What alternatives are available for a patient on Seroquel (quetiapine) who needs to discontinue it prior to starting Mavyret (glecaprevir/pibrentasvir)?

Alternatives to Seroquel (Quetiapine) Prior to Starting Mavyret

If a patient requires discontinuation of Seroquel before starting Mavyret for hepatitis C treatment, consider switching to olanzapine (2.5-5 mg daily) or risperidone (0.5-1 mg twice daily) as alternative antipsychotics, with careful cross-tapering to minimize withdrawal symptoms and maintain psychiatric stability. 1, 2, 3

Why Discontinuation May Be Necessary

While the provided evidence does not explicitly document a direct drug-drug interaction between quetiapine and glecaprevir/pibrentasvir (Mavyret), the clinical concern likely stems from:

• Hepatic metabolism considerations: Both quetiapine and Mavyret are hepatically metabolized, and patients with hepatitis C may have compromised liver function 4, 5, 6
• Cognitive effects: Quetiapine may exacerbate cognitive dysfunction, particularly in vulnerable populations, which could complicate HCV treatment monitoring 2

Recommended Alternative Antipsychotics

First-Line Alternatives

Olanzapine is a reasonable alternative with similar efficacy:

• Starting dose: 2.5-5 mg orally once daily at bedtime 1, 3
• Shares similar adverse effect profile (sedation, orthostatic hypotension) but may be better tolerated in some patients 3
• Critical warning: Fatalities reported with concurrent benzodiazepine use at high doses—avoid combining with sedating agents 3

Risperidone offers another option:

• Starting dose: 0.5-1 mg twice daily 1
• Lower sedation profile than quetiapine in many patients 1
• May have slightly higher risk of extrapyramidal side effects compared to quetiapine 3

Cross-Tapering Strategy

Gradual tapering is essential to prevent withdrawal symptoms and psychiatric decompensation:

1. Initiate the new antipsychotic at low dose while maintaining current quetiapine dose 2, 7

2. Slowly reduce quetiapine by 25-50 mg every 3-7 days while uptitrating the replacement medication 2, 7

3. Monitor closely every 1-2 weeks during the transition for:

   • Psychiatric symptom recurrence 2
   • Excessive sedation from overlapping medications 3
   • Orthostatic hypotension (check vital signs) 3
   • Withdrawal symptoms (insomnia, nausea, irritability) 2

4. Never stop abruptly: Gradual tapering over weeks is typically required 7

Special Considerations for Elderly or Medically Compromised Patients

• Use lower starting doses (olanzapine 2.5 mg, risperidone 0.5 mg) in older adults 3
• Fall risk is significantly elevated with antipsychotic use, particularly during cross-tapering when two sedating agents overlap 7, 3
• Monitor for cumulative sedation during overlap periods 3
• Avoid polypharmacy when possible, as each additional medication increases risk of falls, delirium, and cognitive decline 2

Alternative Non-Pharmacologic Approach

If the psychiatric indication is mild and the patient is stable, consider:

• Structured activities, calming techniques, socialization, and family presence as first-line interventions for mild agitation or behavioral symptoms 2
• This may allow temporary discontinuation of antipsychotic during HCV treatment in select cases 2

Timing Relative to Mavyret Initiation

• Complete the cross-taper and achieve stability on the new antipsychotic before starting Mavyret if possible 2
• Mavyret treatment duration is typically 8-12 weeks, so plan the transition accordingly 5, 6, 8
• Ensure psychiatric stability for at least 2-4 weeks on the new regimen before adding HCV treatment 2

Common Pitfalls to Avoid

• Assuming dose equivalence without considering individual patient response 3
• Inadequate monitoring during the overlap period when sedation risk is highest 3
• Failing to account for dosing schedules: quetiapine is often dosed twice daily while olanzapine is once daily 3
• Overlooking metabolic monitoring: olanzapine carries significant metabolic risk (weight gain, diabetes) 3
• Stopping quetiapine abruptly without gradual taper, risking withdrawal and psychiatric destabilization 7