Fanapt (Iloperidone) Dosing Regimen
Fanapt must be initiated at 1 mg twice daily and titrated slowly over 7 days to reach the target therapeutic dose of 6-12 mg twice daily, with this gradual titration being mandatory to minimize orthostatic hypotension and dizziness. 1
Standard Titration Schedule
The FDA-approved titration protocol is structured as follows to reduce cardiovascular risks 1, 2:
- Day 1: 1 mg twice daily
- Day 2: 2 mg twice daily
- Day 3: 4 mg twice daily
- Day 4: 6 mg twice daily
- Day 5: 8 mg twice daily
- Day 6: 10 mg twice daily
- Day 7: 12 mg twice daily
The target therapeutic dose range is 6-12 mg twice daily, with a maximum recommended dose of 12 mg twice daily. 1, 3
Administration Details
- Administer orally twice daily without regard to meals 1
- The slow titration over 4-7 days is necessary specifically to minimize orthostatic hypotension-related dizziness, which is the most common adverse effect (occurring in 5.1%-23.2% of patients in a dose-dependent manner) 2, 3
- Iloperidone requires this extended titration period before reaching therapeutic dosing, unlike some other atypical antipsychotics that can be initiated at potentially therapeutic doses 4
Special Population: CYP2D6 Poor Metabolizers
For patients who are CYP2D6 poor metabolizers, dose reduction is required with a modified titration schedule. 1 Iloperidone is extensively metabolized, and genetic variations in CYP2D6 significantly affect drug clearance 2, 5.
Clinical Considerations
The twice-daily dosing requirement and slow initial titration are potential disadvantages compared to once-daily atypical antipsychotics, particularly affecting medication adherence 2. However, this careful titration is essential as adverse events appear clearly dose-related 2.
Iloperidone demonstrates efficacy at the 12 mg twice daily dose, with clinical trials showing significant reductions in PANSS scores compared to placebo (−12 vs −7.1; P < 0.01) 2. The maximum behavioral effects occur when plasma concentrations are increasing, typically 1-3 hours post-dose 2.
Key Safety Points
- Monitor for orthostatic hypotension throughout titration, especially during the first week 1, 2
- Iloperidone can prolong the QTc interval, requiring baseline and periodic ECG monitoring 3
- The medication has a favorable extrapyramidal side effect profile, with essentially no akathisia or movement disorders throughout the recommended dose range 4, 3
- Common adverse effects include dizziness, dry mouth (5.2%-10.4%), somnolence (4%-13%), and dyspepsia (4.8%-7.8%), all appearing dose-related 2