Oral Invega Discontinuation When Initiating LAI
Yes, oral Invega (paliperidone ER) should be continued for at least 7 days after the first LAI injection to ensure adequate therapeutic coverage during the initial loading phase. 1
Initiation Protocol for Paliperidone LAI (Invega Sustenna)
The approved initiation regimen does not require oral supplementation when using the recommended loading doses, which are 234 mg (150 mg eq.) on day 1 followed by 156 mg (100 mg eq.) on day 8, both administered into the deltoid muscle. 1
However, this recommendation assumes:
- Patients are antipsychotic-naive or switching from other antipsychotics 1
- The loading dose strategy is followed precisely 1
Critical Consideration for Patients on Higher Oral Doses
For patients taking oral risperidone ≥4 mg/day (equivalent to paliperidone ER ≥6 mg/day), bridging with oral medication for ≥7 days after the first injection is associated with significantly reduced hospitalization days. 2
Evidence Supporting Oral Bridging:
- Patients on higher oral doses who were bridged had statistically significant reductions in hospitalization days compared to those who were not bridged 2
- The paliperidone LAI package insert does not recommend bridging, which may result in inadequate serum concentrations in patients on higher doses 2
- Population pharmacokinetic modeling demonstrates that the biphasic release profile requires time to establish therapeutic concentrations 3, 1
Practical Algorithm for Oral Discontinuation
For Patients on Lower Doses (Paliperidone ER <6 mg/day):
- Administer first LAI injection (234 mg deltoid) on day 1 1
- Discontinue oral paliperidone the same day or next day 1
- Administer second LAI injection (156 mg deltoid) on day 8 (±2 days) 1
For Patients on Higher Doses (Paliperidone ER ≥6 mg/day or Risperidone ≥4 mg/day):
- Administer first LAI injection (234 mg deltoid) on day 1 1
- Continue oral paliperidone at current dose for 7-14 days 2
- Gradually taper oral medication over days 7-14 if desired, though abrupt discontinuation after 7 days is acceptable 2
- Administer second LAI injection (156 mg deltoid) on day 8 (±2 days) 1
Pharmacokinetic Rationale
The biphasic pharmacokinetic profile of paliperidone palmitate consists of an initial relatively fast zero-order input phase followed by a maintained first-order input phase. 3, 1
Key pharmacokinetic considerations:
- The initial loading doses are designed to rapidly attain therapeutic concentrations without oral supplementation in most patients 1
- However, transient excursions below therapeutic concentrations during the transition period can increase relapse risk 3
- Delays in attaining therapeutic plasma concentrations on initiation increase the risk of relapse 3
Common Pitfalls to Avoid
Do not abruptly discontinue oral medication in patients on higher doses without bridging, as this is associated with increased hospitalization risk. 2
Do not skip or delay the day 8 loading dose, as this is critical for establishing adequate steady-state concentrations. 1
Do not administer initial loading doses in the gluteal muscle—deltoid administration is required for the first two injections to ensure proper absorption kinetics. 1
Special Populations
For patients with mild renal impairment (CrCl 50-80 mL/min), dosage adjustments are required for both oral bridging and LAI maintenance doses. 1
Elderly patients with normal renal function can follow the same protocol as younger adults, but age-related decline in creatinine clearance necessitates dose adjustment. 1
Switching from Invega Sustenna to Invega Trinza
When transitioning from monthly (PP1M) to 3-monthly (PP3M) formulations, the first PP3M injection should be given at the time of the next scheduled PP1M dose, with no oral supplementation required. 1
The extended half-life of PP3M provides substantial protection against relapse even if treatment is interrupted—median time to relapse after PP3M discontinuation is 395 days versus 172 days for PP1M and 58 days for oral paliperidone. 4