VRAYLAR® (cariprazine) Tolerability and Safety Skip to Main Content Contact Medical Information Prescribing Information Patient Site Savings Cards Request Samples Speaker Program Request a Rep Indications Adjunctive MDD Overview Bipolar I Overview Schizophrenia Efficacy Adjunctive MDD Bipolar I Depression Bipolar I Acute Manic or Mixed Episodes Schizophrenia Tolerability & Safety Mechanism of Action Dosing Savings & Resources Access Savings Resources VRAYLAR Videos Speaker Program Request a Rep Well-established tolerability and safety across 4 indications Adjunctive MDD BP-I depression BP-I manic or mixed Schizophrenia Well-established tolerability across weight and metabolics In 6-week MDD studies, VRAYLAR + ADT-treated patients demonstrated mean weight change of 1.5 lb 1 Mean change
at endpoint Proportion of patients with
weight increase ≥7% Placebo + ADT (n=503) +0.4 lb 1% VRAYLAR 1.5 mg/day
+ ADT (n=502) +1.5 lb 2% VRAYLAR 3 mg/day
+ ADT (n=503) +1.5 lb 2% In the 8-week study, mean weight change was <2 lb in patients treated with VRAYLAR + antidepressant 1 * In 6-week MDD studies, VRAYLAR demonstrated metabolic shifts similar to placebo for total cholesterol and fasting triglycerides when taken with an antidepressant 1,2 Total cholesterol Proportion of patients with metabolic
shifts was similar to placebo † Fasting triglycerides Fasting glucose 97% of patients did not have a clinically
meaningful increase in blood glucose ‡ Prolactin (ng/mL) § No meaningful increase in mean levels Weight change and metabolic shifts were generally consistent in MDD and bipolar I depression studies 1 (See bipolar I depression tab above) *In the 8-week MDD study, 2.5% of people taking VRAYLAR + ADT had a weight increase of ≥7% vs 2% of those taking placebo. The mean weight changes reported in this study were VRAYLAR 1-2 mg/day + ADT (n=273) = +1.98 lb; VRAYLAR 2-4.5 mg/day + ADT (n=273) = +1.98 lb; placebo + ADT (n=266) = 0 lb. 1 See additional weight data from 26-week MDD study. † In the 6- and 8-week MDD studies, proportion of patients with metabolic shifts was similar to placebo. Shift defined as: total cholesterol: normal/borderline (<240 mg/dL) to high (≥240 mg/dL); fasting triglycerides: normal/borderline (<200 mg/dL) to high (≥200 mg/dL). 1 ‡ In the 6-week studies, the proportion of patients with shifts in fasting glucose from normal (<100 mg/dL) to high (≥126 mg/dL): VRAYLAR 1.5 mg/day + ADT=2%; VRAYLAR 3 mg/day + ADT=3.2%; placebo-treated=1.3%. The proportion of patients with shifts in fasting glucose from normal to borderline (≥100 and <126 mg/dL) or from borderline to high was similar in patients treated with VRAYLAR and placebo. In the 8-week study, the shifts in fasting glucose were similar among the VRAYLAR and placebo + ADT groups. 1 § In two 6-week MDD studies, mean change from baseline in prolactin levels was 4.1 ng/mL and 3.8 ng/mL in the 1.5 mg/day + ADT group (baseline mean: 9.4 - 9.7) and 2.6 ng/mL and 2.9 ng/mL in the 3 mg/day group + ADT (baseline mean: 11.3 - 11.6) vs 1.2 ng/mL and 0.92 ng/mL in the placebo + ADT group (baseline mean: 9.7 - 10.5). In the 8-week MDD study, the mean change from baseline was 3.8 ng/mL in the 1-2 mg/day + ADT group (baseline mean: 8.8) and 4.1 ng/mL in the 2-4.5 mg/day + ADT group (baseline mean 9.4) vs 0.7 ng/mL in the placebo group (baseline mean: 9.4). 2 Well-established safety profile across two 6-week major depressive disorder trials 1 Most common adverse reactions in two 6-week MDD studies (≥5% and at least twice that of placebo) 1 Placebo + ADT (n=503) VRAYLAR 1.5 mg/day + ADT (n=502) VRAYLAR 3 mg/day + ADT (n=503) Insomnia || 5% 9% 10% Nausea 3% 7% 6% Akathisia ¶ 2% 7% 10% Most common adverse events in two trials that followed recommended titration. Rates of somnolence and sedation in VRAYLAR 1.5 mg/day + ADT (5%) and 3 mg/day + ADT (6%) groups were similar to placebo + ADT (4%). 2 || Insomnia terms: initial insomnia, insomnia, middle insomnia, poor sleep quality, sleep disorder, terminal insomnia. ¶ Akathisia terms: akathisia, psychomotor hyperactivity, feeling jittery, nervousness, tension. Discontinuation rates 1.4% of VRAYLAR-treated patients discontinued treatment as a result of akathisia compared with 0.4% of placebo-treated patients 2 In two 6-week MDD studies, 4% of VRAYLAR-treated patients discontinued treatment compared with 2% of placebo-treated patients when following recommended titration schedule. There were no adverse reactions leading to discontinuation that occurred at a rate of ≥2% in VRAYLAR patients and at least twice the rate of placebo. Sexual adverse reactions Less than 1% of VRAYLAR + ADT-treated patients reported sexual adverse reactions in two 6-week MDD studies 2# Placebo + ADT (n=503) VRAYLAR 1.5 mg/day + ADT (n=502) VRAYLAR 3 mg/day + ADT (n=503) Abnormal orgasm 0% 0% 0.2% Decreased libido 0% 0.2% 0% Erectile dysfunction 0% 0.2% 0% Ejaculation failure 0% 0.2% 0% Ejaculation disorder 0% 0% 0% # These are self-reported adverse effects. If an adverse effect was not reported during a study, a value of 0 was used. Additional akathisia data Additional akathisia data from 6-week adjunctive MDD studies 2 Level of severity 94% of akathisia events were mild or moderate in patients treated with VRAYLAR + ADT in the two 6-week MDD studies Management In patients who experienced akathisia, rescue medications were used by approximately 3% of patients taking VRAYLAR + ADT and by 0.4% of patients taking placebo + ADT** Resolution Akathisia resolved, on average, within approximately 2 weeks for patients receiving VRAYLAR + ADT †† **The most common rescue medication used was propranolol. 2 †† The discontinuation rates due to akathisia reported in these studies were placebo + ADT (n=503) = 0.4%; VRAYLAR 1.5 mg/day + ADT (n=502) = 0.6%; VRAYLAR 3 mg/day + ADT (n=503) = 2.2%; VRAYLAR Overall + ADT (n=1005) = 1.4%. 2 Tardive dyskinesia data Incidence of tardive dyskinesia in VRAYLAR clinical studies 1,2 1 out of 1,551 patients taking VRAYLAR + ADT in adjunctive MDD trials experienced tardive dyskinesia ‡‡ In two fixed-dose 6-week and one flexible-dose 8-week placebo-controlled adjunctive MDD trials 8 out of 7,431 patients taking VRAYLAR experienced tardive dyskinesia §§ In 21 clinical trials, across 4 clinical development programs for VRAYLAR indications, ranging from 3 to 72 weeks |||| The Diagnostic and Statistical Manual of Mental Disorders , Fifth Edition (DSM-5) clinically defines tardive dyskinesia as involuntary athetoid or choreiform movements lasting at least a few weeks, developing in association with the use of a neuroleptic medication for at least a few months, and persisting beyond 4 to 8 weeks. 3 Risk of developing tardive dyskinesia (a syndrome of potentially irreversible, involuntary, dyskinetic movements) and the likelihood it will become irreversible may increase with the duration of treatment and the cumulative dose. The syndrome can develop after a relatively brief treatment period, even at low doses, or after treatment discontinuation. If signs and symptoms of tardive dyskinesia appear, drug discontinuation should be considered. 1 ‡‡ Dosing ranged from 1.5 mg–4.5 mg/day. 2 §§ Dosing ranged from 1.5 mg–12 mg/day. 2 |||| VRAYLAR is approved in adults as adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD), for the treatment of depressive episodes associated with bipolar I disorder (bipolar depression), for the acute treatment of manic or mixed episodes associated with bipolar I disorder, and for the treatment of schizophrenia. 1 Well-established tolerability across weight and metabolics Weight change ≤1.5 lb from baseline to endpoint in pivotal 6- and 8-week studies 1 * Mean change
at endpoint Proportion of patients with
weight increase ≥7% Placebo (n=463) -0.2 lb 1% VRAYLAR 1.5 mg/day (n=467) +1.5 lb 3% VRAYLAR 3 mg/day (n=465) +0.9 lb 3% Placebo-like impact on lipids and fasting glucose from baseline to endpoint in pivotal studies 1,2 † Total cholesterol Proportion of patients with metabolic
shifts was similar to placebo Fasting triglycerides Fasting glucose Prolactin (ng/mL) No meaningful increase in mean levels Weight change and metabolic shifts were generally consistent in MDD and bipolar I depression studies (See adjunctive MDD tab above) *Recommended dose range of VRAYLAR is 1.5–3 mg/day for depressive episodes associated with bipolar I. 1 † Metabolic shift defined as: fasting glucose: normal (<100 mg/dL) to high (≥126 mg/dL), borderline (≥100 mg/dL and <126 mg/dL) to high; total cholesterol: normal/borderline (<240 mg/dL) to high (≥240 mg/dL); fasting triglycerides: normal/borderline (<200 mg/dL) to high (≥200 mg/dL). 1,2 Well-established safety profile across 3 bipolar I depression studies Most common adverse reactions (≥5% and at least twice that of placebo) 1 Recommended dose range Placebo (n=468) VRAYLAR 1.5 mg/day (n=470) VRAYLAR 3 mg/day (n=469) Nausea 3% 7% 7% Akathisia 2% 6% 10% Restlessness 3% 2% 7% EPS ‡ 2% 4% 6% Rates of somnolence and sedation in VRAYLAR 1.5 mg/day (7%) and 3 mg/day (6%) groups were similar to placebo (4%) 1 >99% of EPS and akathisia events in bipolar I depression studies were mild or moderate 4 ‡ EPS included akinesia, drooling, dyskinesia, dystonia, extrapyramidal disorder, hypokinesia, muscle tightness, musculoskeletal stiffness, myoclonus, oculogyric crisis, salivary hypersecretion, tardive dyskinesia, and tremor. 1 Discontinuation rates 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 1 VRAYLAR-treated patients discontinued due to EPS at a rate of 0.4% vs 0% for placebo and discontinued due to akathisia at a rate of 1.5% vs 0% for placebo 1§ § EPS excludes akathisia and restlessness. Monitor patients when initiating or changing the dose of VRAYLAR 1 EPS and akathisia were among the most common adverse reactions and were most frequently observed following initiation or up-titration 1,4 Sexual adverse reactions Less than 1% of patients reported sexual adverse reactions across clinical studies 2 Most common reactions included: Placebo
(n=468) VRAYLAR 
1.5 mg/day (n=470) VRAYLAR 
3 mg/day (n=469) Abnormal orgasm 0% 0% 0.4% Decreased libido 0% 0.2% 0% Erectile dysfunction 0% 0.6% 0.9% Delayed ejaculation 0% 0% 0% Additional akathisia data Time to resolution of akathisia observed for patients on VRAYLAR 5 7.35% of patients treated with VRAYLAR experienced akathisia during treatment vs 2.14% on placebo 2 Of the patients who experienced akathisia while taking VRAYLAR, 94.2% resolved either during treatment or within 30 days of the last dose vs 100% on placebo 2 || 18.8% (13/69) of patients with akathisia used beta blocking agents on VRAYLAR vs 30% (3/10) on placebo. 2,5 These are post-hoc descriptive statistics on pooled events occurring during three 6- and 8-week pivotal clinical studies. These analyses were not prespecified and no statistical analyses have been performed. Data are descriptive only, and may not be generalizable to all patients. Extrapyramidal symptoms (EPS) data Time to resolution of EPS observed for patients on VRAYLAR 5 4.26% of patients treated with VRAYLAR experienced EPS during treatment vs 2.14% on placebo 2 Of the patients who experienced EPS while taking VRAYLAR, 90% resolved either during treatment or within 30 days of the last dose vs 80% on placebo 2 ¶ 72.5% (29/40) of patients with EPS used rescue medication on VRAYLAR vs 20% (2/10) on placebo. 2,4 These are post-hoc descriptive statistics on pooled events occurring during three 6- and 8-week pivotal clinical studies. These analyses were not prespecified and no statistical analyses have been performed. Data are descriptive only, and may not be generalizable to all patients. Tardive dyskinesia data Incidence of tardive dyskinesia in VRAYLAR clinical studies 2,4 0.2% (n=2) out of 939 patients taking VRAYLAR in bipolar I depression trials experienced tardive dyskinesia # In two fixed-dose 6-week and one fixed-dose 8-week placebo-controlled bipolar I depression trials. 4 0.1% (n=8) out of 7,431 patients taking VRAYLAR experienced tardive dyskinesia 2 ** In 21 clinical trials, across 4 clinical development programs for VRAYLAR indications, ranging from 3 to 72 weeks. †† The Diagnostic and Statistical Manual of Mental Disorders , Fifth Edition (DSM-5) clinically defines tardive dyskinesia as involuntary athetoid or choreiform movements lasting a few weeks, developing in association with the use of neuroleptic medication for at least a few months, and persisting beyond 4 to 8 weeks. 3 Risk of developing tardive dyskinesia (a syndrome of potentially irreversible, involuntary, dyskinetic movements) and the likelihood it will become irreversible may increase with the duration of treatment and the cumulative dose. The syndrome can develop after a relatively brief treatment period, even at low doses, or after treatment discontinuation. If signs and symptoms of tardive dyskinesia appear, drug discontinuation should be considered. 1 # Dosing ranged from 1.5 mg–3 mg/day. 1 **Dosing ranged from 1.5 mg–12 mg/day. 1 †† VRAYLAR is approved in adults in adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD), for the treatment of depressive episodes associated with bipolar I disorder (bipolar depression), for the acute treatment of manic or mixed episodes associated with bipolar I disorder, and for the treatment of schizophrenia. 1 Well-established tolerability across weight and metabolics Weight change of 1.1 lb from baseline to endpoint in 3-week pivotal studies 1 * † Mean change
at endpoint Proportion of patients with
weight increase ≥7% Placebo (n=439) +0.4 lb 2% VRAYLAR 3-6 mg/day (n=259) +1.1 lb 1% Placebo-like impact on lipids and fasting glucose from baseline to endpoint in pivotal studies 1,2 †‡ Total cholesterol Proportion of patients with metabolic
shifts was similar to placebo Fasting triglycerides Fasting glucose Prolactin (ng/mL) No meaningful increase in mean levels *Recommended dose range of VRAYLAR is 3–6 mg/day for manic and mixed episodes and 1.5–3 mg/day for depressive episodes associated with bipolar I. Doses above 6 mg daily did not appear to have additional benefit over lower doses and a dose-related increase in certain adverse reactions was observed. 1 † Data shown from baseline to endpoint by modal daily dose, defined as most frequently administered dose per patient. 1 ‡ Metabolic shift defined as: fasting glucose: normal (<100 mg/dL) to high (≥126 mg/dL), borderline (≥100 mg/dL and <126 mg/dL) to high total cholesterol: normal/borderline (<240 mg/dL) to high (≥240 mg/dL); fasting triglycerides: normal/borderline (<200 mg/dL) to high (≥200 mg/dL). 1,2 Well-established safety profile across 3 bipolar I acute manic or mixed studies Most common adverse reactions (≥5% and at least twice that of placebo) 1 Recommended dose range Placebo (n=442) VRAYLAR 3-6 mg/day (n=263) § VRAYLAR 9-12 mg/day (n=360) § EPS II 12% 26% 29% Akathisia 5% 20% 21% Vomiting 4% 10% 8% Dyspepsia 4% 7% 9% Somnolence ¶ 4% 7% 8% Restlessness 2% 7% 7% >92% of EPS and akathisia events in bipolar I acute manic studies were mild or moderate 2 § Data shown from baseline to endpoint (Week 3) by modal daily dose, defined as most frequently administered dose per patient. 1 II EPS included bradykinesia, drooling, dyskinesia, dystonia, extrapyramidal disorder, hypokinesia, muscle rigidity, muscle tightness, musculoskeletal stiffness, oromandibular dystonia, parkinsonism, salivary hypersecretion, and tremor. 1 ¶ Somnolence included hypersomnia, sedation, and somnolence. 1 Discontinuation rates 1 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 VRAYLAR-treated patients discontinued due to EPS at a rate of 1% vs 0.2% for placebo and discontinued due to akathisia at a rate of 2% vs 0% for placebo 1# # EPS excludes akathisia and restlessness. Monitor patients when initiating or changing the dose of VRAYLAR 1 EPS and akathisia were among the most common adverse reactions and were most frequently observed following initiation or up‑titration 1,6 Weight, metabolics, and prolactin Weight change ≤2.2 lb from baseline to endpoint in 6-week pivotal studies 1 * † Mean change
at endpoint Proportion of patients with
weight increase ≥7% Placebo (n=573) +0.7 lb 5% VRAYLAR 1.5-3 mg/day (n=512) +1.8 lb 8% VRAYLAR 4.5-6 mg/day (n=570) +2.2 lb 8% Placebo-like impact on lipids and fasting glucose from baseline to endpoint in pivotal studies 1,2 †‡ Total cholesterol Proportion of patients with metabolic
shifts was similar to placebo Fasting triglycerides Fasting glucose Prolactin (ng/mL) No meaningful increase in mean levels *Recommended dose range of VRAYLAR is 1.5–6 mg/day for schizophrenia. Doses above 6 mg daily did not appear to have additional benefit over lower doses and a dose-related increase in certain adverse reactions was observed. 1 † Data shown from baseline to endpoint (Week 6) by modal daily dose, defined as most frequently administered dose per patient. 1,2 ‡ Metabolic shift defined as: fasting glucose: normal (<100 mg/dL) to high (≥126 mg/dL), borderline (≥100 mg/dL and <126 mg/dL) to high; total cholesterol: normal/borderline (<240 mg/dL) to high (≥240 mg/dL); fasting triglycerides: normal/borderline (<200 mg/dL) to high (≥200 mg/dL). 1,2 92-week long-term maintenance study Long-term maintenance treatment of schizophrenia in adults was assessed in a 92-week study of VRAYLAR 1,7 Following a 20-week, open-label phase on a stable dose of VRAYLAR, patients were randomized to VRAYLAR 3-9 mg/day or placebo for a 72-week, double-blind phase. 1,7 72-week, double-blind phase Placebo
(n=99) VRAYLAR 3-9 mg/day
(n=101) Weight change (lb) § +2.1 +2.5 Fasting glucose (mg/dL) +4.1 +5.4 Fasting triglycerides (mg/dL) -7.6 +2.8 Total cholesterol (mg/dL) -6.5 -4.1 Prolactin (ng/mL) -6.4 -6.7 Recommended dose range of VRAYLAR is 1.5-6 mg/day. Doses above 6 mg daily did not appear to have additional benefit over lower doses, and a dose-related increase in certain adverse reactions was observed. § Proportion of patients with weight gain ≥7% was 10.6% during the open-label phase and 27.0% and 32.3% for VRAYLAR and placebo-treated patients, respectively, during the double-blind phase. 7 Observed adverse reactions Most common adverse reactions from short-term schizophrenia studies (≥5% and at least twice that of placebo) 1 Recommended dose range Placebo
(n=584) VRAYLAR
1.5-3 mg/day (n=539) II VRAYLAR
4.5-6 mg/day (n=575) II VRAYLAR
9-12 mg/day (n=203) II EPS ¶ 8% 15% 19% 20% Akathisia 4% 9% 13% 14% >97% of EPS and akathisia events in short-term schizophrenia studies were mild or moderate 2 II Data shown from baseline to endpoint (Week 6) by modal daily dose, defined as most frequently administered dose per patient. 1,2 ¶ EPS included 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, and trismus. 1 Discontinuation rates 1,2 Overall, 9% of the patients who received VRAYLAR discontinued treatment due to an adverse reaction, compared with 12% of placebo-treated patients in these trials These data include patients who discontinued due to worsening of schizophrenia (ie, untreated illness). VRAYLAR-treated patients discontinued due to EPS at a rate of 0.3% vs 0.2% for placebo and discontinued due to akathisia at a rate of 0.5% vs 0.2% for placebo 1# # EPS excludes akathisia and restlessness. Monitor patients when initiating or changing the dose of VRAYLAR 1 EPS and akathisia were among the most common adverse reactions and were most frequently observed following initiation or up‑titration 1,8 View MDD efficacy View BP-I efficacy ADT=antidepressant therapy; BP-I=bipolar I disorder; DSM= Diagnostic and Statistical Manual of Mental Disorders; EPS=extrapyramidal symptoms; MDD=major depressive disorder. INDICATIONS AND USAGE VRAYLAR (cariprazine) is indicated in adults as adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD), for the treatment of depressive episodes associated with bipolar I disorder (bipolar depression), for the acute treatment of manic or mixed episodes associated with bipolar I disorder, and for the treatment of schizophrenia. IMPORTANT SAFETY INFORMATION WARNINGS: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS and SUICIDAL THOUGHTS AND BEHAVIORS Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. VRAYLAR is not approved for treatment of patients with dementia-related psychosis. Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies. Closely monitor antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors. Contraindication: VRAYLAR is contraindicated in patients with known hypersensitivity. Reactions have included rash, pruritus, urticaria, and reactions suggestive of angioedema. Cerebrovascular Adverse Reactions, Including Stroke: In clinical trials with antipsychotic drugs, elderly patients with dementia had a higher incidence of cerebrovascular adverse reactions, including fatalities, vs placebo. VRAYLAR is not approved for the treatment of patients with dementia-related psychosis. Neuroleptic Malignant Syndrome (NMS): NMS, a potentially fatal symptom complex, has been reported with antipsychotic drugs. NMS may cause hyperpyrexia, muscle rigidity, delirium, and autonomic instability. Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. Manage with immediate discontinuation, intensive symptomatic treatment, and monitoring. Tardive Dyskinesia (TD): Risk of developing TD (a syndrome of potentially irreversible, involuntary, dyskinetic movements) and the likelihood it will become irreversible may increase with the duration of treatment and the cumulative dose. The syndrome can develop after a relatively brief treatment period, even at low doses, or after treatment discontinuation. If signs and symptoms of TD appear, drug discontinuation should be considered. Late-Occurring Adverse Reactions: Adverse reactions may first appear several weeks after initiation of VRAYLAR, probably because plasma levels of cariprazine and its major metabolites accumulate over time. As a result, the incidence of adverse reactions in short-term trials may not reflect the rates after longer-term exposures. Monitor for adverse reactions, including extrapyramidal symptoms (EPS) or akathisia, and patient response for several weeks after starting VRAYLAR and after each dosage increase. Consider reducing the dose or discontinuing the drug. Metabolic Changes: Atypical antipsychotics, including VRAYLAR, have caused metabolic changes, such as: Hyperglycemia and Diabetes Mellitus: Hyperglycemia, in some cases associated with ketoacidosis, hyperosmolar coma, or death, has been reported in patients treated with atypical antipsychotics. Assess fasting glucose before or soon after initiation of treatment, and monitor periodically during long-term treatment. Dyslipidemia: Atypical antipsychotics cause adverse alterations in lipids. Before or soon after starting an antipsychotic, obtain baseline fasting lipid profile and monitor periodically during treatment. Weight Gain: Weight gain has been observed with VRAYLAR. Monitor weight at baseline and frequently thereafter. Leukopenia, Neutropenia, and Agranulocytosis: Leukopenia/neutropenia have been reported with antipsychotics, including VRAYLAR. Agranulocytosis (including fatal cases) has been reported with other antipsychotics. Monitor complete blood count in patients with pre-existing low white blood cell count (WBC)/absolute neutrophil count or history of drug-induced leukopenia/neutropenia. Discontinue VRAYLAR at the first sign of a clinically significant decline in WBC and in severely neutropenic patients. Orthostatic Hypotension and Syncope: Atypical antipsychotics cause orthostatic hypotension and syncope, with the greatest risk during initial titration and with dose increases. Monitor orthostatic vital signs in patients predisposed to hypotension and in those with cardiovascular/cerebrovascular diseases. Falls: VRAYLAR may cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries. For patients with diseases, conditions, or medications that could exacerbate these effects, complete fall risk assessments when initiating antipsychotics and recurrently for patients on long-term therapy. Seizures: Use VRAYLAR with caution in patients with a history of seizures or with conditions that lower the seizure threshold. Potential for Cognitive and Motor Impairment: Somnolence was reported with VRAYLAR. Caution patients about performing activities requiring mental alertness (eg, operating hazardous machinery or a motor vehicle). Body Temperature Dysregulation: Use VRAYLAR with caution in patients who may experience conditions that increase body temperature (eg, strenuous exercise, extreme heat, dehydration, or concomitant anticholinergics). Dysphagia: Esophageal dysmotility and aspiration have been associated with antipsychotics. Antipsychotic drugs, including VRAYLAR, should be used cautiously in patients at risk for aspiration. Drug Interactions: Strong and moderate CYP3A4 inhibitors increase VRAYLAR concentrations, so VRAYLAR dose reduction is recommended. Concomitant use with CYP3A4 inducers is not recommended. Adverse Reactions: The most common adverse reactions in adult clinical trials (≥5% and at least twice the rate of placebo) are listed below: Adjunctive Treatment of Major Depressive Disorder: In 6-week, fixed-dose trials the incidences within the recommended doses (VRAYLAR 1.5 mg/day + antidepressant therapy [ADT] or 3 mg/day + ADT vs placebo + ADT) were akathisia (7%, 10% vs 2%), nausea (7%, 6% vs 3%), and insomnia (9%, 10% vs 5%). In one 8-week flexible-dose trial, incidences within the doses (VRAYLAR 1-2 mg/day + antidepressant therapy [ADT] or 2-4.5 mg/day + ADT vs placebo + ADT) were akathisia (8%, 23% vs 3%), restlessness (8%, 8% vs 3%), fatigue (7%, 10% vs 4%), constipation (2%, 5% vs 2%), nausea (7%, 13% vs 5%), increased appetite (2%, 5% vs 2%), dizziness (4%, 5% vs 2%), insomnia (14%, 16% vs 8%), and extrapyramidal symptoms (12%, 18% vs 5%). Bipolar Mania: The incidences within the recommended dose range (VRAYLAR 3–6 mg/day vs placebo) were EPS (26% vs 12%), akathisia (20% vs 5%), vomiting (10% vs 4%), dyspepsia (7% vs 4%), somnolence (7% vs 4%), and restlessness (7% vs 2%). Bipolar Depression: The incidences within the recommended doses (VRAYLAR 1.5 mg/day or 3 mg/day vs placebo) were nausea (7%, 7% vs 3%), akathisia (6%, 10% vs 2%), restlessness (2%, 7% vs 3%), and EPS (4%, 6% vs 2%). Schizophrenia: The incidences within the recommended dose range (VRAYLAR 1.5–3 mg/day and 4.5–6 mg/day vs placebo) were EPS (15%, 19% vs 8%) and akathisia (9%, 13% vs 4%). VRAYLAR is available in 0.5 mg, 0.75 mg, 1.5 mg, 3 mg, 4.5 mg, and 6 mg capsules. INDICATIONS AND USAGE VRAYLAR (cariprazine) is indicated for adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD) in adults, for the treatment of depressive episodes associated with bipolar I disorder (bipolar depression) in adults, for the acute treatment of manic or mixed episodes associated with bipolar I disorder in adult and pediatric patients 10 years of age and older, and for the treatment of schizophrenia in adult and pediatric patients 13 years of age and older. US-VRAA-250443 Please also see full Prescribing Information , including Boxed Warnings. References: VRAYLAR [package insert]. North Chicago, IL: AbbVie Inc.; 2024. Data on file, AbbVie Inc. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-5-TR. 5th ed. American Psychiatric Association; 2022. Citrome L, Yatham LN, Patel MD, Barabássy Á, Hankinson A, Earley WR. Cariprazine and akathisia, restlessness, and extrapyramidal symptoms in patients with bipolar depression. J Affect Disord . 2021;288:191-198. doi:10.1016/j.jad.2021.03.076 Citrome L, Yatham L, Patel M, Earley W. Incidence and characteristics of akathisia and restlessness during cariprazine treatment for bipolar I disorder. Poster presented at: 15th Annual NEI Congress; Colorado Springs, CO; November 7-10, 2019. Earley W, Durgam S, Lu K, et al. Tolerability of cariprazine in the treatment of acute bipolar I mania: A pooled post hoc analysis of 3 phase II/III studies. J Affect Disord . 2017;215:205-212. doi:10.1016/j.jad.2017.03.032 Durgam S, Earley W, Li R, et al. Long-term cariprazine treatment for the prevention of relapse in patients with schizophrenia: A randomized, double-blind, placebo-controlled trial [published correction appears in Schizophr Res. 2018 Feb;192:493]. Schizophr Res. 2016;176(2-3):264-271. doi:10.1016/j.schres.2016.06.030 Earley W, Durgam S, Lu K, Laszlovszky I, Debelle M, Kane JM. Safety and tolerability of cariprazine in patients with acute exacerbation of schizophrenia: a pooled analysis of four phase II/III randomized, double-blind, placebo-controlled studies. Int Clin Psychopharmacol . 2017;32(6):319-328. doi:10.1097/YIC.0000000000000187 Important Safety Information Full Prescribing Information About AbbVie Site Map Accessibility Statement Contact Us Terms of Use Privacy Notice Cookies Settings Your Privacy Choices US-VRAA-240301 If you are a patient, and have any questions, please discuss them with your doctor or healthcare provider. For additional information about VRAYLAR ® , call AbbVie Medical Information toll-free at 1.800.678.1605 . Licensed from Gedeon Richter Plc. © 2025 AbbVie. All rights reserved. VRAYLAR ® and its design are trademarks of Allergan Pharmaceuticals International Limited, an AbbVie company. VRAYPAY SM is a service mark of Allergan Pharmaceuticals International Limited, an AbbVie company. You are about to enter a site that is for U.S. Healthcare Professionals only. By selecting "Yes" below, you certify that you are a Healthcare Professional and that you wish to proceed to the Healthcare Professionals Only section on the AbbVie Medical Information site. Products or treatments described on this site are available in the U.S. but may not be available in all other countries. I am a licensed Healthcare Professional and wish to proceed to the Healthcare Professionals Only AbbVie Medical Information Site. Yes No US-VRAA-240301 WARNINGS: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS and SUICIDAL THOUGHTS AND BEHAVIORS Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. VRAYLAR is not approved for treatment of patients with dementia-related psychosis. Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies. Closely monitor antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors. WARNINGS: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS and SUICIDAL THOUGHTS AND BEHAVIORS Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. VRAYLAR is not approved for treatment of patients with dementia-related psychosis. WARNINGS: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS and SUICIDAL THOUGHTS AND BEHAVIORS Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. VRAYLAR is not approved for treatment of patients with dementia-related psychosis. Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies. Closely monitor antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors. WARNINGS: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS and SUICIDAL THOUGHTS AND BEHAVIORS Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. VRAYLAR is not approved for treatment of patients with dementia-related psychosis. INDICATIONS AND USAGE VRAYLAR (cariprazine) is indicated in adults as adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD), for the treatment of depressive episodes associated with bipolar I disorder (bipolar depression), for the acute treatment of manic or mixed episodes associated with bipolar I disorder, and for the treatment of schizophrenia. IMPORTANT SAFETY INFORMATION WARNINGS: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS and SUICIDAL THOUGHTS AND BEHAVIORS Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. VRAYLAR is not approved for treatment of patients with dementia-related psychosis. Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies. Closely monitor antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors. Contraindication: VRAYLAR is contraindicated in patients with known hypersensitivity. Reactions have included rash, pruritus, urticaria, and reactions suggestive of angioedema. Cerebrovascular Adverse Reactions, Including Stroke: In clinical trials with antipsychotic drugs, elderly patients with dementia had a higher incidence of cerebrovascular adverse reactions, including fatalities, vs placebo. VRAYLAR is not approved for the treatment of patients with dementia-related psychosis. Neuroleptic Malignant Syndrome (NMS): NMS, a potentially fatal symptom complex, has been reported with antipsychotic drugs. NMS may cause hyperpyrexia, muscle rigidity, delirium, and autonomic instability. Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. Manage with immediate discontinuation, intensive symptomatic treatment, and monitoring. Tardive Dyskinesia (TD): Risk of developing TD (a syndrome of potentially irreversible, involuntary, dyskinetic movements) and the likelihood it will become irreversible may increase with the duration of treatment and the cumulative dose. The syndrome can develop after a relatively brief treatment period, even at low doses, or after treatment discontinuation. If signs and symptoms of TD appear, drug discontinuation should be considered. Late-Occurring Adverse Reactions: Adverse reactions may first appear several weeks after initiation of VRAYLAR, probably because plasma levels of cariprazine and its major metabolites accumulate over time. As a result, the incidence of adverse reactions in short-term trials may not reflect the rates after longer-term exposures. Monitor for adverse reactions, including extrapyramidal symptoms (EPS) or akathisia, and patient response for several weeks after starting VRAYLAR and after each dosage increase. Consider reducing the dose or discontinuing the drug. Metabolic Changes: Atypical antipsychotics, including VRAYLAR, have caused metabolic changes, such as: Hyperglycemia and Diabetes Mellitus: Hyperglycemia, in some cases associated with ketoacidosis, hyperosmolar coma, or death, has been reported in patients treated with atypical antipsychotics. Assess fasting glucose before or soon after initiation of treatment, and monitor periodically during long-term treatment. Dyslipidemia: Atypical antipsychotics cause adverse alterations in lipids. Before or soon after starting an antipsychotic, obtain baseline fasting lipid profile and monitor periodically during treatment. Weight Gain: Weight gain has been observed with VRAYLAR. Monitor weight at baseline and frequently thereafter. Leukopenia, Neutropenia, and Agranulocytosis: Leukopenia/neutropenia have been reported with antipsychotics, including VRAYLAR. Agranulocytosis (including fatal cases) has been reported with other antipsychotics. Monitor complete blood count in patients with pre-existing low white blood cell count (WBC)/absolute neutrophil count or history of drug-induced leukopenia/neutropenia. Discontinue VRAYLAR at the first sign of a clinically significant decline in WBC and in severely neutropenic patients. Orthostatic Hypotension and Syncope: Atypical antipsychotics cause orthostatic hypotension and syncope, with the greatest risk during initial titration and with dose increases. Monitor orthostatic vital signs in patients predisposed to hypotension and in those with cardiovascular/cerebrovascular diseases. Falls: VRAYLAR may cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries. For patients with diseases, conditions, or medications that could exacerbate these effects, complete fall risk assessments when initiating antipsychotics and recurrently for patients on long-term therapy. Seizures: Use VRAYLAR with caution in patients with a history of seizures or with conditions that lower the seizure threshold. Potential for Cognitive and Motor Impairment: Somnolence was reported with VRAYLAR. Caution patients about performing activities requiring mental alertness (eg, operating hazardous machinery or a motor vehicle). Body Temperature Dysregulation: Use VRAYLAR with caution in patients who may experience conditions that increase body temperature (eg, strenuous exercise, extreme heat, dehydration, or concomitant anticholinergics). Dysphagia: Esophageal dysmotility and aspiration have been associated with antipsychotics. Antipsychotic drugs, including VRAYLAR, should be used cautiously in patients at risk for aspiration. Drug Interactions: Strong and moderate CYP3A4 inhibitors increase VRAYLAR concentrations, so VRAYLAR dose reduction is recommended. Concomitant use with CYP3A4 inducers is not recommended. Adverse Reactions: The most common adverse reactions in adult clinical trials (≥5% and at least twice the rate of placebo) are listed below: Adjunctive Treatment of Major Depressive Disorder: In 6-week, fixed-dose trials the incidences within the recommended doses (VRAYLAR 1.5 mg/day + antidepressant therapy [ADT] or 3 mg/day + ADT vs placebo + ADT) were akathisia (7%, 10% vs 2%), nausea (7%, 6% vs 3%), and insomnia (9%, 10% vs 5%). In one 8-week flexible-dose trial, incidences within the doses (VRAYLAR 1-2 mg/day + antidepressant therapy [ADT] or 2-4.5 mg/day + ADT vs placebo + ADT) were akathisia (8%, 23% vs 3%), restlessness (8%, 8% vs 3%), fatigue (7%, 10% vs 4%), constipation (2%, 5% vs 2%), nausea (7%, 13% vs 5%), increased appetite (2%, 5% vs 2%), dizziness (4%, 5% vs 2%), insomnia (14%, 16% vs 8%), and extrapyramidal symptoms (12%, 18% vs 5%). Bipolar Mania: The incidences within the recommended dose range (VRAYLAR 3–6 mg/day vs placebo) were EPS (26% vs 12%), akathisia (20% vs 5%), vomiting (10% vs 4%), dyspepsia (7% vs 4%), somnolence (7% vs 4%), and restlessness (7% vs 2%). Bipolar Depression: The incidences within the recommended doses (VRAYLAR 1.5 mg/day or 3 mg/day vs placebo) were nausea (7%, 7% vs 3%), akathisia (6%, 10% vs 2%), restlessness (2%, 7% vs 3%), and EPS (4%, 6% vs 2%). Schizophrenia: The incidences within the recommended dose range (VRAYLAR 1.5–3 mg/day and 4.5–6 mg/day vs placebo) were EPS (15%, 19% vs 8%) and akathisia (9%, 13% vs 4%). VRAYLAR is available in 0.5 mg, 0.75 mg, 1.5 mg, 3 mg, 4.5 mg, and 6 mg capsules. INDICATIONS AND USAGE VRAYLAR (cariprazine) is indicated for adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD) in adults, for the treatment of depressive episodes associated with bipolar I disorder (bipolar depression) in adults, for the acute treatment of manic or mixed episodes associated with bipolar I disorder in adult and pediatric patients 10 years of age and older, and for the treatment of schizophrenia in adult and pediatric patients 13 years of age and older. US-VRAA-250443 Please also see full Prescribing Information , including Boxed Warnings.