Paliperidone Palmitate Second Dose Administration Site
After the first dose of paliperidone palmitate is given in the deltoid muscle on Day 1, the second dose (Day 8) must also be administered in the deltoid muscle, not the gluteal area.
FDA-Approved Initiation Regimen
The approved initiation protocol for paliperidone palmitate requires both loading doses to be administered in the deltoid muscle 1, 2, 3:
- Day 1: 234 mg (150 mg eq.) in the deltoid muscle
- Day 8: 156 mg (100 mg eq.) in the deltoid muscle
- Monthly maintenance (starting Day 36): Either deltoid or gluteal muscle may be used 4, 2, 5
Pharmacokinetic Rationale
The deltoid site is mandatory for both initiation doses because it produces higher and more rapid peak plasma concentrations compared to gluteal injection 4, 5. This pharmacokinetic advantage is critical during the loading phase:
- Median plasma paliperidone concentrations are significantly higher with deltoid administration during the first treatment week 4
- The deltoid route achieves therapeutic blood levels rapidly without requiring oral antipsychotic supplementation 2, 3
- Efficacy data demonstrating symptom improvement by Day 8 were based on deltoid administration for both loading doses 1
At steady state (maintenance dosing), plasma concentrations become comparable between deltoid and gluteal sites, which is why either site may be used for monthly maintenance injections 4, 5.
Technical Administration Details
For the Day 8 deltoid injection, needle selection is weight-based 3:
- Patients <90 kg: Use 1-inch, 23-gauge needle
- Patients ≥90 kg: Use 1.5-inch, 22-gauge needle
The Day 8 dose may be administered ±2 days from the scheduled date without clinically significant impact on plasma concentrations 3.
Critical Pitfall to Avoid
Do not administer the Day 8 dose in the gluteal muscle, even if the patient prefers this site or if deltoid access is challenging. The approved initiation regimen specifically requires deltoid administration for both loading doses to ensure adequate early therapeutic response 1, 2, 3. Switching to gluteal administration should only occur starting with the first monthly maintenance dose (Day 36 and beyond) 4, 2.
Clinical Trial Evidence
The efficacy and safety data supporting paliperidone palmitate approval were based on the deltoid-deltoid initiation sequence 1. In the pivotal 13-week trial, patients receiving 234 mg deltoid on Day 1 followed by 156 mg deltoid on Day 8 showed significantly greater PANSS improvement compared to placebo by Day 8 (p=0.037), with continued improvement at Day 22 (p≤0.007) 1.