Invega Sustenna Steady State Timing
Invega Sustenna (paliperidone palmitate) reaches steady-state plasma concentrations after approximately 4 months (approximately 120 days) of monthly dosing, though therapeutic levels are achieved much earlier due to the recommended loading dose regimen. 1, 2
Pharmacokinetic Profile
The time to steady state for Invega Sustenna is substantially longer than typical oral medications due to its unique biphasic release characteristics:
- The terminal elimination half-life is approximately 25-49 days after intramuscular injection, which is markedly different from oral paliperidone (23 hours) 1, 3
- Steady state is reached after 5 half-lives, which translates to approximately 4 months with monthly dosing 2
- The biphasic pharmacokinetic profile consists of an initial rapid zero-order input phase followed by a sustained first-order release phase, allowing therapeutic concentrations without oral supplementation 2
Clinical Onset vs. Steady State
It is critical to distinguish between clinical response and pharmacokinetic steady state:
- Clinical response begins at 8 days when using the recommended deltoid loading dose regimen (150 mg equivalents on day 1, followed by 100 mg equivalents on day 8) 1
- Therapeutic plasma concentrations are achieved within the first month due to the loading dose strategy, well before steady state is reached 1, 2
- Peak plasma concentrations occur approximately 13 days after injection, with maintained therapeutic levels throughout the monthly dosing interval 1
Practical Implications
The 4-month timeframe to steady state has important clinical consequences:
- Dose adjustments should be made cautiously and infrequently, as changes will not fully manifest for approximately 4 months 2
- Transient excursions above therapeutic concentrations increase risk of adverse effects including tachycardia, hypotension, QT prolongation, and extrapyramidal symptoms 2
- Conversely, delays in attaining therapeutic levels or premature decline before the next dose increases relapse risk 2
Common Pitfall
Do not confuse the 8-day onset of clinical response with steady-state achievement. While patients may show clinical improvement within days to weeks, the plasma concentrations continue to accumulate over 4 months of monthly dosing. 1, 2 This prolonged accumulation phase is inherent to the long-acting injectable formulation and differs fundamentally from oral paliperidone, which reaches steady state in approximately 4-5 days. 3