What is the recommended initiation regimen for Invega (paliperidone palmitate) shot in a patient currently on 6mg daily of oral paliperidone?

Invega Sustenna (Paliperidone Palmitate) Initiation for Patient on 6mg Daily Oral Paliperidone

For a patient currently taking 6mg daily oral paliperidone, initiate Invega Sustenna with 150 mg equivalent (234 mg) on Day 1 via deltoid injection, followed by 100 mg equivalent (156 mg) on Day 8 via deltoid injection, with no oral supplementation required. 1, 2

Initiation Dosing Regimen

The FDA-approved initiation protocol is standardized regardless of prior oral dose:

• Day 1: 150 mg equivalent paliperidone (234 mg paliperidone palmitate) administered into the deltoid muscle 1, 3
• Day 8: 100 mg equivalent paliperidone (156 mg paliperidone palmitate) administered into the deltoid muscle 1, 3
• No oral antipsychotic supplementation is needed during or after initiation 1, 2, 3

Needle Selection for Initiation Doses

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

Rationale for This Dosing Strategy

The biphasic pharmacokinetic profile of paliperidone palmitate requires deltoid administration for the first two doses to achieve rapid therapeutic concentrations 1, 4. Deltoid injection produces approximately 28% higher maximum plasma concentrations compared to gluteal injection, which is critical for quickly establishing therapeutic levels 3. The Day 1 dose of 234 mg initiates a zero-order release phase that achieves therapeutic concentrations by Day 8 without oral supplementation 2, 4.

Efficacy data demonstrates significant symptom improvement by Day 8 compared to placebo (p=0.037), with continued improvement after the Day 8 injection at Day 22 (p≤0.007) and Day 36 (p<0.001) 2.

Flexibility in Day 8 Dosing Window

The Day 8 injection has an expanded window of ±4 days (Days 4-12), meaning it can be administered between Days 4 and 12 without clinically significant impact on plasma concentrations 5. Pharmacokinetic modeling shows median maximum plasma concentrations vary by only ±3 ng/mL across this window 5.

Transition from Oral Paliperidone

Discontinue oral paliperidone the day before initiating Invega Sustenna 1. The patient's current 6mg daily oral dose does not alter the standard initiation regimen—all patients receive the same 150/100 mg equivalent loading doses regardless of prior oral exposure 1, 3.

Maintenance Dosing (After Day 8)

Following the two initiation doses, transition to monthly maintenance dosing starting on Day 36 (approximately 4 weeks after Day 8 dose) 1:

• Recommended maintenance dose: 75 mg equivalent (117 mg paliperidone palmitate) 1
• Dosing range: 25-150 mg equivalent (39-234 mg paliperidone palmitate) 1
• Can be administered in deltoid or gluteal muscle 1, 3
• Monthly doses have a ±7 day window without clinically significant impact 1

For gluteal maintenance injections, use a 1.5-inch, 22-gauge needle regardless of weight 1.

Safety Considerations During Initiation

Days 1-7 (After First Injection)

Common adverse events occurring in ≥2% of patients include 2:

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

Days 8-36 (After Second Injection, 156 mg)

Common adverse events include 2:

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

Extrapyramidal symptoms and weight gain occur at low rates but may be more common at higher doses 3.

Special Populations

Renal Impairment

• Mild impairment (CrCl 50-80 mL/min): Dosage adjustment required 1
• Moderate to severe impairment: Use with caution; specific guidance needed

Hepatic Impairment

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

Elderly Patients

• Use same dosage as younger adults if renal function is normal 1
• Adjust for age-related decline in creatinine clearance if present 1

Critical Clinical Pitfalls to Avoid

1. Do not use gluteal injection for initiation doses—deltoid administration is required for Days 1 and 8 to achieve adequate early exposure 1, 3
2. Do not continue oral supplementation—the loading dose regimen is designed to achieve therapeutic levels without oral overlap 1, 2, 3
3. Do not adjust initiation doses based on prior oral dose—the 150/100 mg equivalent regimen is standardized for all patients 1, 3
4. Do not miss the Day 8 dose window—while flexibility exists (Days 4-12), missing this entirely requires re-initiation planning 5