What is the appropriate initiation and maintenance dosing schedule for Invega Sustenna (paliperidone palmitate) in an adult with schizophrenia or schizoaffective disorder, including contraindications, required monitoring, and alternative options?

Initiating Invega Sustenna (Paliperidone Palmitate)

Recommended Initiation Protocol

For adults with schizophrenia or schizoaffective disorder, initiate Invega Sustenna with 234 mg (150 mg eq.) on Day 1 followed by 156 mg (100 mg eq.) on Day 8, both administered into the deltoid muscle, with no oral supplementation required. 1

Specific Dosing Details

• Day 1 dose: 234 mg (150 mg eq.) deltoid injection 1
• Day 8 dose: 156 mg (100 mg eq.) deltoid injection 1
• Needle selection based on weight:
  • Patients <90 kg: Use 1-inch 23-gauge needle 1
  • Patients ≥90 kg: Use 1.5-inch 22-gauge needle 1
• No oral antipsychotic supplementation is necessary with this initiation regimen 1

Maintenance Dosing

After the two-dose initiation, monthly maintenance doses range from 39-234 mg (25-150 mg eq.), with 117 mg (75 mg eq.) as the recommended standard maintenance dose 1. Maintenance injections can be administered into either the deltoid (using weight-adjusted needle) or gluteal muscle (using 1.5-inch 22-gauge needle) 1.

Dosing flexibility: The Day 8 dose may be given ±2 days, and monthly maintenance doses may be given ±7 days without clinically significant impact on plasma concentrations 1.

Switching from Other Antipsychotics

From Oral Antipsychotics

Initiate Invega Sustenna the day after discontinuing oral antipsychotic treatment using the standard two-dose initiation regimen 1. This approach eliminates the need for oral overlap or bridging therapy 1.

From Other Long-Acting Injectables

Begin Invega Sustenna at the next scheduled injection time of the previous long-acting injectable (including long-acting risperidone), then continue monthly thereafter 1. For switching from aripiprazole to paliperidone, begin paliperidone 6 mg while simultaneously tapering aripiprazole over 5-7 days, given aripiprazole's long half-life of 75 hours 2.

Special Population Dosing Adjustments

Renal Impairment

Patients with mild renal impairment (creatinine clearance 50-80 mL/min) require dosage adjustment 1. No dose adjustment is needed for mild or moderate hepatic impairment, though data are lacking for severe hepatic impairment 1.

Elderly Patients

Elderly patients with normal renal function receive the same dosage as younger adults 1. However, if age-related decline in creatinine clearance is present, adjust dosage accordingly 1.

Timeline for Clinical Response

The onset of clinical response occurs at 8 days in patients receiving the recommended 150 mg eq. initial dose into the deltoid muscle 3. However, antipsychotic effects become more apparent after the first 1-2 weeks rather than immediately 4, and dose adjustments should be made based on clinical response assessed over at least 4 weeks 4.

Avoid declaring treatment failure before 4-6 weeks at therapeutic doses with confirmed adherence, as antipsychotic effects develop gradually 4, 2.

Efficacy and Relapse Prevention

Long-acting injectable antipsychotics like Invega Sustenna significantly reduce relapse rates compared to placebo (30% vs 65% relapse within 1 year) 4. In a longer-term maintenance trial, Invega Sustenna was associated with significantly longer time to relapse than placebo, with the study terminated early due to favorable results after 68 relapse events 3.

In a head-to-head comparison, there was no statistically significant difference in efficacy failure rates between paliperidone palmitate (33.8%) and haloperidol decanoate (32.4%) 5.

Monitoring Requirements

Baseline Assessment

Before initiating Invega Sustenna, obtain:

• Body mass index and waist circumference 2
• Blood pressure 2
• Fasting glucose and lipid panel 2
• Baseline assessment of extrapyramidal symptoms 2

Ongoing Monitoring

• Assess treatment response at 4 weeks minimum at the therapeutic dose with documented adherence 2
• Document ongoing assessment of extrapyramidal symptoms, weight, and metabolic parameters 2
• If significant positive symptoms persist after 4 weeks at therapeutic dose with confirmed adherence, consider switching to an alternative antipsychotic with different pharmacodynamic profile 2

Adverse Effects Profile

Metabolic Effects

Paliperidone palmitate is associated with weight gain: after 6 months, patients gained an average of 2.17 kg (95% CI, 1.25-3.09) 5.

Prolactin Elevation

Paliperidone palmitate causes significantly higher serum prolactin levels compared to haloperidol decanoate: in men, 34.56 µg/L vs 15.41 µg/L (P<0.001), and in women, 75.19 µg/L vs 26.84 µg/L (P<0.001) 5.

Injection Site Reactions

No new safety concerns were revealed compared with oral paliperidone, except for injection site-related reactions 3.

Extrapyramidal Symptoms

Paliperidone palmitate was associated with less akathisia than haloperidol decanoate (global rating increase 0.45 vs 0.73, P=0.006) 5.

Contraindications and Precautions

Do not abruptly discontinue Invega Sustenna without a plan for alternative antipsychotic coverage, as approximately 65% of patients relapse within 1 year without maintenance treatment 4.

The inpatient setting allows for close monitoring during critical transition periods when initiating or switching to Invega Sustenna 2.

Long-Term Outcomes

In a 3-year follow-up study, only 5 of 121 patients (4.1%) experienced relapse during treatment with paliperidone palmitate every 6 months 6. Patients remained clinically and functionally stable, with maintained scores on symptom and functioning scales over the 3-year period 6. 101 patients (83.5%) completed the 2-year open-label extension, with no new safety or tolerability concerns identified 6.

Common Pitfalls to Avoid

• Never skip the Day 8 dose or delay it beyond ±2 days, as this disrupts the pharmacokinetic profile necessary for therapeutic plasma levels 1
• Do not use gluteal injection for the initiation doses (Day 1 and Day 8) – deltoid administration is required for proper loading 1
• Avoid premature dose escalation before 4 weeks, as antipsychotic effects require adequate time to manifest 4, 2
• Do not add oral antipsychotic supplementation with the recommended initiation regimen, as it is unnecessary and increases adverse effect burden 1