xanomeline/trospium

Antipsychotic

Brands: COBENFY

Last reviewed 2026-03-13

Reviewed by PsychMed Editorial Team.

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Quick answers

What is xanomeline/trospium?
Xanomeline/trospium (brand Cobenfy) is the first antipsychotic approved with a non-dopaminergic mechanism of action. FDA-approved in September 2024 for schizophrenia in adults, it represents a fundamentally new approach to treating psychosis after decades of D2-based therapies.
What is COBENFY?
COBENFY is a brand name for xanomeline/trospium.
What is COBENFY (xanomeline/trospium) used for?
Label indications include: Schizophrenia in adults.
What drug class is COBENFY (xanomeline/trospium)?
Antipsychotic.
What is the mechanism of action of COBENFY (xanomeline/trospium)?
First-in-class muscarinic M1/M4 receptor agonist (xanomeline) combined with peripheral muscarinic antagonist (trospium chloride) for schizophrenia; does not block dopamine D2 receptors.
What strengths does COBENFY (xanomeline/trospium) come in?
Capsules: 50 mg/20 mg, 100 mg/20 mg, and 125 mg/30 mg (xanomeline/trospium chloride). A starter pack containing the titration sequence is available.
Is COBENFY (xanomeline/trospium) a controlled substance?
No — it is not scheduled as a controlled substance under U.S. federal law.

Snapshot

Class: Antipsychotic
Common US brands: COBENFY
Therapeutic drug monitoring not routinely recommended.
Last reviewed: 2026-03-13

Label indications

Schizophrenia in adults

View labelExact

Clinical Highlights

Xanomeline/trospium (brand Cobenfy) is the first antipsychotic approved with a non-dopaminergic mechanism of action. FDA-approved in September 2024 for schizophrenia in adults, it represents a fundamentally new approach to treating psychosis after decades of D2-based therapies. Xanomeline is a muscarinic M1/M4 receptor agonist that delivers antipsychotic efficacy without blocking dopamine D2 receptors. Trospium chloride is a peripheral muscarinic antagonist that does not cross the blood-brain barrier, included to reduce cholinergic side effects in the gut, bladder, and other peripheral organs.

Because Cobenfy does not act on dopamine pathways, it avoids the extrapyramidal symptoms, tardive dyskinesia, significant weight gain, metabolic syndrome, and prolactin elevation that characterize traditional antipsychotics.
The EMERGENT clinical trial program (three pivotal trials) demonstrated significant improvement in PANSS total scores versus placebo with effect sizes of 0.60-0.62, comparable to established antipsychotics.
Schizophrenia in adults (FDA 2024)
Brand only: Cobenfy (Bristol-Myers Squibb / Karuna Therapeutics). Annual list price approximately $22,500.
The compare tool and the evidence library, together with the Schizophrenia hub, support side-by-side review and follow-up planning.

Dosing & Formulations

Capsules: 50 mg/20 mg, 100 mg/20 mg, and 125 mg/30 mg (xanomeline/trospium). Titration: 50/20 mg BID (Days 1-2) → 100/20 mg BID (Days 3-7) → 125/30 mg BID (Day 8 onward). Maximum dose 125/30 mg twice daily.

Geriatric patients (≥65 years): Start 50/20 mg BID with slower titration; maximum dose 100/20 mg BID.
Administer on empty stomach: at least 1 hour before or 2 hours after a meal. Food substantially reduces trospium absorption.
A starter pack is available to simplify the titration schedule for new prescriptions.

Monitoring & Risks

No boxed warning. Cobenfy does not carry the class-wide elderly dementia-related psychosis mortality warning because its mechanism is non-dopaminergic. Gastrointestinal effects predominate: nausea (19%), dyspepsia (18%), constipation (17%), and vomiting (15%) are the most common adverse reactions. Extended titration over 2 weeks at the starting dose can substantially reduce GI complaints.

Heart rate increase: mean +9.8 bpm at Week 8; monitor heart rate at baseline and during treatment. This effect attenuates over time.
Hypertension: reported in 11% versus 2% on placebo; blood pressure monitoring is recommended.
Hepatobiliary effects: ALT/AST ≥3× ULN in 2.8% versus 0.4% placebo. Discontinue if jaundice, pruritus, or ALT >5× ULN develops.
Urinary retention: particularly in geriatric patients and those with bladder outlet obstruction; reduce dose or discontinue if symptoms develop.

Drug Interactions

CYP2D6 inhibitors (fluoxetine, paroxetine, bupropion): may increase xanomeline levels; monitor for adverse reactions. CYP3A4 substrates: xanomeline transiently inhibits gut CYP3A4 and P-glycoprotein; monitor for increased effects of sensitive CYP3A4 substrates.

Anticholinergic drugs: additive peripheral anticholinergic effects with trospium; monitor for constipation, urinary retention, dry mouth.
Active tubular secretion drugs: trospium competes for renal tubular secretion; monitor for increased concentrations of either drug.

Practice Notes

Cobenfy is best suited for patients who respond to antipsychotic therapy but experience intolerable D2-mediated side effects such as EPS, weight gain, metabolic disturbance, or prolactin elevation. The side effect profile is GI-predominant rather than metabolic/neurologic, which is an unfamiliar pattern for clinicians accustomed to traditional antipsychotics. Patient education about expected GI effects during titration is important.

Empty-stomach dosing is critical—high-fat meals reduce trospium bioavailability by up to 90%. Twice-daily dosing timed around meals requires patient planning.
In the first 18 months since approval, over 100,000 prescriptions have been written. Real-world reports suggest meaningful improvements in positive symptoms and affect, with some clinicians noting cognitive benefits. Insurance access is broadening but prior authorization remains common.

References

COBENFY (xanomeline and trospium chloride) prescribing information — Bristol-Myers Squibb (2024)
U.s. FDA Approves Bristol Myers Squibb's Cobenfy, A First IN Class Muscarinic Agonist FOR THE Treatment OF Schizophrenia IN Adults — Bristol-Myers Squibb (2024)
Efficacy AND Safety OF Xanomeline Trospium Chloride IN Schizophrenia: Results OF THE Emergent 3 Randomized Clinical Trial — JAMA Psychiatry (2024)
Efficacy AND Safety OF Karxt (xanomeline Trospium) IN Schizophrenia (emergent 2): A Randomised, Double Blind, Placebo Controlled, Flexible Dose, Phase 3 Trial — Lancet (2023)
The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia — American Psychiatric Association (2020)Guidelineschizophreniaclinical
Pooled Analysis OF THE Emergent Program: Efficacy AND Safety OF Xanomeline Trospium IN Schizophrenia — Nature Schizophrenia (2024)

Quick answers

What is xanomeline/trospium?

What is COBENFY?

COBENFY is a brand name for xanomeline/trospium.

What is COBENFY (xanomeline/trospium) used for?

Label indications include: Schizophrenia in adults.

What drug class is COBENFY (xanomeline/trospium)?

Antipsychotic.

What is the mechanism of action of COBENFY (xanomeline/trospium)?

First-in-class muscarinic M1/M4 receptor agonist (xanomeline) combined with peripheral muscarinic antagonist (trospium chloride) for schizophrenia; does not block dopamine D2 receptors.

What strengths does COBENFY (xanomeline/trospium) come in?

Capsules: 50 mg/20 mg, 100 mg/20 mg, and 125 mg/30 mg (xanomeline/trospium chloride). A starter pack containing the titration sequence is available.

Is COBENFY (xanomeline/trospium) a controlled substance?

No — it is not scheduled as a controlled substance under U.S. federal law.

Clinical Highlights

Because Cobenfy does not act on dopamine pathways, it avoids the extrapyramidal symptoms, tardive dyskinesia, significant weight gain, metabolic syndrome, and prolactin elevation that characterize traditional antipsychotics.
The EMERGENT clinical trial program (three pivotal trials) demonstrated significant improvement in PANSS total scores versus placebo with effect sizes of 0.60-0.62, comparable to established antipsychotics.
Schizophrenia in adults (FDA 2024)
Brand only: Cobenfy (Bristol-Myers Squibb / Karuna Therapeutics). Annual list price approximately $22,500.
The compare tool and the evidence library, together with the Schizophrenia hub, support side-by-side review and follow-up planning.

Dosing & Formulations

Geriatric patients (≥65 years): Start 50/20 mg BID with slower titration; maximum dose 100/20 mg BID.
Administer on empty stomach: at least 1 hour before or 2 hours after a meal. Food substantially reduces trospium absorption.
A starter pack is available to simplify the titration schedule for new prescriptions.

Monitoring & Risks

Heart rate increase: mean +9.8 bpm at Week 8; monitor heart rate at baseline and during treatment. This effect attenuates over time.
Hypertension: reported in 11% versus 2% on placebo; blood pressure monitoring is recommended.
Hepatobiliary effects: ALT/AST ≥3× ULN in 2.8% versus 0.4% placebo. Discontinue if jaundice, pruritus, or ALT >5× ULN develops.
Urinary retention: particularly in geriatric patients and those with bladder outlet obstruction; reduce dose or discontinue if symptoms develop.

Drug Interactions

Anticholinergic drugs: additive peripheral anticholinergic effects with trospium; monitor for constipation, urinary retention, dry mouth.
Active tubular secretion drugs: trospium competes for renal tubular secretion; monitor for increased concentrations of either drug.

Practice Notes

Empty-stomach dosing is critical—high-fat meals reduce trospium bioavailability by up to 90%. Twice-daily dosing timed around meals requires patient planning.
In the first 18 months since approval, over 100,000 prescriptions have been written. Real-world reports suggest meaningful improvements in positive symptoms and affect, with some clinicians noting cognitive benefits. Insurance access is broadening but prior authorization remains common.