What oral substitute can be used for a patient currently on Invega Trinza (paliperidone) who is unable to continue with the long-acting injectable formulation?

Oral Paliperidone Extended-Release as Direct Substitute for Invega Trinza

When discontinuing Invega Trinza (paliperidone palmitate 3-month injectable), transition directly to oral paliperidone extended-release tablets at 3-12 mg once daily, with the specific dose determined by the previous injectable maintenance dose and timing of the last injection. 1

Dosing Conversion Strategy

Oral paliperidone ER is available in 1.5 mg, 3 mg, 6 mg, and 9 mg strengths, allowing flexible dose-proportional pharmacokinetics across the therapeutic range. 1

Recommended Conversion Approach:

• Start oral paliperidone ER at the time the next Invega Trinza injection would have been due 2
• For patients on Invega Trinza 273 mg (175 mg eq. paliperidone): initiate oral paliperidone ER 6-9 mg daily 1, 2
• For patients on Invega Trinza 410 mg (263 mg eq. paliperidone): initiate oral paliperidone ER 9-12 mg daily 1, 2
• For patients on Invega Trinza 546 mg (350 mg eq. paliperidone): initiate oral paliperidone ER 12 mg daily 1, 2

Pharmacokinetic Considerations

• Oral paliperidone ER reaches peak plasma concentration approximately 24 hours after dosing with a terminal elimination half-life of approximately 23 hours, providing stable once-daily coverage 1
• The extended-release formulation employs a hydrophilic hydrogel matrix that delivers paliperidone at a controlled rate over 24 hours through slow diffusion and gel erosion 1
• No oral supplementation or loading doses are required when transitioning from long-acting injectable to oral formulation at appropriate maintenance doses 2

Clinical Efficacy Evidence

• Oral paliperidone ER demonstrated significant efficacy in three 6-week trials in acute schizophrenia, with doses of 3-12 mg/day producing clinically meaningful improvements compared to placebo 3
• The recommended therapeutic dose range is 3-12 mg per day, with dose-proportional pharmacokinetics throughout this range 1, 3
• Paliperidone ER was effective in 6-month maintenance studies for prevention of symptom recurrence 3

Monitoring and Tolerability

The most common treatment-emergent adverse events include headache, tremor, dizziness, insomnia, akathisia, somnolence, and extrapyramidal symptoms, with dose-related increases in Parkinsonism and akathisia. 4, 3

Key Monitoring Parameters:

• Assess for extrapyramidal symptoms (EPS) including Parkinsonism and akathisia, which increase in dose-related manner 3
• Monitor for QTc interval prolongation, though clinically significant arrhythmias are rare 3
• Check serum prolactin levels, as paliperidone ER is associated with prolactin elevation similar to risperidone 3
• Evaluate for tachycardia and orthostatic hypotension due to alpha-adrenergic antagonism 1, 3

Special Population Adjustments

• In patients with mild renal impairment (CrCl 50-80 mL/min), reduce the maximum recommended dose to 6 mg once daily 2
• No dose adjustment required for mild or moderate hepatic impairment; insufficient data exist for severe hepatic impairment 2
• Elderly patients with normal renal function receive standard adult dosing, but adjust for age-related decline in creatinine clearance 2

Critical Pitfalls to Avoid

• Do not combine oral paliperidone with aripiprazole, as the partial D2 agonism of aripiprazole conflicts with paliperidone's full D2 antagonism, increasing EPS risk without clear efficacy benefit 5
• Avoid antipsychotic polypharmacy; attempt adequate monotherapy before considering combination therapy 5
• Do not use epinephrine or dopamine for hypotension management in overdose, as beta-stimulation may worsen hypotension due to paliperidone-induced alpha blockade 1
• Recognize that paliperidone undergoes limited hepatic metabolism, minimizing drug-drug interactions compared to extensively metabolized antipsychotics 3

Advantages of Oral Paliperidone ER

• Once-daily dosing with stable serum concentrations throughout the 24-hour period due to OROS delivery system 3
• Minimal hepatic metabolism reduces risks of hepatic drug-drug and drug-disease interactions 3
• Direct continuation of the same active moiety (paliperidone) as Invega Trinza, maintaining therapeutic consistency 1