Transitioning from Invega Sustenna 100mg Monthly to Oral Paliperidone
When switching from paliperidone palmitate 100mg every 4 weeks to oral tablets, initiate oral paliperidone extended-release at 6 mg daily on the day of the next scheduled depot injection, without any initial dose titration required.
Timing of Oral Initiation
Start oral paliperidone ER on the day the next depot injection would have been due (i.e., 4 weeks after the last 100mg injection), as this timing allows for appropriate overlap given the depot's pharmacokinetic profile 1.
The 100mg monthly depot maintains therapeutic plasma concentrations for approximately 4 weeks, with a terminal half-life of the depot formulation extending well beyond this period 1.
Initial Oral Dosing
Begin with 6 mg once daily of paliperidone ER, which is the recommended standard dose for adults with schizophrenia and requires no initial titration 2.
This 6 mg daily dose provides comparable steady-state exposure to the 100mg monthly depot formulation based on population pharmacokinetic modeling 1.
Peak plasma concentrations with oral paliperidone ER occur approximately 24 hours after dosing, with a terminal half-life of approximately 23 hours 2.
Dose Adjustments and Timeframe
If inadequate response after 4-7 days at 6 mg daily, increase to 9 mg daily 3.
Further titration to 12 mg daily (maximum dose) may be considered if needed after another 4-7 days, though higher doses provide additional benefit alongside dose-related increases in adverse reactions, particularly extrapyramidal symptoms 3.
The recommended dose range for oral paliperidone ER is 3-12 mg daily, with doses above 6 mg showing incremental efficacy but also increased risk of Parkinsonism and akathisia in a dose-dependent manner 3.
Critical Monitoring Considerations
Monitor closely for extrapyramidal symptoms (EPS) during the first 2-4 weeks, as the transition period may reveal individual sensitivity to paliperidone that was masked by the depot's steady-state kinetics 4.
Watch for signs of relapse during weeks 2-4, as this represents the period when depot levels are declining while oral steady-state is being established 1.
Assess for adherence issues, as the switch from monthly depot to daily oral administration represents a significant change in treatment burden that may impact compliance 5.
Special Population Adjustments
In patients with mild renal impairment (creatinine clearance 50-80 mL/min), reduce the initial oral dose to 3 mg daily, as paliperidone undergoes primarily renal elimination with limited hepatic metabolism 2.
Elderly patients with normal renal function can receive standard dosing, but age-related decline in creatinine clearance necessitates dose reduction accordingly 1.
Common Pitfalls to Avoid
Do not start oral paliperidone before the next scheduled depot injection is due, as this creates excessive overlap and increases risk of dose-related adverse effects including severe EPS 4.
Avoid starting at doses lower than 6 mg daily in patients with normal renal function, as 3 mg may be subtherapeutic for patients previously stabilized on 100mg monthly depot 3.
Do not assume the transition will be seamless—approximately 10-15% of patients may experience breakthrough symptoms or increased side effects during the switch, requiring close monitoring and potential dose adjustment 5.