Trospium chloride

The drug in overactive bladder disease:
Trospium Chloride

Abstract:
Trospium chloride is a quaternary ammonium compound, which is a competitive antagonist at muscarinic cholinergic receptors. Preclinical studies using porcine and human detrusor muscle strips demonstrated that trospium chloride was many-fold more potent than oxybutynin and tolterodine in inhibiting contractile responses to carbachol and electrical stimulation. The drug is poorly bioavailable orally (< 10%) and food reduces absorption by 70%– 80%.

Pronunciation: (TROSE-pee-um KLOR-ide)

class: Anticholinergic
Trade Names:
Sanctura
- Tablets 20 mg
Trade Names:
Sanctura XR
- Tablets, extended-release 60 mg
Trosec (Canada)
Chemistry1
Trospium chloride also known as azonia-3-α-benziloyloxy-8-spiro-1′-pyrrolidinium chloride,
has the molecular formula C25H30NO3Cl, and a molecular weight of 427.97.
Its chemical name is spiro[8-azoniabicyclo[3,2,1]octane-8,1′-pyrrolidinium]-3-[(hydroxydiphenylacetyl)-oxy]chloride(1α,3β,5α)-(9CI). Solubility in water exceeds 50 mg per mL at room temperature while in light mineral oil it is 9.2 × 10–3 mg/mL Its log partition coefficient between n-octanol and buffer at pH 7.4 is –1.22). Synthesis and pharmacological activity of this compound were first described in 1966.

Chemical Structure of trospium

Dosage and Administration2
Adults
Immediate-release: 20 mg twice daily on an empty stomach or at least 1 h before meals.

Extended-release: 60 mg daily in the morning on an empty stomach, at least 1 h before a meal.

Storage/Stability:
Store at controlled room temperature (68° to 77°F)

Contraindications5
Patients with or at risk of urinary retention; gastric retention; uncontrolled narrow-angle glaucoma; hypersensitivity to any component of product.

Adverse affects:

3
Gastrointestinal disorders: Dry mouth, constipation abdominal pain upper, dyspepsia, flatulence.

Nervous system disorders:Head ache

General disorders:Fatigue

Renal and urinary disorders:Urinary retention

Eye disorders: Dry eyes

Drug interactions:6
Trospium has the potential for pharmacokinetic interactions with other drugs that are eliminated by active tubular secretion (e.g. procainamide, pancuronium, morphine, vancomycin, metformin, tenofovir, pramlintide, acetyl cholinesterase inhibitors and anticholinergic drugs). Coadministration of Trospium with these drugs may increase the serum concentration of Trospium and/or the coadministered drug due to competition for this elimination pathway.

PRECAUTIONS:4
General:

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

Decreased Gastrointestinal Motility: Trospium should be administered with caution to patients with gastrointestinal obstructive disorders because of the risk of gastric retention. Trospium 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, Trospium 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, Trospium should be administered as 20 mg once a day at bed time.

Patients with Hepatic Impairment: Caution should be used when administering Trospium in patients with moderate or severe hepatic dysfunction.

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). There are no adequate and well controlled studies in pregnant women. Trospium should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing mothers:
Trospium is administered to a nursing woman. Trospium should be used during lactation only if the potential benefit justifies the potential risk to the newborn.

REFERENCES:

1. Reuel H-P, Murtz G, Boudy S, et. al safety and tolerance of t.c in the high dose range. Arzeimitte forschung 1993; 43; 461(pubmed)

2. Cardozo L.chapple C.R, toozs-Hobson et al efficacy of T.C in patend with detrusor instability a placebo controlled randomized, double blind multicentre clinical trial. BIUint 2000;85;659-64.

3. http://www.drugs.com/mtm/trospium chloride-htm/

4. http://www.rx list.com/Sanctura drug htm.

5. http://www.medilexicon.com/drugs/sanctura-php.

6. http://med guides.medicines.org.UIC/doc.

7. http://www.drugs bank.com.
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