What are the important things to know about cariprazine (Cariprazine)?

From the Guidelines

Cariprazine is an atypical antipsychotic medication that should be used with caution, particularly in patients with cardiovascular disease, and with regular monitoring of weight, blood glucose, and lipids, as it can cause significant weight gain and other metabolic problems 1. When prescribing cariprazine, it's essential to consider the potential side effects, including akathisia, extrapyramidal symptoms, and metabolic effects. The medication's uniquely long half-life of 2-4 days for the parent compound and up to 3 weeks for its active metabolite means it takes longer to reach steady state and longer for side effects to resolve after discontinuation. Some key points to consider when using cariprazine include:

• Starting dose: 1.5 mg once daily, with maintenance doses ranging from 1.5-6 mg daily for schizophrenia and 3-6 mg daily for bipolar disorder
• Monitoring requirements: baseline body mass index, waist circumference, blood pressure, fasting glucose, and a fasting lipid panel, with follow-up monitoring as recommended by the American Dietetic Association 1
• Potential side effects: akathisia, extrapyramidal symptoms, weight gain, and metabolic effects
• Special considerations: use with caution in patients with cardiovascular disease, and consider the potential for drug interactions and the need for dose adjustments in patients with liver or kidney impairment. It's also important to note that cariprazine works differently from other antipsychotics, acting as a partial agonist at dopamine D2/D3 receptors with higher selectivity for D3 receptors, which may help improve negative symptoms of schizophrenia and cognitive function. However, the provided evidence does not specifically discuss cariprazine, and the information provided is based on general knowledge of the medication and its use in clinical practice 1.

From the FDA Drug Label

VRAYLAR may cause serious side effects, including: Increased risk of death in elderly people with dementia related psychosis Increased risk of suicidal thoughts and actions VRAYLAR and antidepressant medicines may increase suicidal thoughts or actions in some children and young adults especially within the first few months of treatment or when the dose is changed.

VRAYLAR is a prescription medicine used in adults: to treat schizophrenia for short-term (acute) treatment of manic or mixed episodes that happen with bipolar I disorder to treat depressive episodes that happen with bipolar I disorder (bipolar depression) along with antidepressant medicines to treat major depressive disorder (MDD)

Important things to know about cariprazine (Cariprazine):

• Cariprazine may increase the risk of death in elderly people with dementia-related psychosis.
• Cariprazine may increase the risk of suicidal thoughts and actions in some children and young adults.
• Cariprazine is used to treat schizophrenia, bipolar I disorder, and major depressive disorder.
• Patients should be monitored for signs and symptoms of neuroleptic malignant syndrome, tardive dyskinesia, and metabolic changes.
• Patients should be advised to report any changes in mood, behavior, or thoughts to their healthcare provider.
• Cariprazine may interact with other medications, and patients should inform their healthcare provider of all medications they are taking.
• Cariprazine may cause orthostatic hypotension, syncope, and heat exposure, and patients should be cautioned about these risks 2, 2.

From the Research

Overview of Cariprazine

• Cariprazine is an antipsychotic medication that received approval by the U.S. Food and Drug Administration for the treatment of schizophrenia in September 2015 3.
• It is a dopamine D3 and D2 receptor partial agonist, with a preference for the D3 receptor, and also a partial agonist at the serotonin 5-HT1A receptor and acts as an antagonist at 5-HT2B and 5-HT2A receptors 3, 4.

Pharmacokinetics and Metabolism

• Cariprazine is administered once daily and is primarily metabolized in the liver through the CYP3A4 enzyme system and, to a lesser extent, by CYP2D6 3, 5.
• It produces two active metabolites, desmethyl-cariprazine and didesmethyl-cariprazine, with the latter having a longer half-life than cariprazine and higher systemic exposure 3, 5, 4.

Efficacy and Safety

• Cariprazine has demonstrated superiority over placebo in three positive, 6-week, Phase 2/3, randomized controlled trials in acute schizophrenia 3.
• It has also shown efficacy in the treatment of bipolar mania or mixed episodes, with statistically significant therapeutic effects compared to placebo 6, 7.
• Common adverse events associated with cariprazine include extrapyramidal symptoms, akathisia, insomnia, sedation, nausea, dizziness, and constipation 3, 5, 6, 7.
• Cariprazine does not appear to have clinically meaningful alterations in metabolic variables, prolactin, or the ECG QT interval 3, 6, 7.

Clinical Use

• The recommended dose range of cariprazine for the treatment of schizophrenia is 1.5-6 mg/d, with a starting dose of 1.5 mg/d potentially therapeutic 3.
• Cariprazine is also approved for the acute treatment of manic or mixed episodes associated with bipolar I disorder, and clinical trials are ongoing in patients with acute bipolar I depression and as adjunctive treatment to antidepressant therapy in patients with major depressive disorder 3, 4.