Can Fanapt (iloperidone) and Vraylar (cariprazine) be used together?

Concurrent Use of Fanapt (Iloperidone) and Vraylar (Cariprazine)

The concurrent use of Fanapt (iloperidone) and Vraylar (cariprazine) is not recommended due to the risk of additive side effects, particularly QT prolongation, extrapyramidal symptoms, and metabolic effects.

Pharmacological Considerations

• Both Fanapt and Vraylar are atypical antipsychotics with overlapping mechanisms of action. Cariprazine is a dopamine D3-preferring D3/D2 receptor partial agonist 1, while iloperidone also acts on dopamine receptors.

• Using two antipsychotics with similar mechanisms of action should generally be avoided as this practice increases the risk of side effects without necessarily improving efficacy 2.

• Antipsychotic polypharmacy is associated with an increased global side-effect burden, including higher rates of:

  • Parkinsonian side effects
  • Hyperprolactinemia
  • Sexual dysfunction
  • Sedation/somnolence
  • Cognitive impairment
  • Risk of diabetes mellitus 2

Specific Safety Concerns

• QT prolongation risk: Both medications can potentially affect cardiac conduction. Antipsychotics are known to cause QT interval prolongation, which can lead to dangerous cardiac arrhythmias such as torsades de pointes 2.

• Extrapyramidal symptoms: Cariprazine specifically shows a higher risk of akathisia compared to placebo and some other atypical antipsychotics 3. Combining with another antipsychotic may increase this risk.

• Metabolic effects: While cariprazine has relatively favorable metabolic profile compared to some other antipsychotics, the combination could potentially increase the risk of metabolic side effects 3, 4.

Clinical Approach

• If a patient is not responding adequately to one antipsychotic, the recommended approach is to:

  1. Optimize the dose of the current medication
  2. If ineffective, switch to a different antipsychotic monotherapy
  3. Consider clozapine for treatment-resistant cases
  4. Only consider antipsychotic polypharmacy as a last resort when other options have failed 2

• If antipsychotic polypharmacy is deemed necessary in treatment-resistant cases, guidelines recommend selecting antipsychotics with differing side-effect profiles to minimize additive adverse effects 2.

Monitoring Requirements

If, despite these concerns, concurrent therapy is initiated due to clinical necessity, the following monitoring would be essential:

• Cardiac monitoring: Regular ECG monitoring for QT prolongation 2

• Neurological assessment: Frequent evaluation for extrapyramidal symptoms, particularly akathisia 3

• Metabolic monitoring: Regular assessment of weight, blood glucose, and lipid parameters 2

• Drug interactions: Both medications undergo hepatic metabolism, potentially leading to unpredictable plasma levels when used together 4

Alternative Approaches

• Consider optimizing monotherapy with either agent before attempting combination therapy 2.

• If symptoms are not adequately controlled with one antipsychotic, switching to a different agent rather than adding a second antipsychotic is generally preferred 2.

• For treatment-resistant schizophrenia, clozapine monotherapy has stronger evidence than antipsychotic polypharmacy 2.

• If specific symptom domains are targeted (such as negative symptoms), cariprazine monotherapy has shown efficacy for negative symptoms of schizophrenia 5.