What are the side effects of Vraylar (cariprazine)?

Side Effects of Vraylar (Cariprazine)

Vraylar (cariprazine) can cause several significant side effects including extrapyramidal symptoms, akathisia, tardive dyskinesia, metabolic changes, and somnolence, with the most common side effects being difficulty moving, tremors, restlessness, sleepiness, and nausea. 1

Common Side Effects

Vraylar's FDA label identifies the following as the most commonly reported side effects:

• Movement disorders:

  • Difficulty moving or slow movements
  • Tremors
  • Uncontrolled body movements
  • Restlessness and feeling like you need to move around (akathisia)

• Gastrointestinal effects:

  • Nausea
  • Vomiting
  • Indigestion
  • Constipation

• Neurological effects:

  • Sleepiness/drowsiness
  • Trouble sleeping
  • Dizziness

• Other:

  • Feeling tired
  • Increased appetite

Serious Side Effects

Movement Disorders

• Tardive dyskinesia: Involuntary movements that may not resolve even after stopping the medication 1
• Extrapyramidal symptoms: The risk increases with higher doses (NNH 15 for 1.5-3 mg/day and NNH 10 for 4.5-6 mg/day compared to placebo) 2
• Akathisia: Inner restlessness and need to move (NNH 20 for 1.5-3 mg/day and NNH 12 for 4.5-6 mg/day compared to placebo) 2

Metabolic Effects

• Blood glucose abnormalities: Can lead to hyperglycemia and diabetes 1
• Lipid abnormalities: Increased cholesterol and triglycerides 1
• Weight gain: Approximately 8% of patients on cariprazine 1.5-6 mg/day gained ≥7% body weight (NNH 34 compared to placebo) 2

Cardiovascular Effects

• Orthostatic hypotension: Dizziness or fainting when standing up quickly 1

Hematologic Effects

• Low white blood cell count: May require monitoring during treatment 1

Neurological Effects

• Neuroleptic malignant syndrome: A rare but potentially fatal condition with symptoms including high fever, stiff muscles, confusion, sweating, and changes in breathing, heart rate, and blood pressure 1
• Seizures: Cariprazine may lower seizure threshold 1
• Falls: Due to sleepiness, dizziness, or orthostatic hypotension 1

Other Serious Concerns

• Difficulty swallowing: May cause aspiration 1
• Problems controlling body temperature: Feeling too warm 1
• Stroke risk: In elderly patients with dementia-related psychosis 1

Timing of Side Effects

Cariprazine has a unique pharmacokinetic profile with an extremely long half-life:

• Parent compound half-life: 2-5 days 3
• Active metabolite (didesmethyl-cariprazine) half-life: 2-3 weeks 3

Due to this long half-life, some side effects may:

• Not appear immediately after starting treatment
• Begin several weeks after starting or increasing the dose
• Persist for weeks after discontinuation 1

Monitoring Recommendations

• Baseline assessments: Complete metabolic panel, lipid profile, blood pressure, heart rate, weight, and BMI 4
• Regular monitoring: Weight, blood glucose, lipids, blood pressure, and extrapyramidal symptoms 4
• Special attention: Monitor for tardive dyskinesia, which increases in risk with longer treatment duration 4

Risk Factors and Special Populations

• Elderly patients: Higher risk for cerebrovascular events, particularly those with dementia-related psychosis 1
• Patients with cardiovascular disease: Higher risk for orthostatic hypotension 4
• Patients with seizure disorders: Increased risk of seizures 1
• Patients with diabetes or risk factors: Higher risk for worsening glycemic control 1

Comparison to Other Antipsychotics

Cariprazine is a dopamine D3-preferring D3/D2 receptor partial agonist, which distinguishes it from many other antipsychotics 2. This unique receptor profile may explain its specific side effect pattern:

• Less weight gain than many other atypical antipsychotics 2
• No clinically meaningful alterations in prolactin levels 2
• No significant QT interval prolongation 2
• Higher rates of akathisia and extrapyramidal symptoms than some other atypicals 2

Management of Side Effects

• For extrapyramidal symptoms: Dose reduction or addition of anticholinergic medication may help 4
• For metabolic effects: Regular monitoring and management of weight, glucose, and lipids 1
• For orthostatic hypotension: Slow titration and adequate hydration 4
• For akathisia: Dose reduction or divided dosing may be beneficial 4

Vraylar's long half-life means that side effects may persist for weeks after discontinuation, requiring extended monitoring even after stopping the medication.