Can a patient with a history of psychiatric illness, previously treated with Invega Trinza (paliperidone palmitate), be started on paliperidone (Invega) extended release (ER) at 6mg after missing their long-acting injectable (LAI) Invega Trinza for over 4 weeks?

Restarting Paliperidone ER After Missed Invega Trinza

Yes, a patient can be started on paliperidone ER 6 mg after missing Invega Trinza for over 4 weeks, and this is the FDA-recommended dose for schizophrenia without requiring titration. 1

Dosing Rationale

The FDA label explicitly states that 6 mg once daily is the recommended dose for paliperidone ER in adults with schizophrenia, with no initial dose titration required 1. This applies whether the patient is antipsychotic-naive or transitioning from another formulation.

Key Considerations for This Clinical Scenario

After missing Invega Trinza for over 4 weeks, plasma paliperidone levels have likely declined significantly, creating urgent relapse risk:

• Due to flip-flop kinetics in LAI formulations, when doses are missed, plasma levels decline based on the absorption rate from the depot, typically providing a grace period of several days to 1-2 weeks before significant drops occur 2
• If a missed dose exceeds 2 weeks, oral bridging becomes necessary while reinitiating the LAI 2
• At 4+ weeks post-missed injection, the patient is essentially unmedicated and at high relapse risk

The urgency of restarting treatment cannot be overstated:

• Approximately 65% of patients receiving placebo relapse within 1 year, compared to only 30% on antipsychotics 3
• Over 5 years, approximately 80% of patients experience at least one relapse when off medication 3
• Any evidence of disorder recurrence warrants immediate resumption of treatment 3

Practical Implementation

Starting Dose

• Begin paliperidone ER 6 mg once daily immediately 1
• No titration is required per FDA labeling 1
• The 6 mg dose is therapeutically effective from day one 1

Dose Adjustments

• Some patients may require lower (3 mg) or higher (up to 12 mg) doses based on clinical response 1
• Dose increases above 6 mg should only occur after clinical reassessment and at intervals of more than 5 days 1
• When increases are indicated, use 3 mg increments 1

Administration

• Can be taken with or without food 1
• Must be swallowed whole—never chewed, divided, or crushed 1

Special Population Considerations

Renal function must be assessed before dosing:

• Normal/mild impairment (CrCl ≥50 mL/min): Start at 3 mg daily, may increase to maximum 6 mg 1
• Moderate-severe impairment (CrCl 10-49 mL/min): Start at 1.5 mg daily, maximum 3 mg 1
• CrCl <10 mL/min: Not recommended 1

Critical Monitoring

Close monitoring is essential during the first 4 weeks after restarting treatment 3, as this is when relapse risk remains elevated and medication response is being established.

Common Pitfalls to Avoid

• Do not delay treatment initiation—the patient has already been without adequate medication for over 4 weeks, substantially increasing relapse risk 3
• Do not start at lower doses (e.g., 3 mg) unless renal impairment is present—the FDA-recommended starting dose is 6 mg for a reason 1
• Do not assume the patient needs oral supplementation beyond the paliperidone ER—the extended-release formulation provides therapeutic levels without additional coverage 1, 4, 5

Concurrent LAI Reinitiation

If planning to restart Invega Trinza or another LAI:

• Continue paliperidone ER until the LAI reaches therapeutic levels 6
• For paliperidone palmitate monthly (Invega Sustenna), therapeutic levels are achieved with the initiation regimen (150 mg eq. day 1,100 mg eq. day 8) without oral supplementation 6
• The oral paliperidone ER can be discontinued the day the LAI is initiated 6, 7