What is the initiation protocol for long-acting injectable Invega (paliperidone palmitate)?

How to Start Long-Acting Injectable Invega (Paliperidone Palmitate)

Initiate paliperidone palmitate with 234 mg (150 mg eq.) on Day 1 via deltoid injection, followed by 156 mg (100 mg eq.) on Day 8 via deltoid injection, with no oral antipsychotic supplementation required. 1, 2, 3

Initial Dosing Protocol

Day 1 Injection

• Administer 234 mg (150 mg eq. paliperidone) intramuscularly into the deltoid muscle 2, 4
• Use a 1-inch 23-gauge needle for patients weighing <90 kg 2
• Use a 1.5-inch 22-gauge needle for patients weighing ≥90 kg 2
• No oral supplementation is necessary with this initiation regimen, which distinguishes paliperidone palmitate from other long-acting injectables 1, 3, 4

Day 8 Injection

• Administer 156 mg (100 mg eq. paliperidone) intramuscularly into the deltoid muscle 2, 3
• Use the same weight-based needle selection as Day 1 2
• The Day 8 injection can be given within a ±4 day window (Days 4-12) without clinically significant impact on plasma concentrations 2, 5

Onset of Therapeutic Effect

• Significant symptom improvement occurs by Day 8 compared to placebo, following the initial 234 mg injection 3
• Therapeutic blood levels are achieved rapidly without oral supplementation due to the initiation dosing strategy 1, 4
• Continued improvement is observed at Day 22 and Day 36 after the Day 8 injection of 156 mg 3

Maintenance Dosing (After Initiation)

• Begin monthly maintenance injections starting 4 weeks after the Day 8 dose 2, 4
• Recommended maintenance dose is 117 mg (75 mg eq.) monthly, with a range of 39-234 mg (25-150 mg eq.) based on tolerability and efficacy 2, 4
• Maintenance injections can be administered in either deltoid or gluteal muscle 2, 4
• For gluteal injections, use a 1.5-inch 22-gauge needle 2
• Monthly doses can be given ±7 days from the scheduled date without significant impact 2

Practical Advantages

• No refrigeration required 4
• Comes in prefilled syringes 4
• Small injection volume with very small bore needle 4
• Drug release starts as early as Day 1, reaches maximum plasma concentrations at 13 days, and lasts up to 126 days 4

Common Pitfalls to Avoid

Missed Day 8 Dose

• If the Day 8 injection is delayed beyond Day 12, use the expanded ±4 day window guidance, but do not delay further 5
• If significantly delayed (>6 weeks from last dose), re-initiation protocols apply based on duration since last injection 2

Injection Site Selection

• Both initial injections (Day 1 and Day 8) must be given in the deltoid muscle, not gluteal 2, 4
• Deltoid injection produces approximately 28% higher maximum plasma concentrations compared to gluteal injection, which is critical for rapid therapeutic effect 4
• Only maintenance doses (after Day 8) can be given in either deltoid or gluteal sites 2

Oral Supplementation

• Do not add oral antipsychotic supplementation during initiation—this regimen is designed to achieve therapeutic levels without it 1, 3, 4

Switching from Other Antipsychotics

From Oral Antipsychotics

• Initiate paliperidone palmitate the day after discontinuing oral antipsychotic treatment 2
• Use the standard Day 1/Day 8 initiation protocol 2

From Other Long-Acting Injectables

• Begin paliperidone palmitate at the time of the next scheduled injection of the previous long-acting injectable 2
• Continue monthly thereafter using the standard initiation protocol 2

Special Populations

Renal Impairment

• Adjust dosage in patients with mild renal impairment (CrCl 50-80 mL/min) 2
• No data exist for severe renal impairment 2

Hepatic Impairment

• No dose adjustment required for mild or moderate hepatic impairment 2
• No data available for severe hepatic impairment 2

Elderly Patients

• Use the same dosage as younger adults if renal function is normal 2
• Adjust dosage if age-related decline in creatinine clearance is present 2

Tolerability During Initiation

• Injection site pain occurs in 6.7% of patients after the Day 1 injection (vs. 3.8% with placebo) 3
• Other common adverse events in the first week include agitation (3.2%) and headache (4.0%) 3
• Extrapyramidal symptoms and weight gain rates are low, though may be more common at higher doses 4