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