Oral Paliperidone Supplementation with Invega Sustenna
Use oral paliperidone (Invega) as the supplemental antipsychotic with Invega Sustenna (paliperidone palmitate), as it is the same active drug and eliminates concerns about drug-drug interactions, overlapping side effects, and polypharmacy complications.
Rationale for Same-Drug Supplementation
The recommended initiation regimen for Invega Sustenna is 150 mg eq on day 1 and 100 mg eq on day 8, both administered in the deltoid muscle, which achieves therapeutic blood levels rapidly without the necessity of oral supplementation 1. This biphasic pharmacokinetic profile allows for rapid attainment of therapeutic concentrations through an initial relatively fast zero-order input phase, followed by maintained first-order input for once-monthly administration 2.
However, when oral supplementation is clinically necessary during initiation or dose adjustments:
- Oral paliperidone ER (Invega) is the logical choice because it is the identical active compound, eliminating pharmacokinetic and pharmacodynamic concerns about combining different antipsychotic agents 3, 4
- The recommended oral paliperidone dose range is 3-12 mg per day, utilizing the OROS delivery system for once-daily dosing with stable serum concentrations 3
- Paliperidone undergoes limited hepatic metabolism, minimizing risks of drug-drug interactions that would occur with other antipsychotics 3, 4
Why Avoid Antipsychotic Polypharmacy
Routinely, one antipsychotic should be prescribed at a time, and antipsychotic combination treatment should only be considered for individuals who do not respond to single-agent therapy, preferably under supervision of mental health professionals with close clinical monitoring 5.
The risks of combining different antipsychotics include:
- Increased global side-effect burden, including Parkinsonian symptoms, anticholinergic effects, hyperprolactinemia, sexual dysfunction, hypersalivation, sedation, and cognitive impairment 5
- Drug-drug interactions from medications affecting the same metabolic pathways, leading to unpredictable plasma concentrations and adverse reactions 5
- Higher risk of extrapyramidal symptoms, QTc prolongation, and metabolic disturbances when combining agents with overlapping side effect profiles 5, 2
Clinical Considerations
- Transient excursions above therapeutic plasma concentrations can occur with improper supplementation, increasing risk of tachycardia, hypotension, QT prolongation, and extrapyramidal symptoms 2
- Delays in attaining therapeutic concentrations or premature return to low levels before the end of dosing intervals increases relapse risk 2
- The most common adverse events with paliperidone include extrapyramidal symptoms (dose-related), tachycardia, somnolence, and prolactin elevation 3, 4
Common Pitfall to Avoid
Do not combine Invega Sustenna with risperidone or other antipsychotics, as paliperidone is already the active metabolite of risperidone (9-hydroxyrisperidone) 1, 4. This would create unnecessary polypharmacy with the same therapeutic target, compounding side effects without additional benefit.