Are there any interactions between Naltrexone, Bupropion, and Topiramate (Tobramate) and Caplyta (Lumateperone), Lexapro (Escitalopram), and Qelbree (Viloxazine)?

Drug Interactions Between Naltrexone/Bupropion/Topiramate and Caplyta/Lexapro/Qelbree

Critical Interaction: Qelbree (Viloxazine) and Bupropion

The combination of Qelbree and bupropion is not recommended due to significant pharmacokinetic interaction. Bupropion is a moderate CYP1A2 inhibitor, and the FDA label for Qelbree explicitly states that coadministration with moderate sensitive CYP1A2 substrates is not recommended, though dose reduction may be warranted if combination is unavoidable 1.

Serotonin Syndrome Risk: Lexapro (Escitalopram) Combinations

Exercise caution when combining Lexapro with bupropion, as both are serotonergic agents that can contribute to serotonin syndrome risk, though this combination is commonly used in clinical practice. 2

• Serotonin syndrome symptoms include mental status changes, neuromuscular hyperactivity (tremors, clonus, hyperreflexia, muscle rigidity), and autonomic hyperactivity (hypertension, tachycardia, diaphoresis) 2
• When combining two non-MAOI serotonergic drugs, start the second agent at a low dose, increase slowly, and monitor closely for symptoms, especially in the first 24-48 hours after dosage changes 2
• Citalopram/escitalopram has the least effect on CYP450 isoenzymes compared with other SSRIs and may have lower propensity for drug interactions 2

Cardiovascular Monitoring Requirements

Blood pressure and heart rate should be monitored periodically when using naltrexone-bupropion, especially in the first 12 weeks of treatment. 2

• Naltrexone-bupropion should be avoided in patients with uncontrolled hypertension 2, 3
• The combination can cause increases in blood pressure and heart rate, with some studies showing small increases in heart rate 4
• Phentermine-topiramate (if topiramate is part of a combination product) should be avoided in patients with cardiovascular disease or uncontrolled hypertension 2

Seizure Risk Considerations

Bupropion significantly lowers seizure threshold and should be avoided in patients with seizure disorders; this risk may be additive with topiramate, which is an antiepileptic but can paradoxically cause seizures in some contexts. 2, 3

• Naltrexone-bupropion should be avoided in patients with seizure disorders and used with caution in patients at risk of seizures 2
• Maximum bupropion dose should not exceed 450 mg per day to minimize seizure risk 3
• Serious adverse effects with naltrexone-bupropion include seizures, though these are very rare 4

Neuropsychiatric Effects

Monitor closely for neuropsychiatric adverse effects including depression, anxiety, suicidal ideation, and cognitive impairment when using these combinations, particularly in patients younger than 24 years. 2, 3, 5

• Bupropion carries a black box warning for risk of suicidal behavior/ideation in people younger than 24 years with depression 2
• The naltrexone-bupropion combination has caused potentially severe neuropsychiatric disorders including cognitive impairment, dizziness, anxiety, sleep disorders, and psychotic symptoms 5
• Topiramate can cause cognitive impairment, irritability, and mood changes 2

Gastrointestinal Side Effects

Expect additive gastrointestinal side effects when combining these medications, with approximately 50% of patients experiencing nausea, vomiting, or constipation with naltrexone-bupropion. 5, 4

• Most common side effects of naltrexone-bupropion include nausea, constipation, headache, and vomiting 4
• These effects are generally well tolerated in the majority of patients 4

Specific Drug Contraindications

Naltrexone-bupropion should not be used concomitantly with opiate medications due to naltrexone's opioid receptor antagonist properties. 2

• Bupropion should be avoided in patients treated with, or within 14 days of, monoamine oxidase inhibitors 2, 3
• Bupropion is contraindicated in patients taking tamoxifen 3

Renal and Hepatic Dosing Adjustments

For patients with moderate to severe hepatic impairment, bupropion total daily dose should not exceed 150 mg daily; for moderate to severe renal impairment, reduce the total daily dose by half. 3

• Bupropion and its metabolites are cleared renally and may accumulate in renal impairment, requiring close monitoring 3
• Topiramate has carbonic anhydrase inhibitor properties that can increase risk of kidney stones with prolonged exposure 2

Clinical Monitoring Algorithm

1. Baseline assessment: Check blood pressure, heart rate, seizure history, psychiatric history, current opioid use, hepatic/renal function 2, 3
2. First 12 weeks: Monitor blood pressure and heart rate periodically, assess for neuropsychiatric symptoms every 1-2 weeks 2, 3
3. Ongoing: Monitor for serotonin syndrome symptoms if combining with Lexapro, assess efficacy at 6-8 weeks, consider serum bicarbonate monitoring if using topiramate long-term 2, 3