Invega Sustenna (Paliperidone Palmitate) Dosing and Treatment Protocol
Recommended Initiation Regimen
Invega Sustenna should be initiated with 150 mg on day 1 and 100 mg on day 8, both administered into the deltoid muscle, followed by monthly maintenance doses of 75-150 mg into either the deltoid or gluteal muscle. 1, 2
Initial Loading Phase
- Day 1: 150 mg equivalents administered into the deltoid muscle 1, 2
- Day 8: 100 mg equivalents administered into the deltoid muscle 1, 2
- Rationale: Deltoid injection provides approximately 28% higher maximum plasma concentrations compared to gluteal injection, allowing rapid attainment of therapeutic levels without oral supplementation 2, 3
- Clinical response onset: 8 days after the recommended initial deltoid dosing 1
Maintenance Dosing
- Frequency: Monthly injections (every 4 weeks) 2
- Dose range: 75-150 mg equivalents 1, 2
- Injection site: Either deltoid or gluteal muscle 2
- Duration of effect: Drug release lasts up to 126 days after injection 2
Treatment Duration and Monitoring
Acute Phase (First 4-6 Weeks)
- Assess efficacy after at least 4 weeks at therapeutic dose before determining treatment failure 4
- Monitor for effectiveness and side effects throughout this period 4
- If inadequate response after 4 weeks, consider switching to an alternative antipsychotic with different pharmacodynamic profile 4
Maintenance Phase
- Continue the same antipsychotic medication if symptoms have improved 4
- Long-term treatment is necessary for most patients with schizophrenia to prevent relapse 4
- Paliperidone palmitate significantly delays time to relapse compared to placebo (Number Needed to Treat = 5) 2
- Approximately 65% of patients receiving placebo relapse within 1 year versus 30% receiving antipsychotics 4
Clinical Positioning
When to Consider Invega Sustenna
- Preferred for patients with poor or uncertain adherence to oral medications 4
- Appropriate as second-line treatment after D2 partial agonist failure, alongside amisulpride, risperidone, or olanzapine 4
- Useful when guaranteed medication delivery is clinically important 2
- Consider when patient prefers long-acting injectable formulation 4
Treatment Algorithm Position
- Not recommended as first-line unless adherence concerns exist 4
- If symptoms persist after 4 weeks of adequate dosing, switch to alternative antipsychotic 4
- After two failed antipsychotic trials (including at least one atypical agent), consider clozapine 4
Safety Monitoring and Tolerability
Common Adverse Effects
- Injection site reactions: 4-10% (versus 2% placebo) 2
- Extrapyramidal symptoms: Approximately 25% at higher doses (9-12 mg/day oral equivalent) 5
- Prolactin elevation: Monitor throughout treatment 5
- Weight gain: Clinically significant in 15% of patients 5
- Metabolic effects: Monitor glucose, lipids, and insulin levels 5
Critical Safety Considerations
- QT prolongation risk: Monitor ECG in at-risk patients 3
- Hypotension and tachycardia: Particularly with rapid dose escalation 3
- Extrapyramidal symptoms: Risk increases with higher doses 3
- Plasma concentration excursions above therapeutic range increase adverse effect risk 3
Management of Side Effects
- Acute dystonia: Treat with anticholinergic medication 4
- Parkinsonism: Lower dose, switch antipsychotic, or add anticholinergic 4
- Akathisia: Lower dose, switch antipsychotic, add benzodiazepine, or add beta-blocker 4
- Tardive dyskinesia: If moderate to severe, treat with reversible inhibitor 4
Important Clinical Caveats
Pharmacokinetic Complexity
- Biphasic release profile: Initial rapid zero-order input followed by sustained first-order release 3
- Manufacturing changes can substantially alter release characteristics and clinical effects 3
- Particle size variations affect release rate: larger particles delay release, smaller particles accelerate it 3
Switching Considerations
- When switching from oral antipsychotics, use gradual cross-titration based on half-life and receptor profile 4
- No oral supplementation required with recommended deltoid initiation regimen 2