What is the interaction between Xanomeline and Trospium?

From the Guidelines

Xanomeline and Trospium should be used with caution in adult patients due to the potential for anticholinergic side effects, and the dosing should be carefully titrated to minimize these effects while achieving therapeutic efficacy. The combination of xanomeline, a cholinergic agonist, and trospium, an anticholinergic agent, is classified as an antipsychotic treatment, and its unique mechanism allows for better tolerability while maintaining antipsychotic benefits 1.

Key Considerations

• The medication works by xanomeline's activity at muscarinic receptors in the central nervous system to address psychotic symptoms, while trospium works peripherally as an anticholinergic to counteract the peripheral cholinergic side effects of xanomeline.
• Patients should be monitored for both anticholinergic effects (dry mouth, constipation, urinary retention) and potential central nervous system effects.
• The use of anticholinergic medications, including trospium, has been associated with broad muscarinic receptor blockade, which can lead to CNS impairment, delirium, slowed comprehension, and other adverse effects 1.
• The medication represents an innovative approach to antipsychotic therapy by balancing central therapeutic effects with peripheral side effect management.

Evidence-Based Recommendations

• The most recent and highest quality study on polypharmacy management in older patients highlights the importance of careful medication management to minimize adverse effects 1.
• Other studies have shown that trospium can reduce the number of urgency UI episodes, regardless of whether the patient is receiving other drugs, but patients receiving 7 or more concomitant medications had more adverse effects than those receiving fewer than 7 1.
• The American College of Physicians recommends oral anti-muscarinics, including trospium, as second-line therapy for overactive bladder, but notes that these medications are commonly associated with non-life-threatening side effects 1.

Monitoring and Titration

• Patients should be closely monitored for anticholinergic effects and potential central nervous system effects, and the dosing should be carefully titrated to minimize these effects while achieving therapeutic efficacy.
• The medication should be used with caution in adult patients, especially those with a history of anticholinergic sensitivity or those taking other medications that may interact with xanomeline and trospium.

From the FDA Drug Label

The mechanism of action of xanomeline in the treatment of schizophrenia is unclear; however, its efficacy is thought to be due to its agonist activity at M1 and M4 muscarinic acetylcholine receptors in the central nervous system. Trospium chloride is a muscarinic antagonist. Trospium chloride antagonizes the muscarinic receptors primarily in the peripheral tissues.

Key Points:

• Xanomeline is a muscarinic agonist that targets M1 and M4 receptors in the central nervous system.
• Trospium chloride is a muscarinic antagonist that acts on peripheral tissues.
• The combination of xanomeline and trospium chloride is used to treat schizophrenia.
• The exact mechanism of action of xanomeline is unclear, but its efficacy is thought to be due to its agonist activity at M1 and M4 muscarinic acetylcholine receptors. 2

From the Research

Xanomeline and Trospium Overview

• Xanomeline and Trospium are used in the treatment of schizophrenia and overactive bladder.
• Xanomeline is a dual M1/M4 preferring muscarinic receptor agonist, while Trospium is a peripherally restricted muscarinic receptor antagonist.

Pharmacologic Category

• Xanomeline and Trospium can be classified as:
  • Anticholinergic Agent
  • Antipsychotic Agent
  • Cholinergic Agonist

Dosing and Administration

• Adult dosing for Xanomeline and Trospium is available, with a maximum dose of 125 mg of Xanomeline and 30 mg of Trospium per dose.

Efficacy and Safety

• Studies have shown that Xanomeline-Trospium is effective in reducing symptoms of psychosis and improving quality of life in patients with schizophrenia 3, 4.
• The combination of Xanomeline and Trospium has been shown to be well tolerated, with similar discontinuation rates due to treatment-emergent adverse events compared to placebo 3.
• Common adverse events associated with Xanomeline-Trospium include nausea, dyspepsia, vomiting, and constipation 3, 4.

Trospium Chloride for Overactive Bladder

• Trospium chloride has been shown to be effective in relieving overactive bladder symptoms, with a favorable safety profile 5, 6.
• Trospium chloride has been compared to other agents, such as oxybutynin and tolterodine, and has been found to be at least as effective 6, 7.
• The most common adverse events associated with Trospium chloride include dry mouth, constipation, and headache 5, 6.