Xanomeline and trospium (Cobenfy™): Basic information - Simple and Practical Mental Health

Xanomeline and trospium chloride (US brand name Cobenfy™) is a combination of a muscarinic agonist and a muscarinic antagonist respectively.

On this page, we will provide basic information about this medication. Links to other articles on this website with more advanced information and tips related to this medication and related topics are provided below—under Related Pages below.

FDA indication

Treatment of schizophrenia in adults

Mechanism of action/ Pharmacodynamics

Cobenfy™ is a combination of xanomeline, a muscarinic agonist, and trospium chloride, a muscarinic antagonist. The exact mechanism of action is unknown though efficacy of xanomeline in schizophrenia is thought to be due to agonist activity at M1 and M4 acetylcholine receptors in central nervous system while trospium is a muscarinic antagonist in peripheral tissues.

Unlike all previous medications for the treatment of schizophrenia, it does not bind to dopamine receptors and appears to not cause extrapyramidal side effects.

Contraindications

Urinary retention
Moderate or severe hepatic impairment
Gastric retention
History of hypersensitivity to Cobenfy or trospium chloride
Untreated narrow-angle glaucoma

Warnings and Precautions

Urinary retention
Hepatic impairment: Not recommended in mild hepatic impairment. Contraindicated in moderate and severe hepatic impairment.
Biliary disease
Decreased gastrointestinal motility
Angioedema
Narrow-angle glaucoma
Increase in heart rate
Renal impairment: At greater risk of anticholinergic adverse reactions. Not recommended in moderate or severe renal impairment.
Central nervous system effects: Advise patients not drive or operate machinery

Side effects

The commonest side effects of xanomeline and trospium (occurring in 5% or more of patients and at least twice the rate of placebo) were: nausea, dyspepsia, constipation, vomiting, hypertension, abdominal pain, diarrhea, tachycardia, dizziness, and gastrointestinal reflux disease.

Dosage and Administration

Before starting Cobenfy™ and as indicated during treatment:

Assess liver enzymes and bilirubin

Assess heart rate

Dosing

Initial (xanomeline/trospium): 50 mg/20 mg orally twice daily for for at least two days

Then: 100 mg/20 mg twice daily for at least 5 days

Finally: 125 mg/30 mg twice daily based on tolerability and response.

Maximum recommended dose: 125 mg/30 mg twice daily

EXTREMELY important to ask the patient to take xanomeline/trospium “at least one hour before a meal or at least 2 hours after a meal.”

Use in special populations

Geriatric patients: Start at 50 mg/20 mg orally twice daily and then titrate slowly to maximum recommended dose of 100 mg/20 mg twice daily

Moderate or severe renal impairment: Not recommended

Mild hepatic impairment: Not recommended

Dosage forms and strengths

Capsules (xanomeline/trospium): 50 mg/20 mg, 100 mg/20 mg, 125 mg/30 mg

Important! This page does not provide all the information needed to prescribe this medication. Please refer to the full Prescribing Information (see link below) before prescribing this medication.

The rationale for xanomeline+trospium (Cobenfy™), approved for the treatment of schizophrenia

Efficacy of xanomeline+trospium (Cobenfy™) and comparison with second-generation antipsychotics

Xanomeline+trospium (Cobenfy™): Side effects

References

Xanomeline-trospium (Cobenfy™) Prescribing Information. Available at https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=8f0e73bf-6025-44f6-ab64-0983322de0df&type=display. Accessed on December 10, 2024.

Disclaimer: The material on this website is provided as general education for medical professionals. It is not intended or recommended for patients or other laypersons or as a substitute for medical advice, diagnosis, or treatment. Patients must always consult a qualified healthcare professional regarding their diagnosis and treatment. Healthcare professionals should always check this website for the most recently updated information.