Xeplion Paliperidone Palmitate Extended-release Injection (3M)

1. Indications and Usage
Maintenance Treatment of Schizophrenia:
Treatment of schizophrenia in adult patients.
Prerequisite: Indicated for patients who have been adequately treated with Paliperidone Palmitate 1-Month Formulation for at least 4 months.
2. Dosage and Administration
Route of Administration:
For Intramuscular (IM) Injection ONLY.
Recommended Dosage:
Dosing Frequency: Administered once every 3 months.
Dose Conversion: The dose is determined by the previous 1-month formulation dose.
Previous 150 mg (1M) → Switch to 525 mg (3M).
Previous 100 mg (1M) → Switch to 350 mg (3M).
Previous 75 mg (1M) → Switch to 263 mg (3M).
Previous 50 mg (1M) → Switch to 175 mg (3M).
Critical Administration Instructions:
Injection Site: Gluteal (buttocks) or Deltoid (shoulder) muscle.
Needle Selection: Must use the special thin-wall needle provided in the package. (Standard needles may cause clogging due to the suspension).
Shaking: Vial must be shaken vigorously for at least 15 seconds immediately before injection to ensure uniform suspension.
3. Mechanism of Action
Dopamine & Serotonin Antagonism:
Paliperidone is the active metabolite of Risperidone. It acts as an antagonist at dopamine D2 and serotonin 5-HT2A receptors.
Long-Acting Kinetics:
After intramuscular injection, the drug dissolves slowly, forming a subcutaneous depot. It is hydrolyzed to active paliperidone, providing a steady release over 3 months, which minimizes peak-to-trough fluctuations in plasma levels.
4. Safety and Warnings
Increased Mortality in Elderly with Dementia:
Analyses of antipsychotic drugs show an increased risk of death in elderly patients with dementia-related psychosis.
QTc Prolongation:
Paliperidone causes a mean increase in QTc of approximately 10–12 ms. Use caution in patients with cardiac history or those taking QT-prolonging drugs.
Metabolic Changes:
May cause hyperglycemia, dyslipidemia, and weight gain. Monitor blood glucose and lipids periodically.
Hyperprolactinemia:
Can elevate prolactin levels, potentially leading to galactorrhea, amenorrhea, or gynecomastia.
5.Adverse Reactions and Clinical Research
Most Common Adverse Reactions:
Injection site reactions (pain, redness), headache, somnolence, anxiety, and upper respiratory tract infections.
Clinical Research Highlights:
Efficacy: In a pivotal randomized, double-blind, placebo-controlled trial, the 3-month formulation demonstrated superior efficacy in delaying time to relapse compared to placebo.
Non-Inferiority: Studies confirmed that switching from the 1-month formulation to the 3-month formulation maintained symptom control.
6.Drug Interactions
CYP3A4 Inhibitors:
Potent CYP3A4 inhibitors (e.g., ketoconazole) may increase paliperidone levels.
Dopamine Agonists:
Paliperidone may antagonize the effects of dopamine agonists (e.g., pramipexole).
Antihypertensives:
May enhance the hypotensive effect of antihypertensive agents.
Alcohol:
Concomitant use is not recommended.
7.Pharmaceutical Information
Chemical Composition:
Active Ingredient: Paliperidone Palmitate.
Appearance: Sterile, white to off-white aqueous suspension.
Packaging: Prefilled syringe with a specific thin-wall needle.
Storage: Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F).