Cariprazine
Indications
Cariprazine is an atypical antipsychotic indicated for:
- Treatment of schizophrenia in adults
- Acute treatment of manic or mixed episodes associated with bipolar I disorder in adults
- Treatment of depressive episodes associated with bipolar I disorder (bipolar depression) in adults
- Adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD) in adults
Pharmacology
The mechanism of action of cariprazine is unknown. However, the efficacy of cariprazine could be mediated through a combination of partial agonist activity at central dopamine D2 and serotonin 5-HT1A receptors and antagonist activity at serotonin 5-HT2A receptors. Cariprazine forms two major metabolites, desmethylcariprazine (DCAR) and didesmethylcariprazine (DDCAR), that have in vitro receptor binding profiles similar to the parent drug.
Dosage & Administration
General Dosing Information: Cariprazine 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 Cariprazine and after each dosage change.
Recommended Dosage in Schizophrenia: The starting dosage of Cariprazine is 1.5 mg once daily. The recommended dosage range is 1.5 mg to 6 mg 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 daily. In short-term controlled trials, dosages above 6 mg daily do not confer increased effectiveness sufficient to outweigh dose-related adverse reactions.
Recommended Dosage in Manic or Mixed Episodes Associated with Bipolar I Disorder: The starting dosage of Cariprazine is 1.5 mg once daily and should be increased to 3 mg once daily on Day 2. The recommended dosage range is 3 mg to 6 mg once daily. 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 daily. In short-term controlled trials, dosages above 6 mg daily do not confer increased effectiveness sufficient to outweigh dose-related adverse reactions.
Recommended Dosage in Depressive Episodes Associated with Bipolar I Disorder (Bipolar Depression): The starting dosage of Cariprazine is 1.5 mg once daily. Depending upon clinical response and tolerability, the dosage can be increased to 3 mg once daily on Day 15. Maximum recommended dosage is 3 mg once daily.
Recommended Dosage for Adjunctive Therapy to Antidepressants for the Treatment of Major Depressive Disorder: The starting dosage of Cariprazine is 1.5 mg once daily. Depending upon clinical response and tolerability, the dosage can be increased to 3 mg once daily on Day 15. In clinical trials, dosage titration at intervals of less than 14 days resulted in a higher incidence of adverse reactions. Maximum recommended dosage is 3 mg once daily.
Recommended Dosage in Schizophrenia: The starting dosage of Cariprazine is 1.5 mg once daily. The recommended dosage range is 1.5 mg to 6 mg 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 daily. In short-term controlled trials, dosages above 6 mg daily do not confer increased effectiveness sufficient to outweigh dose-related adverse reactions.
Recommended Dosage in Manic or Mixed Episodes Associated with Bipolar I Disorder: The starting dosage of Cariprazine is 1.5 mg once daily and should be increased to 3 mg once daily on Day 2. The recommended dosage range is 3 mg to 6 mg once daily. 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 daily. In short-term controlled trials, dosages above 6 mg daily do not confer increased effectiveness sufficient to outweigh dose-related adverse reactions.
Recommended Dosage in Depressive Episodes Associated with Bipolar I Disorder (Bipolar Depression): The starting dosage of Cariprazine is 1.5 mg once daily. Depending upon clinical response and tolerability, the dosage can be increased to 3 mg once daily on Day 15. Maximum recommended dosage is 3 mg once daily.
Recommended Dosage for Adjunctive Therapy to Antidepressants for the Treatment of Major Depressive Disorder: The starting dosage of Cariprazine is 1.5 mg once daily. Depending upon clinical response and tolerability, the dosage can be increased to 3 mg once daily on Day 15. In clinical trials, dosage titration at intervals of less than 14 days resulted in a higher incidence of adverse reactions. Maximum recommended dosage is 3 mg once daily.
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Interaction
Strong CYP3A4 inhibitors: Reduce VRAYLAR dosage by half.
CYP3A4 inducers: Concomitant use is not recommended.
CYP3A4 inducers: Concomitant use is not recommended.
Contraindications
Cariprazine 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).
Side Effects
Most common adverse reactions (incidence ≥ 5% and at least twice the rate of placebo) were:
- 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
Pregnancy & Lactation
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Cariprazine during pregnancy. Lactation studies have not been conducted to assess the presence of cariprazine in human milk, the effects on the breastfed infant, or the effects on milk production.
Precautions & Warnings
Cerebrovascular Adverse Reactions in Elderly Patients with Dementia-Related Psychosis: Increased incidence of cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack).
Neuroleptic Malignant Syndrome: Manage with immediate discontinuation and close monitoring.
Tardive Dyskinesia: Discontinue if appropriate.
Late-Occurring Adverse Reactions: Because of Cariprazine long half- life, monitor for adverse reactions and patient response for several weeks after starting Cariprazine and with each dosage change.
Metabolic Changes: Monitor for hyperglycemia/diabetes mellitus, dyslipidemia and weight gain.
Leukopenia, Neutropenia, and Agranulocytosis: Perform complete blood counts (CBC) in patients with pre-existing low white blood cell counts (WBC) or history of leukopenia or neutropenia. Consider discontinuing Cariprazine if a clinically significant decline in WBC occurs in absence of other causative factors.
Orthostatic Hypotension and Syncope: Monitor heart rate and blood pressure and warn patients with known cardiovascular or cerebrovascular disease, and risk of dehydration or syncope.
Seizures: Use cautiously in patients with a history of seizures or with conditions that lower the seizure threshold.
Potential for Cognitive and Motor Impairment: Use caution when operating machinery.
Neuroleptic Malignant Syndrome: Manage with immediate discontinuation and close monitoring.
Tardive Dyskinesia: Discontinue if appropriate.
Late-Occurring Adverse Reactions: Because of Cariprazine long half- life, monitor for adverse reactions and patient response for several weeks after starting Cariprazine and with each dosage change.
Metabolic Changes: Monitor for hyperglycemia/diabetes mellitus, dyslipidemia and weight gain.
Leukopenia, Neutropenia, and Agranulocytosis: Perform complete blood counts (CBC) in patients with pre-existing low white blood cell counts (WBC) or history of leukopenia or neutropenia. Consider discontinuing Cariprazine if a clinically significant decline in WBC occurs in absence of other causative factors.
Orthostatic Hypotension and Syncope: Monitor heart rate and blood pressure and warn patients with known cardiovascular or cerebrovascular disease, and risk of dehydration or syncope.
Seizures: Use cautiously in patients with a history of seizures or with conditions that lower the seizure threshold.
Potential for Cognitive and Motor Impairment: Use caution when operating machinery.
Use in Special Populations
Pediatric Use: Safety and effectiveness in pediatric patients have not been established. Pediatric studies of Cariprazine have not been conducted. Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric patients.
Geriatric Use: Clinical trials of Cariprazine did not include sufficient numbers of patients aged 65 and older to determine whether or not they respond differently from younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Geriatric Use: Clinical trials of Cariprazine did not include sufficient numbers of patients aged 65 and older to determine whether or not they respond differently from younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Storage Conditions
Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.
