Cobenfy

Pronunciation: co-BEN-fee
Generic name: xanomeline and trospium chloride
Dosage form: capsules (50mg/20mg, 100mg/20mg, 125mg/30mg) xanomeline/trospium

Medically reviewed by Melisa Puckey, BPharm. Last updated on Sep 30, 2024.

What is Cobenfy?

Cobenfy (xanomeline and trospium chloride) is a new treatment for schizophrenia used to improve positive and negative symptoms. Cobenfy contains xanomeline, which helps schizophrenia symptoms, and trospium, which works to reduce the side effects. Cobenfy is a new class of medicine and works differently than traditional schizophrenia medications so it does not have a boxed warning and atypical antipsychotic class warnings and precautions.

Schizophrenia is related to imbalances in messenger systems in the brain involving muscarinic acetylcholine and dopamine. It is thought that Cobenfy works by xanomeline activating muscarinic receptors  (M1 and M4) in the brain (central nervous system), which improves schizophrenia. Trospium chloride cannot enter the brain easily, so it works mainly around the body, reducing side effects by blocking muscarinic receptors.

Cobenfy has two mechanisms of action (MOA). Cobenfy's active ingredient xanomeline's MOA is a muscarinic agonist that selectively targets M1 and M4 receptors in the brain without blocking D2 receptors. Cobenfy's active ingredient tiospium chloride's MOA is a muscarinic antagonist that blocks the muscarinic receptors primarily in the peripheral tissues.

Cobenfy FDA approval is for the treatment of schizophrenia in adults. Cobenfy capsules are taken twice daily on an empty stomach, at least 1 hour before a meal or at least 2 hours after a meal. During drug development, it was named KarXT, and once approved, Bristol Myers Squibb renamed it Cobenfy.

What is the schizophrenia?

Schizophrenia is a mental illness that affects how you think, feel, and behave. Signs and symptoms usually appear first in the teenage years or early adulthood. There are three main areas of symptoms areas, which are positive (hallucinations and delusions), negative (social withdrawal, lack of enjoyment in life), and cognitive impairment (problems with concentration, memory, and decision-making).
Tradition schizophrenia medicines mainly target positive symptoms, whereas Cobenfy helps to improve positive and negative symptoms.

Cobenfy side effects 

Common Cobenfy side effects

The most common Cobenfy side effects were feeling sick (nausea), indigestion (dyspepsia), constipation, vomiting, high blood pressure (hypertension), abdominal pain, diarrhea, fast heart rate (tachycardia), dizziness, and heartburn (gastrointestinal reflux disease). These side effects occurred in 5% or more of patients, and at least twice the placebo rates in clinical trials.

Serious Cobenfy side effects

Urinary Retention: Cobenfy cause the side effect of urinary retention. Patients may be at increased risk of urinary retention if they are geriatric patients, patients with clinically significant bladder outlet obstruction and incomplete bladder emptying (e.g., patients with benign prostatic hyperplasia (BPH), or diabetic cytopathic patients). It should not be used in patients with pre-existing urinary retention and is not recommended in patients with moderate or severe renal impairment.

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 an increased incidence of adverse reactions.

It should not be used in patients with moderate or severe hepatic impairment and is not recommended in patients with mild hepatic impairment. Assess liver enzymes before starting treatment and as clinically indicated during treatment.

Biliary Disease: In clinical studies with Cobenfy, side effects included transient increases in liver enzymes with rapid decline occurred, consistent with transient biliary obstruction due to biliary contraction and possible gallstone passage.

It is not recommended for patients with active biliary disease, such as symptomatic gallstones. Assess liver enzymes and bilirubin before starting treatment 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.

Cobenfy should be stopped 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 which like other antimuscarinic agents, may decrease gastrointestinal motility. Use this medicine with caution in patients with gastrointestinal obstructive disorders due to the risk of gastric retention. Use these capsules 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, an ingredient 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 medicine and initiate appropriate therapy and/or measures necessary to ensure a patent airway. This medicine is contraindicated in patients with a history of hypersensitivity to trospium chloride.

Patients with Narrow-angle Glaucoma: Pupillary dilation may occur due to the anticholinergic effects of this medicine. 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 so assess heart rate at baseline and as clinically indicated during treatment with this medicine.

Anticholinergic Adverse Reactions in Patients with Renal Impairment: Trospium chloride, an active ingredient in this medicine, is substantially excreted by the kidney. It 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, an active ingredient in this medicine 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. Patients should not to drive or operate heavy machinery until they know how this medicine affects them. If a patient experiences anticholinergic CNS effects, consider dose reduction or drug discontinuation.

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Who should not take this medicine?

Cobenfy should not be taken if you have:

• urinary retention 
• moderate or severe hepatic impairment 
• gastric retention  
• history of hypersensitivity to Cobenfy or trospium chloride (4) 
• untreated narrow-angle glaucoma 

Before taking this medicine

Before taking this Cobenfy, tell your healthcare provider about all of your medical conditions, including if you: 

• have an enlarged prostate, problems passing urine, or a blockage in your urinary bladder 
• have liver problems 
• have or had gallstones or problems with your bile ducts or pancreas 
• have stomach or intestinal problems including constipation, ulcerative colitis, slow emptying of your stomach, or myasthenia gravis 
• have an eye condition called narrow-angle glaucoma 
• have kidney problems 

Pregnancy

Tell your healthcare provider if you are pregnant or plan to become pregnant, as it is not known if this Cobenfy may harm your unborn baby. If you become pregnant or think you are pregnant during treatment with this medicine, tell your healthcare provider. There is a pregnancy exposure registry for women who take this medicine during pregnancy. The purpose of this registry is to collect information about the health of women exposed to Cobenfy and their baby. If you become pregnant during treatment while taking this medicine, your healthcare provider will register you by calling 1-866-961-2388. 

Breastfeeding

Tell your healthcare provider if you are breastfeeding or plan to breastfeed. It is not known if Cobenfy passes into your breast milk or if it can harm your baby.

How should I take Cobenfy?

• Take capsule 2 times each day at least 1 hour before a meal or at least 2 hours after a meal. 
• Do not open the capsules. 
• Take this medicine exactly as your healthcare provider tells you. Do not change the dose or stop taking this medicine without first talking to your healthcare provider. 

Cobenfy Dosing Information

Recommended starting Cobenfy dosage

•  50mg/20mg orally twice daily for at least two days, then increase the dosage to 100mg/20mg twice daily for at least five days.
• Dosage may be increased to 125 mg/30 mg orally twice daily based on patient tolerability and response. 
• See the full prescribing information for the recommended titration and maximum recommended dosage.

Geriatric patients: Recommended starting dosage is 50 mg/20mg orally twice daily. Consider a slower titration. The maximum recommended dosage is 100mg/20mg twice daily. (2.3)

General dosing information

• Take at least 1 hour before a meal or at least 2 hours after a meal. 
• Do not open capsules. (2.2) 
• Assess liver enzymes and bilirubin before starting treatment with this medicine and as clinically indicated during treatment. 
• Assess heart rate at baseline and as clinically indicated during treatment with Cobenfy.

Cobenfy capsules are available in strengths: 50mg/20mg, 100mg/20mg, 125mg/30mg (xanomeline/trospium chloride)

What happens if I overdose?

If you take too much Cobenfy call your healthcare provider or Poison Help Line at 1-800-222-1222, or go to the nearest hospital emergency room right away.

Interactions

Tell your healthcare provider about all of the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Cobenfy and other medicines may affect each other, causing side effects. Know the medicines you take and keep a list of them to show your healthcare provider or pharmacist when you get a new medicine.

Medications that interact with Cobenfy include:

Drugs Eliminated by Active Tubular Secretion: Monitor for increased frequency and/ or severity of adverse reactions related to Cobenfy and to drugs eliminated by active tubular secretion. 

Strong CYP2D6 Inhibitors: Monitor for increased frequency and/or severity of Cobenfy related adverse reactions.

Sensitive Substrates of CYP3A4 or P-glycoprotein: Monitor for increased frequency and/ or severity of adverse reactions from these substrates. 

Antimuscarinic Drugs: Monitor for increased frequency or severity of anticholinergic adverse reactions.

Not all possible interactions are listed here. Other drugs may interact with Cobenfy, including prescription and over-the-counter medicines, vitamins, and herbal products. 

Storage

Store at room temperature between 68°F to 77°F (20°C to 25°C)

Cobenfy ingredients 

Active ingredients:  xanomeline and trospium chloride 

Inactive ingredients: ascorbic acid, lactose monohydrate, microcrystalline cellulose, and talc Capsule shell: contains black iron oxide (only100mg/20mg), hypromellose, red iron oxide, titanium dioxide, and yellow iron oxide (only 50mg/20mg and 100mg/20mg)

Company

Cobenfy Bristol-Myers Squibb Company Princeton, NJ 08543 USA.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Medical Disclaimer