Trospium

G04B - Urologicals ATC G04BD09 Small molecule approved 2004 Oral First-in-class Natural product

JFDA label: Spasmex 30mg Tablet

Mechanism of Action

Trospium antagonizes the effects of acetylcholine on muscarinic receptors in cholinergically innervated organs. It reduces the smooth muscle tone of the bladder.

Indications

Approved

Overactive bladder

Contraindications

Source: Lexicomp

Hypersensitivity to trospium or any component of the formulation Absolute
patients with or at risk of urinary retention, gastric retention, uncontrolled narrow-angle glaucoma Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Cardiac disorders (1)

Common Tachycardia, fatigue

Skin and subcutaneous tissue disorders (1)

Common Skin rash, abdominal pain, dyspepsia, flatulence, abdominal distention, urinary retention

Eye disorders (2)

Common blurred vision · Dry eye syndrome

Infections and infestations (1)

Common Influenza

Other (1)

Very Common Gastrointestinal: Xerostomia

Respiratory, thoracic and mediastinal disorders (2)

Common dry nose · Nasopharyngitis

Dosing

Source: Lexicomp

Overactive bladder: Oral: Immediate release: 20 mg twice daily Extended release: 60 mg once daily in the morning

Elderly ≥75 years: Immediate release: Consider initial dose of 20 mg once daily (based on tolerability); Extended release: Refer to adult dosing.

CrCl ≥30 mL/minute: No dosage adjustment provided in manufacturer's labeling. However, renal impairment increases systemic exposure to trospium. Monitor for increased adverse effects. CrCl Immediate release: 20 mg once daily at bedtime Extended release: Use not recommended

Mild impairment: No dosage adjustment provided in manufacturer's labeling. Moderate to severe impairment: No dosage adjustment provided in manufacturer's labeling; use with caution.

Warnings & Precautions

Source: Lexicomp

Angioedema

Cases of angioedema involving the face, lips, tongue, and/or larynx have been reported. Immediately discontinue if tongue, hypopharynx, or larynx are involved.

CNS effects

May cause drowsiness, confusion, dizziness, hallucinations, and/or blurred vision, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Disease-related concerns:

Alzheimer's disease

Use with caution in patients with Alzheimer's disease.

Bladder flow obstruction

Use with caution in patients with bladder flow obstruction; may increase the risk of urinary retention.

Gastrointestinal obstructive disorders

Use with caution in patients with gastrointestinal obstructive disorders (ie, pyloric stenosis); may increase the risk of gastric retention.

Glaucoma

Use with caution in patients with controlled (treated) narrow-angle glaucoma.

Hepatic impairment

Use with caution in patients with moderate or severe hepatic impairment.

Myasthenia gravis

Use with caution in patients with myasthenia gravis due to decreased GI motility.

Renal impairment

Use immediate release formulation with caution in patients with renal impairment; dosage adjustment is required. Use of the extended release formulation is contraindicated in patients with severe renal impairment (CrCl • Ulcerative colitis: Use with caution in patients with ulcerative colitis due to decreased GI motility. Concurrent drug therapy issues:

Medications eliminated by active tubular secretion (ATS)

ATS is a route of elimination; use caution with other medications that are eliminated by ATS (eg, procainamide, pancuronium, vancomycin, morphine, metformin, and tenofovir).

Sedatives

Effects with other sedative drugs or ethanol may be potentiated. Dosage form specific issues:

Extended release

Ethanol should not be ingested within 2 hours of the administration of the extended release formulation; may increase incidence of drowsiness.

Pregnancy & Lactation

Pregnancy

FDA category C

Adverse events were observed in animal studies. There are no adequate or well-controlled studies in pregnant women; use only if clearly needed.

Lactation

It is not known if trospium is excreted in breast milk. According to the manufacturer, the decision to continue or discontinue breast-feeding during therapy should take into account the risk of exposure to the infant and the benefits of treatment to the mother.

Monitoring

Clinical pearl	Anticholinergic effects (eg, dry mouth, constipation, dizziness); renal function; postvoid residual (PVR) urine volume and urinary tract infection prior to initiation of therapy (ACOG 2015)

Chemistry & Properties

Formula	C25H30NO3+
Molecular weight	392.52 g/mol
IUPAC name	[(1R,5S)-spiro[8-azoniabicyclo[3.2.1]octane-8,1'-azolidin-1-ium]-3-yl] 2-hydroxy-2,2-diphenylacetate
CAS	47608-32-2
PubChem CID	5284632
InChIKey	`OYYDSUSKLWTMMQ-JKHIJQBDSA-N`
logP	3.77 (XLogP 4.4)
Polar surface area	46.53 Å²
H-bond acceptors / donors	3 / 1
Drug-likeness (QED)	0.64
Lipinski violations	0

SMILES

O=C(O[C@H]1C[C@H]2CC[C@@H](C1)[N+]21CCCC1)C(O)(c1ccccc1)c1ccccc1

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	70.0%
Half-life	0.527 h
Volume of distribution	6.031 L/kg
Protein binding	74.6%
BBB penetrant	Yes

Enzyme interactions

Enzyme	Role	Detail
CYP2B6	Inhibitor	—
CYP2C19	Substrate	—
CYP3A4	Substrate	—

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)MATE1 (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OCT1 (Inhibitor)OCT2 (Inhibitor)OCT3 (Inhibitor)P-gp (Inhibitor)MATE2 (Substrate)OCT1 (Substrate)OCT2 (Substrate)P-gp (Substrate)

Drug–drug interactions (100+, DDInter)

Interacting drug	Severity	Management
Potassium chloride	major
Potassium citrate	major
Topiramate	major
Zonisamide	major
Acebutolol	moderate
Acetylcholine	moderate
Aclidinium	moderate
Acrivastine	moderate
Acyclovir	moderate
Alfentanil	moderate
Alimemazine	moderate
Amantadine	moderate
Ambenonium	moderate
Amitriptyline	moderate
Amoxapine	moderate
Arbutamine	moderate
Aripiprazole	moderate
Asenapine	moderate
Atenolol	moderate
Atropine	moderate
Azatadine	moderate
Belladonna	moderate
Benzatropine	moderate
Benzhydrocodone	moderate
Betaxolol	moderate
Bethanechol	moderate
Biperiden	moderate
Bisoprolol	moderate
Botulinum Toxin Type B	moderate
Botulinum toxin type A	moderate
Brexpiprazole	moderate
Brompheniramine	moderate
Buprenorphine	moderate
Butorphanol	moderate
Carbamoylcholine (ophthalmic)	moderate
Carbinoxamine	moderate
Cariprazine	moderate
Carteolol	moderate
Carvedilol	moderate
Cevimeline	moderate

Showing 40 of 100+.

Registered Products (1)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Spasmex	Tablet 30 mg	50 tab	مستودع ادوية بيتا	20.440