Cariprazine
FDA Drug Information • Also known as: Vraylar
- Brand Names
- Vraylar
- Dosage Form
- CAPSULE, GELATIN COATED
- Product Type
- DRUG FOR FURTHER PROCESSING
⚠ Boxed Warning (Black Box)
WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS and SUICIDAL THOUGHTS AND BEHAVIORS Increased Mortality in Elderly Patients with Dementia-Related Psychosis Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. VRAYLAR is not approved for the treatment of patients with dementia-related psychosis [see Warnings and Precautions ( 5.1 )]. Suicidal Thoughts and Behaviors Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies. Closely monitor all antidepressant-treated patients for clinical worsening, and for the emergence of suicidal thoughts and behaviors [see Warnings and Precautions ( 5.2 )] . WARNING : INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS and SUICIDAL THOUGHTS AND BEHAVIORS See full prescribing information for complete boxed warning. Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. VRAYLAR is not approved for the treatment of patients with dementia-related psychosis. ( 5.1 ) Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients. Closely monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors. ( 5.2 )
Description
11 . DESCRIPTION The active ingredient of VRAYLAR is cariprazine, an atypical antipsychotic, in hydrochloride salt form. The chemical name is trans -N-{4-[2-[4-(2,3-dichlorophenyl)piperazine-1-yl]ethyl]cyclohexyl}-N’,N’-dimethylurea hydrochloride; its empirical formula is C 21 H 3 2 Cl 2 N 4 O
What Is Cariprazine Used For?
1 . INDICATIONS AND USAGE VRAYLAR ® is indicated for:
Dosage and Administration
2 . DOSAGE AND ADMINISTRATION Administer VRAYLAR orally once daily with or without food ( 2 ) Starting Dose Recommended Dose Schizophrenia in Adults ( 2.2 ) 1.5 mg daily 1.5 mg to 6 mg daily Schizophrenia in Pediatric Patients (13-17 years) ( 2.2 ) 0.5 mg daily 1.5 mg to 4.5 mg daily Bipolar Mania in Adults ( 2.3 ) 1.5 mg daily 3 mg to 6 mg daily Bipolar Mania in Pediatric Patients (10-17 years) ( 2.3 ) 0.5 mg daily 3 mg or 4.5 mg daily Bipolar Depression in Adults ( 2.4 ) 1.5 mg daily 1.5 mg or 3 mg daily Adjunctive therapy to antidepressants for MDD in Adults ( 2.5 ) 1.5 mg daily 1.5 mg or 3 mg daily Adults with Schizophrenia and Bipolar Mania: Maximum recommended daily dosage is 6 mg. Dosages above 6 mg daily do not confer significant benefit, but increase the risk of dose-related adverse reactions ( 2.2 , 2.3 ) Pediatric patients with Schizophrenia and Bipolar Mania: Maximum recommended daily dosage is 4.5 mg. Adults with Bipolar Depression: Maximum recommended daily dosage is 3 mg ( 2.4 ) Adjunctive therapy for treatment of MDD in Adults: Maximum recommended daily dosage is 3 mg ( 2.5 ) 2.1 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 [see Warnings and Precautions ( 5.6 ) , Clinical Pharmacology ( 12.3 )] . 2.2 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. The maximum recommended dosage is 6 mg orally once daily. In short-term controlled trials, dosages above 6 mg daily do not confer increased effectiveness sufficient to outweigh dose-related adverse reactions [see Adverse Reactions ( 6.1 ), Clinical Studies ( 14.1 )] . Pediatric Patients (13 to 17 years of age) The starting dosage of VRAYLAR is 0.5 mg orally once daily. The recommended dosage range is 1.5 mg to 4.5 mg orally once daily. Increase the dosage to 1.5 mg orally once daily on Day 3. Depending upon clinical response and tolerability, the dosage may be increased to 3 mg orally once daily starting on Day 5, and to 4.5 mg orally once daily starting on Day 8. The maximum recommended dosage is 4.5 mg orally once daily. 2.3 Recommended Dosage in Manic or M ixed E pisodes Associated with Bipolar I Disorder Adult Patients The starting dosage of VRAYLAR is 1.5 mg orally once daily. Increase the dosage to 3 mg orally once daily on Day 2. The recommended dosage range is 3 mg to 6 mg orally once daily. Depending upon clinical response and tolerability,...
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following adverse reactions are discussed in more detail in other sections of the labeling: Increased Mortality in Elderly Patients with Dementia-Related Psychosis [see Boxed Warning and Warnings and Precautions ( 5.1 )] Suicidal Thoughts and Behaviors [see Boxed Warning and Warnings and Precautions ( 5.2 )] Cerebrovascular Adverse Reactions, Including Stroke, in Elderly Patients with Dementia-Related Psychosis [see Warnings and Precautions ( 5.3 )] Neuroleptic Malignant Syndrome [see Warnings and Precautions ( 5.4 )] Tardive Dyskinesia [see Warnings and Precautions ( 5.5 )] Late Occurring Adverse Reactions [see Warnings and Precautions ( 5.6 )] Metabolic Changes [see Warnings and Precautions ( 5.7 )] Leukopenia, Neutropenia, and Agranulocytosis [see Warnings and Precautions ( 5.8 )] Orthostatic Hypotension and Syncope [see Warnings and Precautions ( 5.9 )] Falls [see Warnings and Precautions ( 5.10 )] Seizures [ see Warnings and Precautions ( 5.11 )] Potential for Cognitive and Motor Impairment [see Warnings and Precautions ( 5.12 )] Body Temperature Dysregulation [see Warnings and Precautions ( 5.13 )] Dysphagia [see Warnings and Precautions ( 5.14 )] Most common adverse reactions in adults (incidence ≥ 5% and at least twice the rate of placebo) were ( 6.1 ) : Schizophrenia: extrapyramidal symptoms and akathisia Bipolar mania: extrapyramidal symptoms, akathisia, dyspepsia, vomiting, somnolence, and restlessness Bipolar depression: nausea, akathisia, restlessness, and extrapyramidal symptoms Adjunctive treatment of MDD: akathisia, restlessness, fatigue, constipation, nausea, insomnia, increased appetite, dizziness, and extrapyramidal symptoms To report SUSPECTED ADVERSE REACTIONS, contact AbbVie at 1-800-633-9110 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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. A total of 4,329 VRAYLAR-treated patients had at least 6 weeks and 296 VRAYLAR-treated patients had at least 48 weeks of exposure. 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 VRAYLAR * System Organ Class / Preferred Term Placebo (N= 584) (%) 1.5 to 3 mg/day (N=539) (%) 4.5 to 6 mg/day (N=575) (%) 9 to 12 mg/day ⸰ (N=203) (%) Cardiac Disorder s Tachycardia a 1 2 2 3 Gastrointestinal Disorders Abdominal pain b 5 3 4 7 Constipation 5 6 7 10 Diarrhea c 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 Fatigue d 1 1 3 2 Infections and Infestations Nasopharyngitis 1 1 1 2 Urinary...
Drug Interactions
7 DRUG INTERACTIONS 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 [see Clinical Pharmacology ( 12.3 ) ]. Intervention: If VRAYLAR is used with a strong or moderate CYP3A4 inhibitor, reduce VRAYLAR dosage [see D osage and A dministration ( 2.6 ) ] . 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 [see Clinical Pharmacology ( 12.3 ) ]. Intervention: Concomitant use of VRAYLAR with a CYP3A4 inducer is not recommended [see Dosage and Administration ( 2.1 , 2.6 ) ] . Strong and Moderate CYP3A4 inhibitors: Reduce VRAYLAR dosage ( 2.6 , 7 ) CYP3A4 inducers: Concomitant use is not recommended ( 2.6 , 7 )
Contraindications
4 . 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 ( 4 )
Pregnancy and Breastfeeding
8.1 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 [see Clinical Pharmacology ( 12.3 )]. 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 [see Data] . 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...
Overdosage
10 OVERDOSAGE 10.1 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. 10.2 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.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied VRAYLAR (cariprazine) capsules are supplied as follows: Capsule Strength Imprint Codes Capsule Color Package Configuration NDC Code 0.5 mg FL 0.5 Ivory to yellow cap and grey to green body Bottle of 30 61874-250-30 0.75 mg FL 0.75 Grey to green cap and blue body Bottle of 30 61874-275-30 1.5 mg FL 1.5 White cap and body Blister pack of 7 61874-115-17 Bottle of 30 61874-115-30 Bottle of 90 61874-115-90 Box of 20 (Hospital Unit Dose) 61874-115-20 3 mg FL 3 Green to blue-green cap and white body Bottle of 30 61874-130-30 Bottle of 90 61874-130-90 Box of 20 (Hospital Unit Dose) 61874-130-20 4.5 mg FL 4.5 Green to blue-green cap and body Bottle of 30 61874-145-30 Bottle of 90 61874-145-90 6 mg FL 6 Purple cap and white body Bottle of 30 61874-160-30 Bottle of 90 61874-160-90 (1) 1.5 mg, (6) 3 mg FL 1.5, FL 3 Mixed Blister pack of 7 61874-170-08 16.2 Storage and Handling Store at 20ºC to 25°C (68ºF to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature] . Protect 3 mg and 4.5 mg capsules from light to prevent potential color fading. 16.1 How Supplied VRAYLAR (cariprazine) capsules are supplied as follows: Capsule Strength Imprint Codes Capsule Color Package Configuration NDC Code 0.5 mg FL 0.5 Ivory to yellow cap and grey to green body Bottle of 30 61874-250-30 0.75 mg FL 0.75 Grey to green cap and blue body Bottle of 30 61874-275-30 1.5 mg FL 1.5 White cap and body Blister pack of 7 61874-115-17 Bottle of 30 61874-115-30 Bottle of 90 61874-115-90 Box of 20 (Hospital Unit Dose) 61874-115-20 3 mg FL 3 Green to blue-green cap and white body Bottle of 30 61874-130-30 Bottle of 90 61874-130-90 Box of 20 (Hospital Unit Dose) 61874-130-20 4.5 mg FL 4.5 Green to blue-green cap and body Bottle of 30 61874-145-30 Bottle of 90 61874-145-90 6 mg FL 6 Purple cap and white body Bottle of 30 61874-160-30 Bottle of 90 61874-160-90 (1) 1.5 mg, (6) 3 mg FL 1.5, FL 3 Mixed Blister...
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.