What is the recommended initiation protocol for Invega Sustenna (paliperidone palmitate)?

Initiating Invega Sustenna (Paliperidone Palmitate)

Invega Sustenna requires a specific two-injection deltoid loading regimen: 234 mg on Day 1 followed by 156 mg on Day 8, both administered into the deltoid muscle, with no oral antipsychotic supplementation needed. 1, 2, 3

Loading Dose Protocol

Day 1 Initial Injection

• Administer 234 mg (150 mg equivalent paliperidone) into the deltoid muscle 3
• Use a 1-inch 23-gauge needle for patients <90 kg 3
• Use a 1.5-inch 22-gauge needle for patients ≥90 kg 3
• No oral antipsychotic supplementation is required with this regimen 1, 2

Day 8 Second Loading Injection

• Administer 156 mg (100 mg equivalent paliperidone) into the deltoid muscle 3
• May be given ±2 days from Day 8 without clinically significant impact 3
• Use the same weight-based needle selection as Day 1 3

Rationale for This Approach

• The deltoid injection produces approximately 28% higher maximum concentrations compared to gluteal administration, allowing rapid attainment of therapeutic levels 1
• Significant symptom improvement occurs by Day 8 compared to placebo, with continued improvement after the Day 8 injection 2
• The biphasic pharmacokinetic profile provides initial rapid zero-order input followed by sustained first-order release, enabling monthly dosing without oral supplementation 1, 4

Maintenance Dosing (Starting Day 36)

• Administer monthly injections in the range of 39-234 mg (25-150 mg equivalent paliperidone) 3
• Recommended maintenance dose is 117 mg (75 mg equivalent paliperidone) 3
• Maintenance injections can be given in either deltoid or gluteal muscle 3
  • Deltoid: use weight-adjusted needle size as above 3
  • Gluteal: use 1.5-inch 22-gauge needle 3
• Monthly doses may be administered ±7 days without significant plasma concentration impact 3

Critical Safety Considerations Before Initiation

Screen patients carefully before using the standard loading regimen, as it can cause severe and prolonged extrapyramidal symptoms in susceptible individuals. 5 Specifically assess:

• Prior sensitivity to antipsychotics or extrapyramidal symptoms 5
• Baseline movement disorder risk factors 5
• Current medications that may increase paliperidone levels 5

The standard loading dose can result in transient excursions above therapeutic concentrations associated with tachycardia, hypotension, QT prolongation, and extrapyramidal symptoms 4. Consider therapeutic drug monitoring (using plasma levels or prolactin as a surrogate) if adverse reactions develop 5.

Special Population Adjustments

Renal Impairment

• Mild renal impairment (CrCl 50-80 mL/min): adjust dosage downward 3
• Severe renal impairment: use with caution as paliperidone is renally eliminated 3

Hepatic Impairment

• No dose adjustment needed for mild or moderate hepatic impairment 3
• Insufficient data for severe hepatic impairment 3

Elderly Patients

• Use same dosage as younger adults if renal function is normal 3
• Adjust dose if age-related decline in creatinine clearance is present 3

Switching from Other Antipsychotics

From Oral Antipsychotics

• Initiate paliperidone palmitate the day after discontinuing oral antipsychotic 3
• Follow the standard Day 1/Day 8 loading regimen 3

From Other Long-Acting Injectables

• Initiate paliperidone palmitate at the time of the next scheduled injection of the previous LAI 3
• Continue monthly thereafter 3
• No additional loading doses required when switching from LAIs 3

Managing Missed Doses

Re-initiation strategy depends on time elapsed since last injection: 3

• ≤6 weeks since last dose: Resume with the next scheduled monthly maintenance dose 3
• >6 weeks since last dose: Restart with the full Day 1/Day 8 loading regimen 3

Onset of Efficacy

• Therapeutic effect begins by Day 8 after the initial 234 mg injection 2
• Continued improvement occurs at Day 22 (p≤0.007 vs placebo) and Day 36 (p<0.001) following the 156 mg Day 8 injection 2
• Evidence suggests a dose-dependent response trend across the dosing range 2

Common Adverse Events During Initiation

Days 1-7 (After 234 mg)

• Injection site pain: 6.7% (vs 3.8% placebo) 2
• Headache: 4.0% (vs 3.8% placebo) 2
• Agitation: 3.2% (vs 1.3% placebo) 2

Days 8-36 (After 156 mg)

• Anxiety: 3.1% (vs 2.5% placebo) 2
• Injection site pain: 2.5% (vs 1.3% placebo) 2
• Dizziness: 2.5% (vs 1.3% placebo) 2

Overall, paliperidone palmitate demonstrates low rates of extrapyramidal symptoms and weight gain at recommended doses, though these may increase at higher doses 1.