Transitioning from Invega LAI to Risperdal
When transitioning from Invega LAI (paliperidone palmitate) to oral Risperdal (risperidone), start oral risperidone at a dose of 2-3 mg/day when the next scheduled Invega LAI injection would be due, and gradually titrate to the target dose over 1-2 weeks based on clinical response and tolerability.
Understanding the Pharmacological Relationship
Paliperidone (9-hydroxyrisperidone) is the active metabolite of risperidone. Despite this relationship, they are not identical in their clinical effects:
- Paliperidone is primarily eliminated renally, while risperidone undergoes extensive hepatic metabolism via CYP2D6 1
- Individual patient factors like CYP2D6 metabolizer status can affect the risperidone-to-paliperidone ratio 1
- The extended-release formulation of Invega LAI provides different pharmacokinetics than oral risperidone
Transition Protocol
Step 1: Timing
- Initiate oral risperidone when the next scheduled Invega LAI injection would be due
- This timing prevents gaps in antipsychotic coverage while avoiding excessive dopamine blockade
Step 2: Initial Dosing
- Start with risperidone 2-3 mg/day, divided into two doses
- For patients previously on higher doses of Invega LAI (≥100 mg eq.), consider starting at 3 mg/day
- For patients on lower doses of Invega LAI (<100 mg eq.), consider starting at 2 mg/day
Step 3: Dose Titration
- Increase the risperidone dose by 1 mg every 3-4 days as needed
- Target dose should be determined based on the previous Invega LAI dose:
- Invega LAI 39-78 mg monthly → Risperidone 2-4 mg/day
- Invega LAI 117 mg monthly → Risperidone 4-5 mg/day
- Invega LAI 156-234 mg monthly → Risperidone 5-6 mg/day
Step 4: Monitoring
- Assess for signs of relapse or withdrawal during the first 4-6 weeks after the last Invega LAI injection
- Monitor for extrapyramidal symptoms, sedation, and orthostatic hypotension, particularly in the first 1-2 weeks of risperidone treatment
Special Considerations
Pharmacokinetic Factors
- Invega LAI has a long half-life, with plasma concentrations detectable for up to 4-6 months after the last injection 2
- The biphasic release pattern of Invega LAI means plasma levels will gradually decline over several weeks 2
- Risperidone reaches steady state within 1 week of consistent dosing
Metabolic Differences
- Some patients may respond differently to risperidone than they did to paliperidone despite their structural similarity 1
- CYP2D6 poor metabolizers may experience higher risperidone-to-paliperidone ratios and potentially different side effect profiles
Cost Considerations
- Switching from paliperidone to risperidone typically results in significant cost savings 3
- A conversion ratio of 2:3 (paliperidone:risperidone) has been suggested for cost analysis purposes 3
Common Pitfalls to Avoid
- Abrupt discontinuation: Failing to account for the long half-life of Invega LAI can lead to inadequate antipsychotic coverage
- Excessive dosing: Starting with too high a dose of risperidone while Invega LAI is still active can lead to dopamine hypoblockade and increased side effects
- Inadequate monitoring: Not closely following patients during the transition period when relapse risk may be elevated
- Assuming identical effects: Despite their pharmacological relationship, some patients may respond differently to risperidone than to paliperidone 1
By following this structured approach to transitioning from Invega LAI to oral risperidone, clinicians can help maintain symptom control while minimizing the risk of adverse effects during the switch.