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 trospium 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.

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)

Auvelity is a combination antidepressant medicine used to treat major depressive disorder (MDD) in adults. Auvelity contains dextromethorphan, an NMDA receptor antagonist, and bupropion, a norepinephrine-dopamine reuptake inhibitor (NDRI). 

Auvelity works by targeting multiple brain pathways involved in depression. Dextromethorphan works by blocking NMDA receptors, increasing the levels of glutamate, a chemical messenger (neurotransmitter),  to improve mood and brain connectivity. While bupropion helps dextromethorphan last longer in the body and increases dopamine and norepinephrine levels to improve depression symptoms.

Auvelity’s usual dose is 1 tablet taken once daily for 3 days, followed by 1 tablet twice daily, separated by at least 8 hours.  Tablets should be swallowed whole and not crushed or chewed.

Auvelity is a rapid-acting antidepressant that started working as early as 1 week, and patients’ depression symptoms continued to improve over time when compared to placebo in a 6-week clinical study for MDD (Study 1, NCT04019704).

Auvelity became an FDA-approved medicine on August 18, 2022, for adults with major depressive disorder (MDD).

How does Auvelity work?

Auvelity’s active ingredient, dextromethorphan, works as a N-methyl D-aspartate (NMDA) receptor antagonist and is also an agonist at the sigma-1 receptors. This helps to improve depressive symptoms by increasing glutamate levels, changing glutamate signalling, and regulating other neurotransmitters.

The second active ingredient, bupropion, helps dextromethorphan work more effectively by slowing how quickly it’s broken down in the body. It does this by blocking an enzyme called CYP2D6, allowing dextromethorphan to stay active longer. As a norepinephrine-dopamine reuptake inhibitor, bupropion also helps improve mood by increasing levels of dopamine and norepinephrine in the brain.

What is the cost of Auvelity?

The cost of prescription drugs varies depending on your insurance plan and which pharmacy you use. Refer to our price guide page for more information about the cost of Auvelity.

You may also be eligible for an Auvelity savings card or an Auvelity coupon. Ask your doctor or pharmacist if you qualify.

Auvelity side effects

Common Auvelity side effects

The most common Auvelity side effects include:

• dizziness
• diarrhea
• dry mouth
• excessive sweating
• headache
• feeling sleepy
• sexual function problems

Serious Auvelity side effects

Also, see Warnings.

Auvelity may cause serious side effects, including:

Seizures. There is a risk of seizures during treatment with this medicine. The risk is higher in people who:

• take higher doses of this medicine
• have certain medical problems
• take it with certain other medicines

Do not take Auvelity with other medicines unless your healthcare provider tells you to.
If you have a seizure during treatment, stop taking this medicine and call your healthcare provider right away. Do not take this medicine again if you have a seizure.

Increases in blood pressure (hypertension). Some people may get high blood pressure during treatment. Your healthcare provider should check your blood pressure before you start taking and during treatment.

Manic episodes. Manic episodes may happen in people with bipolar disorder who take Auvelity. Symptoms may include:

• greatly increased energy
• racing thoughts
• unusually grand ideas
• talking more or faster than usual
• severe trouble sleeping
• reckless behavior
• excessive happiness or irritability

Unusual thoughts or behaviors. One of the ingredients in Auvelity (bupropion), can cause unusual thoughts or behaviors, including delusions (believing you are someone else), hallucinations (seeing or hearing things that are not there), paranoia (feeling that people are against you), or feeling confused. If this happens to you, call your healthcare provider.

Eye problems (angle-closure glaucoma). Auvelity may cause a type of eye problem called angle-closure glaucoma in people with certain other eye conditions. You may want to undergo an eye examination to see if you are at risk and receive preventative treatment if you are. Call your healthcare provider if you have eye pain, changes in your vision, or swelling or redness in or around the eye.

Dizziness. this medicine may cause dizziness, increasing your fall risk.

Serotonin syndrome. A potentially life-threatening problem called serotonin syndrome can happen when you take Auvelity with certain other medicines. Call your healthcare provider or go to the nearest hospital emergency room right away if you have any of the following signs and symptoms of serotonin syndrome:

• agitation
• seeing or hearing things that are not there (hallucinations)
• confusion
• coma
• fast heartbeat
• changes in blood pressure
• dizziness
• sweating
• flushing
• high body temperature (hyperthermia)
• shaking (tremors), stiff muscles, or muscle twitching
• loss of coordination
• seizures
• nausea, vomiting, diarrhea

What is Lybalvi?

Lybalvi is a combination antipsychotic/opioid antagonist  prescription medicine that is used to treat adults with manic or mixed episodes associated with bipolar I disorder (either alone or in combination with valproate or lithium) or adults with schizophrenia. It is an oral tablet that is taken once a day.

Lybalvi combines two active ingredients:

• olanzapine to help manage symptoms like hallucinations, delusions, and disorganized thinking. It is an atypical antipsychotic 
• samidorphan to help mitigate weight gain often associated with olanzapine use. It is an opioid antagonist.

Lybalvi is not a controlled substance.

Lybalvi (olanzapine and samidorphan) gained FDA approval on May 28, 2021. There is no generic. 

How does Lybalvi work?

Lybalvi combines 2 ingredients, olanzapine and samidorphan, each with different mechanisms of action.

• Olanzapine is thought to affect multiple neurotransmitters in the brain, including dopamine and serotonin, to improve symptoms of bipolar disorder and schizophrenia, although the exact way it works is unknown
• Samidorphan blocks opioid receptors in the brain and gut and this action is thought to counteract some of the metabolic effects of olanzapine, particularly its tendency to increase appetite and cause weight gain. 

Lybalvi side effects

The most common side effects of Lybalvi when used to treat people with schizophrenia include:

• weight gain
• sleepiness
• dry mouth
• headache.

The most common side effects of Lybalvi when used alone to treat people with mixed or manic episodes that happen with bipolar I disorder include:

• weakness
• dry mouth
• constipation
• increased appetite
• sleepiness
• dizziness
• shaking.

Additional common side effects of Lybalvi reported in clinical trials that may happen when it is used in combination with lithium or valproate for bipolar I disorder include:

• back pain
• problems speaking
• mouth-watering
• memory problems
• numbness and tingling in your arms and legs.

Serious side effects and warnings

Lybalvi may cause serious side effects and carries a Boxed Warning for an increased risk of death in elderly people with dementia-related psychosis.

Lybalvi increases the risk of death in elderly people who have lost touch with reality (psychosis) due to confusion and memory loss (dementia). Lybalvi is not approved for the treatment of people with dementia-related psychosis.

Lybalvi may cause other serious side effects, including the following.

Stroke (cerebrovascular problems) in elderly people with dementia-related psychosis that can lead to death. Lybalvi is not approved for the treatment of people with dementia-related psychosis.

Opioid withdrawal. Do not take Lybalvi for at least 7 days after you stop taking short-acting opioids and for at least 14 days after you stop taking long-acting opioids. One of the medicines in Lybalvi (samidorphan) can cause opioid withdrawal that may be severe and cause hospitalization in people who are physically dependent on opioids. Talk to your healthcare provider if you have questions about the type of opioid you take.

Risk of life-threatening opioid overdose. You should not start taking opioids for at least 5 days after you stop treatment with Lybalvi. One of the medicines in Lybalvi (samidorphan) can increase your chance of having an opioid overdose that can cause death if you take opioids during treatment or within 5 days after stopping treatment with Lybalvi. You can accidentally overdose in 2 ways:

• Lybalvi blocks the effects of opioids, such as heroin, methadone, or opioid pain medicines. Do not take large amounts of opioids to try to overcome the opioid-blocking effects of Lybalvi. This can lead to serious injury, coma, or death.
• After you take Lybalvi, its blocking effect slowly decreases and completely goes away over time. You may be more sensitive to the effects of opioids. If you have used opioid street drugs or opioid-containing medicines in the past, using opioids in amounts that you used before treatment with Lybalvi can lead to overdose or death. It is important that you tell your family and the people closest to you of this increased sensitivity to opioids and the risk of overdose. You or someone close to you should get emergency medical help right away if you:
  • have trouble breathing
  • become very drowsy with slowed breathing
  • have slow, shallow breathing (little chest movement with breathing)
  • feel faint, very dizzy, confused, or have unusual symptoms.

Tell your healthcare provider if you are taking Lybalvi before a medical procedure or surgery.

Neuroleptic malignant syndrome (NMS), is a serious condition that can lead to death. Call your healthcare provider or go to the nearest hospital emergency room right away if you have some or all of the following signs and symptoms of NMS:

• high fever
• sweating
• stiff muscles
• changes in your breathing, pulse, heart rate, and blood pressure
• confusion.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): One of the medicines in Lybalvi (olanzapine) can cause DRESS which can cause death. Tell your healthcare provider right away if you develop any of the following symptoms of DRESS, including:

• rash
• fever
• swollen glands
• kidney problems
• liver problems
• lung problems
• heart problems.

Problems with your metabolism such as:

• high blood sugar (hyperglycemia) and diabetes. Clinical trials have shown blood sugar increases in some people who take Lybalvi. Extremely high blood sugar can lead to coma or death. Your healthcare provider should check your blood sugar before you start and regularly during treatment with Lybalvi. Call your healthcare provider if you have any of these symptoms of high blood sugar during treatment with Lybalvi:
  • feel very thirsty
  • need to urinate more than usual
  • feel very hungry
  • feel weak or tired
  • feel sick to your stomach
  • feel confused, or your breath smells fruity
• increased fat levels (cholesterol and triglycerides) in your blood. Your healthcare provider should check the fat levels in your blood before you start and regularly during treatment with Lybalvi.
• weight gain. You and your healthcare provider should check your weight before you start and often during treatment with Lybalvi.

Uncontrolled body movements (tardive dyskinesia). Lybalvi may cause movements you cannot control in your face, tongue, or other body parts. Tardive dyskinesia may not go away, even if you stop taking Lybalvi. Tardive dyskinesia may also start after you stop taking Lybalvi.

Decreased blood pressure (orthostatic hypotension) and fainting. You may feel lightheaded or faint when you rise too quickly from a sitting or lying position.

Falls. Lybalvi may make you sleepy or dizzy, may cause a decrease in your blood pressure when changing position (orthostatic hypotension), and slow your thinking and motor skills, leading to falls that can cause fractures or other injuries.

Low white blood cell count. Your healthcare provider may do blood tests during the first few months of treatment with Lybalvi.

Difficulty swallowing that can cause food or liquid to get into your lungs.

Seizures (convulsions).

Problems controlling your body temperature so that you feel too warm. See “What should I avoid while taking Lybalvi?”

Increased prolactin levels in your blood. Your healthcare provider may do blood tests to check your prolactin levels during treatment with Lybalvi.

It is not known if Lybalvi is safe or effective in children.

These are not all the possible side effects of Lybalvi. Call your healthcare provider for medical advice about side effects. You may report side effects to the FDA .

Lybalvi false positives

Tell your healthcare provider if you take a urine drug screening test because Lybalvi may cause false positive results in opioid urine screening tests.

If you do experience a positive result for an opioid urine drug screening test and you also take Lybalvi, ask the testing provider to use a different analytical technique, such as chromatography to confirm or negate positive opioid urine drug screen results.

Before taking

Do not take Lybalvi if you are taking opioids or are experiencing acute opioid withdrawal.

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

• have or had heart problems or a stroke
• use or abuse street (illegal) drugs
• have or had low or high blood pressure
• have kidney problems
• have diabetes or high blood sugar or a family history of diabetes or high blood sugar
• have or have had high levels of total cholesterol, LDL cholesterol, or triglycerides or low levels of HDL cholesterol
• have or had a low white blood cell count
• have problems swallowing
• have or had seizures (convulsions)
• have or had problems with urination or prostate problems
• have or had breast cancer
• have or had constipation or a bowel obstruction
• have or had high prolactin levels
• are pregnant or plan to become pregnant
• are breastfeeding or plan to breastfeed.

Pregnancy

Talk to your healthcare provider about the risks to you and your unborn or newborn baby if you take Lybalvi during pregnancy.

Tell your healthcare provider right away if you become pregnant or think you are pregnant during treatment with Lybalvi.

If you become pregnant during treatment with Lybalvi, talk to your healthcare provider about registering with the National Pregnancy Registry for Atypical Antipsychotics. You can register by calling 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/

Breastfeeding

Lybalvi passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby during treatment with Lybalvi.

How should I take Lybalvi?

Take Lybalvi exactly as your healthcare provider tells you to take it. Do not change the dose or stop taking Lybalvi without first talking to your healthcare provider.

• Take Lybalvi 1 time each day with or without food.
• Swallow Lybalvi tablets whole. Do not split or combine different-strength Lybalvi tablets.

Lybalvi doses

Recommended Lybalvi dosage for schizophrenia

Starting dose: Lybalvi 5-10 mg or 10-10 mg

Maintenance dosage: Lybalvi 10-10 mg, 15-10 mg, or 20-10 mg

Recommended Lybalvi dosage for Bipolar 1 disorder (manic or mixed episodes)

Starting dose: Lybalvi 10-10 mg or 15-10 mg

Maintenance dosage: Lybalvi 5-10 mg, 10-10 mg, or 15-10 mg, or 20-10 mg

Recommended Lybalvi dosage for Bipolar 1 disorder (manic or mixed episodes) with lithium or valproate

Starting dose: Lybalvi 10-10 mg

Maintenance dosage: Lybalvi 10-10 mg, or 15-10 mg, or 20-10 mg

What happens if I overdose?

If you take too much Lybalvi, call your Poison Control Center or go to the nearest hospital emergency room right away.

What should I avoid while taking Lybalvi?

Lybalvi may make you sleepy. Do not drive a car, operate machinery, or do other dangerous activities until you know how Lybalvi affects you.

Avoid drinking alcohol during treatment with Lybalvi.

Avoid getting over-heated or dehydrated.

• Do not exercise too much.
• In hot weather, stay inside in a cool place if possible.
• Stay out of the sun. Do not wear too much clothing or heavy clothing.
• Drink plenty of water.