Do I need to restart the titration regimen for Invega Sustenna (paliperidone palmitate) if a dose is missed for 2 weeks?

Invega Sustenna Missed Dose Management After 2 Weeks

If you miss Invega Sustenna doses for 2 weeks (14 days), you do NOT need to restart the full titration regimen, but your approach depends on where you are in the treatment schedule and how long the gap has been.

Decision Algorithm Based on Treatment Phase

If Missing Doses During Maintenance Phase (After Initial Loading)

For gaps of 2 weeks (14 days):

• Resume at your previous maintenance dose without restarting titration 1
• The long half-life of paliperidone palmitate (25-49 days) means therapeutic levels persist well beyond 2 weeks 1
• No oral supplementation is required when resuming 1

Critical timing thresholds:

• Less than 4 weeks missed: Continue with your established maintenance dose 1
• 4-7 weeks missed: Consider whether to resume maintenance dose or use a modified loading approach based on symptom stability 1
• More than 7 weeks missed: Treat as a new start with full loading dose regimen 1

If Missing Doses During Initial Loading Phase (First 2 Months)

During weeks 1-8 of treatment:

• If you miss the Day 8 second loading dose: Give it as soon as possible, then continue monthly dosing 2
• If 2+ weeks have passed since the first injection: Resume with the second loading dose (typically 117 mg deltoid), then proceed to monthly maintenance 2
• The biphasic release profile means the initial injection continues releasing medication for several weeks 1

Key Pharmacokinetic Considerations

Why 2 weeks doesn't require full restart:

• Paliperidone palmitate has a biphasic release pattern with an initial rapid phase followed by sustained first-order release 1
• Steady-state concentrations are maintained for extended periods due to the depot formulation 1
• The medication continues releasing from the injection site for 4-5 months after administration 1

Risk assessment for the 2-week gap:

• Low risk of relapse: Therapeutic plasma concentrations typically persist beyond 2 weeks 1
• Minimal risk of adverse effects: Resuming at maintenance dose avoids the excessive plasma levels that can occur with unnecessary loading doses 2

Common Pitfalls to Avoid

Do NOT automatically restart full titration:

• Unnecessary loading doses can cause severe extrapyramidal symptoms, including prolonged Parkinsonism 2
• Excessive plasma concentrations increase risk of tachycardia, hypotension, QT prolongation, and movement disorders 1

Do NOT assume oral bridging is needed:

• The package insert does not recommend oral supplementation when resuming after short gaps 3
• Oral bridging is only beneficial when switching FROM oral risperidone ≥4 mg/day TO paliperidone palmitate initially 3

Monitoring After Resumption

Clinical monitoring priorities:

• Assess for early signs of relapse (sleep disturbance, social withdrawal, paranoia) in the first 2-4 weeks after resuming 4
• Monitor for extrapyramidal symptoms, particularly if any dose adjustment was made 2, 4
• Check for tachycardia and orthostatic hypotension at follow-up visits 4
• Consider prolactin-related adverse effects (sexual dysfunction, gynecomastia, amenorrhea) 5

When to consider therapeutic drug monitoring:

• If patient develops unexpected adverse effects after resuming 2
• If clinical response is inadequate despite resuming injections 2
• Note: Serum prolactin levels can serve as a proxy when direct paliperidone level testing is unavailable 2

Special Circumstances Requiring Modified Approach

Consider a modified loading approach (not full restart) if:

• Patient experienced acute symptom worsening during the 2-week gap 3
• Gap approaches 4 weeks rather than exactly 2 weeks 1
• Patient was on higher maintenance doses (234 mg monthly) and shows early relapse signs 3

Maintain standard maintenance dosing if:

• Patient remains clinically stable 3
• Gap is clearly under 4 weeks 1
• No acute psychiatric decompensation occurred 3