Converting from Invega Trinza IM to Oral Risperidone
There is no established guideline or FDA-approved protocol for converting from Invega Trinza (3-month paliperidone palmitate) to oral risperidone, so you must account for the prolonged release kinetics and use a cross-titration approach with oral supplementation. 1, 2
Understanding the Pharmacokinetic Challenge
- Invega Trinza has an extremely prolonged release profile with detectable plasma concentrations persisting for 18 months or longer after the last injection 3
- The medication exhibits biphasic release: an initial zero-order input followed by sustained first-order release, making abrupt switching problematic 3, 4
- Paliperidone is the active metabolite (9-hydroxyrisperidone) of risperidone, so you are essentially converting between the same active compound 2
Recommended Conversion Strategy
Step 1: Calculate Equivalent Oral Dose
- Determine the patient's current Invega Trinza dose (ranging from 273 mg to 819 mg every 3 months) 4
- Use the relationship that paliperidone palmitate releases approximately 3.5-12 mg equivalent paliperidone daily depending on the dose 4
- Convert to oral risperidone using a 1:1 ratio, as risperidone is metabolized to paliperidone (the same active compound) 2
- For example: A patient on Invega Trinza 546 mg every 3 months (approximately 6 mg equivalent daily) would convert to risperidone 6 mg daily 1, 4
Step 2: Initiate Oral Risperidone with Overlap
- Start oral risperidone at the calculated equivalent dose on the day the next Invega Trinza injection would have been due 5, 6
- Begin with risperidone 0.5-1 mg twice daily (total 1-2 mg/day) initially, then titrate up by 1-2 mg per day at 24-hour intervals to reach the target dose 1
- The FDA label recommends risperidone can be administered once or twice daily, with a usual effective range of 4-8 mg per day for schizophrenia 1
Step 3: Monitor and Adjust
- Reassess the patient within 24-48 hours after initiating oral risperidone, as residual paliperidone from the LAI will still be present 5, 4
- Watch for signs of under-treatment (worsening psychotic symptoms, agitation) or over-treatment (excessive sedation, extrapyramidal symptoms) 1, 3
- Extrapyramidal symptoms increase in a dose-related manner, particularly above 6 mg/day 1, 2
Critical Pitfalls to Avoid
- Do not stop the LAI and wait for washout before starting oral medication—the prolonged release means therapeutic gaps of weeks to months, dramatically increasing relapse risk 3, 4
- Do not use fixed conversion ratios without clinical judgment—patients on higher LAI doses may need proportionally less oral medication due to incomplete cross-tolerance 5, 4
- Do not ignore renal function—both paliperidone and risperidone require dose adjustment in renal impairment (CrCl <50 mL/min warrants starting at 0.5 mg twice daily) 1, 4
- Avoid doses above 6 mg/day initially—higher doses increase extrapyramidal symptoms without proven additional efficacy 1, 2
Special Populations
- Elderly patients: Start with risperidone 0.5 mg twice daily and titrate more slowly, as age-related decline in renal function affects clearance 1, 6
- Renal impairment (CrCl 50-80 mL/min): Use lower starting dose of 0.5 mg twice daily, increase to maximum 1.5 mg twice daily at weekly intervals 1
- Hepatic impairment: Start with 0.5 mg twice daily in severe hepatic disease 1
Monitoring Parameters
- Assess for relapse indicators: increased hospitalization days, emergency department visits, or missed appointments—these are validated outcomes when switching antipsychotic formulations 5
- Monitor for prolactin elevation, as both paliperidone and risperidone significantly increase serum prolactin levels 2
- Watch for QTc prolongation, particularly if combining with other QTc-prolonging medications 2, 3
- Evaluate for metabolic effects including weight gain and glucose dysregulation with chronic use 1