presence of Concomitant Drugs
For patients who are taking drugs that are potent inhibitors of CYP3A4 [e.g., ketoconazole, clarithromycin, ritonavir], the recommended dose of DETROL LA is 2 mg once daily

CONTRAINDICATIONS:
DETROL Tablets are contraindicated in patients with urinary retention, gastric retention, or uncontrolled narrow-angle glaucoma. DETROL is also contraindicated in patients who have demonstrated hypersensitivity to the drug or its ingredients, or to fesoterodine fumarate extended-release tablets which, like DETROL, are metabolized to 5-hydroxymethyl tolterodine.

WARNINGS AND PRECAUTIONS:
WARNINGS
Anaphylaxis and angioedema requiring hospitalization and emergency medical treatment have occurred with the first or subsequent doses of DETROL. In the event of difficulty in breathing, upper airway obstruction, or fall in blood pressure, DETROL should be discontinued and appropriate therapy promptly provided.

PRECAUTIONS
General

Risk of Urinary Retention and Gastric Retention
DETROL Tablets should be administered with caution to patients with clinically significant bladder outflow obstruction because of the risk of urinary retention and to patients with gastrointestinal obstructive disorders, such as pyloric stenosis, because of the risk of gastric retention (see CONTRAINDICATIONS).

Decreased Gastrointestinal Motility
DETROL, like other antimuscarinic drugs, should be used with caution in patients with decreased gastrointestinal motility.

Controlled Narrow-Angle Glaucoma
DETROL should be used with caution in patients being treated for narrow-angle glaucoma.

Central Nervous System (CNS) Effects
Detrol is associated with anticholinergic central nervous system (CNS) effects including dizziness and somnolence (see Adverse Reactions). 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 the drug's effects have been determined. If a patient experiences anticholinergic CNS effects, dose reduction or drug discontinuation should be considered.

Reduced Hepatic and Renal Function
For patients with significantly reduced hepatic function or renal function, the recommended dose of DETROL is 1 mg twice daily (see package insert: CLINICAL PHARMACOLOGY, Pharmacokinetics in Special Populations).

Myasthenia Gravis
DETROL should be used with caution in patients with myasthenia gravis, a disease characterized by decreased cholinergic activity at the neuromuscular junction.

Patients with Congenital or Acquired QT Prolongation
In a study of the effect of tolterodine immediate release tablets on the QT interval (see package insert - CLINICAL PHARMACOLOGY, Cardiac Electrophysiology), the effect on the QT interval appeared greater for 8 mg/day (two times the therapeutic dose) compared to 4 mg/day and was more pronounced in CYP2D6 poor metabolizers (PM) than extensive metabolizers (EMs). The effect of tolterodine 8 mg/day was not as large as that observed after four days of therapeutic dosing with the active control moxifloxacin. However, the confidence intervals overlapped. These observations should be considered in clinical decisions to prescribe DETROL for patients with a known history of QT prolongation or patients who are taking Class IA (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmic medications (see PRECAUTIONS, Drug Interactions). There has been no association of Torsade de Pointes in the international post-marketing experience with DETROL or DETROL LA.

Information for Patients
Patients should be informed that antimuscarinic agents such as DETROL may produce the following effects: blurred vision, dizziness, or drowsiness. Patients should be advised to exercise caution in decisions to engage in potentially dangerous activities until the drug's effects have been determined.

Drug Interactions
CYP3A4 Inhibitors
Ketoconazole, an inhibitor of the drug metabolizing enzyme CYP3A4, significantly increased plasma concentrations of tolterodine when coadministered to subjects who were poor metabolizers (see package insert - CLINICAL PHARMACOLOGY, Variability in Metabolism and Drug-Drug Interactions). For patients receiving ketoconazole or other potent CYP3A4 inhibitors such as other azole antifungals (e.g., itraconazole, miconazole) or macrolide antibiotics (e.g., erythromycin, clarithromycin) or cyclosporine or vinblastine, the recommended dose of DETROL is 1 mg twice daily (see DOSAGE AND ADMINISTRATION).

USE IN SPECIFIC POPULATIONS:
SEE PACKAGE INSERT

DOSAGE FORMS AND STRENGTHS:
DETROL Tablets 1 mg (white, round, biconvex, film-coated tablets engraved with arcs above and below the letters "TO") and DETROL Tablets 2 mg (white, round, biconvex, film-coated tablets engraved with arcs above and below the letters "DT")
-----
EXTENDED RELEASE CAPSULES:
DETROL LA Capsules are supplied as follows:
The 2 mg capsules are blue-green with symbol and 2 printed in white ink.
The 4 mg capsules are blue with symbol and 4 printed in white ink.

SOURCE:
Package insert data:

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.

INDICATIONS AND USAGE
SANCTURA® is indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency.

CONTRAINDICATIONS
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.

WARNINGS AND PRECAUTIONS
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

Angioedema
Angioedema of the face, lips, tongue, and/or larynx has been reported with trospium chloride, the active ingredient in SANCTURA®. In one case, angioedema occurred after the first dose of trospium chloride. Angioedema associated with upper airway swelling may be life threatening. If involvement of the tongue, hypopharynx, or larynx occurs, SANCTURA® should be promptly discontinued and appropriate therapy and/or measures necessary to ensure a patent airway should be promptly provided.

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 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.

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 [see Contraindications].

Central Nervous System Effects
SANCTURA® is associated with anticholinergic central nervous system (CNS) effects [see PACKAGE INSERT - Adverse Reactions (6.2)]. 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 SANCTURA® affects them. If a patient experiences anticholinergic CNS effects, dose reduction or drug discontinuation should be considered.

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

-------------------------------------------------------
DOSAGE AND ADMINISTRATION
-------------------------------------------------------
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 (creatinine clearance less than 30 mL/min), the recommended dose is 20 mg once daily at bedtime.

In geriatric patients greater than or equal to 75 years of age, dose may be titrated down to 20 mg once daily based upon tolerability.

XR CAPSULES:
The recommended dosage of SANCTURA XR® is one 60 mg capsule daily in the morning. SANCTURA XR® capsules should be dosed with water on an empty stomach, at least one hour before a meal.

SANCTURA XR® is not recommended for use in patients with severe renal impairment (creatinine clearance less than 30 mL/minute)

Supplied:
SANCTURA® is supplied as 20 mg tablets (brownish yellow, biconvex, glossy coated tablets printed with S in black ink).

XR CAPSULES:
SANCTURA XR® is supplied as 60 mg capsules (white opaque body and orange opaque cap, printed with SAN 60): 60 mg capsule, 30 count, HDPE bottle: NDC 0023-9350-30

Store at controlled room temperature 20° to 25°C (68° to 77°F). Excursion permitted at 15° to 30°C (see USP).