paliperidone palmitate
Last reviewed 2025-12-30
Reviewed by PsychMed Editorial Team.
Brands: INVEGA SUSTENNA, INVEGA TRINZA, INVEGA HAFYERA
Sources updated 2025 • 4 references
General Information
Paliperidone palmitate is a long-acting injectable prodrug of paliperidone with multiple interval options: monthly (PP1M), every 3 months (PP3M), and every 6 months (PP6M), depending on product and prior stabilization.
In the U.S., paliperidone palmitate products are used for schizophrenia maintenance, and the monthly formulation is also labeled for schizoaffective disorder. Longer-interval options are usually introduced after sustained stability on a shorter interval.
Pharmacology mirrors paliperidone/risperidone-class D2/5-HT2A blockade: prolactin elevation and EPS are frequent clinical constraints, and metabolic monitoring remains important.
Because renal excretion is the dominant clearance pathway, renal function meaningfully influences dosing and eligibility for longer intervals.
U.S. approvals
- Schizophrenia ()
- Schizoaffective disorder (monthly formulation) ()
Formulations & strengths
- PP1M: intramuscular injection monthly after labeled loading sequence.
- PP3M: intramuscular injection every 3 months after stabilization.
- PP6M: intramuscular injection every 6 months after stabilization.
Generic availability
- Long-acting injectable remains brand-only in the United States as of 2025.
Paliperidone palmitate is widely used when teams want a predictable depot schedule with limited hepatic interaction complexity. The trade-offs are a higher prolactin signal and meaningful EPS risk in some patients, plus a strong dependence on renal function for dose selection.
View labelExactMechanism of Action
Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.
Paliperidone (the active drug released from paliperidone palmitate) is a dopamine D2 and serotonin 5-HT2A antagonist and is the major active metabolite of risperidone.
Therapeutic effect is generally attributed to sustained D2 receptor occupancy with serotonergic modulation, while prolactin elevation and EPS reflect dopamine blockade in pituitary and nigrostriatal pathways.
- Dopamine D2 receptor antagonism.
- Serotonin 5-HT2A receptor antagonism.
- Additional alpha-adrenergic and histaminergic effects contribute to orthostasis/sedation in some patients.
Metabolism and Pharmacokinetics
- Paliperidone palmitate is hydrolyzed to paliperidone after injection; the depot formulation produces a prolonged apparent half-life measured in weeks.
- Paliperidone has limited hepatic metabolism and is eliminated primarily via renal excretion, with a substantial fraction excreted unchanged in urine.
- Longer-interval products (PP3M/PP6M) further extend exposure; missed-dose management differs by product and often involves re-loading sequences rather than simple “late injection” dosing.
Dosing and Administration
- PP1M initiation uses a labeled loading sequence (deltoid injections on day 1 and day 8) followed by monthly maintenance. Oral overlap is not typically required after the loading sequence.
- Maintenance dosing is individualized to symptom control and tolerability within labeled dose ranges; deltoid versus gluteal administration can influence absorption.
- PP3M and PP6M products require prior stabilization; conversion is based on the stabilized PP1M/PP3M dose and the specific product’s conversion table.
- Missed-dose management is time- and product-dependent; many clinics use standing protocols to decide when re-loading is needed and how to bridge symptom risk.
Monitoring & Labs
- Weight/BMI and waist circumference; fasting lipids and glucose/HbA1c at baseline and periodically.
- Movement disorder monitoring (parkinsonism, akathisia, tardive dyskinesia).
- Prolactin-related symptoms (sexual dysfunction, menstrual changes, galactorrhea); targeted labs when indicated.
- Renal function assessment (baseline and when clinically indicated for dosing decisions).
- ECG monitoring when baseline QTc risk is elevated or QT-prolonging co-medications are present.
Adverse Effects
FDA boxed warnings
- Increased mortality in elderly patients with dementia-related psychosis (antipsychotic class warning).
Common side effects (≥10%)
- Prolactin-related adverse effects: Prolactin elevation is common and can present as sexual dysfunction, menstrual changes, galactorrhea, and long-term bone health concerns. Monitoring is often symptom-driven with targeted lab testing.
- Extrapyramidal symptoms: Parkinsonism, akathisia, or other EPS can occur, especially at higher doses or when combined with other dopamine-blocking agents. Routine movement-disorder screening is common.
- Weight gain and metabolic change: Weight gain and cardiometabolic change can still occur; monitor weight/BMI, lipids, and glucose/HbA1c per routine antipsychotic practice.
- Orthostatic hypotension: Alpha-adrenergic effects can contribute to dizziness or orthostasis, particularly early in treatment or when combined with antihypertensives.
- Injection-site reactions: Local pain or swelling may occur; rotating sites and documenting deltoid versus gluteal administration support consistent tolerability.
Other notable effects
- QTc prolongation risk is generally modest but can become clinically relevant in patients with baseline cardiac risk or when combined with other QT-prolonging medications.
- Renal impairment increases exposure and can amplify adverse effects; reassess dosing when renal function changes.
Interactions
- Paliperidone is not heavily metabolized by hepatic CYP enzymes, so classic inhibitor/inducer interactions are less prominent than with many other antipsychotics.
- Additive sedation, orthostasis, or QTc effects can occur with CNS depressants or QT-prolonging agents; individualize monitoring based on baseline cardiac risk.
- Combined dopamine antagonists increase EPS burden; movement-disorder monitoring and careful dose selection are common.
Other Useful Information
- A sequencing approach is common: use PP1M to establish stability, then consider PP3M/PP6M to reduce visit burden once symptoms and logistics are stable.
- Standardized documentation (product, dose, site, date) plus missed-dose algorithms reduce the risk of accidental undertreatment.
- Renal function should be documented at initiation and revisited if clinical status changes (e.g., dehydration, chronic kidney disease progression).
References
- INVEGA SUSTENNA (paliperidone palmitate) prescribing information — DailyMed / Janssen Pharmaceuticals (2025)
- INVEGA TRINZA (paliperidone palmitate) prescribing information — DailyMed / Janssen Pharmaceuticals (2025)
- INVEGA HAFYERA (paliperidone palmitate) prescribing information — DailyMed / Janssen Pharmaceuticals (2025)
- Paliperidone palmitate maintenance treatment in delaying time to relapse in patients with schizophrenia — Schizophrenia Research (2010)