What is vraylar used for?

IMPORTANT RISK INFORMATION AND INDICATION

What is the most important information I should know about VRAYLAR?

Elderly people with dementia-related psychosis (having lost touch with reality due to confusion and memory loss) taking medicines like VRAYLAR are at an increased risk of death. VRAYLAR is not approved for treating patients with dementia-related psychosis.

Antidepressants may increase suicidal thoughts or actions in some children and young adults within the first few months of treatment and when the dose is changed. Depression and other serious mental illnesses are the most important causes of suicidal thoughts and actions. Patients on antidepressants and their families or caregivers should watch for new or worsening depression symptoms, especially sudden changes in mood, behaviors, thoughts, or feelings. This is very important when an antidepressant is started or when the dose is changed. Report any change in these symptoms immediately to the doctor.

VRAYLAR may cause serious side effects, including:

  • Stroke (cerebrovascular problems) in elderly people with dementia-related psychosis that can lead to death
  • Neuroleptic malignant syndrome (NMS): Call your healthcare provider right away if you have high fever, stiff muscles, confusion, increased sweating, or changes in breathing, heart rate, and blood pressure. These can be symptoms of a rare but potentially fatal side effect called NMS. VRAYLAR should be stopped if you have NMS
  • Uncontrolled body movements (tardive dyskinesia or TD): Tell your healthcare provider if you cannot control the movements of your face, tongue, or other body parts. These could be signs of a serious and sometimes permanent side effect called TD. Risk of developing TD and the chance that it will become permanent are thought to increase the longer a person takes the medicine and the more medicine a person takes over time. TD can develop even after a person has been taking the medicine for a short time at low doses. TD may partially or completely go away if you stop taking VRAYLAR. TD may also start after you stop taking VRAYLAR
  • Late-occurring side effects: VRAYLAR stays in the body for a long time. Some side effects may not happen right away and can start a few weeks after starting VRAYLAR, or if your dose increases. Your healthcare provider should monitor you for side effects for several weeks after starting or increasing dose of VRAYLAR
  • Problems with your metabolism, such as:
    • High blood sugar and diabetes: Increases in blood sugar can happen in some people who take VRAYLAR. Complications of diabetes can be serious and even life threatening. Your healthcare provider should check your blood sugar before or soon after starting VRAYLAR and regularly during treatment. Tell your healthcare provider if you have symptoms such as feeling very thirsty, very hungry, or sick to your stomach, urinating more than usual, feeling weak, tired, confused, or your breath smells fruity
    • Increased fat levels (cholesterol and triglycerides) in your blood: Your healthcare provider should check fat levels in your blood before or soon after starting VRAYLAR and during treatment
    • Weight gain: Weight gain has been reported with VRAYLAR. You and your healthcare provider should check your weight before and regularly during treatment
  • Low white blood cell count: Low white blood cell counts have been reported with antipsychotic drugs, including VRAYLAR. This may increase your risk of infection. Very low white blood cell counts, which can be fatal, have been reported with other antipsychotics. Your healthcare provider may do blood tests during the first few months of treatment with VRAYLAR
  • Decreased blood pressure (orthostatic hypotension): You may feel lightheaded or faint when you rise too quickly from a sitting or lying position
  • Falls: VRAYLAR may make you sleepy or dizzy, may cause a decrease in blood pressure when changing position (orthostatic hypotension), and can slow thinking and motor skills, which may lead to falls that can cause fractures or other injuries
  • Seizures (convulsions)
  • Impaired judgment, thinking, and motor skills: Do NOT drive, operate machinery, or do other dangerous activities until you know how VRAYLAR affects you. VRAYLAR may make you drowsy
  • Increased body temperature: Do not become too hot or dehydrated during VRAYLAR treatment. Do no 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 heaving clothing. Drink plenty of water
  • Difficulty swallowing that can cause food or liquid to get into your lungs

Who should not take VRAYLAR?

Do not take VRAYLAR if you are allergic to any of its ingredients. Get emergency medical help if you are having an allergic reaction (eg, rash, itching, hives, swelling of the tongue, lip, face or throat).

What should I tell my healthcare provider before taking VRAYLAR?

Tell your healthcare provider about any medical conditions and 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 in you or your family
  • 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 low white blood cell count
  • are pregnant or plan to become pregnant. VRAYLAR may harm your unborn baby. Using VRAYLAR in the third trimester may cause uncontrolled movements of the body and face, muscle stiffness, or feelings of restlessness and/or withdrawal symptoms in newborn babies. If you become pregnant during treatment, talk to your healthcare provider about registering with the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or http://www.womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/
  • are breastfeeding or plan to breastfeed. It is not known if VRAYLAR passes into breast milk. Talk to your healthcare provider about the best way to feed your baby during treatment with VRAYLAR

Tell your healthcare provider about all medicines that you take, including prescriptions, over-the-counter medicines, vitamins, and supplements. VRAYLAR may affect the way other medicines work, and other medicines may affect how VRAYLAR works. Do not start or stop any medicines while taking VRAYLAR without talking to your healthcare provider.

What are the most common side effects of VRAYLAR?

  • The most common side effects include difficulty moving or slow movements, tremors, uncontrolled body movements, restlessness and feeling like you need to move around, sleepiness, nausea, vomiting, and indigestion.

These are not all possible side effects of VRAYLAR.

INDICATION AND USAGE

VRAYLAR (cariprazine) is a once-a-day pill, taken with or without food, for the treatment of schizophrenia in adults.

Please see the full Prescribing Information, including Boxed Warnings, and Medication Guide.

Advice & Tips: About 40 years ago in the late 1970’s I started having problems with my sleep. My sleep problem grew very BAD, to a point that if I did not fall asleep in about 5 minutes I would be TORTURED to the point that I would have to get out of bed. The TORMENT could last for a couple hours or as short as a couple of minutes. After the TORMENT ended, I would try and go to sleep again, repeating the process. This made life HELL and I did not want to be alive. Each time I have add an atypical antipsychotic medication, my sleep has imported. This is my third atypical antipsychotic medication that I am now taking. My first atypical antipsychotic was Latuda and I thought it was a miracle medication, but then lost it’s ability to aid in improving my sleep. Adding Invega to 120 mg of Latuda per day, was even a greater miracle. But after about two months it lost some of it miracle working medicated effect. Then I added Vraylar to 120 mg/day of Latuda and 15 mg/day of Invega and my sleep was just about perfect, I only woke up to go to the bathroom and was able to go back to sleep after going to the bathroom with only an occasionally wakeful period. When not on any antipsychotic medications, I could hardly sleep and I felt like; others could hear my thoughts (broadcasting), that I could hear other people thoughts (mind reading), that I could communicate by thought with others without speaking a word (telepathic communication), not only could I communicate with other people in this way but I could communicate with other things as if they had human like qualities (anthropomorphic telepathic communication), believing that I am super important to the world (grandiose thinking), that others were out to kill me (paranoia), and I would become very delusional. But, now after taking the antipsychotic medications for some time, not only do I not believe in these things (powers) were never true for me, I also believe that no one else has these powers. Maybe some people may have others out to kill them, but this is not true for me. Also, for over 35 years (1977 – 2013) I believed that God would talk to me personally and would give me personal instructions, but now, I don’t believe this is/was probably ever true. Now, I believe God gave me a brain/mind so that I could figure out how to love other, which is what He wants me to do. Relief of the psychotic symptoms comes with a price, the side effects of those antipsychotic medications. The antipsychotic medications of today, work better with less side effects. than those in 1977 when I started taking them. I am still experiencing periods of torment it was like if a BLACK HOLE was sucking my mind DRY, LIQUID ACID to my soul, HELL, my mind would collapses, and I was unable to function as usual. These periods would last only a few minutes or can last up to as long as several hours and happen quite regularly and had been going on for about the last 40 years, but now on the three atypical antipsychotic I hardy experience this any more. But I have periods of not wanting to live because life has been so bad.

IMPORTANT RISK INFORMATION

What is the most important information I should know about VRAYLAR?

Elderly people with dementia-related psychosis (having lost touch with reality due to confusion and memory loss) taking medicines like VRAYLAR are at an increased risk of death. VRAYLAR is not approved for treating patients with dementia-related psychosis.

Antidepressants may increase suicidal thoughts or actions in some children and young adults within the first few months of treatment and when the dose is changed. Depression and other serious mental illnesses are the most important causes of suicidal thoughts and actions. Patients on antidepressants and their families or caregivers should watch for new or worsening depression symptoms, especially sudden changes in mood, behaviors, thoughts, or feelings. This is very important when an antidepressant is started or when the dose is changed. Report any change in these symptoms immediately to the doctor.

    VRAYLAR may cause serious side effects, including:

    • Stroke (cerebrovascular problems) in elderly people with dementia-related psychosis that can lead to death
    • Neuroleptic malignant syndrome (NMS): Call your healthcare provider or go to the nearest hospital emergency room right away if you have high fever, stiff muscles, confusion, increased sweating, or changes in breathing, heart rate, and blood pressure. These can be symptoms of a rare but potentially fatal side effect called NMS. VRAYLAR should be stopped if you have NMS
    • Uncontrolled body movements (tardive dyskinesia or TD): VRAYLAR 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 VRAYLAR. Tardive dyskinesia may also start after you stop taking VRAYLAR
    • Late-occurring side effects: VRAYLAR stays in your body for a long time. Some side effects may not happen right away and can start a few weeks after starting VRAYLAR, or if your dose increases. Your healthcare provider should monitor you for side effects for several weeks after starting or increasing dose of VRAYLAR
    • Problems with your metabolism, such as:
      • High blood sugar and diabetes: Increases in blood sugar can happen in some people who take VRAYLAR. Extremely high blood sugar can lead to coma or death. Your healthcare provider should check your blood sugar before or soon after starting VRAYLAR and regularly during treatment. Tell your healthcare provider if you have symptoms such as feeling very thirsty, very hungry, or sick to your stomach, urinating more than usual, feeling weak, tired, confused, or your breath smells fruity
      • Increased fat levels (cholesterol and triglycerides) in your blood: Your healthcare provider should check fat levels in your blood before or soon after starting VRAYLAR and during treatment
      • Weight gain: Weight gain has been reported with VRAYLAR. You and your healthcare provider should check your weight before and regularly during treatment
    • Low white blood cell count: Low white blood cell counts have been reported with antipsychotic drugs, including VRAYLAR. This may increase your risk of infection. Very low white blood cell counts, which can be fatal, have been reported with other antipsychotics. Your healthcare provider may do blood tests during the first few months of treatment with VRAYLAR
    • Decreased blood pressure (orthostatic hypotension): You may feel lightheaded or faint when you rise too quickly from a sitting or lying position
    • Falls: VRAYLAR may make you sleepy or dizzy, may cause a decrease in blood pressure when changing position (orthostatic hypotension), and can slow thinking and motor skills, which may lead to falls that can cause fractures or other injuries
    • Seizures (convulsions)
    • Impaired judgment, thinking, and motor skills: Do NOT drive, operate machinery, or do other dangerous activities until you know how VRAYLAR affects you. VRAYLAR may make you drowsy
    • Increased body temperature: Do not become too hot or dehydrated during VRAYLAR treatment. 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
    • Difficulty swallowing that can cause food or liquid to get into your lungs

    Do not take VRAYLAR if you are allergic to any of its ingredients. Get emergency medical help if you are having an allergic reaction (eg, rash, itching, hives, swelling of the tongue, lip, face or throat).

    Tell your healthcare provider about any medical conditions and 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 in you or your family
    • 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 low white blood cell count
    • are pregnant or plan to become pregnant. VRAYLAR may harm your unborn baby. Talk to your healthcare provider about the risk to your unborn baby if you take VRAYLAR during pregnancy. If you become pregnant or think you are pregnant during treatment, talk to your healthcare provider about registering with the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or
      http://www.womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/
    • are breastfeeding or plan to breastfeed. It is not known if VRAYLAR passes into breast milk. Talk to your healthcare provider about the best way to feed your baby during treatment with VRAYLAR

    Tell your healthcare provider about all medicines that you take, including prescriptions, over-the-counter medicines, vitamins, and supplements. VRAYLAR may affect the way other medicines work, and other medicines may affect how VRAYLAR works. Do not start or stop any medicines while taking VRAYLAR without talking to your healthcare provider.

    • The most common side effects were difficulty moving or slow movements, tremors, uncontrolled body movements, restlessness and feeling like you need to move around, sleepiness, nausea, vomiting, and indigestion.

    These are not all possible side effects of VRAYLAR.

    VRAYLAR is approved in adults to treat depressive episodes (bipolar depression) and for the short-term treatment of manic or mixed episodes that happen with bipolar I disorder.

    Please see the full Prescribing Information, including Boxed Warnings, and Medication Guide.

SIDE EFFECTS

The following adverse reactions are discussed in more detail in other sections of the labeling:

  • Increased Mortality in Elderly Patients with Dementia-Related Psychosis
  • Suicidal Thoughts and Behaviors
  • Cerebrovascular Adverse Reactions, Including Stroke, in Elderly Patients with Dementia-Related Psychosis
  • Neuroleptic Malignant Syndrome
  • Tardive Dyskinesia
  • Late Occurring Adverse Reactions
  • Metabolic Changes
  • Leukopenia, Neutropenia, and Agranulocytosis
  • Orthostatic Hypotension and Syncope
  • Falls
  • Seizures
  • Potential for Cognitive and Motor Impairment
  • Body Temperature Dysregulation
  • Dysphagia

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The information below is derived from an integrated clinical study database for VRAYLAR consisting of 4753 adult patients exposed to one or more doses of VRAYLAR for the treatment of schizophrenia, manic or mixed episodes associated with bipolar I disorder, and bipolar depression in placebo-controlled studies. This experience corresponds with a total experience of 940.3 patient-years. A total of 2568 VRAYLAR-treated patients had at least 6 weeks and 296 VRAYLAR-treated patients had at least 48 weeks of exposure.

Patients With Schizophrenia

The following findings are based on four placebo-controlled, 6-week schizophrenia trials with VRAYLAR doses ranging from 1.5 to 12 mg once daily. The maximum recommended dosage is 6 mg daily.

Adverse Reactions Associated with Discontinuation of Treatment

There was no single adverse reaction leading to discontinuation that occurred at a rate of ≥ 2% in VRAYLAR-treated patients and at least twice the rate of placebo.

Common Adverse Reactions (≥ 5% and at least twice the rate of placebo): extrapyramidal symptoms and akathisia.

Adverse Reactions with an incidence of ≥ 2% and greater than placebo, at any dose are shown in Table 5.

Table 5. Adverse Reactions Occurring in ≥ 2% of VRAYLAR-treated Patients and > Placebo-treated Adult Patients in 6-Week Schizophrenia Trials

System Organ Class / Preferred Term Placebo
(N= 584)
(%)
VRAYLAR*
1.5 -3 mg/day
(N=539
) (%)
4.5 -6 mg/day
(N=575)
(%)
9 -12 mg/day°
(N=203)
(%)
Cardiac Disorders
Tachycardiaa 1 2 2 3
Gastrointestinal Disorders
Abdominal painb 5 3 4 7
Constipation 5 6 7 10
Diarrheac 3 1 4 5
Dry Mouth 2 1 2 3
Dyspepsia 4 4 5 5
Nausea 5 5 7 8
Toothache 4 3 3 6
Vomiting 3 4 5 5
General Disorders/Administration Site Conditions
Fatigued 1 1 3 2
Infections and infestations
Nasopharyngitis 1 1 1 2
Urinary tract infection 1 1 <1 2
Investigations
Blood creatine phosphokinase increased 1 1 2 3
Hepatic enzyme increasede <1 1 1 2
Weight increased 1 3 2 3
Metabolism and nutrition disorders
Decreased appetite 2 1 3 2
Musculoskeletal and Connective Tissue Disorders
Arthralgia 1 2 1 2
Back pain 2 3 3 1
Pain in extremity 3 2 2 4
Nervous System Disorders
Akathisia 4 9 13 14
Extrapyramidal Symptomsf 8 15 19 20
Headacheg 13 9 11 18
Somnolenceh 5 5 8 10
Dizziness 2 3 5 5
Psychiatric Disorders
Psychiatric Disorders 4 3 5 3
Insomniai 11 12 13 11
Restlessness 3 4 6 5
Anxiety 4 6 5 3
Respiratory, thoracic and mediastinal disorders
Cough 2 1 2 4
Skin and subcutaneous disorders
Rash 1 <1 1 2
Vascular Disorders
Hypertensionj 1 2 3 6
Note: Figures rounded to the nearest integer
* Data shown by modal daily dose, defined as most frequently administered dose per patient
aTachycardia terms: heart rate increased, sinus tachycardia, tachycardia
bAbdominal pain terms: abdominal discomfort, abdominal pain, abdominal pain lower, abdominal pain upper, gastrointestinal pain
cDiarrhea terms: diarrhea, frequent bowel movements
dFatigue terms: asthenia, fatigue
eHepatic enzyme increase terms: alanine aminotransferase increased, aspartate aminotransferase increased, hepatic enzyme increased
fExtrapyramidal Symptoms terms: bradykinesia, cogwheel rigidity, drooling, dyskinesia, dystonia, extrapyramidal disorder, hypokinesia, masked facies, muscle rigidity, muscle tightness, Musculoskeletal stiffness, oculogyric crisis, oromandibular dystonia, parkinsonism, salivary hypersecretion, tardive dyskinesia, torticollis, tremor, trismus
gHeadache terms: headache, tension headache
hSomnolence terms: hypersomnia, sedation, somnolence
iInsomnia terms: initial insomnia, insomnia, middle insomnia, terminal insomnia
jHypertension terms: blood pressure diastolic increased, blood pressure increased, blood pressure systolic increased, hypertension
° The maximum recommended daily dose is 6 mg. Doses above 6 mg daily do not confer increased effectiveness sufficient to outweigh dose-related adverse reactions.

Patients With Bipolar Mania

The following findings are based on three placebo-controlled, 3-week bipolar mania trials with VRAYLAR doses ranging from 3 to 12 mg once daily. The maximum recommended dosage is 6 mg daily.

The adverse reaction leading to discontinuation that occurred at a rate of ≥ 2% in VRAYLAR-treated patients and at least twice the rate of placebo was akathisia (2%). Overall, 12% of the patients who received VRAYLAR discontinued treatment due to an adverse reaction, compared with 7% of placebo-treated patients in these trials.

Common Adverse Reactions (≥ 5% and at least twice the rate of placebo): extrapyramidal symptoms, akathisia, dyspepsia, vomiting, somnolence, and restlessness.

Adverse Reactions with an incidence of ≥ 2% and greater than placebo at any dose are shown in Table 6.

Table 6. Adverse Reactions Occurring in ≥ 2% of VRAYLAR-treated Patients and > Placebo-treated Adult Patients in 3-Week Bipolar Mania Trials

System Organ Class / Preferred Term Placebo
(N= 442)
(%)
VRAYLAR*
3 -6 mg/day
(N=263)
(%)
9 -12 mg/day°
(N=360)
(%)
Cardiac Disorders
Tachycardiaa 1 2 1
Eye Disorders
Vision blurred 1 4 4
Gastrointestinal Disorders
Nausea 7 13 11
Constipation 5 6 11
Vomiting 4 10 8
Dry mouth 2 3 2
Dyspepsia 4 7 9
Abdominal painb 5 6 8
Diarrheac 5 5 6
Toothache 2 4 3
General Disorders/Administration Site Conditions
Fatigued 2 4 5
Pyrexiae 2 1 4
Investigations
Blood creatine phosphokinase increased 2 2 3
Hepatic enzymes increasedf <1 1 3
Weight increased 2 2 3
Metabolism and Nutrition Disorders
Decreased appetite 3 3 4
Musculoskeletal and Connective Tissue Disorders
Pain in extremity 2 4 2
Back pain 1 1 3
Nervous System Disorders
Akathisia 5 20 21
Extrapyramidal Symptomsg 12 26 29
Headacheh 13 14 13
Dizziness 4 7 6
Somnolencei 4 7 8
Psychiatric Disorders
Insomniaj 7 9 8
Restlessness 2 7 7
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain 2 1 3
Vascular Disorders
Hypertensionk 1 5 4
Note: Figures rounded to the nearest integer
*Data shown by modal daily dose, defined as most frequently administered dose per patient
aTachycardia terms: heart rate increased, sinus tachycardia, tachycardia
bAbdominal pain terms: abdominal discomfort, abdominal pain, abdominal pain upper, abdominal tenderness,
cDiarrhea: diarrhea, frequent bowel movements
dFatigue terms: asthenia, fatigue
ePyrexia terms: body temperature increased, pyrexia
fHepatic enzymes increased terms: alanine aminotransferase increased, aspartate aminotransferase increased, hepatic enzyme increased, transaminases increased
gExtrapyramidal Symptoms terms: bradykinesia, drooling, dyskinesia, dystonia, extrapyramidal disorder, hypokinesia, muscle rigidity, muscle tightness, musculoskeletal stiffness, oromandibular dystonia, parkinsonism, salivary hypersecretion, tremor
hHeadache terms: headache, tension headache
iSomnolence terms: hypersomnia, sedation, somnolence
jInsomnia terms: initial insomnia, insomnia, middle insomnia
kHypertension terms: blood pressure diastolic increased, blood pressure increased, hypertension
° The maximum recommended daily dose is 6 mg. Doses above 6 mg daily do not confer increased effectiveness sufficient to outweigh dose-related adverse reactions.

Patients With Bipolar Depression

The following findings are based on three placebo-controlled, two 6-week and one 8-week bipolar depression trials with VRAYLAR doses of 1.5 mg and 3 mg once daily.

There were no adverse reaction leading to discontinuation that occurred at a rate of ≥ 2% in VRAYLAR-treated patients and at least twice the rate of placebo. Overall, 6% of the patients who received VRAYLAR discontinued treatment due to an adverse reaction, compared with 5% of placebo-treated patients in these trials.

Common Adverse Reactions

(≥ 5% and at least twice the rate of placebo): nausea, akathisia, restlessness, and extrapyramidal symptoms.

Adverse Reactions with an incidence of ≥ 2% and greater than placebo at 1.5 mg or 3 mg doses are shown in Table 7.

Table 7. Adverse Reactions Occurring in ≥ 2% of VRAYLAR-treated Patients and > Placebo-treated Adult Patients in two 6-week trials and one 8-week trial

Placebo
(N=468)
(%)
VRAYLAR
1.5 mg/day
(N=470)
(%)
3 mg/day
(N=469)
(%)
Restlessness 3 2 7
Akathisia 2 6 10
Extrapyramidal symptomsa 2 4 6
Dizziness 2 4 3
Somnolenceb 4 7 6
Nausea 3 7 7
Increased appetite 1 3 3
Weight increase <1 2 2
Fatiguec 2 4 3
Insomniad 7 7 10
aExtrapyramidal symptoms terms: akinesia, drooling, dyskinesia, dystonia, extrapyramidal disorder, hypokinesia, muscle tightness, musculoskeletal stiffness, myoclonus, oculogyric crisis, salivary hypersecretion, tardive dyskinesia, tremor
bSomnolence terms: hypersomnia, sedation, somnolence
cFatigue terms: asthenia, fatigue, malaise
dInsomnia terms: initial insomnia, insomnia, insomnia related to another mental condition, middle insomnia, sleep disorder terminal insomnia

Dystonia

Symptoms of dystonia, prolonged abnormal contractions of muscle groups, may occur in susceptible individuals during the first few days of treatment. Dystonic symptoms include: spasm of the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the tongue. Although these symptoms can occur at low doses, they occur more frequently and with greater severity with high potency and higher doses of first-generation antipsychotic drugs. An elevated risk of acute dystonia is observed in males and younger age groups.

Extrapyramidal Symptoms (EPS) And Akathisia

In schizophrenia, bipolar mania, and bipolar depression trials, data were objectively collected using the Simpson Angus Scale (SAS) for treatment-emergent EPS (parkinsonism) (SAS total score ≤ 3 at baseline and > 3 post-baseline) and the Barnes Akathisia Rating Scale (BARS) for treatment-emergent akathisia (BARS total score ≤ 2 at baseline and > 2 post-baseline).

In 6-week schizophrenia trials, the incidence of reported events related to extrapyramidal symptoms (EPS), excluding akathisia and restlessness was 17% for VRAYLAR-treated patients versus 8% for placebo-treated patients. These events led to discontinuation in 0.3% of VRAYLAR-treated patients versus 0.2% of placebo-treated patients. The incidence of akathisia was 11% for VRAYLAR-treated patients versus 4% for placebo-treated patients. These events led to discontinuation in 0.5% of VRAYLAR-treated patients versus 0.2% of placebo-treated patients. The incidence of EPS is shown in Table 8.

Table 8. Incidence of EPS Compared to Placebo in 6-Week Schizophrenia Studies

Adverse Event Term Placebo
(N= 584)
(%)
VRAYLAR*
1.5 -3 mg/day
(N=539)
(%)
4.5 -6 mg/day
(N=575)
(%)
9-12 mg/day°
(N=203)
(%)
All EPS events 14 24 32 33
All EPS events, excluding Akathisia/Restlessness 8 15 19 20
Akathisia 4 9 13 14
Dystonia** <1 2 2 2
Parkinsonism§ 7 13 16 18
Restlessness 3 4 6 5
Musculoskeletal stiffness 1 1 3 1
Note: Figures rounded to the nearest integer
*Data shown by modal daily dose, defined as most frequently administered dose per patient
** Dystonia includes adverse event terms: dystonia, oculogyric crisis, oromandibular dystonia, trismus, torticollis
§ Parkinsonism includes adverse event terms: bradykinesia, cogwheel rigidity, drooling, dyskinesia, extrapyramidal disorder, hypokinesia, masked facies, muscle rigidity, muscle tightness, parkinsonism, tremor, salivary hypersecretion
° The maximum recommended daily dose is 6 mg. Doses above 6 mg daily do not confer increased effectiveness sufficient to outweigh dose-related adverse reactions.

In 3-week bipolar mania trials, the incidence of reported events related to extrapyramidal symptoms (EPS), excluding akathisia and restlessness, was 28% for VRAYLAR-treated patients versus 12% for placebo-treated patients. These events led to a discontinuation in 1% of VRAYLAR-treated patients versus 0.2% of placebo-treated patients. The incidence of akathisia was 20% for VRAYLAR-treated patients versus 5% for placebo-treated patients. These events led to discontinuation in 2% of VRAYLAR-treated patients versus 0% of placebo-treated patients. The incidence of EPS is provided in Table 9.

Table 9. Incidence of EPS Compared to Placebo in 3-Week Bipolar Mania Trials

Adverse Event Term Placebo
(N= 442)
(%)
VRAYLAR*
3 -6 mg/day
(N=263)
(%)
9 -12 mg/day°
(N=360)
(%)
All EPS events 18 41 45
All EPS events, excluding Akathisia/Restlessness 12 26 29
Akathisia 5 20 21
Dystonia** 1 5 3
Parkinsonism§ 10 21 26
Restlessness 2 7 7
Musculoskeletal stiffness 1 2 2
Note: Figures rounded to the nearest integer
*Data shown by modal daily dose, defined as most frequently administered dose per patient
** Dystonia includes adverse event terms: dystonia, oromandibular dystonia
§ Parkinsonism includes adverse event terms: bradykinesia, drooling, dyskinesia, extrapyramidal disorder, hypokinesia, muscle rigidity, muscle tightness, parkinsonism, salivary hypersecretion, tremor
° The maximum recommended daily dose is 6 mg. Doses above 6 mg daily do not confer increased effectiveness sufficient to outweigh dose-related adverse reactions.

In the two 6-week and one 8-week bipolar depression trials, the incidence of reported events related to EPS, excluding akathisia and restlessness was 4% for VRAYLAR-treated patients versus 2% for placebo-treated patients. These events led to discontinuation in 0.4% of VRAYLAR-treated patients versus 0% of placebo-treated patients. The incidence of akathisia was 8% for VRAYLAR-treated patients versus 2% for placebo-treated patients. These events led to discontinuation in 1.5% of VRAYLAR-treated patients versus 0% of placebo-treated patients. The incidence of EPS is shown in Table 10.

Table 10. Incidence of EPS Compared to Placebo in two 6-Week and one 8-Week Bipolar Depression Trials

Adverse Event Term Placebo
(N=468)
(%)
VRAYLAR*
1.5 mg/day
(N=470)
(%)
3 mg/day
(N=469)
(%)
All EPS events 7 10 19
All EPS events, excluding Akathisia/Restlessness 2 4 6
Akathisia 2 6 10
Dystonia* <1 <1 <1
Parkinsonism§ 2 3 4
Restlessness 3 2 7
Musculoskeletal stiffness <1 <1 1
Tardive Dyskinesia 0 0 <1
Note: Figures rounded to the nearest integer
*Dystonia includes adverse event terms: dystonia, myoclonus, oculogyric crisis
§ Parkinsonism includes adverse event terms: akinesia, drooling, dyskinesia, extrapyramidal disorder, hypokinesia, muscle tightness, salivary hypersecretion, and tremor.

Cataracts

In the long-term uncontrolled schizophrenia (48-week) and bipolar mania (16-week) trials, the incidence of cataracts was 0.1% and 0.2%, respectively. The development of cataracts was observed in nonclinical studies . The possibility of lenticular changes or cataracts cannot be excluded at this time.

Vital Signs Changes

There were no clinically meaningful differences between VRAYLAR-treated patients and placebo-treated patients in mean change from baseline to endpoint in supine blood pressure parameters except for an increase in supine diastolic blood pressure in the 9 -12 mg/day VRAYLAR-treated patients with schizophrenia.

Pooled data from 6-week schizophrenia trials are shown in Table 11 and from 3-week bipolar mania trials are shown in Table 12.

Table 11. Mean Change in Blood Pressure at Endpoint in 6-Week Schizophrenia Trials

Table 12. Mean Change in Blood Pressure at Endpoint in 3-Week Bipolar Mania Trials

In the two 6-week and one 8-week bipolar depression trials, there were no clinically meaningful differences between VRAYLAR-treated patients and placebo-treated patients in mean change from baseline to endpoint in supine systolic and diastolic blood pressure.

Pooled data from two 6-week and one 8-week bipolar depression trials are shown in Table 13.

Table 13. Mean Change in Blood Pressure at Endpoint in two 6-Week and one 8-Week Bipolar Depression Trials

Changes In Laboratory Tests

The proportions of patients with transaminase elevations of ≥3 times the upper limits of the normal reference range in 6-week schizophrenia trials ranged between 1% and 2% for VRAYLAR-treated patients, increasing with dose, and was 1% for placebo-treated patients. The proportions of patients with transaminase elevations of ≥3 times the upper limits of the normal reference range in 3-week bipolar mania trials ranged between 2% and 4% for VRAYLAR-treated patients depending on dose group administered and 2% for placebo-treated patients. The proportions of patients with transaminase elevations of ≥3 times the upper limits of the normal reference range in 6-week and 8-week bipolar depression trials ranged between 0% and 0.5% for VRAYLAR-treated patients depending on dose group administered and 0.4% for placebo-treated patients.

The proportions of patients with elevations of creatine phosphokinase (CPK) greater than 1000 U/L in 6-week schizophrenia trials ranged between 4% and 6% for VRAYLAR-treated patients, increasing with dose, and was 4% for placebo-treated patients. The proportions of patients with elevations of CPK greater than 1000 U/L in 3-week bipolar mania trials was about 4% in VRAYLAR and placebo-treated patients. The proportions of patients with elevations of CPK greater than 1000 U/L in 6-week and 8-week bipolar depression trials ranged between 0.2% and 1% for VRAYLAR-treated patients versus 0.2% for placebo-treated patients.

Other Adverse Reactions Observed During The Pre-Marketing Evaluation Of Vraylar

Adverse reactions listed below were reported by patients treated with VRAYLAR at doses of ≥ 1.5 mg once daily within the premarketing database of 3988 VRAYLAR-treated patients. The reactions listed are those that could be of clinical importance, as well as reactions that are plausibly drug-related on pharmacologic or other grounds. Reactions that appear elsewhere in the VRAYLAR label are not included.

Reactions are further categorized by organ class and listed in order of decreasing frequency, according to the following definition: those occurring in at least 1/100 patients (frequent) ; those occurring in 1/100 to 1/1000 patients (infrequent); and those occurring in fewer than 1/1000 patients (rare).

Gastrointestinal Disorders: Infrequent: gastroesophageal reflux disease, gastritis

Hepatobiliary Disorders: Rare: hepatitis

Metabolism and Nutrition Disorders: Frequent: decreased appetite; Infrequent: hyponatremia

Musculoskeletal and Connective Tissue Disorders: Rare: rhabdomyolysis

Nervous System Disorders: Rare: ischemic stroke

Psychiatric Disorders: Infrequent: suicide attempts, suicide ideation; Rare: completed suicide

Renal and Urinary Disorders: Infrequent: pollakiuria

Skin and Subcutaneous Tissue Disorders: Infrequent: hyperhidrosis

Postmarketing Experience

The following adverse reaction has been identified during post approval use of VRAYLAR. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency or establish a causal relationship to drug exposure.

Skin and Subcutaneous Tissue Disorders – Stevens-Johnson syndrome

Read the entire FDA prescribing information for Vraylar (Cariprazine Capsules)

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FDA Approves Vraylar (Cariprazine) for Bipolar Depression

The FDA has approved the supplemental new drug application for Vraylar (cariprazine, Allergan) for the treatment of depressive episodes associated with bipolar I disorder in adults.

Originally approved in 2015, Vraylar is an oral once daily atypical antipsychotic that is also indicated for treatment of schizophrenia and the acute treatment of manic or mixed episodes associated with bipolar I disorder in adults.

For treatment of depression in bipolar disorder, Vraylar can be taken once daily with or without food at a starting dose of 1.5 mg or at a dose between 1.5 mg and 3 mg.

Trending: The Role of Data Mitigating Drug Diversion

Vraylar is contraindicated for patients who have a known hypersensitivity to cariprazine. Adverse reactions have included rash, pruritus, urticaria, and events suggestive of angioedema.

The recent indication addition is based on results of three trials in which cariprazine demonstrated a greater improvement than the placebo for the change from baseline to week six on the Montgomery Asberg Depression Rating scale total score. Common adverse events reported in the trials included nausea, akathisia, restlessness, and extrapyramidal symptoms.

“Treating bipolar disorder can be very difficult because people living with the illness experience a range of depressive and manic symptoms, sometimes both at the same time, and this FDA approval gives healthcare providers a new option to treat the full spectrum of bipolar I disorder symptoms, specifically manic, mixed, and depressive episodes, with just one medication,” said Dr. Stephen Stahl, MD, PhD, Professor of Psychiatry at the University of California San Diego and lead author of the post hoc analysis. “Treating depression, mania and mixed episodes with a single medication is important for people living with, and healthcare providers treating, this complex illness. This approval can streamline a treatment decision while helping to stabilize the disorder.”

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