Oral Paliperidone Discontinuation After Invega Sustenna Initiation
Oral paliperidone (Invega) should be discontinued immediately after initiating paliperidone palmitate (Invega Sustenna) with the recommended loading dose regimen—no oral supplementation is required. 1
Recommended Initiation Protocol
The FDA-approved initiation regimen for paliperidone palmitate eliminates the need for oral bridging through a specific loading dose strategy 1:
- Day 1: 150 mg equivalent paliperidone (234 mg paliperidone palmitate) injected into the deltoid muscle
- Day 8: 100 mg equivalent paliperidone (156 mg paliperidone palmitate) injected into the deltoid muscle
- Monthly maintenance: Begin at day 36 (±7 days) with 75 mg equivalent paliperidone (117 mg paliperidone palmitate), range 25-150 mg equivalent 1
This loading dose regimen was specifically designed through population pharmacokinetic modeling to achieve therapeutic plasma concentrations rapidly without requiring oral supplementation. 1
Pharmacokinetic Rationale
The biphasic pharmacokinetic profile of paliperidone palmitate supports immediate oral discontinuation 2:
- Initial phase: Relatively fast zero-order input allows rapid attainment of therapeutic concentrations without oral supplementation 2
- Maintenance phase: Sustained first-order input maintains therapeutic levels for monthly dosing 2
Population pharmacokinetic simulations demonstrated that the approved loading dose regimen achieves adequate plasma concentrations from day 1 forward, making oral bridging unnecessary 1.
Critical Timing Considerations
The day 8 dose may be administered ±2 days without clinically significant impact on plasma concentrations, but monthly maintenance doses should be administered ±7 days from the scheduled date. 1
Exception: Switching from Oral Risperidone ≥4 mg/day
While the FDA-approved regimen does not recommend oral bridging, clinical evidence suggests that patients switching from oral risperidone ≥4 mg/day may benefit from bridging with oral risperidone for ≥7 days after the first paliperidone palmitate injection. 3
- Bridged patients (risperidone ≥4 mg/day continued for ≥7 days) showed statistically significant reductions in hospitalization days compared to non-bridged patients 3
- This bridging strategy addresses the concern that the loading dose may result in inadequate serum concentrations in patients on higher oral risperidone doses 3
However, this represents off-label practice, as the package insert does not recommend oral bridging. 3
Common Pitfalls to Avoid
Do not continue oral paliperidone "just to be safe"—this increases the risk of adverse effects from excessive dopamine blockade, including extrapyramidal symptoms, tachycardia, hypotension, and QT prolongation. 2
Transient excursions above therapeutic plasma concentrations from unnecessary oral supplementation can produce clinically significant adverse effects 2. The loading dose regimen was specifically validated to avoid both subtherapeutic levels (which increase relapse risk) and supratherapeutic levels (which increase adverse effect risk) 2.
Needle Selection for Loading Doses
Both day 1 and day 8 loading doses must be administered into the deltoid muscle with weight-adjusted needle selection 1:
- Patients <90 kg: 1-inch 23-gauge needle
- Patients ≥90 kg: 1.5-inch 22-gauge needle
Maintenance doses may be administered into either deltoid (weight-adjusted needle) or gluteal muscle (1.5-inch 22-gauge needle) 1.