Brand Name:  Sanctura ®

Generic Name: Trospium Chloride

Manufacturer: Odyssey Pharmaceuticals, Inc., East Hanover, New Jersey

                          Indevus Pharmaceuticals, Inc., Lexington, Massachusetts

Uses:

Labeled: overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency^1,2,3,4

Unlabeled: enuresis¹, IV antispasmodic for endoscopy⁴

Mechanism of Action:² Sanctura® is an antispasmodic, antimuscarinic agent that antagonizes acetylcholine on muscarinic receptors in organs that are innervated by the cholinergic nerves.  It allows for decreased tonicity of the smooth muscle in the bladder due to parasympatholytic activity.

Pharmacokinetics:²

Metabolism:² Has not been fully defined.  10% of dose absorbed and 40% account for metabolites.  Sanctura® is an inhibitor of CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4.

Excretion:² Major route of elimination is via the feces.  It is also eliminated renally.  60% excreted unchanged in urine.

Efficacy: 

Cardozo L, Chapple CR, et al.  Efficacy of Trospium chloride in patients with detrusor instability: a placebo-controlled, randomized, double-blind, multicentre clinical trial.  BJU International. 2000;(85):659-664.

 Study design: Placebo-control, double-blind, multicentre Phase III clinical trial with two parallel treatments.⁵ 

Description of study: This prospective study included 208 patients that had detrusor inactivity.⁵  They had to be between 18 and 70 years old with normal body weight, vital signs, and normal ECG results.⁵  Patients received either Trospium 20 mg BID or placebo for three weeks.⁵  Results of the study showed Trospium produced significant improvements in maximum cystometric bladder capacity and urinary volume at first unstable contraction.⁵  There were similar frequencies of adverse events reported for both groups.⁵ 

Limitations:  The study was supported by the manufacturers of Trospium and some of the authors of the study were employed by the manufacturers of Trospium.⁵  This could have led to a bias in the results.⁵

Conclusion: Trospium chloride is a safe and effective alternative for detrusor instability.⁵

Halaska M, Ralph G, Wiedmann A, et al.  Controlled, double blind, multicentre clinical trial to investigate long-term tolerability and efficacy of Trospium chloride in patients with detrusor instability.  World Journal of Urology. 2003

Study design: Prospective randomized, placebo-controlled, multicentre clinical trial.⁶

Description of study:  The purpose of the study was to compare the tolerability and the efficacy of Trospium chloride and oxybutinin in patients with an unstable bladder over a long period of time.⁶ The study involved 358 patients from six European countries that presented with symptoms of urge syndrome or urge incontinence.⁶  Patients were randomized to receive either Trospium 20 mg BID or oxybutinin 5 mg BID continuously for 52 weeks.⁶  There were no statistically significant differences in urodynamic variables when comparing Trospium to oxybutinin.⁶  There were not more adverse events that occurred during long term therapy as compared to short term therapy.⁶  Also, the number of adverse effects and frequency was less in the trospium group as opposed to the oxybutynin group.⁶ 

Limitations: A large percentage of people discontinued the study early.⁶  Tolerability was assessed subjectively by physicians.⁶  Many efficacy variables were self reported by the patients.⁶ 

Conclusion: The normal dose of Trospium chloride presented with a better risk-benefit profile in long term therapy than oxybutinin.⁶  Although effectiveness was similar, the fewer side effects seen with Trospium led to the better risk versus benefit profile.⁶

Zinner N, Gittelman M, Harris R, et al.  Trospium chloride improves overactive bladder symptoms: a multicenter phase III trial.  J Urol. 2004 Jun;171(6 Pt 1):2311-15. [abstract] 

Study Design: A multicenter, parallel, double-blind, placebo controlled trial.⁷ 

Description of study: The purpose of the study was to look at the effectiveness of Trospium in treating overactive bladder (OAB) and urge incontinence.⁷  It involved 523 patients from 51 sites.⁷  Patients were randomized to receive Trospium 20 mg BID or placebo for 12 weeks.⁷  Trospium was found to decrease the average frequency of toilet voids and urge incontinent episodes.⁷  It significantly increased the average volume per void, decreased urge severity, and decreased daytime and nighttime frequency.⁷

 Conclusion: Trospium has helped patients to decrease the number of daily toilet voids, episodes of urge incontinence, urge severity, and has increased the volume per void.⁷

Adverse Effects^1,2,3,4:   

>1%: Dry mouth (20.1%), Constipation (9.6%), Upper abdominal pain (1.5%), Headache (4.2%), Fatigue (1.9%), Aggravated constipation (1.4%), Dyspepsia (1.2%), Flatulence (1.2%), Urinary Retention (1.2%), Dry eyes not otherwise specified (1.2%)

Drug Interactions²: Using Sanctura ® with other anticholinergics can cause dry mouth, constipation, and other anticholinergic effects.  Also, there can be a change in gastric motility due to anticholinergic effects.  

Digixon, Pancuronium, Morphine, Vancomycin, Metformin, and Tenofovir: Possible pharmacokinetic interactions involving elimination by renal tubular secretion.

Cisapride: Cisapride efficacy is decreased when it interacts with Sanctura®.⁴

Procainamide: Additive antivagal effects on A-V nodal conduction.⁴  Also possible pharmacokinetic interactions involving elimination by renal tubular secretion.²

Dosing/Administration:  

Usual Dosage: 20 mg twice daily.^1,2,3,4  Administer dose one hour before meals or take on an empty stomach.^1,2,4

Pediatric: The safety and effectiveness has not been determined for children.^2,4

Geriatric: Decrease dose for patients ≥ 75 years old, 20 mg once daily based upon tolerability.^1,2,4 

Renal Impairment: For a CrCl < 30: Recommended dose is 20 mg once daily at bedtime.^1,2,4    

Hepatic Impairment: No information regarding the effect of hepatic impairment is present.^1,2,4

Contraindications^1,2,4

Urinary Retention

Gastric Retention

Uncontrolled narrow angle glaucoma

Patients at risk for this problem

Hypersensitivity to the drug or ingredients

Pyloric Stenosis

Toxic Megacolon

Ileus

Precautions/Warnings^1,2,4

1.  Risk of urinary retention     

Caution should be taken for patients who have clinically significant bladder outflow due to a risk of urinary retention.

2. Decreased gastrointestinal motility  

Can decrease GI motility similar to other anticholinergic drugs.

            Use with caution in patients that have GI disorder such as ulcerative colitis, intestinal atony, and myasthenia gravis.

3.  Controlled Narrow-Angle Glaucoma

Must use only when have careful monitoring.

4.  Patients with renal insufficiency      

If patients have severe renal insufficiency, (CrCl < 30), 20 mg should be given at bedtime.

5.  Patients with hepatic impairment  

Caution should be used when giving Sanctura® in patients with moderate to severe hepatic impairment.

6.  Hot environments

Can have a risk of fever and heat stroke due to reduced sweating

Pregnancy Category C^1,2,4

Sanctura® has been shown to cause maternal toxicity in rats

            No adequate and well controlled studies are present in pregnant women

            It should be used only if the benefits outweigh the risks to the fetus.

Nursing Mothers^1,2,4

It is not known whether Sanctura® passes into the human breast milk

            Caution should be used when giving Sanctura® to a nursing mother.

            It should be used during lactation if benefits outweigh risks

Information for patients²

            Sanctura® may produce many anticholinergic types of adverse effects

            It may produce dizziness or blurred vision.

            Alcohol may worsen drowsiness caused by anticholinergic agents.

Conclusion:  Based on the available information, Sanctura ® can be considered to be an appropriate therapy for patients that have overactive bladders that lead to urinary incontinence.

Recommended References:

1. Clinical Pharmacology
2. Package Insert- Sanctura® Trospium Chloride
3. Website: Newly Approved Drug Therapies (862), Drugs Approved by the FDA
4.  DRUGDEX® System

Hutchison TA & Shahan DR (Eds): DRUGDEX® System.  MICROMEDEX,

Greenwood Village, Colorado (2004).

5. Cardozo L, Chapple CR, et al.  Efficacy of Trospium chloride in patients with

      detrusor instability: a placebo-controlled, randomized, double-blind, multicentre

      clinical trial.  BJU International. 2000;(85):659-664.

6. Halaska M, Ralph G, Wiedmann A, et al.  Controlled, double blind, multicentre

      clinical trial to investigate long-term tolerability and efficacy of Trospium chloride

      in patients with detrusor instability.  World Journal of Urology. 2003.

7. Zinner N, Gittelman M, Harris R, et al.  Trospium chloride improves overactive

      bladder symptoms: a multicenter phase III trial.  J Urol. 2004 Jun;171(6 Pt

      1):2311-15. [abstract]

Sekhar Mamidi

Pharm.D. Candidate