Getting started with COBENFY

A maintenance dose for COBENFY can be achieved by Day 31

Starting and maintenance doses of Cobenfy

Capsules not shown at actual size.
50 mg/20 mg is not a therapeutic dose.
COBENFY is taken orally and dose is expressed as mg xanomeline/mg trospium chloride.1
The recommended starting dosage of COBENFY in geriatric patients is 50 mg/20 mg orally BID. Consider a slower titration for geriatric patients. The maximum recommended dosage in geriatric patients is 100 mg/20 mg BID.1
Assess liver enzymes, bilirubin, and heart rate before starting COBENFY and as clinically indicated.1

Steps to start patients on Cobenfy. Identify patients, plan initiation, and set expectations.

Confidently get your patients started on COBENFY

The approach to initiating should be individualized based on the patient’s current regimen and guided by the clinician’s judgment.

PATIENTS ON A D2 TREATMENT EXPERIENCING SYMPTOMS2-4

Can you identify patients on a D2 treatment experiencing symptoms?

Experiencing burdensome symptoms, such as:

  • Hallucinations
  • Social withdrawal, limited engagement
  • Struggles to initiate and complete tasks

Two randomized, double-blind, placebo-controlled, phase 3 studies assessed the safety and efficacy of COBENFY with a primary end point of the change from baseline in PANSS total score at Week 5 vs placebo (EMERGENT-2: –21.2 vs –11.6; EMERGENT-3: –20.6 vs –12.2, P<0.0001).3,5-7 See data

Silhouette of patient

CHECK FOR CLINICALLY RELEVANT DRUG INTERACTIONS BEFORE AND DURING TREATMENT WITH COBENFY1

Crossed out circle

COBENFY has no contraindicated medications1:

Antimuscarinic drugs in combination with COBENFY may increase frequency and/or severity of anticholinergic side effects1,8,9

Examples of commonly used drugs*:

Benztropine Diphenhydramine Hydroxyzine

COBENFY is contraindicated in patients with urinary retention, moderate or severe hepatic impairment, gastric retention, history of hypersensitivity to COBENFY or trospium chloride, and untreated narrow-angle glaucoma.1

Strong Inhibitors of CYP2D61,10

Examples:
fluoxetine
paroxetine
bupropion
terbinafine

Drugs Eliminated by Active Tubular Secretion1,11,12

Examples:
metformin
hydrochlorothiazide
furosemide

May increase plasma concentration and frequency and/or severity of side effects of:

Xanomeline

Trospium or other drug administered

COBENFY may increase plasma concentration and frequency and/or severity of side effects of1,10,13-16:

Sensitive Substrates of CYP3A4

Examples:
buspirone
eletriptan

Narrow Therapeutic Index Substrates of P-glycoprotein

Examples:
digoxin
colchicine
apixaban

Effects on Absorption of Drugs: COBENFY may potentially alter the absorption of some concomitantly administered drugs due to anticholinergic effects on gastrointestinal motility. Dosage adjustment of concomitant medications may be necessary based on clinical response and tolerability.1

Additional Consideration: Anticholinergics (muscarinic antagonists) and muscarinic agonists may affect the pharmacological activity of one another.

* This is not an exhaustive list of medications and is only used to show select examples from each category. For additional examples, visit FDA.gov.
  Certain medications may increase the frequency and intensity of side effects! The approach to initiating should be individualized based on the patient's current regimen and guided by the clinician's judgment.
CYP2D6=cytochrome P450 2D6; CYP3A4=cytochrome P450 3A4.

A MAINTENANCE DOSE FOR COBENFY CAN BE ACHIEVED BY DAY 31

Starting and maintenance doses of Cobenfy

Capsules not shown at actual size. 50 mg/20 mg is not a therapeutic dose. COBENFY is taken orally and dose is expressed as mg xanomeline/mg trospium chloride.1

Titration1

Titration of Cobenfy

The recommended starting dosage of COBENFY in geriatric patients is 50 mg/20 mg orally BID. Consider a slower titration for geriatric patients. The maximum recommended dosage in geriatric patients is 100 mg/20 mg BID.1

Assess liver enzymes, bilirubin, and heart rate before starting COBENFY and as clinically indicated.1

* This example represents the fastest titration schedule. Patients must be on the 50 mg/20 mg dose for a minimum of 2 days and the 100 mg/20 mg for a minimum of 5 days.1
  BID=twice daily.

YOUR PATIENTS CAN START AND END THEIR DAY WITH COBENFY1,17

Sun and moon

TAKE TWICE DAILY

Talk to your patients about how to best fit COBENFY into their routine. Consider 1 pill when they wake up and 1 pill before bed.

Crossed out fork and spoon

COBENFY ON EMPTY

Taking COBENFY with food can increase the risk of procholinergic side effects.

Clock

WAIT BEFORE YOU TAKE

Wait at least 1 hour before eating or at least 2 hours after eating.

Pill bottle

Consider prescribing antiemetics prophylactically4*

* Ondansetron was the antiemetic most used in COBENFY clinical trials. 4% of patients were prescribed ondansetron as needed in EMERGENT-1, -2, & -3 clinical trials (pooled data).4

The approach to initiating should be individualized based on the patient's current regimen and guided by the clinician's judgment.

Initial onset of nausea and vomiting were mild to moderate*†, transient, and generally declined with continued titration to 125 mg/30 mg1,4,18

Nausea and vomiting initial occurrences generally declined after the titration period (EMERGENT-2 & -3)1,4

Graph of nausea and vomiting occurrences during initial onset of Cobenfy. Nausea and vomiting declined after the titration period.
Stomach

Nausea and vomiting were reported by 19% and 15% of patients, respectively1

~70% of nausea and vomiting were mild†‡

97%

of patients did not discontinue COBENFY due to nausea or vomiting4‖

* A mild adverse reaction was defined as an event that is easily tolerated by the patient, causing minimal discomfort, and not interfering with everyday activities; a moderate adverse reaction was defined as an event that was sufficiently discomforting to interfere with-but not prevent—normal everyday activities.4
† EMERGENT-2 & -3, 13.9% and 5.2% of patients treated with COBENFY had mild or moderate nausea, respectively, and 10.4% and 4.8% had mild or moderate vomiting, respectively. No patients had severe nausea or vomiting.4
‡ In EMERGENT-1, -2, and -3, 87% of patients on COBENFY increased to 125 mg/30 mg BID, and 5% of patients reduced their maintenance dosage down to 100 mg/20 mg BID.4
§ 4% of patients were prescribed ondansetron in EMERGENT-1, -2, & -3 clinical trials (pooled data).4
‖ 6% of patients treated with COBENFY and 4% of patients treated with placebo discontinued due to adverse reactions in the 5-week, placebo-controlled studies. In EMERGENT-2 & -3, adverse reactions that led to study discontinuation in ≥1% of patients treated with COBENFY included nausea (2%) and. vomiting (1%).4

In EMERGENT-1, -2, & -3, 87% of patients on COBENFY increased to 125 mg/30 mg BID, and 5% of patients reduced their maintenance dosage back down to 100 mg/20 mg BID.4

BID=twice daily; Wk=week.

Treatment compliance and continued patient interest with COBENFY

97%

OUTPATIENT COMPLIANCE4,19

On average, patients took 97% of their COBENFY twice-daily doses for the duration of their enrollment in EMERGENT-5, a 52-week, long-term, outpatient study*

* This represents patients who took at least 1 dose of COBENFY in the EMERGENT-5 clinical study. 566 patients were enrolled in EMERGENT-5, and 277 completed the 52-week outpatient trial. Patients included in this analysis may not have completed the 52-week outpatient trial. Compliance was ensured by study site personnel (during in-clinic visits) and by a digital compliance tool. Treatment compliance was calculated as number of doses taken compared to the number planned.4,19
78%

CONTINUED INTEREST SURVEY20,21

After 6 months of treatment, 78% of patients said they would continue COBENFY if given the option after the trial (EMERGENT-5) concluded (n=46)

Interviews included study-specific, semi-structured interview guides including 10-point, self-reported preference ratings. Patients receiving COBENFY were asked 6 weeks and 6 months after treatment initiation whether they would choose to continue treatment if they had the option. 23 patients discontinued between these time points.20

SAMPLES TO START logo

Get your patients started on COBENFY today

Learn about COBENFY and request samples

Cobenfy sample and titration packs
Cobenfy representative

Request a COBENFY representative or samples through our chatbot

Explore the efficacy data of COBENFY

Learn more about the safety profile of COBENFY

See how COBENFY is thought to work

References:

  1. COBENFY. Prescribing Information. Bristol-Myers Squibb Company; 2024.
  2. Paul SM, Yohn SE, Popiolek M, Miller AC, Felder CC. Muscarinic acetylcholine receptor agonists as novel treatments for schizophrenia. Am J Psychiatry. 2022;179(9):611-627.
  3. Kaul I, Sawchak S, Claxton A, et al. Efficacy of xanomeline and trospium chloride in schizophrenia: pooled results from three 5-week, randomized, double-blind, placebo-controlled, EMERGENT trials. Schizophrenia (Heidelb). 2024;10(1):102.
  4. Data on file. Karuna Therapeutics, Inc., a Bristol Myers Squibb company; Boston, MA.
  5. Kaul I, Sawchak S, Correll CU, et al. Efficacy and safety of the muscarinic receptor agonist KarXT (xanomeline-trospium) in schizophrenia (EMERGENT-2) in the USA: results from a randomised, double-blind, placebo-controlled, flexible-dose phase 3 trial. Lancet. 2024;403(10422):160-170.
  6. Kaul I, Sawchak S, Walling DP, et al. Efficacy and safety of xanomeline-trospium chloride in schizophrenia: a randomized clinical trial. JAMA Psychiatry. 2024;81(8):749-756.
  7. Kaul I, Sawchak S, Walling DP, et al. Efficacy and safety of xanomeline-trospium chloride in schizophrenia: a randomized clinical trial. JAMA Psychiatry. 2024;81(8)(suppl):749-756.
  8. Muscarinic antagonists. DrugBank Online. Accessed March 6, 2025. https://go.drugbank.com/categories/DBCAT000534
  9. Hydroxyzine. DrugBank Online. Accessed July 14, 2025. https://go.drugbank.com/drugs/DB00557
  10. For healthcare professionals | FDA’s examples of drugs that interact with CYP enzymes and transporter systems. U.S. Food & Drug Administration. Accessed March 6, 2025. https://www.fda.gov/drugs/drug-interactions-labeling/healthcare-professionals-fdas-examples-drugs-interact-cyp-enzymes-and-transporter-systems#table%201
  11. Gong L, Goswami S, Giacomini KM, Altman RB, Klein TE. Metformin pathways: pharmacokinetics and pharmacodynamics. Pharmacogenet Genomics. 2012;22(11):820-827.
  12. Ritter JM, Flower R, Henderson G, Loke YK, MacEwan D, Rang HP. Rang & Dale’s Pharmacology. 9th ed. Elsevier; 2020.
  13. P-glycoprotein substrates with a narrow therapeutic index. DrugBank Online. Accessed March 6, 2025. https://go.drugbank.com/categories/DBCAT004027
  14. Hansten PD, Tan MS, Horn JR, et al. Colchicine drug interaction errors and misunderstandings: recommendations for improved evidence-based management. Drug Saf. 2023;46(3):223-242.
  15. Ammar H, Govindu RR. A dangerous and unrecognized interaction of apixaban. Cureus. 2021;13(11):e19688.
  16. Xu Y, Zhang L, Dou X, Dong Y, Guo X. Physiologically based pharmacokinetic modeling of apixaban to predict exposure in populations with hepatic and renal impairment and elderly populations. Eur J Clin Pharmacol. 2024;80(2):261-271.
  17. Foster DJ, Bryant ZK, Conn PJ. Targeting muscarinic receptors to treat schizophrenia. Behav Brain Res. 2021;405:113201.
  18. Dyme R, Hoogerheyde J, Pavithran A, Tiwari R, Appio J, Vuocolo S. Symptom stability during treatment transition to xanomeline and trospium chloride: post hoc analysis of an inpatient trial in schizophrenia. Poster presented at: Psych Congress; September 17-21, 2025; San Diego, CA.
  19. Kaul I, Claxton A, Sauder C, et al. Long-term safety, tolerability, and efficacy of xanomeline and trospium chloride in people with schizophrenia: results from the 52-week, open-label EMERGENT-5 trial. Poster presented at: Psych Congress; October 29-November 2, 2024; Boston, MA.
  20. Horan W, Saucier C, Weiden P, et al. Patient satisfaction with xanomeline and trospium chloride treatment for schizophrenia: a qualitative interview-based study. Poster presented at: Psych Congress; October 29-November 2, 2024; Boston, MA.
  21. U.S. National Library of Medicine. An open-label study to assess the long-term safety, tolerability, and efficacy of KarXT in adult patients with schizophrenia (EMERGENT-5). ClinicalTrials.gov identifier: NCT04820309. Updated September 17, 2025. Accessed September 18, 2025. https://clinicaltrials.gov/study/NCT04820309

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

COBENFY™ is contraindicated in patients with: urinary retention; moderate or severe (Child-Pugh Class B or C) hepatic impairment; gastric retention; history of hypersensitivity to COBENFY or trospium chloride—angioedema has been reported with COBENFY and trospium chloride; and untreated narrow-angle glaucoma.

WARNINGS AND PRECAUTIONS

Risk of Urinary Retention: COBENFY can cause urinary retention. Geriatric patients and patients with clinically significant bladder outlet obstruction and incomplete bladder emptying (e.g., patients with benign prostatic hyperplasia (BPH), diabetic cystopathy) may be at increased risk of urinary retention.

COBENFY is contraindicated in patients with pre-existing urinary retention and is not recommended in patients with moderate or severe renal impairment.

In patients taking COBENFY, monitor for symptoms of urinary retention, including urinary hesitancy, weak stream, incomplete bladder emptying, and dysuria. Instruct patients to be aware of the risk and promptly report symptoms of urinary retention to their healthcare provider. Urinary retention is a known risk factor for urinary tract infections. In patients with symptoms of urinary retention, consider reducing the dose of COBENFY, discontinuing COBENFY, or referring patients for urologic evaluation as clinically indicated.

Risk of Use in Patients with Hepatic Impairment: Patients with hepatic impairment have higher systemic exposures of xanomeline, a component of COBENFY, compared to patients with normal hepatic function, which may result in increased incidence of COBENFY-related adverse reactions.

COBENFY is contraindicated in patients with moderate or severe hepatic impairment. COBENFY is not recommended in patients with mild hepatic impairment.

Assess liver enzymes prior to initiating COBENFY and as clinically indicated during treatment.

Risk of Use in Patients with Biliary Disease: In clinical studies with COBENFY, transient increases in liver enzymes with rapid decline occurred, consistent with transient biliary obstruction due to biliary contraction and possible gallstone passage.

COBENFY is not recommended for patients with active biliary disease such as symptomatic gallstones. Assess liver enzymes and bilirubin prior to initiating COBENFY and as clinically indicated during treatment. The occurrence of symptoms such as dyspepsia, nausea, vomiting, or upper abdominal pain should prompt assessment for gallbladder disorders, biliary disorders, and pancreatitis, as clinically indicated.

Discontinue COBENFY in the presence of signs or symptoms of substantial liver injury such as jaundice, pruritus, or alanine aminotransferase levels more than five times the upper limit of normal or five times baseline values.

Decreased Gastrointestinal Motility: COBENFY contains trospium chloride. Trospium chloride, like other antimuscarinic agents, may decrease gastrointestinal motility. Administer COBENFY with caution in patients with gastrointestinal obstructive disorders because of the risk of gastric retention. Use COBENFY with caution in patients with conditions such as ulcerative colitis, intestinal atony, and myasthenia gravis.

Risk of Angioedema: Angioedema of the face, lips, tongue, and/or larynx has been reported with COBENFY and trospium chloride, a component of COBENFY. In one case, angioedema occurred after the first dose of trospium chloride. Angioedema associated with upper airway swelling may be life-threatening. If involvement of the tongue, hypopharynx, or larynx occurs, discontinue COBENFY and initiate appropriate therapy and/or measures necessary to ensure a patent airway. COBENFY is contraindicated in patients with a history of hypersensitivity to trospium chloride.

Risk of Use in Patients with Narrow-angle Glaucoma: Pupillary dilation may occur due to the anticholinergic effects of COBENFY. This may trigger an acute angle closure attack in patients with anatomically narrow angles. In patients known to have anatomically narrow angles, COBENFY should only be used if the potential benefits outweigh the risks and with careful monitoring.

Increases in Heart Rate: COBENFY can increase heart rate. Assess heart rate at baseline and as clinically indicated during treatment with COBENFY.

Anticholinergic Adverse Reactions in Patients with Renal Impairment: Trospium chloride, a component of COBENFY, is substantially excreted by the kidney. COBENFY is not recommended in patients with moderate or severe renal impairment (estimated glomerular filtration rate (eGFR) <60 mL/min). Systemic exposure of trospium chloride is higher in patients with moderate and severe renal impairment. Therefore, anticholinergic adverse reactions (including dry mouth, constipation, dyspepsia, urinary tract infection, and urinary retention) are expected to be greater in patients with moderate and severe renal impairment.

Central Nervous System Effects: Trospium chloride, a component of COBENFY, is associated with anticholinergic central nervous system (CNS) effects. A variety of CNS anticholinergic effects have been reported with trospium chloride, including dizziness, confusion, hallucinations, and somnolence. Monitor patients for signs of anticholinergic CNS effects, particularly after beginning treatment or increasing the dose. Advise patients not to drive or operate heavy machinery until they know how COBENFY affects them. If a patient experiences anticholinergic CNS effects, consider dose reduction or drug discontinuation.

Most Common Adverse Reactions (≥5% and at least twice placebo): nausea, dyspepsia, constipation, vomiting, hypertension, abdominal pain, diarrhea, tachycardia, dizziness, and gastroesophageal reflux disease.

Use in Specific Populations:

 
  • Moderate or Severe Renal Impairment: Not recommended
  • Mild Hepatic Impairment: Not recommended

Pregnancy and Lactation: There is a pregnancy exposure registry that monitors outcomes in women exposed to psychiatric medications, including COBENFY, during pregnancy. Healthcare providers are encouraged to advise patients to register by calling 1-866-961-2388 or visiting https://womensmentalhealth.org/research/pregnancyregistry/atypicalantipsychotic/.

There are no available data on COBENFY use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Additionally, there are no data on the presence of xanomeline or trospium in human milk, the effects on the breastfed infant, or the effects on milk production. However, xanomeline and trospium are present in animal milk, suggesting they may also be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for COBENFY and any potential adverse effects on the breastfed infant from COBENFY or the underlying maternal condition.

COBENFY (xanomeline and trospium chloride) is available in 50mg/20mg, 100mg/20mg, and 125mg/30mg capsules.

INDICATION

COBENFY™ (xanomeline and trospium chloride) is indicated for the treatment of schizophrenia in adults.

Please see U.S. Full Prescribing Information, including Patient Information.

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Cobenfy, Cobenfy Cares, and the Cobenfy logo are trademarks of Karuna Therapeutics, Inc., a Bristol Myers Squibb company.
© 2025 Bristol-Myers Squibb Company.

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