What is the recommended dosing regimen to initiate Invega Sustenna (paliperidone palmitate) in an adult with schizophrenia or schizoaffective disorder who has not been previously stabilized on paliperidone or risperidone and has creatinine clearance ≥ 50 mL/min?

Initiating Invega Sustenna (Paliperidone Palmitate)

Recommended Initiation Regimen

For adults with schizophrenia or schizoaffective disorder who have not been previously stabilized on paliperidone or risperidone and have creatinine clearance ≥ 50 mL/min, initiate Invega Sustenna with 150 mg equivalent (234 mg) on Day 1 followed by 100 mg equivalent (156 mg) on Day 8, both administered into the deltoid muscle. 1, 2, 3

Detailed Dosing Protocol

Initial Loading Doses

• Day 1: Administer 150 mg eq. paliperidone (234 mg paliperidone palmitate) into the deltoid muscle 1, 2, 3
• Day 8: Administer 100 mg eq. paliperidone (156 mg paliperidone palmitate) into the deltoid muscle 1, 2, 3
• The Day 8 dose may be given ±2 days without clinically significant impact on plasma concentrations 1, 2

Needle Selection for Initial Doses

• Patients weighing <90 kg: Use a 1-inch 23-gauge needle 1, 2, 3
• Patients weighing ≥90 kg: Use a 1.5-inch 22-gauge needle 1, 2, 3

No Oral Supplementation Required

• Unlike some other long-acting injectable antipsychotics, no oral antipsychotic supplementation is needed during the initiation phase with this dosing regimen 1, 2, 3
• The onset of clinical response occurs as early as 8 days after the initial 150 mg eq. dose 3

Monthly Maintenance Dosing (Starting Day 36)

Standard Maintenance Dose

• Recommended dose: 75 mg eq. paliperidone (117 mg paliperidone palmitate) administered monthly 1, 2, 3
• Dosing range: 25-150 mg eq. paliperidone (39-234 mg) based on individual tolerability and efficacy 1, 2, 3
• Monthly maintenance doses may be administered ±7 days without clinically significant impact on plasma concentrations 1, 2

Injection Site Options for Maintenance

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

Special Population Dosing Adjustments

Mild Renal Impairment (CrCl 50-80 mL/min)

• Day 1: 100 mg eq. paliperidone (156 mg) in the deltoid 1, 2
• Day 8: 75 mg eq. paliperidone (117 mg) in the deltoid 1, 2
• Monthly maintenance: 50-100 mg eq. paliperidone (78-156 mg), with 75 mg eq. (117 mg) recommended 1, 2

Elderly Patients

• Elderly patients with normal renal function should receive the same dosage as younger adults 1, 2
• If age-related decline in creatinine clearance is present, adjust dosage according to renal function guidelines above 1, 2

Hepatic Impairment

• No dose adjustment required for mild or moderate hepatic impairment 1, 2
• No data exist for severe hepatic impairment 1, 2

Switching from Other Antipsychotics

From Oral Antipsychotics

• Initiate paliperidone palmitate the day after discontinuing the previous oral antipsychotic 1, 2
• Use the standard initiation regimen (150 mg eq. Day 1,100 mg eq. Day 8) 1, 2

From Other Long-Acting Injectable Antipsychotics

• Initiate paliperidone palmitate at the time of the next scheduled injection of the previous long-acting injectable 1, 2
• Use the standard initiation regimen, then continue monthly thereafter 1, 2
• This applies to switching from long-acting risperidone or other long-acting injectable antipsychotics 1, 2

Managing Missed Doses

If Last Maintenance Dose Was >6 Weeks Ago

• The re-initiation schedule depends on the duration since the last injection 1
• If the gap is substantial, consider restarting with the full initiation regimen (150 mg eq. Day 1,100 mg eq. Day 8) to rapidly achieve therapeutic levels 1

Clinical Monitoring

Efficacy Assessment

• Clinical response should be evident by Day 8 after the initial loading dose 3
• Full therapeutic benefit develops over the first few weeks as steady-state concentrations are achieved 1, 3

Safety Monitoring

• Monitor for common antipsychotic adverse effects including extrapyramidal symptoms, weight gain, metabolic changes, and prolactin elevation 3, 4
• Paliperidone palmitate is associated with weight gain and elevated prolactin levels compared to older antipsychotics 4
• Monitor for injection site reactions, which are specific to the long-acting injectable formulation 3

Common Pitfalls to Avoid

• Do not use oral supplementation during initiation—the loading dose regimen is designed to achieve therapeutic levels without oral overlap 1, 2, 3
• Do not administer initial doses in the gluteal muscle—deltoid administration is required for Days 1 and 8 to ensure proper absorption kinetics 1, 2, 3
• Do not skip the Day 8 dose—both loading doses are essential to achieve therapeutic plasma concentrations rapidly 1, 2
• Do not forget to adjust for renal impairment—patients with CrCl 50-80 mL/min require lower doses 1, 2
• Do not use in patients with CrCl <50 mL/min without careful consideration, as dosing recommendations are not well established below this threshold 1, 2