What is the recommended initiation regimen for Invega Sustenna (paliperidone palmitate) in an adult with schizophrenia, including loading doses, renal dose adjustments, oral antipsychotic coverage, and monitoring?

Invega Sustenna Initiation Protocol

Recommended Loading Dose Regimen

Invega Sustenna (paliperidone palmitate) should be initiated with 234 mg on Day 1 and 156 mg on Day 8, both administered via deltoid intramuscular injection, with no oral antipsychotic supplementation required. 1, 2, 3

Day 1 Loading Dose

• Administer 234 mg (150 mg eq. paliperidone) into the deltoid muscle on Day 1 2, 3
• Use a 1-inch 23-gauge needle for patients weighing <90 kg 2, 3
• Use a 1.5-inch 22-gauge needle for patients weighing ≥90 kg 2, 3
• This deltoid loading achieves therapeutic plasma concentrations more rapidly than gluteal injection 4

Day 8 Loading Dose

• Administer 156 mg (100 mg eq. paliperidone) into the deltoid muscle on Day 8 2, 3
• The Day 8 dose may be given ±2 days without clinically significant impact on plasma concentrations 2, 3
• Use the same weight-adjusted needle selection as Day 1 2, 3
• Significant symptom improvement versus placebo is evident by Day 8 after the first injection, with continued improvement after the Day 8 dose 1

Critical Advantage: No Oral Supplementation Required

• No oral antipsychotic coverage is needed during the initiation phase, which distinguishes Invega Sustenna from other long-acting injectables 2, 3
• This loading regimen achieves therapeutic plasma levels immediately, eliminating the need for oral bridging 2

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Monthly Maintenance Dosing

Standard Maintenance Regimen

• Begin monthly maintenance injections starting on Day 36 (4 weeks after Day 8 dose) 2, 3
• Recommended maintenance dose: 117 mg (75 mg eq. paliperidone) monthly 2, 3
• Maintenance dose range: 39–234 mg (25–150 mg eq. paliperidone) based on efficacy and tolerability 2, 3, 5
• Monthly doses may be administered ±7 days without clinically significant impact 2, 3

Injection Site Flexibility for Maintenance

• Maintenance doses may be given in either deltoid or gluteal muscle 2, 3
• For deltoid injections: use weight-adjusted needle (1-inch 23G if <90 kg; 1.5-inch 22G if ≥90 kg) 2, 3
• For gluteal injections: use 1.5-inch 22-gauge needle regardless of weight 2, 3
• Gluteal injections demonstrate slightly better local tolerability, though systemic adverse events are similar between sites 4

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Renal Dose Adjustments

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

• Reduce initiation doses: 156 mg on Day 1, followed by 117 mg on Day 8 2, 3
• Reduce maintenance dose: 78 mg monthly 2, 3
• Dosage adjustment is mandatory because paliperidone is primarily renally eliminated 2

Moderate to Severe Renal Impairment (CrCl <50 mL/min)

• Invega Sustenna is not recommended in patients with moderate to severe renal impairment 2, 3

Elderly Patients

• Elderly patients with normal renal function receive the same dosage as younger adults 2, 3
• In the event of age-related decline in CrCl, adjust dosage according to renal function guidelines above 2, 3

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Switching from Other Antipsychotics

From Oral Antipsychotics

• Initiate Invega Sustenna the day after discontinuing the previous oral antipsychotic 2, 3
• Use the standard loading regimen (234 mg Day 1,156 mg Day 8) 2, 3
• No oral overlap or bridging is required 2, 3

From Other Long-Acting Injectables

• Initiate Invega Sustenna at the time of the next scheduled injection of the previous long-acting injectable 2, 3
• Use the standard loading regimen (234 mg Day 1,156 mg Day 8) 2, 3
• Continue monthly thereafter 2, 3

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Baseline and Ongoing Monitoring

Baseline Assessment (Before First Injection)

• Metabolic parameters: BMI, waist circumference, blood pressure, fasting glucose (or HbA1c), fasting lipid panel 6
• Renal function: serum creatinine and calculated creatinine clearance 2, 3
• Hepatic function: liver function tests (AST, ALT, bilirubin) 6
• Hematologic: complete blood count 6
• Cardiovascular: ECG to assess QTc interval 6
• Endocrine: prolactin level, thyroid function tests 6
• Pregnancy test in females of childbearing potential 6

Intensive Monitoring (First 6 Weeks)

• Weekly: BMI, waist circumference, blood pressure 6
• Week 4: repeat fasting glucose 6
• Assess for extrapyramidal symptoms (akathisia, parkinsonism, dystonia) at each visit 6
• Monitor for injection site reactions (pain, swelling, redness) 1

Ongoing Maintenance Monitoring

• Monthly (first 3 months): BMI, waist circumference 6
• Quarterly (after 3 months): BMI 6
• At 3 months: repeat all baseline metabolic parameters (fasting glucose, lipid panel, blood pressure) 6
• Annually: repeat all baseline assessments (metabolic panel, ECG, prolactin, liver function, renal function) 6
• Every 3–6 months: assess for tardive dyskinesia using standardized scales 6

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Expected Efficacy Timeline

• Day 8: Significant improvement in PANSS total score versus placebo is evident after the first 234 mg injection 1
• Day 22: Continued symptom improvement after the Day 8 (156 mg) injection 1
• Day 36: Further improvement with trend toward dose-dependent response 1
• 4–6 weeks: Full therapeutic effect requires at least 4–6 weeks at therapeutic doses before concluding treatment failure 7, 5

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Common Adverse Events During Initiation

Days 1–7 (After First Injection)

• Injection site pain: 6.7% (vs. 3.8% placebo) 1
• Headache: 4.0% (vs. 3.8% placebo) 1
• Agitation: 3.2% (vs. 1.3% placebo) 1

Days 8–36 (After Second Injection and Beyond)

• Anxiety: 3.1–3.9% (vs. 2.5% placebo) 1
• Psychotic disorder: 2.5–2.6% (vs. 1.3% placebo) 1
• Dizziness: 2.5% (vs. 1.3% placebo) 1
• Injection site pain: 2.5% (vs. 1.3% placebo) 1

No Unexpected Tolerability Findings

• No unexpected safety signals were identified during the first week or month after initiation dosing 1
• Systemic adverse events were similar between deltoid and gluteal injection sites 4

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Managing Missed Doses

If Last Injection Was ≤6 Weeks Ago

• Resume with the next scheduled monthly maintenance dose 2
• No re-initiation loading doses are required 2

If Last Injection Was >6 Weeks Ago

• Re-initiate with the full loading regimen: 234 mg Day 1,156 mg Day 8 2
• The duration since the last injection determines whether re-initiation is necessary 2

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Special Populations

Hepatic Impairment

• Mild or moderate hepatic impairment: No dose adjustment required 2, 3
• Severe hepatic impairment: No data exist; use with caution 2, 3

Pregnancy and Lactation

• Obtain pregnancy test before initiation in all females of childbearing potential 6
• Discuss risks and benefits if pregnancy is detected or planned 6

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Common Pitfalls to Avoid

• Do not use gluteal injection for loading doses on Days 1 and 8—deltoid injection achieves faster therapeutic levels 2, 4
• Do not add oral antipsychotic supplementation—the loading regimen is designed to achieve therapeutic levels without oral coverage 2, 3
• Do not skip renal function assessment—dose adjustment is mandatory in mild renal impairment 2, 3
• Do not conclude treatment failure before 4–6 weeks—adequate trial duration is essential 7, 5
• Do not forget weight-adjusted needle selection—incorrect needle length may result in subcutaneous rather than intramuscular delivery 2, 3