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Cariprazine

Class: Atypical Antipsychotics
- Dopamine Receptor Partial Agonists
ATC Class: N05AX15
VA Class: CN709
Chemical Name: N′-[trans-4-[2-[4-(2,3-Dichlorophenyl)-1-piperazinyl]ethyl]cyclohexyl]-N,N-dimethyl-urea
Molecular Formula: C21H32Cl2N4OC21H32Cl2N4O•HCl
CAS Number: 839712-12-8
Brands: Vraylar

Medically reviewed by Drugs.com on Oct 18, 2021. Written by ASHP.

Warning

    Increased Mortality in Geriatric Patients with Dementia-related Psychosis
  • Geriatric patients with dementia-related psychosis treated with antipsychotic agents are at an increased risk of death.

  • Antipsychotic agents, including cariprazine, are not approved for the treatment of dementia-related psychosis. (See Increased Mortality in Geriatric Patients with Dementia-related Psychosis under Cautions.)

    Suicidal Thoughts and Behaviors in Children, Adolescents, and Young Adults
  • Antidepressants increased risk of suicidal thoughts and behaviors compared with placebo in children, adolescents, and young adults (≤24 years of age) receiving antidepressants for major depressive disorder and other indications. (See Suicidal Thoughts and Behaviors in Children, Adolescents, and Young Adults under Cautions.)

  • Safety and efficacy of cariprazine have not been established in pediatric patients.

Introduction

Atypical or second-generation antipsychotic agent.

Uses for Cariprazine

Schizophrenia

Treatment of schizophrenia.

American Psychiatric Association (APA) recommends that patients with schizophrenia be treated with an antipsychotic agent and that patients whose symptoms have improved with an antipsychotic agent continue to receive such therapy. APA also suggests that patients whose symptoms have improved with an antipsychotic agent should continue to be treated with the same antipsychotic agent; however, some circumstances (e.g., patient preferences, drug availability, adverse effects) may necessitate a change in antipsychotic agent.

APA and other experts consider antipsychotic agents (i.e., first- and second-generation antipsychotic agents) first-line drugs for management of schizophrenia (including first psychotic episodes). Initial choice of an antipsychotic agent should be individualized and generally be made in the context of shared decision-making, taking into consideration multiple patient- and drug-related factors (e.g., adverse effect profiles, concurrent medical conditions or risk factors, potential for drug interactions, potential pharmacogenomic considerations, patient preferences, prior responses to treatment, available formulations, cost).

Patients who do not respond to or tolerate one antipsychotic agent may be successfully treated with another drug with different receptor binding or adverse effect profile.

Drug therapy should be used as part of a comprehensive, patient-centered treatment plan that includes evidence-based nonpharmacologic and pharmacologic treatments for schizophrenia. Consult APA’s Practice Guideline for the Treatment of Patients with Schizophrenia (at [Web]) for additional information on treatment of schizophrenia.

Bipolar Disorder

Acute treatment of manic or mixed episodes associated with bipolar I disorder.

Treatment of depressive episodes associated with bipolar I disorder (bipolar depression).

Cariprazine Dosage and Administration

General

  • Monitor for worsening of depression and emergence of suicidal thoughts or behaviors, especially at the beginning of therapy or during periods of dosage adjustments. (See Suicidal Thoughts and Behaviors in Children, Adolescents, and Young Adults under Cautions.)

Administration

Oral Administration

Administer capsules orally once daily without regard to meals.

Dosage

Available as cariprazine hydrochloride; dosage expressed in terms of cariprazine.

Because of the long half-life of cariprazine and its active metabolites, dosage changes will not be fully reflected in plasma for several weeks. Monitor patients for adverse effects and treatment response for several weeks after initiation of therapy and after each dosage change. In addition, plasma concentrations of cariprazine and its active metabolites may not be immediately reflected in patients' clinical symptoms following discontinuance of the drug. (See Pharmacokinetics.)

No systematically collected data available to specifically address switching patients from cariprazine to other antipsychotic agents or concerning concomitant administration of cariprazine with other antipsychotic agents.

If used with a potent CYP3A4 inhibitor, dosage adjustment is recommended; avoid concurrent use with CYP3A4 inducers. (See Interactions.)

Adults

Schizophrenia
Oral

Initially, 1.5 mg once daily; may increase to 3 mg once daily on day 2. May make further dosage adjustments in 1.5- or 3-mg increments based on clinical response and tolerability. Recommended dosage range is 1.5–6 mg once daily.

In patients whose symptoms have improved, continued treatment (i.e., maintenance therapy) with an antipsychotic agent is recommended to reduce the risk of relapse. Some experts generally recommend maintenance antipsychotic therapy for at least 1–2 years after the first psychotic episode and for 2–5 years or longer following recurrent episodes. Indefinite maintenance treatment may be necessary; however, periodically assess the benefits and risks of continued antipsychotic therapy in the context of shared decision-making, taking into consideration each patient's risk of relapse, drug-associated adverse effects, course of disease, and specific goals and needs.

Bipolar Disorder
Manic or Mixed Episodes associated with Bipolar Disorder
Oral

Initially, 1.5 mg once daily; increase to 3 mg once daily on day 2. May make further dosage adjustments in 1.5- or 3-mg increments based on clinical response and tolerability. Recommended dosage range is 3–6 mg once daily.

Depressive Episodes associated with Bipolar Disorder
Oral

Initially, 1.5 mg once daily; may increase to 3 mg once daily on day 15 based on clinical response and tolerability. Recommended dosage is 1.5 or 3 mg once daily.

Prescribing Limits

Adults

Schizophrenia
Oral

Maximum 6 mg daily. Increased efficacy of higher dosages not sufficient to outweigh risk of dose-related adverse effects.

Bipolar Disorder
Manic or Mixed Episodes associated with Bipolar Disorder
Oral

Maximum 6 mg daily. Increased efficacy of higher dosages not sufficient to outweigh risk of dose-related adverse effects.

Depressive Episodes associated with Bipolar Disorder
Oral

Maximum 3 mg daily.

Special Populations

Hepatic Impairment

Mild to moderate hepatic impairment (Child-Pugh score 5–9): Dosage adjustment not necessary.

Severe hepatic impairment (Child-Pugh score 10–15): Not studied; use not recommended.

Renal Impairment

Mild to moderate renal impairment (Clcr ≥30 mL/minute): Dosage adjustment not necessary.

Severe renal impairment (Clcr <30 mL/minute): Not studied; use not recommended. (See Renal Impairment under Cautions.)

Geriatric Patients

Cautious dosage selection recommended, usually starting at the lower end of the recommended dosage range, reflecting the greater frequency of decreased hepatic, renal, and cardiac function; concomitant illnesses; and other drug therapy in this population.

Gender, Race, or Smoking Status

Dosage adjustment not required based on gender, race, or smoking status.

Pharmacogenomics and CYP2D6 Poor Metabolizer Phenotype

Dosage adjustment unlikely to be necessary in patients who are CYP2D6 poor metabolizers. (See Special Populations under Pharmacokinetics: Elimination.)

Cautions for Cariprazine

Contraindications

  • Known hypersensitivity to cariprazine. Rash, pruritus, urticaria, and manifestations of possible angioedema (e.g., swollen tongue, lip swelling, facial edema and swelling, pharyngeal edema) reported.

Warnings/Precautions

Warnings

Increased Mortality in Geriatric Patients with Dementia-related Psychosis

Increased risk of death with antipsychotic agents in geriatric patients with dementia-related psychosis.

Analyses of 17 placebo-controlled trials in geriatric patients mainly receiving atypical antipsychotic agents revealed an approximate 1.6- to 1.7-fold increase in mortality compared with that in patients receiving placebo.

Most fatalities appeared to result from cardiovascular-related events (e.g., heart failure, sudden death) or infections (mostly pneumonia).

Antipsychotic agents, including cariprazine, are not approved for the treatment of dementia-related psychosis. (See Increased Mortality in Geriatric Patients with Dementia-related Psychosis in Boxed Warning and see Cerebrovascular Events in Geriatric Patients with Dementia-related Psychosis under Cautions.)

Suicidal Thoughts and Behaviors in Children, Adolescents, and Young Adults

Antidepressants increased risk of suicidal thoughts and behaviors compared with placebo in children, adolescents, and young adults (≤24 years of age) receiving antidepressants for major depressive disorder and other indications.

Closely monitor all patients receiving antidepressants for any reason, particularly during initiation of therapy (i.e., the first few months) and during periods of dosage adjustments.

Consider changing or discontinuing therapy in patients whose depression is persistently worse or in those with emerging suicidal thoughts or behaviors.

Other Warnings and Precautions

Cerebrovascular Events in Geriatric Patients with Dementia-related Psychosis

Increased incidence of adverse cerebrovascular events (cerebrovascular accidents and TIAs), including fatalities, observed in geriatric patients with dementia-related psychosis treated with certain atypical antipsychotic agents (aripiprazole, olanzapine, risperidone) in placebo-controlled studies. Cariprazine is not approved for the treatment of patients with dementia-related psychosis. (See Increased Mortality in Geriatric Patients with Dementia-related Psychosis in Boxed Warning.)

Neuroleptic Malignant Syndrome

Neuroleptic malignant syndrome (NMS), a potentially fatal syndrome characterized by hyperpyrexia, muscle rigidity, delirium, and autonomic instability, reported with antipsychotic agents.

If NMS is suspected, immediately discontinue therapy and provide intensive symptomatic treatment and monitoring.

Tardive Dyskinesia

Tardive dyskinesia, a syndrome of potentially irreversible, involuntary dyskinetic movements, reported with use of antipsychotic agents, including cariprazine.

Reserve long-term antipsychotic treatment for patients with chronic illness known to respond to antipsychotic agents, and for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate. In patients requiring chronic treatment, use smallest dosage and shortest duration of treatment producing a satisfactory clinical response; periodically reassess need for continued therapy.

APA recommends clinically assessing patients receiving antipsychotic agents for abnormal involuntary movements at baseline and at each follow-up visit and assessing such patients using a structured instrument (e.g., the Abnormal Involuntary Movement Scale [AIMS], Dyskinesia Identification System: Condensed User Scale [DISCUS]) at least every 6 months in patients considered at high risk for tardive dyskinesia (e.g., patients ≥55 years of age; women; individuals with a mood disorder, substance use disorder, intellectual disability, or CNS injury; individuals with high cumulative exposure to antipsychotic medications, particularly high-potency dopamine type 2 [D2] receptor antagonists; and patients who experience acute dystonic reactions, clinically significant parkinsonism, or akathisia) or at least every 12 months in other patients as well as if new onset or exacerbation of preexisting movements is observed at any follow-up visit. In some jurisdictions, the frequency of monitoring for involuntary movements in individuals receiving antipsychotic therapy may be subject to local regulations.

Consider discontinuance of cariprazine if signs and symptoms of tardive dyskinesia appear. However, some patients may require treatment despite presence of the syndrome.

APA recommends that patients who have moderate to severe or disabling tardive dyskinesia associated with antipsychotic therapy be treated with a vesicular monoamine transporter 2 (VMAT2) inhibitor (e.g., deutetrabenazine, valbenazine, tetrabenazine); may also consider VMAT2 inhibitor therapy in patients with mild tardive dyskinesia based on factors such as patient preference, associated impairment, and effect on psychosocial functioning.

Late-occurring Adverse Effects

Adverse effects may first appear several weeks after initiation of cariprazine, probably because plasma concentrations of cariprazine and its principal metabolites accumulate over time (see Bioavailability under Pharmacokinetics). Therefore, incidence of adverse effects reported in short-term clinical trials may not reflect the incidence after longer-term exposure to the drug.

Monitor for adverse effects, including adverse extrapyramidal effects and akathisia, for several weeks after initiation of therapy and after each dosage increase. (See Dosage under Dosage and Administration.)

Metabolic Changes

Atypical antipsychotic agents are associated with metabolic changes that may increase cardiovascular and cerebrovascular risk (e.g., hyperglycemia, dyslipidemia, weight gain). While all atypical antipsychotics produce some metabolic changes, each drug has its own specific risk profile. (See Hyperglycemia and Diabetes Mellitus, see Dyslipidemia, and also see Weight Gain under Cautions.)

Hyperglycemia and Diabetes Mellitus

Hyperglycemia, sometimes severe and associated with ketoacidosis, hyperosmolar coma, or death, reported in patients receiving atypical antipsychotic agents. In short-term controlled trials, clinically important differences between cariprazine and placebo in shifts from normal or borderline to high fasting glucose concentrations not observed. In longer-term studies, 4% of cariprazine-treated patients experienced a shift from normal to elevated HbA1c concentrations.

Monitor fasting glucose concentration before or soon after initiation of cariprazine and periodically during long-term therapy.

Dyslipidemia

Undesirable changes in lipid parameters observed in patients treated with some atypical antipsychotics. However, clinically important effects of cariprazine on serum total cholesterol, LDL, HDL, and triglycerides not observed in short-term clinical studies.

Manufacturer recommends baseline and periodic follow-up lipid evaluations in patients receiving cariprazine.

Weight Gain

Weight gain observed with atypical antipsychotic therapy, including cariprazine.

Manufacturer recommends baseline and frequent monitoring of weight during therapy.

Leukopenia, Neutropenia, and Agranulocytosis

Leukopenia and neutropenia reported during treatment with antipsychotic agents, including cariprazine. Agranulocytosis (including fatal cases) also reported with other antipsychotic agents.

Possible risk factors for leukopenia and neutropenia include preexisting low WBC count and a history of drug-induced leukopenia or neutropenia. Monitor CBC frequently during the first few months of therapy in patients with such risk factors. Discontinue cariprazine at the first sign of a decline in WBC count in the absence of other causative factors.

Carefully monitor patients with neutropenia for signs and symptoms of infection (e.g., fever) and treat promptly if they occur. Discontinue cariprazine if severe neutropenia (ANC <1000/mm3) occurs; monitor WBC until recovery occurs.

Orthostatic Hypotension and Syncope

Risk of orthostatic hypotension and syncope reported with atypical antipsychotics, particularly during initial dosage titration and when dosage is increased.

In clinical trials, incidence of symptomatic orthostatic hypotension with cariprazine was infrequent and not higher than that reported with placebo; syncope not observed.

Monitor orthostatic vital signs in patients who are susceptible to hypotension (e.g., geriatric patients, patients with dehydration or hypovolemia, patients concomitantly receiving antihypertensive therapy), patients with cardiovascular disease (e.g., history of MI, ischemic heart disease, heart failure, or conduction abnormalities), and patients with cerebrovascular disease.

Falls

May cause somnolence, postural hypotension, and motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries.

In patients with diseases, conditions, or other drugs that could exacerbate these effects, complete fall risk assessments when initiating antipsychotic therapy and repeat such testing periodically during long-term antipsychotic therapy.

Seizures

Cariprazine may cause seizures. Higher risk of seizures in patients with a history of seizures or with conditions that lower the seizure threshold; conditions that lower seizure threshold may be more prevalent in older patients.

Cognitive and Motor Impairment

Judgment, thinking, or motor skills may be impaired. Somnolence (including hypersomnia and sedation) reported in 7 and 8% of cariprazine-treated patients in short-term schizophrenia and bipolar mania clinical trials, respectively. (See Advice to Patients.)

Body Temperature Dysregulation

Antipsychotic agents may disrupt ability to regulate core body temperature.

Use appropriate caution in patients who will be experiencing conditions that may contribute to an elevation in core body temperature (e.g., strenuous exercise, extreme heat, dehydration, concomitant use of agents with anticholinergic activity).

Dysphagia

Esophageal dysmotility and aspiration associated with the use of antipsychotic agents. Dysphagia reported with cariprazine. Use with caution in patients at risk for aspiration.

Specific Populations

Pregnancy

No adequate and well-controlled studies to date in pregnant women. The principal active metabolite of cariprazine, didesmethyl cariprazine (DDCAR), has been detected in adult patients ≤12 weeks following discontinuance of cariprazine. Based on animal findings, cariprazine may cause fetal harm. Fetal developmental toxicity (e.g., reduced body weight, skeletal and external malformations, lower pup survival, developmental delays) observed in animals.

Risk for extrapyramidal and/or withdrawal symptoms (e.g., agitation, hypertonia, hypotonia, tardive dyskinetic-like symptoms, tremor, somnolence, respiratory distress, feeding disorder) in neonates exposed to antipsychotic agents during the third trimester; monitor neonates exhibiting such symptoms. Symptoms were self-limiting in some neonates but varied in severity; some infants required intensive support and prolonged hospitalization.

National Pregnancy Registry for Atypical Antipsychotics: 866-961-2388 and [Web].

Lactation

Cariprazine distributes into milk in rats; not known whether cariprazine distributes into human milk. Effects of the drug on nursing infants and on milk production not known.

Weigh benefit of cariprazine therapy to the woman and benefits of breast-feeding against potential risk of infant exposure to the drug or from the underlying maternal condition.

Pediatric Use

Safety and efficacy not established in pediatric patients. Pediatric clinical studies with cariprazine have not been conducted to date.

Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric patients. (See Suicidal Thoughts and Behaviors in Children, Adolescents, and Young Adults under Cautions.)

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether they respond differently than younger adults. (See Geriatric Patients under Dosage and Administration and also see Elimination: Special Populations, under Pharmacokinetics.)

Geriatric patients with dementia-related psychosis treated with either conventional or atypical antipsychotic agents are at an increased risk of death; increased incidence of cerebrovascular events also observed with certain atypical antipsychotic agents. Cariprazine is not approved for the treatment of patients with dementia-related psychosis. (See Boxed Warning and also see Cerebrovascular Events in Geriatric Patients with Dementia-related Psychosis under Cautions.)

Hepatic Impairment

Dosage adjustment not necessary in patients with mild to moderate hepatic impairment (Child-Pugh score 5–9). (See Absorption: Special Populations, under Pharmacokinetics.)

Not studied in patients with severe hepatic impairment (Child-Pugh score 10–15); use not recommended.

Renal Impairment

Renal impairment unlikely to substantially alter the pharmacokinetics of cariprazine; the drug and its active metabolites are minimally excreted in urine. (See Renal Impairment under Dosage and Administration and also see Elimination: Special Populations, under Pharmacokinetics.)

Common Adverse Effects

Schizophrenia: Extrapyramidal symptoms (e.g., parkinsonian symptoms, dystonia, dyskinesia, tardive dyskinesia), akathisia.

Bipolar mania: Extrapyramidal symptoms (e.g., parkinsonism, dystonia, dyskinesia, tardive dyskinesia), akathisia, dyspepsia, vomiting, somnolence, restlessness.

Bipolar depression: Nausea, akathisia, restlessness, extrapyramidal symptoms.

Interactions for Cariprazine

Metabolized principally by CYP3A4 and, to a lesser extent, by CYP2D6. (See Metabolism under Pharmacokinetics.)

In vitro, cariprazine and its major active metabolites are weak inhibitors of CYP isoenzymes 1A2, 2A6, 2C9, 2C19, 2D6, 2E1, and 3A4 and do not induce CYP1A2 and CYP3A4. Cariprazine and its major active metabolites possess little or no inhibitory effects on organic anion transport proteins (OATP) 1B1 and 1B3, breast cancer resistance protein (BCRP), organic cation transporter (OCT) 2, and organic anion transporters (OAT) 1 and 3 in vitro. Clinically important interactions between cariprazine and substrates of these enzymes or transporters unlikely.

In vitro, cariprazine and its major active metabolites are not substrates of P-glycoprotein (P-gp), OATP 1B1 and 1B3, or BCRP.

Cariprazine's major active metabolites possess little or no inhibitory effects on P-gp; however, the drug probably inhibits P-gp.

Drugs Affecting Hepatic Microsomal Enzymes

Potent CYP3A4 inhibitors: Potential increased exposure to cariprazine and didesmethyl cariprazine (DDCAR); reduce cariprazine dosage during concurrent use. Reduce cariprazine dosage to 50% of the current dosage if a potent CYP3A4 inhibitor is initiated in patients receiving a stable cariprazine dosage. For patients taking 4.5 mg of cariprazine daily, reduce dosage to 1.5 or 3 mg daily. For patients taking 1.5 mg of cariprazine daily, reduce dosing frequency to every other day. If initiating cariprazine in patients already receiving a potent CYP3A4 inhibitor, administer cariprazine 1.5 mg on day 1 and on day 3 (skipping day 2), then give 1.5 mg daily from day 4 onward; increase dosage up to a maximum dosage of 3 mg daily. When the potent CYP3A4 inhibitor is withdrawn, cariprazine dosage increase may be needed.

Moderate CYP3A4 inhibitors: Effects on pharmacokinetics of cariprazine and its metabolites not studied.

CYP3A4 inducers: Potential pharmacokinetic interaction; effects not studied. Concomitant use not recommended.

CYP2D6 inhibitors: Clinically important pharmacokinetic interaction unlikely.

Specific Drugs

Drug

Interaction

Comments

Anticholinergic agents

Possible disruption of body temperature regulation

Use with caution

Antifungals, azoles (e.g., itraconazole, ketoconazole)

Potent CYP3A4 inhibitors: Possible increased exposure to cariprazine and DDCAR

Ketoconazole (potent CYP3A4 inhibitor) increased cariprazine peak concentration and AUC by about 3.5-fold and fourfold, respectively; increased DDCAR peak concentration and AUC by about 1.5-fold; and decreased desmethyl cariprazine (DCAR) peak concentration and AUC by about one-third

If initiating therapy with a potent CYP3A4 inhibitor, reduce current cariprazine dosage by 50%

For patients taking 4.5 mg of cariprazine daily, reduce dosage to 1.5 or 3 mg daily; for patients taking cariprazine 1.5 mg daily, reduce dosing frequency to every other day

If initiating cariprazine in patients receiving a potent CYP3A4 inhibitor, initiate cariprazine therapy at a dosage of 1.5 mg daily on days 1 and 3, administer 1.5 mg daily from day 4 onward, then increase dosage up to a maximum dosage of 3 mg daily

When the potent CYP3A4 inhibitor is withdrawn, an increase in cariprazine dosage may be necessary

Carbamazepine

Potential pharmacokinetic interaction with carbamazepine (potent CYP3A4 inducer); not studied

Concomitant use not recommended

Hypotensive agents

Possible additive hypotensive effects; may result in orthostatic hypotension and syncope

Monitor orthostatic vital signs

Pantoprazole

Does not substantially affect exposure to cariprazine, DCAR, or DDCAR

Rifampin

Potential pharmacokinetic interaction with rifampin (potent CYP3A4 inducer); not studied

Concomitant use not recommended

Smoking

Cariprazine is not a substrate for CYP1A2; smoking unlikely to alter cariprazine pharmacokinetics

Cariprazine Pharmacokinetics

Absorption

Bioavailability

Peak plasma concentrations of cariprazine achieved within approximately 3–6 hours following oral administration.

Mean steady-state concentrations of cariprazine and DCAR achieved within about 1–2 weeks. Mean steady-state concentration of DDCAR achieved within about 4–8 weeks; however, time varies and may take >12 weeks in some patients.

The principal active metabolites, DCAR and DDCAR, are present at mean plasma concentrations approximately 30 and 400% of plasma cariprazine concentrations after 12 weeks, respectively.

Food

High-fat meal did not substantially affect peak plasma concentration or AUC of cariprazine or DCAR.

Special Populations

In patients with mild or moderate hepatic impairment, cariprazine exposure is approximately 25% higher and DCAR and DDCAR exposure is approximately 20–30% lower than in individuals with normal hepatic function.

Distribution

Extent

Cariprazine distributes into milk in rats; not known if drug or metabolites distribute into human milk.

Plasma Protein Binding

Cariprazine and its principal active metabolites: 91–97% bound.

Elimination

Metabolism

Extensively metabolized by CYP3A4 and, to a lesser extent, CYP2D6 to DCAR and DDCAR, which are pharmacologically active with similar potency to cariprazine.

DCAR metabolized by CYP3A4 and CYP2D6 to DDCAR.

DDCAR metabolized by CYP3A4 to a hydroxylated metabolite.

Elimination Route

Following chronic administration of cariprazine, approximately 21% of daily dose recovered in urine; approximately 1.2% of dose excreted in urine as unchanged cariprazine.

Half-life

Cariprazine: 2–4 days.

DDCAR: Approximately 1–3 weeks.

Following discontinuance, mean plasma concentrations of cariprazine and DCAR decrease by about 50% in about 1 day and mean plasma concentrations of DDCAR decrease by about 50% after 1 week.

Special Populations

Pharmacokinetic analyses indicate no substantial relationship between clearance of the drug and its metabolites and Clcr. Not studied in severe renal impairment.

Age, gender, and race do not have clinically important effects on pharmacokinetics of cariprazine, DCAR, or DDCAR.

CYP2D6 poor metabolizer status also does not appear to affect the pharmacokinetics of cariprazine and its metabolites.

Stability

Storage

Oral

Capsules

20–25°C (may be exposed to 15–30°C). Protect 3- and 4.5-mg capsules from light to prevent potential color fading.

Actions

  • Exact mechanism of action in schizophrenia and bipolar disorder unknown; efficacy may be mediated through a combination of partial agonist activity at central dopamine type 2 (D2) and serotonin type 1 (5-hydroxytryptamine [5-HT1A]) receptors and antagonist activity at serotonin type 2 (5-HT2A) receptors.

  • Demonstrates partial agonist activity at D2 and D3 receptors and 5-HT1A receptors and antagonist activity at 5-HT2A and 5-HT2B receptors.

  • Exhibits approximately 3- to 10-fold higher binding affinity at D3 compared with D2 receptors; clinical implications of D3 receptor selectivity not known.

  • Exhibits moderate to low binding affinity for histamine (H1) receptors, lower affinity for 5-HT2C and α1A-adrenergic receptors than aripiprazole, and no appreciable affinity for muscarinic receptors.

Advice to Patients

  • Importance of advising patients and/or caregivers to read the patient information (medication guide).

  • Importance of advising patients and caregivers that geriatric patients with dementia-related psychosis treated with antipsychotic agents are at an increased risk of death. Inform patients and caregivers that cariprazine is not approved for treating geriatric patients with dementia-related psychosis.

  • Risk of suicidal thoughts and behaviors; importance of patients, family, and caregivers being alert to and reporting emergence of suicidality, especially during the first few months of therapy or during periods of dosage adjustment. (See Suicidal Thoughts and Behaviors in Children, Adolescents, and Young Adults under Cautions.)

  • Importance of advising patients that capsules can be taken with or without food. Importance of advising patients to follow the dosage titration instructions for the drug.

  • Importance of informing patients and caregivers about the risk of NMS, a rare but potentially life-threatening syndrome that can cause high fever, stiff muscles, confusion, sweating, or changes in respiration, heart rate, or BP. Importance of immediately contacting clinician or seeking emergency medical attention if signs and symptoms of this syndrome develop.

  • Importance of informing patients of the signs and symptoms of tardive dyskinesia. Advise patients to report any abnormal movements to a healthcare professional.

  • Importance of informing patients that, because plasma concentrations of cariprazine and its metabolites accumulate over time, adverse effects may not appear until several weeks after the initiation of therapy.

  • Importance of informing patients and caregivers about the risk of metabolic changes (e.g., hyperglycemia and diabetes mellitus, dyslipidemia, weight gain) with cariprazine and the need for specific monitoring, including blood glucose, lipids, and weight, for such changes during therapy. Importance of patients and caregivers being aware of the symptoms of hyperglycemia and diabetes mellitus (e.g., increased thirst, increased urination, increased appetite, weakness).

  • Risk of leukopenia/neutropenia. Importance of advising patients with a preexisting low WBC count or history of drug-induced leukopenia/neutropenia that their CBC should be monitored during cariprazine therapy.

  • Risk of orthostatic hypotension and syncope, especially when initiating or reinitiating treatment or increasing the dosage.

  • Risk of somnolence and impairment of judgment, thinking, or motor skills. Importance of advising patients to exercise caution when performing activities requiring mental alertness (e.g., driving, operating hazardous machinery) until they gain experience with the drug’s effects.

  • Importance of avoiding overheating and dehydration.

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription (see Interactions) and OTC drugs or herbal supplements, as well as any concomitant illnesses (e.g., cardiovascular disease, diabetes mellitus, seizures).

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. Importance of clinicians informing patients about the benefits and risks of taking antipsychotics during pregnancy (see Pregnancy under Cautions). Importance of advising patients not to stop taking cariprazine if they become pregnant without consulting their clinician; abruptly stopping antipsychotic agents may cause complications.

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Cariprazine Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

1.5 mg (of cariprazine)

Vraylar

Allergan

3 mg (of cariprazine)

Vraylar

Allergan

4.5 mg (of cariprazine)

Vraylar

Allergan

6 mg (of cariprazine)

Vraylar

Allergan

Titration Pack

1 Capsule, 1.5 mg (of cariprazine) (Vraylar)

6 Capsules, 3 mg (of cariprazine) (Vraylar)

Vraylar Titration Pack

Allergan

AHFS DI Essentials™. © Copyright 2022, Selected Revisions October 18, 2021. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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