Cariprazine

• Schizophrenia:
  Approved for the treatment of schizophrenia in adults to manage acute and maintenance phases.
• Bipolar Disorder:
  Indicated for the treatment of manic or mixed episodes associated with bipolar I disorder.
  Also approved for bipolar depression as monotherapy or adjunctive therapy.
• Off-label / Clinically Accepted Uses:
• Adjunctive treatment in major depressive disorder.
• Psychotic symptoms in other psychiatric disorders (investigational).

• Route: Oral.
• Schizophrenia:
• Initial dose: 1.5 mg once daily.
• Maintenance dose: 3 to 6 mg once daily.
• Dose adjustments made in increments of 1.5 mg based on clinical response and tolerability.
• Bipolar Mania or Mixed Episodes:
• Starting dose: 1.5 mg twice daily (3 mg total).
• Maintenance dose: 3 to 6 mg daily, given once or divided doses.
• Bipolar Depression:
• Starting dose: 1.5 mg once daily.
• Maintenance dose: 3 mg once daily.
• Elderly:
  Use with caution; start at lower doses; monitor for orthostatic hypotension and sedation.
• Renal/Hepatic Impairment:
• No specific dose adjustments recommended; monitor carefully in severe impairment.
• Administration:
• Take with or without food.
• Swallow whole; do not crush or chew.

Cariprazine is an atypical antipsychotic that acts as a partial agonist at dopamine D3 and D2 receptors, with preferential binding affinity for D3 receptors. It also exhibits partial agonism at serotonin 5-HT1A receptors and antagonism at 5-HT2A receptors. By modulating dopaminergic and serotonergic neurotransmission, Cariprazine restores the dopamine-serotonin balance in key brain regions, reducing psychotic symptoms and mood disturbances. The preferential D3 receptor activity is hypothesized to contribute to improvements in cognitive and negative symptoms of schizophrenia.

• Absorption:
  Well absorbed orally; peak plasma concentrations reached in approximately 3–4 hours.
• Distribution:
  Highly lipophilic; large volume of distribution; extensively distributed in tissues.
• Metabolism:
  Metabolized primarily by CYP3A4 and to a lesser extent by CYP2D6 to active metabolites, including desmethyl cariprazine and didesmethyl cariprazine (long-acting active metabolite).
• Elimination:
  Terminal half-life of cariprazine approximately 2–4 days; didesmethyl metabolite half-life up to 1–3 weeks, leading to prolonged pharmacologic activity.
  Excreted mainly via feces and urine.

• Pregnancy:
• FDA Category C. Animal studies show adverse fetal effects at high doses.
• Use only if potential benefit justifies potential risk to fetus.
• Lactation:
• Unknown if excreted in human milk.
• Potential for serious adverse reactions in nursing infants; breastfeeding not recommended during treatment.

• Primary Class: Atypical antipsychotic
• Subclass: Dopamine-serotonin receptor partial agonist

• Known hypersensitivity to Cariprazine or any formulation components.
• Concurrent use with strong CYP3A4 inhibitors or inducers requires caution; avoid if possible.
• Severe hepatic impairment (use with caution).

• Increased risk of orthostatic hypotension and syncope, especially during initiation.
• Risk of extrapyramidal symptoms (EPS) including akathisia and dystonia.
• Possible neuroleptic malignant syndrome (NMS); monitor for hyperthermia and muscle rigidity.
• May cause hyperglycemia, weight gain, and dyslipidemia; monitor metabolic parameters.
• Increased risk of suicidal ideation in young adults; close monitoring advised.
• Caution in patients with a history of seizures or cardiovascular disease.
• Use caution in elderly patients with dementia-related psychosis due to increased mortality risk.

Common:

• Akathisia, insomnia, headache, nausea, dizziness, anxiety, constipation.

Less Common:

• Extrapyramidal symptoms, sedation, vomiting, blurred vision, orthostatic hypotension.

Rare but Serious:

• Neuroleptic malignant syndrome, tardive dyskinesia, severe allergic reactions, QT prolongation.

• CYP3A4 inhibitors (e.g., ketoconazole): Increase Cariprazine plasma levels; dose reduction recommended.
• CYP3A4 inducers (e.g., carbamazepine): Decrease plasma levels; avoid concomitant use or adjust dose.
• Other CNS depressants may potentiate sedation.
• Avoid drugs that prolong QT interval when possible.

• Recent clinical guidelines incorporate Cariprazine as an effective option for schizophrenia and bipolar disorder, emphasizing its favorable profile for negative and cognitive symptoms.
• Ongoing studies support safety in long-term use, with updated recommendations for metabolic monitoring.
• FDA updates stress caution in elderly dementia patients and reinforce suicide risk monitoring.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep in original packaging until use.
• Do not freeze.
• Keep out of reach of children.