Vraylar Drug Information

General Dosing Information VRAYLAR is given orally once daily and can be taken with or without food. 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 reactions and treatment response for several weeks after starting VRAYLAR and after each dosage change.

Recommended Dosage in Schizophrenia Adult Patients

The starting dosage of VRAYLAR is 1.5 mg orally once daily. The recommended dosage range is 1.5 mg to 6 mg orally once daily. The dosage can be increased to 3 mg on Day 2.

Depending upon clinical response and tolerability, further dose adjustments can be made in 1.5 mg or 3 mg increments. In short-term controlled trials, dosages above 6 mg daily do not confer increased effectiveness sufficient to outweigh dose-related adverse reactions. Increase the dosage to 1.5 mg orally once daily on Day 3.

The maximum recommended dosage is 4.5 mg orally once daily.

In clinical trials, dosage titration at intervals of less than 14 days resulted in a higher incidence of adverse reactions. Initiating VRAYLAR is not recommended in pediatric patients while taking a strong or moderate CYP3A4 Inhibitor. Initiating a Strong or Moderate CYP3A4 Inhibitor While Taking a Stable Dosage of VRAYLAR Dosage recommendations for adult and pediatric patients initiating a strong or moderate CYP3A4 inhibitor while on a stable dose of VRAYLAR (see Table 2): Table 2: Dosage Modifications for VRAYLAR When Initiating a Strong or Moderate CYP3A4 Inhibitor and While Taking a Stable Dos ag e of VRAYLAR in Adult and Pediatric Patients When the strong or moderate CYP3A4 inhibitor is discontinued, the VRAYLAR dosage may need to be increased based on clinical response and tolerability.

Dosage Modifications for Patients Concomitantly Taking VRAYLAR with CYP3A4 Inducers Concomitant use of VRAYLAR and a CYP3A4 inducer has not been evaluated and is not recommended. 2. 7 Treatment Discontinuation Following discontinuation of VRAYLAR, the decline in plasma concentrations of active drug and metabolites may not be immediately reflected in patients’ clinical symptoms; the plasma concentration of cariprazine and its active metabolites will decline by 50% in ~1 week. There are no systematically collected data to specifically address switching patients from VRAYLAR to other antipsychotics or concerning concomitant administration with other antipsychotics.

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 6,722 adult patients exposed to one or more doses of VRAYLAR for the treatment of schizophrenia, manic or mixed episodes associated with bipolar I disorder, bipolar depression, and adjunctive treatment of major depressive disorder in placebo-controlled studies. This experience corresponds with a total experience of 1,182.8 patient-years.

Adult 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 8. Table 8.

Adverse Reactions Occurring in ≥ 2% of VRAYLAR-treated Patients and > Placebo-treated Adult Patients in 6-Week Schizophrenia Trials Note: Figures rounded to the nearest integer Data shown by modal daily dose, defined as most frequently administered dose per patient a Tachycardia terms: heart rate increased, sinus tachycardia, tachycardia b Abdominal pain terms: abdominal discomfort, abdominal pain, abdominal pain lower, abdominal pain upper, gastrointestinal pain c Diarrhea terms: diarrhea, frequent bowel movements d Fatigue terms: asthenia, fatigue e Hepatic enzyme increase terms: alanine aminotransferase increased, aspartate aminotransferase increased, hepatic enzyme increased f Extrapyramidal 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 g Headache terms: headache, tension headache h Somnolence terms: hypersomnia, sedation, somnolence i Insomnia terms: initial insomnia, insomnia, middle insomnia, terminal insomnia j Hypertension 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. Adult 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.

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. Table 9. Adverse Reactions Occurring in ≥ 2% of VRAYLAR-treated Patients and > Placebo-treated Adult Patients in 3-Week Bipolar Mania Trials 1 5 4 Note: Figures rounded to the nearest integer *Data shown by modal daily dose, defined as most frequently administered dose per patient a Tachycardia terms: heart rate increased, sinus tachycardia, tachycardia b Abdominal pain terms: abdominal discomfort, abdominal pain, abdominal pain upper, abdominal tenderness c Diarrhea: diarrhea, frequent bowel movements d Fatigue terms: asthenia, fatigue e Pyrexia terms: body temperature increased, pyrexia f Hepatic enzymes increased terms: alanine aminotransferase increased, aspartate aminotransferase increased, hepatic enzyme increased, transaminases increased g Extrapyramidal Symptoms terms: bradykinesia, drooling, dyskinesia, dystonia, extrapyramidal disorder, hypokinesia, muscle rigidity, muscle tightness, musculoskeletal stiffness, oromandibular dystonia, parkinsonism, salivary hypersecretion, tremor h Headache terms: headache, tension headache i Somnolence terms: hypersomnia, sedation, somnolence j Insomnia terms: initial insomnia, insomnia, middle insomnia k Hypertension terms: blood pressure diastolic increased, blood pressure increased, hypertension ⸰ The maximum recommended daily dose is 6 mg.

Adult 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. Table 10. Common Adverse Reactions (≥ 5% and at least twice the rate of placebo): Akathisia, nausea, and insomnia occurred in two 6-week, fixed-dose trials.

Akathisia, restlessness, fatigue, constipation, nausea, increased appetite, dizziness, insomnia, and extrapyramidal symptoms occurred in one 8-week flexible-dose trial. Table 11. Adverse Reactions Occurring in ≥ 2% of VRAYLAR-Treated Patients and > Placebo-Treated Adult Patients in Two Fixed-Dose 6-Week Placebo-Controlled Trials of Adjunctive Treatment of Major Depressive Disorder 1 1 2 Note: Figures rounded to the nearest integer a Akathisia terms: akathisia, psychomotor hyperactivity, feeling jittery, nervousness, tension b Somnolence terms: hypersomnia, sedation, lethargy, somnolence c Extrapyramidal symptoms terms: drooling, dyskinesia, extrapyramidal disorder, hypotonia, muscle contractions involuntary, muscle rigidity, muscle spasms, muscle tightness, muscle twitching, musculoskeletal stiffness, myoclonus, oromandibular dystonia, parkinsonism, resting tremor, restless legs syndrome, stiff leg syndrome, salivary hypersecretion, stiff tongue, tardive dyskinesia, tremor, trismus d Insomnia terms: initial insomnia, insomnia, middle insomnia, poor sleep quality, sleep disorder, terminal insomnia Adverse Reactions with an incidence of ≥ 2% and greater than placebo at 1 mg to 2 mg per day or 2 mg to 4.5 mg per day doses are shown in Table 12.

Table 12. Adverse Reactions Occurring in ≥ 2% of VRAYLAR-Treated Patients and > Placebo-Treated Adult Patients in a Flexible-dose 8-Week Placebo-Controlled Trial of Adjunctive Treatment of Major Depressive Disorder 1 3 a A kathisia terms: akathisia, feeling jittery, nervousness, tension b Extrapyramidal symptoms terms: cogwheel rigidity, drooling, dyskinesia, extrapyramidal disorder, hypertonia, jaw stiffness, muscle contractions involuntary, muscle disorder, muscle rigidity, muscle spasms, muscle tightness, muscle twitching, musculoskeletal stiffness, nuchal rigidity, parkinsonism, psychomotor retardation, reduced facial expression, resting tremor, restless legs syndrome, sensation of heaviness, salivary hypersecretion, tremor c Somnolence terms: hypersomnia, sedation, lethargy, somnolence d Insomnia terms: initial insomnia, insomnia, middle insomnia, terminal insomnia, sleep disorder, poor sleep quality D ystonia 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, bipolar depression and adjunctive treatment of major depressive disorder 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 adverse reactions related to extrapyramidal symptoms (EPS), excluding akathisia and restlessness was 17% for VRAYLAR-treated patients versus 8% for placebo-treated patients. These reactions 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.

In 3-week bipolar mania trials, the incidence of reported adverse reactions related to extrapyramidal symptoms (EPS), excluding akathisia and restlessness, was 28% for VRAYLAR-treated patients versus 12% for placebo-treated patients. The incidence of akathisia was 20% for VRAYLAR-treated patients versus 5% for placebo-treated patients. These reactions led to discontinuation in 1.5% of VRAYLAR-treated patients versus 0% of placebo-treated patients.

Cataracts The development of cataracts was observed in nonclinical studies. Cataracts were reported during the premarketing clinical trials of cariprazine; however, the duration of trials was too short to assess any association to cariprazine usage. 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 13, and from 3-week bipolar mania trials are shown in Table 14. Table 13. Mean Change in Blood Pressure at Endpoint in 6-Week Schizophrenia Trials (Adult Patients) Data shown by modal daily dose, defined as most frequently administered dose per patient ⸰ The maximum recommended daily dose is 6 mg.

Table 14. 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. VRAYLAR-treated patients’ supine blood pressure increased by 0.1 to 0.3 mmHg; placebo-treated patients’ supine blood pressure increased by 0.2 mmHg.

At the end of the 6-week trials, VRAYLAR-treated patients’ supine systolic blood pressure decreased by 0.1 to 0.7 mmHg; placebo-treated patients’ supine systolic blood pressure decreased by 0.1 mmHg. VRAYLAR-treated patients’ supine diastolic blood pressure increased by 0.1 mmHg and placebo-treated patients’ supine diastolic blood pressure increased by 0.2 mmHg. 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 two 6-week adjunctive treatment of major depressive disorder trials ranged between 0% and 1% for VRAYLAR-treated patients depending on dose group administered and 0% 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 two 6-week adjunctive treatment of major depressive disorder trials ranged between 0.6% and 0.8% for VRAYLAR-treated patients versus 0% 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 5,763 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 1/1,000 patients (rare).

Gastrointestinal D isorders: Infrequent: gastroesop hageal reflux disease, gastritis Hepatobiliary D isorders: Rare: hepatitis Metabolism and N utrition D isorders: Frequent: decreased appetite; Rare: hyponatremia Musculoskeletal and C onnective T issue D isorders: Rare: rhabdomyolysis Nervous S ystem D isorders: Rare: ischemic stroke Psychiatric D isorders: Infrequent: suicide ideation; Rare: completed suicide, suicide attempts Renal and U rinary D isorders: Infrequent: pollakiuria Skin and S ubcutaneous T issue D isorders: Infrequent: hyperhidrosis Pediatric Patients with Schizophrenia (13 to 17 years of age) or Bipolar Mania/Mixed Episodes (10 to 17 years of age) In a long-term open-label study, safety was assessed in 164 pediatric patients with schizophrenia or bipolar I disorder, of whom 72 received VRAYLAR for at least 6 months. Adverse reactions reported in clinical studies for this age group were generally similar to those observed in adult patients.

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

Table 15 displays clinically significant drug interactions with VRAYLAR. Table 15. Clinically Significant Drug Interactions with VRAYLAR Strong or Moderate CYP3A4 Inhibitors Clinical Impact: Concomitant use of VRAYLAR with a strong or moderate CYP3A4 inhibitor increases the exposures of cariprazine and its major active metabolite, didesmethylcariprazine (DDCAR), compared to use of VRAYLAR alone.

Intervention: If VRAYLAR is used with a strong or moderate CYP3A4 inhibitor, reduce VRAYLAR dosage. CYP3A4 Inducers Clinical Impact: CYP3A4 is responsible for the formation and elimination of the active metabolites of cariprazine. The effect of CYP3A4 inducers on the exposure of VRAYLAR has not been evaluated, and the net effect is unclear.

Intervention: Concomitant use of VRAYLAR with a CYP3A4 inducer is not recommended. Strong and Moderate CYP3A4 inhibitors: Reduce VRAYLAR dosage CYP3A4 inducers: Concomitant use is not recommended

Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to VRAYLAR during pregnancy. For more information, contact the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/. Risk Summary Neonates exposed to antipsychotic drugs during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery (see Clinical Considerations).

There are no available data on VRAYLAR use in pregnant women to inform any drug-associated risks for birth defects or miscarriage. The major active metabolite of cariprazine, DDCAR, has been detected in adult patients up to 12 weeks after discontinuation of VRAYLAR. Based on animal data, VRAYLAR may cause fetal harm.

Administration of cariprazine to rats during the period of organogenesis caused malformations, lower pup survival, and developmental delays at drug exposures less than the human exposure at the maximum recommended human dose (MRHD) of 6 mg/day. However, cariprazine was not teratogenic in rabbits at doses up to 4.6 times the MRHD of 6 mg/day. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Advise pregnant women of the potential risk to a fetus. Clinical Considerations Fetal/Neonatal Adverse Reactions Extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder have been reported in neonates whose mothers were exposed to antipsychotic drugs during the third trimester of pregnancy.

These symptoms have varied in severity. Some neonates recovered within hours or days without specific treatment; others required prolonged hospitalization. Monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately.

Data Animal Data Administration of cariprazine to pregnant rats during the period of organogenesis at oral doses of 0.5, 2.5, and 7.5 mg/kg/day, which are 0.2 to 3.5 times the maximum recommended human dose (MRHD) of 6 mg/day based on AUC of total cariprazine (i.e. sum of cariprazine, DCAR, and DDCAR), caused fetal developmental toxicity at all doses, which included reduced body weight, decreased male anogenital distance, and skeletal malformations of bent limb bones, scapula, and humerus. These effects occurred in the absence or presence of maternal toxicity. Maternal toxicity, observed as a reduction in body weight and food consumption, occurred at doses 1.2 and 3.5-times the MRHD of 6 mg/day based on AUC of total cariprazine.

At these doses, cariprazine caused fetal external malformations (localized fetal thoracic edema), visceral variations (undeveloped/underdeveloped renal papillae and/or distended urethrae), and skeletal developmental variations (bent ribs, unossified sternebrae). Cariprazine had no effect on fetal survival. Administration of cariprazine to pregnant rats during pregnancy and lactation at oral doses of 0.1, 0.3, and 1 mg/kg/day, which are 0.03 to 0.4 times the MRHD of 6 mg/day based on AUC of total cariprazine, caused a decrease in postnatal survival, birth weight, and post-weaning body weight of first generation pups at the dose that is 0.4 times the MRHD of 6 mg/day based on AUC of total cariprazine in absence of maternal toxicity.

First generation pups also had pale, cold bodies and developmental delays (renal papillae not developed or underdeveloped and decreased auditory startle response in males). Reproductive performance of the first generation pups was unaffected; however, the second generation pups had clinical signs and lower body weight similar to those of the first generation pups. Maternal body weight and food consumption were decreased at 4.6 times the MRHD of 6 mg/day based on AUC of total cariprazine; however, no adverse effects were observed on pregnancy parameters or reproductive organs.

Pediatric Use Schizophrenia The safety and effectiveness of VRAYLAR for treatment of schizophrenia have been established in pediatric patients 13 years of age and older. Use of VRAYLAR in this population is supported by evidence from adequate and well-controlled studies in adults with schizophrenia, pharmacokinetic data from adults and pediatric patients, and safety data in pediatric patients 13 to 17 years of age. Manic and Mixed Episodes Associated with Bipolar I Disorder The safety and effectiveness of VRAYLAR for treatment of manic and mixed episodes associated with bipolar I disorder have been established in pediatric patients 10 years of age and older.

Bipolar Depression The safety and effectiveness of VRAYLAR for treatment of bipolar depression in pediatric patients have not been established. Adjunctive Therapy for Treatment of MDD The safety and effectiveness of VRAYLAR as adjunctive therapy for treatment of MDD in pediatric patients have not been established. Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric patients.

Irritability Associated with Autism Spectrum Disorder​ The safety and effectiveness of VRAYLAR for the treatment of irritability associated with autism spectrum disorder in pediatric patients have not been established. In a single, 8-week, double-blind, placebo-controlled, flexible-dose clinical study conducted in pediatric patients 5 to 17 years of age with irritability associated with autism spectrum disorder diagnosed by the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition criteria, a total of 161 patients were enrolled, of which 76 patients received cariprazine and 79 received placebo. In this study, patients 5 to 9 years of age who were randomized to active treatment received cariprazine oral solution, which is not an approved formulation.

Somnolence, including sedation, occurred in 18% of cariprazine-treated compared to 1% of placebo-treated pediatric patients and was observed at a higher rate than reported in other VRAYLAR studies evaluating adult patients. The mean increase in age-and-sex adjusted body weight z-score from baseline to last visit was 0.2 for cariprazine-treated versus less than 0.1 for placebo-treated pediatric patients. Increases in age- and sex-adjusted body weight z-score of at least 0.5 SD from baseline was higher in cariprazine-treated versus placebo-treated pediatric patients (19% versus 1%).

In a long term, open-label study in pediatric patients 5 to 17 years of age with irritability associated with autism spectrum disorder, the mean change in weight from baseline to last available visit was 5.3 kg; two patients discontinued due to increased weight. When body weight was adjusted for age and sex, the mean z-score change from baseline to last visit was 0.4 for cariprazine-treated patients, and 32% of patients had an increase in age- and sex-adjusted body weight z-score of at least 0.5 SD from baseline. At 10 mg/kg/day, there were decreases in growth (decreased body weight and bone mass in both sexes and altered bone geometry and size in males), microscopic findings in the lung suggestive of phospholipidosis, and increased motor activity, which persisted following dose cessation.

In addition, impaired learning and memory performance was observed during the dosing period, however, this effect did not persist following dose cessation. Microscopic findings in the mammary gland and/or reproductive tract (vagina, uterus and ovary) at ≥1 mg/kg/day and altered findings in the adrenal gland at doses ≥3 mg/kg/day were considered secondary to the increase in prolactin levels and were consistent with findings observed in adult rats. The no observed adverse effect level (NOAEL) was 3 mg/kg/day which is associated with systemic exposures approximately equal to clinical exposures produced at the maximum recommended pediatric dose of 4.5 mg/day based on AUC of total cariprazine.

At doses ≥1 mg/kg/day, CNS clinical signs of decreased activity, lack of coordination, and reduced food intake were observed. At doses ≥3 mg/kg/day reversible effects on growth and non-reversible lens opacities/lens degeneration, that were not associated with retinal changes, were observed.

. CONTRAINDICATIONS VRAYLAR is contraindicated in patients with history of a hypersensitivity reaction to cariprazine. Reactions have ranged from rash, pruritus, urticaria, and reactions suggestive of angioedema (e.g., swollen tongue, lip swelling, face edema, pharyngeal edema, and swelling face).

Known hypersensitivity to VRAYLAR

Human Experience

In pre-marketing clinical trials involving VRAYLAR in approximately 5000 patients or healthy subjects, accidental acute overdosage (48 mg/day) was reported in one patient. This patient experienced orthostasis and sedation. The patient fully recovered the same day.

Management of Overdosage

No specific antidotes for VRAYLAR are known. In managing overdose, provide supportive care, including close medical supervision and monitoring, and consider the possibility of multiple drug involvement. In case of an overdose, consult a Certified Poison Control Center (1-800-222-1222) for up-to-date guidance and advice.