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)

Clozapine is an antipsychotic medicine. It works by changing the actions of chemicals in the brain.

Clozapine is used to treat schizophrenia in adults after other treatments have failed.

Clozapine is also used to reduce the risk of suicidal behavior in adults with schizophrenia or similar disorders.

Warnings

Clozapine affects your immune system. You may get infections more easily, even serious or fatal infections. Call your doctor if you have a fever, sore throat, weakness, or lack of energy.

Clozapine can increase your risk of seizure, especially at high doses. Avoid any activity that could be dangerous if you have a seizure or lose consciousness.

Clozapine can cause serious heart problems. Call your doctor right away if you have chest pain, trouble breathing, fast or pounding heartbeats or sudden dizziness.

Clozapine is not approved for use in older adults with dementia-related psychosis.

Before taking this medicine

Clozapine may increase the risk of death in older adults with dementia-related psychosis and is not approved for this use.

You should not take clozapine if you are allergic to it.

To make sure this medicine is safe for you, tell your doctor if you have ever had:

• heart problems, high blood pressure,
• a heart attack or stroke (including “mini-stroke”);
• long QT syndrome (in you or a family member);
• an electrolyte imbalance (such as low levels of potassium or magnesium in your blood);
• a seizure, head injury, or brain tumor;
• diabetes, or risk factors such as being overweight or having a family history of diabetes;
• high cholesterol or triglycerides;
• constipation or problems with your bowel movements;
• liver or kidney disease;
• an enlarged prostate or urination problems;
• glaucoma;
• malnourishment or dehydration; or
• if you smoke.

Taking antipsychotic medicine in the last 3 months of pregnancy may cause breathing problems, feeding problems, or withdrawal symptoms in the newborn. However, you may have withdrawal symptoms or other problems if you stop taking your medicine during pregnancy. If you get pregnant, tell your doctor right away. Do not stop taking clozapine without your doctor’s advice.

You should not breastfeed while using this medicine.

Clozapine is not approved for use by anyone younger than 18 years old.

How should I take clozapine?

Take clozapine exactly as prescribed by your doctor. Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose.

You may take clozapine with or without food.

Shake the oral suspension (liquid) for 10 seconds before you measure a dose. Use the dosing syringe provided, or use a medicine dose-measuring device (not a kitchen spoon).

Remove an orally disintegrating tablet from the package only when you are ready to take the medicine. Place the tablet in your mouth and allow it to dissolve, without chewing. Swallow several times as the tablet dissolves.

Clozapine affects your immune system and can have long lasting effects on your body. You may get infections more easily, even serious or fatal infections. You may need frequent medical tests while using this medicine and for a short time after your last dose.

You should not stop using clozapine suddenly. Follow your doctor’s instructions about tapering your dose.

If you start taking clozapine again after 2 or more days off the medicine, you may need to use a lower dose than when you stopped. Follow your doctor’s dosing instructions very carefully.

Your doctor may recommend you use a laxative while taking clozapine. Use only the type of laxative your doctor recommends.

Store at room temperature away from moisture and heat.

Dosing information

Usual Adult Dose for Schizophrenia:

Initial dose: 12.5 mg orally once or twice a day
Titration and Maintenance dose: May increase total daily dose in increments of 25 mg to 50 mg per day to a target dose of 300 mg to 450 mg per day (administered in divided doses) by the end of week 2. Subsequent dose increases can be in increments of up to 100 mg once or twice weekly.
Maximum dose: 900 mg per day

Comments:
-The absolute neutrophil count (ANC) must be 1500/microL or greater for the general population and at least 1000/microL for patients with documented Benign Ethnic Neutropenia (BEN) prior to initiating treatment; to continue therapy, the ANC must be monitored regularly.
-A low starting dose, gradual titration, and divided doses are necessary to minimize the risk of orthostatic hypotension, bradycardia, and syncope.
-When therapy is interrupted for 2 or more days, re-initiate with 12.5 mg once or twice a day; based on tolerability, a dose that is restarted may be increased to a previously therapeutic dose more quickly than it was for initial treatment.

Uses:
-For the treatment of severely ill patients with schizophrenia who fail to respond adequately to standard antipsychotic treatment
-To reduce the risk of recurrent suicidal behavior in patients with schizophrenia or schizoaffective disorder, who are judged to be at chronic risk for re-experiencing suicidal behavior, based on history and recent clinical state

What happens if I miss a dose?

Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.

If you miss taking clozapine for more than 2 days in a row, call your doctor before you start taking it again.

Get your prescription refilled before you run out of medicine completely.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line .

Overdose symptoms may include drowsiness, confusion, fast heartbeats, feeling light-headed, weak or shallow breathing, drooling, choking, or seizure.

What to avoid

Do not drink alcohol. Dangerous side effects or death could occur.

Avoid coffee, tea, cola, energy drinks or other sources of caffeine.

Avoid driving or hazardous activity until you know how clozapine will affect you. Dizziness or drowsiness can cause falls, accidents, or severe injuries.

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy.

Clozapine side effects

Get emergency medical help if you have signs of an allergic reaction to clozapine (hives, difficult breathing, swelling in your face or throat) or a severe skin reaction (fever, sore throat, burning eyes, skin pain, red or purple skin rash with blistering and peeling).

You may get infections more easily, even serious or fatal infections. Call your doctor right away if you have signs of infection such as:

• fever, flu-like symptoms, extreme weakness;
• mouth sores, skin sores;
• new or worsening cough, trouble breathing;
• pain or burning when you urinate; or
• vaginal itching or discharge.

Further doses may be delayed until your infection clears up.

High doses or long-term use of clozapine can cause a serious movement disorder that may not be reversible. The longer you use clozapine, the more likely you are to develop this disorder, especially if you are a woman or an older adult.

Clozapine can increase your risk of seizure, especially at high doses. Avoid any activity that could be dangerous if you have a seizure or lose consciousness.

Call your doctor at once if you have:

• uncontrolled muscle movements in your face (chewing, lip smacking, frowning, tongue movement, blinking or eye movement);
• a seizure (blackout or convulsions);
• severe constipation;
• dry or hard bowel movements, or painful gas;
• nausea, vomiting, stomach pain or bloating;
• heart problems – chest pain, fast or pounding heartbeats, fluttering in your chest, slow heartbeats, shortness of breath, and sudden dizziness (like you might pass out);
• liver problems – loss of appetite, stomach pain (upper right side), tiredness, itching, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);
• severe nervous system reaction – very stiff (rigid) muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, feeling like you might pass out; or
• signs of a blood clot in the lung – chest pain, sudden cough, wheezing, rapid breathing, coughing up blood.

Untreated constipation may lead to serious bowel complications, hospitalization, or death. Tell your doctor right away if you are not having bowel movements at least 3 times per week.

Common clozapine side effects may include:

• weight gain;
• dizziness, tremor;
• fast heart rate;
• headache, drowsiness;
• nausea, constipation;
• dry mouth, or increased salivation;
• vision problems; or
• fever, increased sweating.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.

What other drugs will affect clozapine?

When you start or stop taking clozapine, your doctor may need to adjust the doses of any other medicines you take on a regular basis.

Clozapine can cause a serious heart problem. Your risk may be higher if you also use certain other medicines for infections, asthma, heart problems, high blood pressure, depression, mental illness, cancer, malaria, or HIV.

Using clozapine with other drugs that make you drowsy or slow your breathing can cause dangerous side effects or death. Ask your doctor before using opioid medication, a sleeping pill, a muscle relaxer, cold or allergy medicine, or medicine for anxiety or seizures.

Many drugs can affect clozapine. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed here. Tell your doctor about all your current medicines and any medicine you start or stop using.

Caplyta is used to treat adults with schizophrenia, depression associated with bipolar I or bipolar II disorder (manic depression), or along with antidepressant medicines to treat major depressive disorder (MDD). Caplyta is a once-daily capsule. When used to treat bipolar disorder, this medicine can be used alone or with lithium or valproic acid.

Clinical trials have reported improvement in the positive and negative symptoms of schizophrenia within one week of starting Caplyta (lumateperone), but symptoms may take longer to resolve when used for depression .

Important Information

Caplyta carries a Boxed Warning for increased risk of death in elderly patients with dementia-related psychosis and an increased risk of suicidal thoughts and behaviors in younger patients.

• Increased risk of death in elderly people with dementia related psychosis. Medicines like Caplyta can raise the risk of death in elderly people who have lost touch with reality (psychosis) due to confusion and memory loss (dementia). Caplyta is not approved for the treatment of people with dementia-related psychosis.
• Increased risk of suicidal thoughts and actions. Caplyta and antidepressant medicines increase the risk of suicidal thoughts and actions in people 24 years of age and younger, especially within the first few months of treatment or when the dose is changed.
  • Depression and other mental illnesses are the most important causes of suicidal thoughts and actions.

How can I watch for and try to prevent suicidal thoughts and actions in myself or a family member?

• • Pay close attention to any changes, especially sudden changes in mood, behaviors, thoughts, or feelings. This is very important when Caplyta or the antidepressant medicine is started or when the dose is changed.
  • Call your healthcare provider right away to report new or sudden changes in mood, behavior, thoughts, or feelings, or if you develop suicidal thoughts or actions.
  • Keep all follow-up visits with your healthcare provider as scheduled. Call your healthcare provider between visits as needed, especially if you have concerns about symptoms.

Call a healthcare provider right away if you or your family member has any of the following symptoms, especially if they are new, worse, or worry you:

• • Thoughts about suicide or dying
  • New or worse depression
  • Feeling very agitated or restless
  • Trouble sleeping
  • Acting aggressively, being angry, or violent
  • An extreme increase in activity and talking (mania)
  • Suicide attempts
  • New or worse anxiety
  • Panic attacks
  • New or worse irritability
  • Acting on dangerous impulses
  • Other unusual changes in behavior or mood.

Side Effects

Common side effects

The most common side effects of Caplyta are:

• Sleepiness
• Dizziness
• Nausea
• Dry mouth
• Feeling tired
• Diarrhea.

Caplyta may cause fertility problems in females and males. Talk to your healthcare provider if this is a concern for you.

Caplyta does not appear to be associated with weight gain like many other antipsychotics are.

Serious Side Effects

Caplyta can also cause the following other serious side effects:

• Stroke (cerebrovascular problems) in elderly people with dementia-related psychosis, which can lead to death. Caplyta is not approved for the treatment of people with dementia-related psychosis.
• Neuroleptic malignant syndrome (NMS) 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
  • Confusion
  • Changes in your breathing, heart rate, and blood pressure
  • Stiff muscles
  • Increased sweating.
• Uncontrolled body movements (tardive dyskinesia). Caplyta may cause movements that you cannot control in your face, tongue, or other body parts. Tardive dyskinesia may not go away, even if you stop taking Caplyta. Tardive dyskinesia may also start after you stop taking Caplyta.
• Problems with your metabolism, such as:
  • High blood sugar (hyperglycemia) and diabetes. Increases in blood sugar can happen in some people who take Caplyta. Extremely high blood sugar can lead to coma or death. Your healthcare provider should check your blood sugar before you start, or soon after you start Caplyta, and then regularly during long-term treatment with Caplyta.

Call your healthcare provider if you have any of these symptoms of high blood sugar during treatment with Caplyta:

• • • 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, or soon after you start Caplyta, and then periodically during treatment with Caplyta.
  • Weight gain. Weight gain is uncommon, but you and your healthcare provider should check your weight before you start and regularly during treatment with Caplyta.
• Low white blood cell counts. Your healthcare provider may do blood tests during the first few months of treatment with Caplyta.
• Decreased blood pressure (orthostatic hypotension). You may feel lightheaded or faint when you rise too quickly from a sitting or lying position after taking Caplyta.
• Falls. Caplyta may make you sleepy or dizzy, may cause a decrease in your blood pressure when changing position (orthostatic hypotension), and can slow your thinking and motor skills, which may lead to falls that can cause fractures or other injuries.
• Seizures (convulsions). Caplyta may increase your risk of seizures.
• Sleepiness, drowsiness, feeling tired, difficulty thinking, and doing normal activities.
• Difficulty swallowing, which can cause food or liquid to get into your lungs. Tell your healthcare provider immediately if this happens.
• Problems controlling your body temperature so that you feel too warm.

This is not a complete list of Caplyta side effects, and others may occur. Call your doctor for medical advice about side effects.

How Does Caplyta Work?

Caplyta works by changing the activity of neurotransmitters in the brain, such as dopamine, glutamate, and serotonin, to increase or balance their levels. This helps to relieve symptoms such as hallucinations, delusions, and disorganized thoughts associated with schizophrenia, and low mood associated with depression. 

Caplyta belongs to the drug class called atypical antipsychotics.

Caplyta Cost and Insurance Coverage

Eligible patients may pay as little as $0 for 30-day or 90-day prescriptions with the Caplyta Savings Card. 

• Text Caplyta to 26789 to download a digital Caplyta Savings Card to your phone and receive useful text messages about your prescription.
• 90% of Americans with commercial insurance have coverage for Caplyta.
• Caplyta is covered for more than 99% of people with Medicaid and Medicare Part D.

Before taking this medicine

Do not use Caplyta if you are allergic to Caplyta, lumateperone, or any of the ingredients in the capsules. Caplyta may also increase the risk of death in older adults with dementia-related psychosis and is not approved for this use.

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

• Have or have had heart problems or a stroke
• Have or have had low or high blood pressure
• Have or have had 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 have had a low white blood cell count
• Have or have had seizures (convulsions)
• Have or have had kidney or liver problems
• Are pregnant or plan to become pregnant
• Are breastfeeding or plan to breastfeed.

Pregnancy

Caplyta may harm your unborn baby. Taking Caplyta during your third trimester of pregnancy may cause your baby to have abnormal muscle movements or withdrawal symptoms after birth. Talk to your healthcare provider about the risk to your unborn baby if you take Caplyta during pregnancy.

• Tell your healthcare provider if you become pregnant or think you are pregnant during treatment with Caplyta.
• There is a pregnancy registry for females who are exposed to Caplyta during pregnancy. If you become pregnant during treatment, 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 go to https://womensmentalhealth.org/research/pregnancyregistry/

Breastfeeding

Caplyta passes into your breast milk. Talk to your healthcare provider about the risks and benefits of breastfeeding and the best way to feed your baby during treatment with Caplyta.

Fertility

This medicine may affect fertility in both men and women.

How should I take Caplyta?

Take Caplyta as prescribed by your healthcare provider. Follow all directions on your prescription label and read all medication guides or instruction sheets. Use the medicine exactly as directed.

• Take Caplyta 1 time each day with or without food.
• You can take Capylta in the morning or at night, but try to take it around the same time each day.

What happens if I miss a dose?

Take Caplyta as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.

What happens if I take too much?

If you take too much Caplyta, call your healthcare provider or Poison Help Line or go to the nearest hospital emergency room right away.

Dosing Information

Dose of Caplyta for Schizophrenia

• 42 mg orally once daily with or without food.

Dose of Caplyta for Depression Associated with MDD or Bipolar I or II Disorder

• 42 mg orally once daily with or without food.
• Use in addition to antidepressants for MDD.
• Use as monotherapy or as adjunctive therapy with lithium or valproate for Bipolar I or II disorder.

Liver Impairment

• Moderate to severe liver disease: 21 mg orally once daily with or without food.

What to avoid while taking Caplyta?

Do not drive, operate machinery, or do other dangerous activities until you know how Caplyta affects you. Caplyta may make you drowsy.

Do not become too hot or dehydrated during treatment with Caplyta.

• 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

What other drugs will affect Caplyta?

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Caplyta and other medicines may affect each other, causing possible serious side effects. Caplyta may affect the way other medicines work, and other medicines may affect how Caplyta works. Especially tell your doctor if you take:

• An antibiotic, antifungal, or antiviral medicine
• Blood pressure medication
• Bronchodilator asthma medication
• Cold or allergy medicine (Benadryl and others)
• Medicine to treat depression, anxiety, mood disorders, or mental illness
• Medicine to treat an overactive bladder
• Medicine to treat Parkinson’s disease
• Medicine to treat stomach problems, motion sickness, or irritable bowel syndrome
• Seizure medication

Brexpiprazole is used to treat major depressive disorder in adults (in addition to other medications), schizophrenia in adults and children aged 13 years and older, and agitation that may happen with dementia due to Alzheimer’s disease. It is an oral tablet taken once a day.

Brexpiprazole belongs to the drug class called atypical antipsychotics.

Brexpiprazole first gained FDA approval on July 10, 2015 under the brand name Rexulti. There is a generic brexpiprazole but it is only approved for adults with depression or schizophrenia. The brand Rexulti has additional approvals for adolescents 13 years and older with schizophrenia and for Alzheimer’s disease-related agitation.

Mechanism

Brexpiprazole works by correcting the imbalance of natural chemical messengers  (neurotransmitters), such as dopamine and serotonin in the brain. This imbalance is thought to be associated with several psychiatric disorders such as schizophrenia, depression, and agitation associated with Alzheimer’s disease.

Brexpiprazole uses

Brexpiprazole is an atypical antipsychotic used:

• along with antidepressant medicines to treat major depressive disorder (MDD) in adults
• to treat schizophrenia in adults and children ages 13 years and older
• to treat agitation that may happen with dementia due to Alzheimer’s disease.

Brexpiprazole should not be used as an “as needed” treatment for agitation that may happen with dementia due to Alzheimer’s disease.

Clinical trials have not been conducted in children so it is not known if brexpiprazole is safe and effective for the treatment of MDD in children under the age of 18 or for the treatment of schizophrenia in children under 13 years.

Brexpiprazole side effects

The most common side effects of brexpiprazole are:

• weight gain
• sleepiness
• dizziness
• common cold symptoms
• restlessness or feeling like you need to move (akathisia).

Serious side effects and warnings

Brexpiprazole carries a Boxed Warning for an increased risk of death in elderly patients with dementia-related psychosis.

Increased risk of death in elderly people with dementia-related psychosis. Trials have reported medicines like brexpiprazole can raise the risk of death in elderly people who have lost touch with reality (psychosis) due to confusion and memory loss (dementia). Brexpiprazole is not approved for dementia-related psychosis without agitation that may happen with Alzheimer’s disease.

Increased risk of suicidal thoughts and actions. Brexpiprazole and antidepressant medicines increase the risk of suicidal thoughts and actions in people 24 years of age and younger, especially within the first few months of treatment or when the dose is changed. Depression and other mental illnesses are the most important causes of suicidal thoughts and actions.

• Pay close attention to any changes, especially sudden changes in mood, behaviors, thoughts, or feelings, or if you develop suicidal thoughts or actions. This is very important when brexpiprazole or the antidepressant medicine is started or when the dose is changed.
• Call your healthcare provider right away to report new or sudden changes in mood, behavior, thoughts, or feelings, or if you develop suicidal thoughts or actions.
• Keep all follow-up visits with your healthcare provider as scheduled. Call your healthcare provider between visits as needed, especially if you have concerns about symptoms.

Call a healthcare provider right away if you or your family member have any of the following symptoms, especially if they are new, worse, or worry you:

• thoughts about suicide or dying
• attempts to commit suicide
• new or worsening depression
• new or worsening anxiety
• feeling very agitated or restless
• panic attacks
• trouble sleeping (insomnia)
• new or worsening irritability
• acting aggressive, being angry, or violent
• acting on dangerous impulses
• an extreme increase in activity or talking (mania)
• other unusual changes in behavior or mood.

Other serious side effects of brexpiprazole include the following.

Cerebrovascular problems (these involve the blood vessels of the brain), including stroke, in elderly people with dementia-related psychosis that can lead to death.

Neuroleptic malignant syndrome (NMS), which is a rare and life-threatening reaction to antipsychotic drugs. 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
• stiff muscles
• confusion
• changes in your pulse, blood pressure, heart rate, and breathing
• increased sweating.

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

Brexpiprazole may also cause problems with your metabolism such as:

• High blood sugar (hyperglycemia) and diabetes. Increases in blood sugar can happen in some people who take brexpiprazole. Extremely high blood sugar can lead to coma or death. Your healthcare provider should check your blood sugar before you start, or soon after you start brexpiprazole and then regularly during long term treatment with brexpiprazole. Call your healthcare provider if you have any of these symptoms of high blood sugar during treatment with brexpiprazole:
  • feel very thirsty
  • feel very hungry
  • feel sick to your stomach
  • need to urinate more than usual
  • feel weak or tired
  • 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, or soon after you start brexpiprazole, and then periodically during treatment with brexpiprazole.
• Weight gain. You and your healthcare provider should check your weight before you start and often during treatment with brexpiprazole.

Unusual and uncontrollable (compulsive) urges. Some people taking brexpiprazole have had strong unusual urges, to gamble and gambling that cannot be controlled (compulsive gambling). Other compulsive urges include sexual urges, shopping, and eating or binge eating. If you or your family members notice that you are having new or unusual strong urges or behaviors, talk to your healthcare provider.

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

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

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

Seizures (convulsions). Brexpiprazole may increase your risk of seizures.

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

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

Sleepiness, drowsiness, feeling tired, difficulty thinking and doing normal activities. See “What should I avoid while taking brexpiprazole?”

Brexpiprazole may harm an unborn baby.

These are not all the possible side effects of brexpiprazole. Call your doctor for medical advice about side effects.

Before taking

Do not take brexpiprazole if you are allergic to brexpiprazole, Rexulti, or any inactive ingredient in the tablets.

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

• have or have had heart problems or a stroke
• have or have had low or high blood pressure
• have or have had 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 have had seizures (convulsions)
• have or have had kidney or liver problems
• have or have had a low white blood cell count
• are pregnant or plan to become pregnant
• are breastfeeding or plan to breastfeed.

Pregnancy

Brexpiprazole may harm your unborn baby. Taking brexpiprazole during your third trimester of pregnancy may cause your baby to have abnormal muscle movements or withdrawal symptoms after birth. Talk to your healthcare provider about the risk to your unborn baby if you take brexpiprazole during pregnancy.

Tell your healthcare provider if you become pregnant or think you are pregnant during treatment with brexpiprazole.

There is a pregnancy exposure registry for women who are exposed to brexpiprazole during pregnancy. If you become pregnant during treatment with brexpiprazole, talk to your healthcare provider about registering with the National Pregnancy Registry for Psychiatric Medications. You can register by calling 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-researchprograms/pregnancyregistry/.

Breastfeeding

It is not known if brexpiprazole passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby during treatment with brexpiprazole.

How should I take brexpiprazole?

Take brexpiprazole exactly as your healthcare provider tells you to take it. Your healthcare provider may change your dose if needed. Do not change the dose or stop taking brexpiprazole without first talking to your healthcare provider.

• Take brexpiprazole 1 time each day.
• Brexpiprazole may be taken with or without food.

Brexpiprazole dosing

The dosage of Brexpiprazole varies depending on the condition being treated and the age of the patient.

The dosage may need to be adjusted for moderate to severe liver disease, kidney disease, and interacting medications.

Note that generic brexpiprazole is only approved for depression and schizophrenia in adults, not for all the uses Rexulti is approved for.

What should I avoid while taking brexpiprazole?

Do not drive a car, operate machinery, or do other dangerous activities until you know how brexpiprazole affects you. Brexpiprazole may make you feel drowsy.

Do not become too hot or dehydrated during treatment with brexpiprazole.

• 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.

What happens if I take too much brexpiprazole?

If you take too much brexpiprazole, call your healthcare provider or Poison Help Line or go to the nearest hospital emergency room right away.

What other drugs affect brexpiprazole?

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Brexpiprazole and other medicines may affect each other causing possible serious side effects. Brexpiprazole may affect the way other medicines work, and other medicines may affect how brexpiprazole works. Especially tell your healthcare provider if you take:

• Strong CYP2D6 or CYP3A4 inhibitors, such as clarithromycin, diltiazem, erythromycin, itraconazole, ketoconazole, paroxetine, fluoxetine, or bupropion. Administer half the recommended dosage of brexpiprazole
• Strong/moderate CYP2D6 with strong/moderate CYP3A4 inhibitors: Administer one-quarter of the recommended dosage of brexpiprazole
• strong/moderate CYP3A4 inhibitors and you are a known CYP2D6 poor metabolizer: Administer one-quarter of the recommended dosage of brexpiprazole
• Strong CYP3A4 inducers, such as phenobarbital, phenytoin, rifampicin, St. John’s Wort, or glucocorticoids. Double the recommended dosage of brexpiprazole and further adjust based on the clinical response.

Your healthcare provider can tell you if it is safe to take brexpiprazole with your other medicines. Do not start or stop any medicines during treatment with brexpiprazole without first talking to your healthcare provider. Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

Storage

Store brexpiprazole tablets at room temperature between 68°F to 77°F (20°C to 25°C). Keep out of the reach of children.

Ingredients

Brexpiprazole is available as the brand Rexulti and as generic brexpiprazole.

Active ingredient: brexpiprazole

Inactive ingredients (Rexulti brand): lactose monohydrate, corn starch, microcrystalline cellulose, hydroxypropyl cellulose, low-substituted hydroxypropyl cellulose, magnesium stearate, hypromellose, and talc. For color: titanium dioxide, iron oxide, and ferrosoferric oxide.

Inactive ingredients (generic brexpiprazole [Ajanta Pharma USA Inc.]: lactose monohydrate, microcrystalline cellulose, hydroxypropyl cellulose unspecified, low-substituted hydroxypropyl cellulose unspecified, magnesium stearate, Hypromellose unspecified, talc, titanium dioxide, propylene glycol, ferric oxide red

Inactive ingredients (generic brexpiprazole [Amneal Pharmaceuticals NY LLC]: ferric oxide red, ferric oxide yellow, ferrosoferric oxide, hypromellose unspecified, lactose monohydrate, microcrystalline cellulose, magnesium stearate, corn starch,  talc, titanium dioxide.

Who makes brexpiprazole?

Rexulti (the brand of brexpiprazole) is manufactured through a partnership between two pharmaceutical companies:

• Otsuka Pharmaceutical (Tokyo, Japan)
  • Also makes Abilify, Samsca, and other medications
• Lundbeck (Copenhagen, Denmark)
  • Also makes Lexapro, Vyepti, and other medications.

These companies have a long-standing partnership in developing psychiatric medications, with Rexulti being one of their major joint products.

Generic brexpiprazole is packaged by Ajanta Pharma USA Inc. and Amneal Pharmaceuticals NY LLC.