Is it safe to take Vraylar (cariprazine) and Luvox (fluvoxamine) together?

Safety of Combining Vraylar (Cariprazine) and Luvox (Fluvoxamine)

The combination of Vraylar (cariprazine) and Luvox (fluvoxamine) should be avoided due to significant risk of drug interactions that could lead to increased cariprazine levels and potential toxicity.

Pharmacological Interaction Mechanism

Fluvoxamine is a potent inhibitor of several cytochrome P450 enzymes, particularly:

• CYP1A2 (strong inhibition) 1
• CYP2C19 (moderate inhibition)
• CYP3A4 (moderate inhibition)

Cariprazine is primarily metabolized by CYP3A4 and to a lesser extent by CYP2D6 2. When these medications are combined:

1. Fluvoxamine's inhibition of CYP3A4 can significantly impair cariprazine metabolism
2. This leads to increased cariprazine plasma concentrations
3. Higher cariprazine levels increase the risk of dose-dependent adverse effects

Potential Consequences

The interaction could result in:

• Increased extrapyramidal symptoms (tremor, rigidity, akathisia)
• Enhanced sedation
• Greater risk of QT interval prolongation
• Orthostatic hypotension
• Metabolic effects (weight gain, hyperglycemia)

Evidence of Fluvoxamine's Interaction Potential

Fluvoxamine has a well-documented history of clinically significant drug interactions:

• It increases plasma concentrations of multiple medications metabolized by CYP enzymes 1
• It has been shown to increase levels of other psychotropic medications by up to 8-fold in some cases 3
• It is deliberately used to increase clozapine levels in clinical practice (2.3-fold increase documented) 4
• It has caused carbamazepine toxicity when added to stable carbamazepine regimens 5

Alternative Options

If both medications are clinically indicated, consider these alternatives:

1. Alternative SSRIs: Consider sertraline or citalopram which have less impact on CYP enzymes than fluvoxamine 6

2. Alternative antipsychotics: If fluvoxamine must be continued, consider antipsychotics with less dependence on CYP3A4 metabolism

3. Dose adjustment: If no alternatives are viable, significant cariprazine dose reduction would be necessary with careful monitoring for toxicity

Monitoring If Combination Cannot Be Avoided

If the combination must be used despite risks:

• Start with substantially reduced cariprazine dosing (consider 50% reduction)
• Monitor closely for signs of cariprazine toxicity
• Check vital signs regularly, particularly for orthostatic changes
• Monitor mental status for excessive sedation
• Assess for emergence or worsening of extrapyramidal symptoms
• Consider ECG monitoring for QT prolongation

Conclusion

Given fluvoxamine's known inhibitory effects on CYP enzymes involved in cariprazine metabolism, and the documented history of significant interactions with other medications, this combination presents substantial risks. The safest approach is to use alternative medications that don't share this interaction potential.