What to do if a dose of Invega Sustenna (paliperidone palmitate) is missed for 6 weeks?

Management of Missed Invega Sustenna Dose at 6 Weeks

When Invega Sustenna (paliperidone palmitate) has been missed for 6 weeks, you must restart the medication using the full loading dose protocol as if initiating a new patient, because therapeutic plasma levels have been lost and the patient is at high risk for psychotic relapse.

Critical Time Window Assessment

The 6-week gap far exceeds the therapeutic coverage window for monthly Invega Sustenna:

• Invega Sustenna provides therapeutic coverage for approximately 4-5 weeks after a single injection 1, 2
• At 6 weeks post-injection, paliperidone plasma concentrations have returned to subtherapeutic levels, eliminating the medication's antipsychotic effect 1
• This creates the same clinical scenario as a treatment-naive patient requiring initiation therapy 2

Restart Protocol: Loading Dose Strategy

You must use the deltoid loading dose regimen to rapidly re-establish therapeutic plasma concentrations:

• Day 1: Administer 234 mg (150 mg equivalents) into the deltoid muscle 2
• Day 8 (±4 days): Administer 156 mg (100 mg equivalents) into the deltoid muscle 2
• Day 36 and monthly thereafter: Administer 117 mg (75 mg equivalents) into either deltoid or gluteal muscle 2

The deltoid route for the first two doses is essential because it provides faster absorption and allows therapeutic concentrations to be reached within 8 days, preventing the need for oral antipsychotic supplementation 2.

Critical Safety Considerations Before Restarting

Before administering the loading doses, you must assess the patient's current antipsychotic sensitivity to prevent severe extrapyramidal symptoms:

• Determine if the patient has been taking any oral antipsychotics during the 6-week gap 3
• Review the patient's previous response to paliperidone or risperidone, particularly any history of severe Parkinsonism or extrapyramidal symptoms 3
• If the patient previously experienced significant extrapyramidal symptoms with standard dosing, consider using lower loading doses (e.g., 156 mg on Day 1,117 mg on Day 8) to reduce the risk of severe and prolonged Parkinsonism 3

The loading dose strategy can cause transient plasma concentration excursions that increase the risk of tachycardia, hypotension, QT prolongation, and extrapyramidal symptoms 1.

Relapse Risk Management

The 6-week gap without therapeutic coverage places the patient at immediate risk for psychotic relapse:

• Without therapeutic paliperidone levels, patients with schizophrenia experience significantly shorter time to relapse (median 23 days without medication vs. 83 days with paliperidone) 4, 2
• Consider bridging with oral paliperidone 6-12 mg daily starting immediately while arranging the first loading dose injection within 24-48 hours 4
• This oral bridge can be discontinued after the Day 8 loading dose when therapeutic depot levels are established 2

Common Pitfall to Avoid

Do not simply resume monthly maintenance dosing (117 mg) as if the patient were on schedule - this approach will fail to rapidly re-establish therapeutic levels and leaves the patient vulnerable to continued psychotic symptoms or relapse for several additional weeks 1, 2. The biphasic pharmacokinetic profile of Invega Sustenna requires the initial rapid-release phase provided only by the loading dose regimen 1.

Monitoring After Restart

• Assess for extrapyramidal symptoms at each visit, particularly within the first 2 weeks after loading doses 3, 2
• Monitor for injection site reactions, which are the primary new safety concern compared to oral paliperidone 2
• If severe extrapyramidal symptoms develop, plasma prolactin levels can serve as a surrogate marker for paliperidone exposure when direct drug level testing is unavailable 3