Importance of Long-Acting Injectable Antipsychotic Preparation, Administration, and Injection Site Tolerability: A Focus on Paliperidone Palmitate Once-Every-6-Months Formulation

Purpose. This post hoc analysis assessed the importance of proper paliperidone palmitate (PP) dose preparation prior to administration and evaluated injection site reactions after dorsogluteal injection of PP once-every-6-months (PP6M) and once-every-3-months (PP3M) formulations from a double-blind (DB) noninferiority study. Design and Methods. Clinically stable patients receiving moderate/high doses of PP once-monthly (PP1M) (156 mg/mL; 234 mg/1.5 mL) or PP3M (546 mg/1.75 mL; 819 mg/2.63 mL) were randomly assigned 2:1 to corresponding dorsogluteal injections of PP6M (1092 mg/3.5 mL; 1560 mg/5 mL) or PP3M (546 mg/1.75 mL; 819 mg/2.63 mL) during a 12-month DB phase. Patients receiving PP6M injections received alternating matching placebo injections every 3 months between active doses to maintain blinding. Prior to administration, each PP formulation was prepared per specific instructions to ensure complete resuspension of the medication. Findings. Of 895 PP6M injections, one of two incomplete injections was possibly related to insufficient shaking before administration; neither resulted in an adverse reaction. After dorsogluteal administration, 59 of 478 patients who received PP6M (12.3%) and 11 of 224 patients who received PP3M (4.9%) reported an injection site–related treatment-emergent adverse event (TEAE), with pain being the most commonly reported (7.7% and 4.0%, respectively). Patient-reported pain decreased from baseline to end point in both groups. During the DB phase, injection site-related TEAEs associated with PP6M injections up to 5 mL and PP3M injections up to 2.63 mL were mild to moderate in severity; none were reported as serious, resulted in treatment discontinuation, or required dermatological consultation. Practice Implications. These results inform provider and patient expectations of PP6M administration and reinforce the importance of proper PP dose preparation and administration; future work could assess safety data from real-world clinical practice. This trial is registered with NCT03345342.