Cobenfy (KarXT) is an oral capsule formulation composed of xanomeline (a muscarinic agonist) and trospium chloride (a muscarinic antagonist). It was first approved in the United States in 2024 for the treatment of schizophrenia in adults. Its unique dual mechanism exerts therapeutic effects through the activation of M1/M4 receptors in the central nervous system and the antagonism of muscarinic receptors in peripheral tissues.

How to Use Cobenfy (KarXT)

Standard Dosing Regimen

Basic Dose: The recommended starting dose of Cobenfy is 50 mg/20 mg (xanomeline/trospium chloride), administered orally twice daily.

Meal Requirements: It must be taken at least 1 hour before a meal or at least 2 hours after a meal.

Capsule Handling: Opening the capsules is strictly prohibited; they must be swallowed whole.

Pre-Medication Assessment and Monitoring

Evaluate liver enzyme and bilirubin levels before treatment and when clinically necessary.

Monitor changes in heart rate at baseline and during treatment.

Confirm the absence of contraindications before each dose administration.

Special Administration Instructions

The starter pack contains 4 capsules of 50 mg/20 mg and 10 capsules of 100 mg/20 mg.

Ensure the continuity of medication throughout the entire treatment cycle.

Dosage Adjustment of Cobenfy (KarXT)

Standard Titration Regimen

Phase 1: Starting dose of 50 mg/20 mg twice daily, continued for at least 2 days.

Phase 2: Increased to 100 mg/20 mg twice daily, maintained for at least 5 days.

Target Dose: Based on the patient’s tolerability and treatment response, the dose can be further adjusted to 125 mg/30 mg twice daily.

Maximum Dose Limitations

Standard Population: The maximum recommended dose is 125 mg/30 mg twice daily.

Adjustment Principle: If a higher dose is not tolerated, the dose can be reverted to the previous level.

Efficacy Assessment Timeframe

Clinical studies have shown that after completing dose titration, it usually takes several consecutive weeks of medication to fully assess efficacy, and frequent dose adjustments should be avoided during this period.

Medication for Special Populations with Cobenfy (KarXT)

Elderly Patients

Starting Dose: 50 mg/20 mg twice daily is recommended.

Titration Strategy: Consider a slower dose escalation rate.

Maximum Dose: The maximum recommended dose for elderly patients is 100 mg/20 mg twice daily.

Patients with Renal Impairment

Mild Impairment (eGFR 60–<90 mL/min): The standard dosing regimen can be used.

Moderate to Severe Impairment (eGFR <60 mL/min): Use of Cobenfy is not recommended.

Patients with Hepatic Impairment

Mild Impairment: Use is not recommended.

Moderate to Severe Impairment: Use is absolutely contraindicated.

Pregnancy and Lactation

Pregnancy: There is insufficient data to assess risks; a careful balance of benefits and risks is recommended.

Lactation: The drug may be excreted in breast milk, so the necessity of breastfeeding should be evaluated.