Cariprazine

Before taking cariprazine,

• tell your doctor and pharmacist if you are allergic to cariprazine, any other medications, or any of the ingredients in cariprazine capsules. Ask your pharmacist for a list of the ingredients.
• tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, and nutritional supplements you are taking or plan to take. Be sure to mention any of the following: anticholinergics such as atropine (Atropen, Duodote, Enlon-Plus), benztropine (Cogentin), dicyclomine (Bentyl), glycopyrrolate (Robinul), hyoscyamine, propantheline (Pro-Banthine), and scopolamine (Transderm Scop); carbamazepine (Carbatrol, Epitol, Equetro, Tegretol, Teril); itraconazole (Onmel, Sporanox); ketoconazole; medications for blood pressure; and rifampin (Rifadin, Rimactane, in Rifamate, Rifater). Your doctor may need to change the doses of your medications or monitor you carefully for side effects. Many other medications may also interact with cariprazine, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list.
• tell your doctor what herbal products you are taking, especially St. John's wort.
• tell your doctor if you have a low number of white blood cells, or if you have ever developed a low number of white blood cells as a side effect of a medication that you took. Tell your doctor if you have or have ever had seizures; a stroke; a ministroke; a heart attack; heart failure; irregular heartbeat;; trouble keeping your balance; difficulty swallowing;or heart, liver, or kidney disease. Also tell your doctor if you have severe vomiting, diarrhea or signs of dehydration now, or if you develop these symptoms at any time during your treatment.
• tell your doctor if you are pregnant, especially if you are in the last few months of your pregnancy, or if you plan to become pregnant or are breastfeeding. If you become pregnant while taking cariprazine, call your doctor. Cariprazine may cause problems in newborns following delivery if it is taken during the last months of pregnancy.
• you should know that cariprazine may make you drowsy, and may affect your ability to think clearly, make decisions, and react quickly. Do not drive a car or operate machinery during your treatment with cariprazine until you know how this medication affects you.
• you should know that you may experience hyperglycemia (increases in your blood sugar) while you are receiving this medication, even if you do not already have diabetes. If you have schizophrenia, you are more likely to develop diabetes than people who do not have schizophrenia and receiving cariprazine or similar medications may increase this risk. Tell your doctor immediately if you have any of the following symptoms during your treatment: extreme thirst, frequent urination, extreme hunger, blurred vision, or weakness. It is very important to call your doctor as soon as you have any of these symptoms, because high blood sugar can cause a serious condition called ketoacidosis. Ketoacidosis may become life-threatening if it is not treated at an early stage. Symptoms of ketoacidosis include: dry mouth, nausea and vomiting, shortness of breath, breath that smells fruity, and decreased consciousness.
• you should know that cariprazine may cause dizziness, lightheadedness, and fainting when you get up too quickly from a lying position. This is more common when you first start taking cariprazine. To avoid this problem, get out of bed slowly, resting your feet on the floor for a few minutes before standing up.
• you should know that cariprazine may make it harder for your body to cool down when it gets very hot. Tell your doctor if you plan to do vigorous exercise or be exposed to extreme heat. Be sure to drink plenty of water and call your doctor if you experience any of the following symptoms: feeling very hot, sweating heavily, not sweating even though it is hot, dry mouth, excessive thirst, or decreased urination.

Unless your doctor tells you otherwise, continue your normal diet.

Keep all appointments with your doctor and the laboratory. Your doctor may order certain lab tests to check your body's response to cariprazine.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

• Vraylar^®

Cariprazine is an antipsychotic medication that affects chemicals in the brain.

Cariprazine is used to treat schizophrenia. This medicine is also used to treat manic or mixed episodes in people with bipolar disorder type I.

Cariprazine may also be used for purposes not listed in this medication guide.

Cariprazine is not approved for use in psychotic conditions related to dementia. Cariprazine may increase the risk of death in older adults with dementia-related conditions.

Cariprazine is not approved for use in psychotic conditions related to dementia. Cariprazine may increase the risk of death in older adults with dementia-related conditions.

You should not use cariprazine if you are allergic to it.

To make sure cariprazine is safe for you, tell your doctor if you have:

• heart disease, high blood pressure;
• a history of stroke or blood clot;
• high cholesterol or triglycerides (a type of fat in the blood);
• liver or kidney disease;
• diabetes; or
• if you are dehydrated.

Taking antipsychotic medicine in the last 3 months of pregnancy may cause problems in the newborn, such as withdrawal symptoms, breathing problems, feeding problems, fussiness, tremors, and limp or stiff muscles. However, you may have withdrawal symptoms or other problems if you stop taking your medicine during pregnancy. If you become pregnant, do not stop taking cariprazine without your doctor's advice.

If you are pregnant, your name may be listed on a pregnancy registry. This is to track the outcome of the pregnancy and to evaluate any effects of cariprazine on the baby.

It is not known whether cariprazine passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

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

Dosage Forms & Strengths

capsule

• 1.5mg
• 3mg
• 4.5mg
• 6mg

Schizophrenia

Starting dose: 1.5 mg PO qDay

Dose may be increased to 3 mg on Day 2

Depending upon clinical response and tolerability, further dose adjustments can be made in 1.5 to 3-mg increments

Dosage range: 1.5-6 mg PO qDay

Bipolar Disorder

Indicated for manic or mixed episodes associated with bipolar I disorder

Starting dose: 1.5 mg PO qDay

Dose should be increased to 3 mg on Day 2

Depending on clinical response and tolerability, further dose adjustments can be made in 1.5 to 3-mg increments

Dosage range: 3-6 mg PO qDay

Dosage Modifications

Initiating a strong CYP3A4 inhibitor while on stable dose of cariprazine

• Reduce current cariprazine dose by 50%
• For patients taking cariprazine 4.5 mg/day, the dose should be reduced to 1.5 mg or 3 mg daily
• For patients taking 1.5 mg daily, the dosing regimen should be adjusted to every other day
• When the CYP3A4 inhibitor is discontinued, cariprazine dosage may need to be increased

Initiating cariprazine while already on a strong CYP3A4 inhibitor

• Cariprazine 1.5 mg PO on Days 1 and 3 (no dose on Day 2)
• From Day 4 onward, the dose should be administered at 1.5 mg PO qDay, then increased to a maximum of 3 mg/day
• When CYP3A4 inhibitor is discontinued, cariprazine dosage may need to be increased

Coadministration with CYP3A4 inducers

• Concomitant administration has not been evaluated and is not recommended because the net effect on active drug and metabolites is unclear

Hepatic impairment

• Mild-to-moderate (Child-Pugh score 5-9): No dosage adjustment required
• Severe (Child-Pugh score 10-15): Not recommended

Renal impairment

• Mild-to-moderate (CrCl ≥30 mL/min) No dosage adjustment required
• Severe (CrCl <30 mL/min): Not evaluated

Dosing Considerations

Because of the long half-life of cariprazine and its active metabolites, changes in dose will not be fully reflected in plasma for several weeks

Prescribers should monitor patients for adverse effects and treatment response for several weeks after initiating the drug and after each dosage change

Safety and efficacy not established

>10% (Schizophrenia)

Extrapyramidal symptoms, all (24-33%)

Parkinsonism (13-18%)

Headache (9-18%)

Akathisia (9-14%)

Insomnia (11-13%)

>10% (Bipolar Disorder)

Extrapyramidal symptoms, all (41-45%)

Parkinsonism (21-26%)

Akathisia (20-21%)

Headache (13-14%)

Nausea (11-13%)

Constipation (6-11%)

1-10% (Schizophrenia)

Constipation (6-10%)

Somnolence (5-10%)

Nausea (5-8%)

Abdominal pain (3-7%)

Restlessness (4-6%)

Anxiety (3-6%)

Toothache (3-6%)

Hypertension (2-6%)

Dyspepsia (4-5%)

Vomiting (4-5%)

Dizziness (3-5%)

Agitation (3-5%)

Diarrhea (1-5%)

Pain in extremity (2-4%)

Cough (1-4%)

Tachycardia (2-3%)

Increased weight (2-3%)

Decreased appetite (1-3%)

Dry mouth (1-3%)

Fatigue (1-3%)

Increased CPK (1-3%)

Musculoskeletal stiffness (1-3%)

Back pain (1-3%)

Dystonia (2%)

Tachycardia (1-2%)

Arthralgia (1-2%)

Increased LFTs (1-2%)

Nasopharyngitis (1-2%)

Urinary tract infections (1-2%)

Rash (1-2%)

1-10% (Bipolar Disorder)

Vomiting (8-10%)

Insomnia (8-9%)

Dyspepsia (7-9%)

Somnolence (7-8%)

Abdominal pain (6-8%)

Restlessness (7%)

Dizziness (6-7%)

Diarrhea (5-6%)

Hypertension (4-5%)

Fatigue (4-5%)

Dystonia (3-5%)

Blurred vision (4%)

Decreased appetite (3-4%)

Toothache (3-4%)

Pain in extremity (2-4%)

Pyrexia (1-4%)

Weight increased (2-3%)

Increased CPK (2-3%)

Dry mouth (2-3%)

Oropharyngeal pain (1-3%)

Back pain (1-3%)

Increased LFTs (1-3%)

Musculoskeletal stiffness (2%)

Postmarketing Reports

Falls

Cariprazine may be found in some form under the following brand names:

• Vraylar

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The dose your doctor recommends may be based on the following:

• the condition being treated
• other medical conditions you have
• other medications you are taking
• how you respond to this medication
• your age

The recommended dose range of Vraylar (cariprazine) for the treatment of bipolar I disorder in adults is 3 to 6 mg/day.

The recommended dose range of Vraylar (cariprazine) for the treatment of schizophrenia in adults is 1.5 to 6 mg/day.

Cariprazine is an antipsychotic medication that affects chemicals in the brain.

Cariprazine is used to treat schizophrenia. This medicine is also used to treat manic or mixed episodes in people with bipolar disorder type I.

Cariprazine may also be used for purposes not listed in this medication guide.

Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not use this medicine in larger or smaller amounts or for longer than recommended.

You may take cariprazine with or without food.

It may take several weeks before your symptoms improve. Keep using the medication as directed and tell your doctor if your symptoms do not improve.

Tell your doctor if you have any changes in weight while taking this medicine.

Your blood pressure and heart rate will need to be checked often. You may also need frequent blood tests.

Store at room temperature away from moisture, heat, and light.

Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

Avoid drinking alcohol. Dangerous side effects could occur.

Cariprazine may impair your thinking or reactions. Avoid driving or operating machinery until you know how this medicine will affect you.

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Dizziness or severe drowsiness can cause falls, fractures, or other injuries.

While you are taking cariprazine, you may be more sensitive to temperature extremes such as very hot conditions. Avoid becoming overheated or dehydrated. Drink plenty of fluids, especially in hot weather and during exercise.

Take cariprazine exactly as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. To do so may increase the chance of side effects.

You may take cariprazine with or without food.

Dosing

The dose of cariprazine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of cariprazine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (capsules):
  • For bipolar disorder and schizophrenia:
    • Adults—At first, 1.5 milligrams (mg) once a day. Your doctor will adjust your dose as needed. However, the dose is usually not more than 6 mg per day.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of cariprazine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take with or without food.
• To gain the most benefit, do not miss doses.
• Keep taking cariprazine as you have been told by your doctor or other health care provider, even if you feel well.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of high blood sugar like confusion, feeling sleepy, more thirst, more hungry, passing urine more often, flushing, fast breathing, or breath that smells like fruit.
• Signs of high or low blood pressure like very bad headache or dizziness, passing out, change in eyesight.
• Shakiness, trouble moving around, or stiffness.
• Seizures.
• Trouble swallowing.
• Feeling agitated.
• A very bad and sometimes deadly health problem called neuroleptic malignant syndrome (NMS) may happen. Call your doctor right away if you have any fever, muscle cramps or stiffness, dizziness, very bad headache, confusion, change in thinking, fast heartbeat, heartbeat that does not feel normal, or are sweating a lot.
• Some people who take this medicine may get a very bad muscle problem called tardive dyskinesia. This muscle problem may not go away even if cariprazine is stopped. Sometimes, signs may lessen or go away over time after this medicine is stopped. The risk of tardive dyskinesia may be greater in people with diabetes and in older adults, especially older women. The risk is also greater the longer you take cariprazine or with higher doses. Muscle problems may also occur after short-term use with low doses. Call your doctor right away if you have trouble controlling body movements or if you have muscle problems with your tongue, face, mouth, or jaw like tongue sticking out, puffing cheeks, mouth puckering, or chewing.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take cariprazine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to cariprazine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

(kar IP ra zeen)

Cmax and AUC for cariprazine was increased in patients with mild to moderate hepatic impairment and exposure was decreased for the active metabolites.

Psychosis/agitation associated with dementia

Based on the American Psychiatric Association practice guideline on the use of antipsychotics to treat agitation or psychosis in patients with dementia, antipsychotics, such as cariprazine, may be considered for the treatment of agitation and psychosis in certain patients with dementia; however, evidence for efficacy is modest and use should be limited to patients whose symptoms are dangerous, severe, or cause significant patient distress due to safety risks associated with antipsychotic use.

CrCl ≥30 mL/minute: No dosage adjustment necessary.

CrCl <30 mL/minute: Use not recommended (has not been studied).

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F). Protect 3 mg and 4.5 mg capsules from light to prevent color fading.

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Cariprazine is not approved for the treatment of patients with dementia-related psychosis.