What is the appropriate dosing regimen to switch a patient taking 9 mg oral Invega (paliperidone) to the long‑acting injectable Invega Sustenna (paliperidone palmitate)?

Switching from 9 mg Oral Invega to Long-Acting Injectable

For a patient taking 9 mg oral paliperidone (Invega), initiate paliperidone palmitate (Invega Sustenna) with 234 mg (150 mg eq.) deltoid injection on Day 1, followed by 156 mg (100 mg eq.) deltoid injection on Day 8, then monthly maintenance doses of 117 mg (75 mg eq.) starting on Day 36—no oral supplementation is required. 1, 2

Initiation Regimen (Loading Doses)

Day 1 Loading Dose:

• Administer 234 mg (150 mg eq. paliperidone) into the deltoid muscle 1, 2
• Use 1-inch 23-gauge needle if patient weighs <90 kg 1, 2
• Use 1.5-inch 22-gauge needle if patient weighs ≥90 kg 1, 2

Day 8 Loading Dose:

• Administer 156 mg (100 mg eq. paliperidone) into the deltoid muscle 1, 2
• Same weight-based needle selection as Day 1 1, 2
• This dose may be given ±2 days (Days 6-10) without clinically significant impact 1, 2

Critical Point: No oral paliperidone supplementation is needed during or after initiation because the biphasic release profile provides rapid attainment of therapeutic concentrations from Day 1 1, 3, 4

Timing of Switch from Oral Medication

• Discontinue the 9 mg oral paliperidone and initiate the first paliperidone palmitate injection the next day 1, 2
• The LAI formulation begins releasing drug as early as Day 1, with maximum plasma concentrations reached at 13 days 3

Monthly Maintenance Dosing (Starting Day 36)

Standard Maintenance Dose:

• 117 mg (75 mg eq. paliperidone) administered monthly 1, 2
• Dosing range: 39-234 mg (25-150 mg eq.) based on efficacy and tolerability 1, 2, 5

Injection Site Options for Maintenance:

• Deltoid muscle: Use weight-adjusted needle (1-inch 23G if <90 kg; 1.5-inch 22G if ≥90 kg) 1, 2
• Gluteal muscle: Use 1.5-inch 22-gauge needle regardless of weight 1, 2

Dosing Flexibility:

• Monthly doses may be administered ±7 days from the scheduled date without clinically significant impact on plasma concentrations 1, 2

Rationale for Deltoid Loading Doses

The deltoid injection site for the two loading doses is mandatory, not optional, because:

• Deltoid injection produces approximately 28% higher maximum plasma concentrations compared to gluteal injection 3
• This higher bioavailability is essential to rapidly achieve therapeutic concentrations without oral supplementation 3
• After loading, maintenance injections can be given in either deltoid or gluteal sites 1, 2

Pharmacokinetic Considerations

The paliperidone palmitate formulation has a biphasic release profile that is critical to its clinical effectiveness 4:

• Phase 1: Initial relatively fast zero-order input allows rapid attainment of therapeutic concentrations 4
• Phase 2: Sustained first-order input maintains therapeutic levels for monthly dosing 4

Clinical Importance: Changes in particle size or manufacturing can substantially alter release characteristics—larger particles delay release (risking relapse), while smaller particles accelerate release (risking adverse effects including tachycardia, hypotension, QT prolongation, and extrapyramidal symptoms) 4

Dose Adjustments for Special Populations

Renal Impairment:

• Mild impairment (CrCl 50-80 mL/min): Reduce initiation doses to 156 mg on Day 1 and 117 mg on Day 8, with monthly maintenance of 78 mg 1, 2
• Moderate to severe impairment (CrCl <50 mL/min): Paliperidone palmitate is not recommended 1

Hepatic Impairment:

• Mild to moderate: No dose adjustment required 1, 2
• Severe: No data available 1, 2

Elderly Patients:

• Same dosing as younger adults if renal function is normal 1, 2
• Adjust for age-related decline in creatinine clearance if present 1, 2

Common Pitfalls to Avoid

• Never use gluteal injections for the Day 1 and Day 8 loading doses—this will result in inadequate plasma concentrations and potential treatment failure 3
• Do not provide oral paliperidone supplementation—the loading dose regimen is specifically designed to eliminate this need 1, 3
• Do not skip the Day 8 loading dose—both loading doses are required to establish therapeutic levels 1, 2
• Avoid switching to monthly dosing before Day 36—premature transition can result in subtherapeutic levels 1, 2

Monitoring for Efficacy and Safety

Efficacy Monitoring:

• Higher dose strengths (156 mg and 234 mg) showed consistently lower numbers needed to treat for 30% or greater symptom reduction 3
• The 117 mg maintenance dose represents the recommended middle-range option balancing efficacy and tolerability 1, 2

Safety Monitoring:

• Monitor for extrapyramidal symptoms and weight gain, which may be more common at higher doses 3, 5
• Injection site reactions occur in 4-10% of patients (vs. 2% with placebo) 3
• Monitor for prolactin elevation, which is generally greater in women than men 5
• Watch for cardiovascular effects including tachycardia, hypotension, and QT prolongation if plasma levels become excessive 4