What are the guidelines for combining oral Invega (paliperidone) with a long-acting injectable antipsychotic?

Guidelines for Combining Oral Invega (Paliperidone) with Long-Acting Injectable Antipsychotics

When transitioning from oral paliperidone (Invega) to a long-acting injectable antipsychotic, the recommended approach is to initiate the long-acting injectable with the appropriate loading dose regimen while continuing oral medication for a bridging period, particularly for patients on higher oral doses (≥4 mg/day). 1

Initiation Protocol for Paliperidone Palmitate Injectable

Initial Loading Doses

• The recommended initiation regimen for paliperidone palmitate (Invega Sustenna) is:
  • Day 1: 150 mg eq. (234 mg) administered into the deltoid muscle 2, 3
  • Day 8: 100 mg eq. (156 mg) administered into the deltoid muscle 2, 3
  • Use appropriate needle size based on patient weight:
    • <90 kg: 1-inch 23-gauge needle 2
    • ≥90 kg: 1.5-inch 22-gauge needle 2

Oral Medication Bridging

• For patients on oral risperidone/paliperidone ≥4 mg/day, bridging with oral medication for ≥7 days after the first injection is associated with significant reductions in hospitalization days 1
• Patients on lower doses (<4 mg/day) may not require oral supplementation after initiation of the long-acting injectable 1, 3

Maintenance Dosing

• Monthly maintenance doses range from 25-150 mg eq. (39-234 mg) 2, 3
• The recommended maintenance dose is 75 mg eq. (117 mg) 2, 3
• Maintenance injections can be administered in either:
  • Deltoid muscle (using weight-adjusted needle) 2
  • Gluteal muscle (using 1.5-inch 22-gauge needle) 2

Timing Flexibility

• The Day 8 dose may be administered ±2 days without clinically significant impact on plasma concentrations 2, 3
• Monthly maintenance doses may be administered ±7 days without clinically significant impact 2, 3

Special Considerations

Renal Impairment

• Dosage adjustment is required for patients with mild renal impairment (creatinine clearance: 50-80 mL/min) 2, 3
• Elderly patients with normal renal function should receive the same dosage as younger adults with normal renal function 2
• If age-related decline in creatinine clearance occurs, dosage should be adjusted accordingly 2, 3

Hepatic Impairment

• No dose adjustment is required in patients with mild or moderate hepatic impairment 2
• Limited data exists for severe hepatic impairment 2

Switching from Other Antipsychotics

From Oral Antipsychotics

• Paliperidone palmitate can be initiated the day after discontinuing previous oral antipsychotic treatment 2, 3
• No oral supplementation is required with the recommended loading dose regimen 2, 3

From Other Long-Acting Injectables

• When switching from other long-acting injectable antipsychotics (including long-acting risperidone), initiate paliperidone palmitate at the time of the next scheduled injection of the previous LAI 2, 3
• Continue with monthly paliperidone palmitate injections thereafter 2

Clinical Outcomes and Monitoring

• Switching patients from oral risperidone/paliperidone to paliperidone LAI is associated with reductions in:
  • Hospitalization days 1
  • Emergency department/mental health urgent care visits 1
• The pharmacokinetic profile of paliperidone palmitate is biphasic, allowing for rapid attainment of therapeutic concentrations without oral supplementation in most patients 4
• Monitor for potential adverse effects, particularly during the initiation phase, including:
  • Tachycardia, hypotension, QT prolongation, and extrapyramidal symptoms 4

Common Pitfalls to Avoid

• Inadequate loading doses may result in subtherapeutic plasma concentrations 4
• Lack of oral bridging in patients on higher doses (≥4 mg/day) may lead to inadequate serum concentrations 1
• Changes in the release characteristics of paliperidone palmitate LAI can substantially alter its pharmacokinetic profile and clinical effects 4
• Failure to adjust dosing for renal impairment may lead to adverse effects 2, 3