Paliperidone

Paliperidone is the major active metabolite of risperidone. The mechanism of action of paliperidone in schizophrenia is unclear.

• Paliperidone extended-release tablets are an atypical antipsychotic agent indicated for Treatment of schizophrenia (1.1) Adults: Efficacy was established in three 6-week trials and one maintenance trial. (14.1) Adolescents (ages 12 to 17): Efficacy was established in one 6-week trial.ICD-10: F20.9

• Paliperidone extended-release tablets are contraindicated in patients with a known hypersensitivity to either paliperidone or risperidone, or to any of the excipients in the paliperidone extended-release tablet formulation. Hypersensitivity reactions, including anaphylactic reactions and angioedema, have been reported in patients treated with risperidone and in patients treated with paliperidone.contraindicated

Initial Dose Recommended Dose Maximum Dose Schizophrenia - adults (2.1) 6 mg/day 3 to 12 mg/day 12 mg/day Schizophrenia-adolescents (2.1) Weight < 51 kg 3 mg/day 3 to 6 mg/day 6 mg/day Weight ≥ 51 kg 3 mg/day 3 to 12 mg/day 12 mg/day Schizoaffective disorder - adults (2.2) 6 mg/day 3 to 12 mg/day 12 mg/day Tablet should be swallowed whole and should not be chewed, divided, or crushed. (2.3) 2.1 Schizophrenia Adults The recommended dose of paliperidone extended-release tablets for the treatment of schizophrenia in adults is 6 mg administered once daily. Initial dose titration is not required. Although it has not been systematically established that doses above 6 mg have additional benefit, there was a general trend for greater effects with higher doses. This must be weighed against the dose-related increase in adverse reactions. Thus, some patients may benefit from higher doses, up to 12 mg/day, and for some patients, a lower dose of 3 mg/day may be sufficient. Dose increases above 6 mg/day should be made only after clinical reassessment and generally should occur at intervals of more than 5 days. When dose increases are indicated, increments of 3 mg/day are recommended. The maximum recommended dose is 12 mg/day. In a longer-term study, paliperidone extended-release tablets have been shown to be effective in delaying time to relapse in patients with schizophrenia who were stabilized on paliperidone extended-release tablets for 6 weeks [see Clinical Studies (14) ].

Cerebrovascular Adverse Reactions: An increased incidence of cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack, including fatalities) has been seen in elderly patients with dementia-related psychoses treated with atypical antipsychotics. (5.2) Neuroleptic Malignant Syndrome: Manage with immediate discontinuation of drug and close monitoring. (5.3) QT Prolongation: Increase in QT interval, avoid use with drugs that also increase QT interval and in patients with risk factors for prolonged QT interval. (5.4) Tardive Dyskinesia: Discontinue drug if clinically appropriate. (5.5) Metabolic Changes: Atypical antipsychotic drugs have been associated with metabolic changes that may increase cardiovascular/cerebrovascular risk. These metabolic changes include hyperglycemia, dyslipidemia, and weight gain. (5.6) Hyperglycemia and Diabetes Mellitus: Monitor patients for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Monitor glucose regularly in patients with diabetes or at risk for diabetes. (5.6) Dyslipidemia: Undesirable alterations have been observed in patients treated with atypical antipsychotics. (5.6) Weight Gain: Significant weight gain has been reported. Monitor weight gain. (5.6) Hyperprolactinemia: Prolactin elevations occur and persist during chronic administration. (5.7) Gastrointestinal Narrowing: Obstructive symptoms may result in patients with gastrointestinal disease.

The following adverse reactions are discussed in more detail in other sections of the labeling: Increased mortality in elderly patients with dementia-related psychosis [see Boxed Warning and Warnings and Precautions (5.1) ] Cerebrovascular adverse reactions, including stroke, in elderly patients with dementia-related psychosis [see Warnings and Precautions (5.2) ] Neuroleptic malignant syndrome [see Warnings and Precautions (5.3) ] QT prolongation [see Warnings and Precautions (5.4) ] Tardive dyskinesia [see Warnings and Precautions (5.5) ] Metabolic changes [see Warnings and Precautions (5.6) ] Hyperprolactinemia [see Warnings and Precautions (5.7) ] Potential for gastrointestinal obstruction [see Warnings and Precautions (5.8) ] Orthostatic hypotension and syncope [see Warnings and Precautions (5.9) ] Falls [see Warnings and Precautions (5.10) ] Leukopenia, neutropenia, and agranulocytosis [see Warnings and Precautions (5.11) ] Potential for cognitive and motor impairment [see Warnings and Precautions (5.12) ] Seizures [see Warnings and Precautions (5.13) ] Dysphagia [see Warnings and Precautions (5.14) ] Priapism [see Warnings and Precautions (5.15) ] Disruption of body temperature regulation [see Warnings and Precautions (5.16) ] Commonly observed adverse reactions (incidence ≥ 5% and at least twice that for placebo) were (6) Adults with schizophrenia: extrapyramidal symptoms, tachycardia, and akathisia. Adolescents with schizophrenia: somnolence, akathisia, tremor, dystonia, cogwheel rigidity, anxiety, weight increased, and tachycardia.

Renal impairment: Dosing must be individualized according to renal function status. (2.5) Elderly: Same as for younger adults (adjust dose according to renal function status). (2.4) Pregnancy: May cause extrapyramidal and/or withdrawal symptoms in neonates with third trimester exposure. (8.1) Pediatric Use: Safety and effectiveness in the treatment of schizophrenia not established in patients less than 12 years of age. Safety and effectiveness in the treatment of schizoaffective disorder not established in patients less than 18 years of age. (8.4) 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including paliperidone, during pregnancy. Healthcare providers are encouraged to register patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or online at http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/ . Risk Summary Neonates exposed to antipsychotic drugs during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery (see Clinical Considerations ) .

Metabolism

Following a single dose, the plasma concentrations of paliperidone gradually rise to reach peak plasma concentration (C max ) approximately 24 hours after dosing. The pharmacokinetics of paliperidone following paliperidone administration are dose-proportional within the available dose range.

10.1 Human Experience While experience with paliperidone overdose is limited, among the few cases of overdose reported in pre-marketing trials, the highest estimated ingestion of paliperidone was 405 mg. Observed signs and symptoms included extrapyramidal symptoms and gait unsteadiness. Other potential signs and symptoms include those resulting from an exaggeration of paliperidone’s known pharmacological effects, i.e., drowsiness and somnolence, tachycardia and hypotension, and QT prolongation. Torsade de pointes and ventricular fibrillation have been reported in a patient in the setting of overdose. Paliperidone is the major active metabolite of risperidone. Overdose experience reported with risperidone can be found in the OVERDOSAGE section of the risperidone package insert. 10.2 Management of Overdosage There is no specific antidote to paliperidone, therefore, appropriate supportive measures should be instituted and close medical supervision and monitoring should continue until the patient recovers. Consideration should be given to the extended-release nature of the product when assessing treatment needs and recovery. Multiple drug involvement should also be considered.

• Dec 19, 2006NDANDA021999Janssen Pharms
• Jul 31, 2009NDANDA022264Janssen Pharms
• May 18, 2015NDANDA207946Janssen Pharms
• Sep 24, 2015ANDAANDA203802Rk Pharma
• Apr 6, 2018ANDAANDA205618Sun Pharm
• Jun 12, 2019ANDAANDA204452Inventia
• Sep 23, 2019ANDAANDA204707Amneal Pharms
• Jul 26, 2024NDANDA216352Luye Innomind Pharma

1. 1Off Label Use4,3888.4%
2. 2Injury4,3618.3%
3. 3Gynaecomastia4,2328.1%
4. 4Drug Ineffective3,5636.8%
5. 5Weight Increased2,8085.4%
6. 6Hospitalisation2,1574.1%
7. 7Abnormal Weight Gain1,8283.5%
8. 8Galactorrhoea1,6473.2%
9. 9Drug Dose Omission1,6143.1%
10. 10Schizophrenia1,5713.0%
11. 11Hyperprolactinaemia1,5052.9%
12. 12Product Dose Omission Issue1,4712.8%
13. 13Treatment Noncompliance1,4552.8%
14. 14Condition Aggravated1,3212.5%
15. 15Psychotic Disorder1,2692.4%

Recent PubMed references pinned to Paliperidone as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

• Study on independent influencing factors of compliance in patients with schizophrenia treated with paliperidone palmitate injection.
  Rivista di psichiatria · 2026 · Yu H, Di Y, Jiahuan L, et al.
  PMID 42200256DOI 10.1708/4685.47000
• Quality of life in early-phase schizophrenia patients starting treatment with long-acting injectable vs. oral antipsychotic drugs: Data from the European Long-acting Antipsychotics in Schizophrenia Trial (EULAST).
  European psychiatry : the journal of the Association of European Psychiatrists · 2026 · Schulze AT, Tschiderer L, Post F, et al.
  PMID 42011073DOI 10.1192/j.eurpsy.2026.12209
• Virtual Bioequivalence Assessment of Long-acting Injectable Suspensions Using PBPK Modeling: Part 1. Impact of particle Size on Formulation Variability.
  The AAPS journal · 2026 · Morris NM, Djehizian A, Mittapelly N, et al.
  PMID 41927954DOI 10.1208/s12248-026-01213-2
• Virtual Bioequivalence Assessment of Long-Acting Injectable Suspensions Using PBPK Modeling: Part 2. Type I Error and Safe Space Analyses.
  The AAPS journal · 2026 · Morris NM, Jamei M, Alam K, et al.
  PMID 41927781DOI 10.1208/s12248-026-01215-0
• Antipsychotic Treatment Pathways, Real-World Adherence, Healthcare Resource Utilization, and Healthcare Costs Among Patients With Schizophrenia Treated With Once-Monthly, Once-Every-Three-Months, and Once-Every-Six-Months Paliperidone Palmitate in the United States.
  Clinical therapeutics · 2026 · Morrison L, Pilon D, Voegel A, et al.
  PMID 41862353DOI 10.1016/j.clinthera.2026.02.006
• Impact of macrophages on the dissolution of LAI suspension prodrugs.
  International journal of pharmaceutics · 2026 · Malavia N, Maurus K, Sabatella M, et al.
  PMID 41802501DOI 10.1016/j.ijpharm.2026.126762
• Risperidone- and paliperidone-induced hyperprolactinemia in routine clinical practice: demographic and pharmacological determinants from the UAE.
  International clinical psychopharmacology · 2026 · Aly El-Gabry D, Mohd Ahmed H, Andrade G, et al.
  PMID 41762719DOI 10.1097/YIC.0000000000000619
• A Multicentre, 4-Year Mirror-Image Study Comparing the Effectiveness of Long-Acting Injectable Antipsychotics in the Treatment of Bipolar Disorder: Results From the LAICO Study.
  Bipolar disorders · 2026 · García-Carmona JA, Barnett J, Campos-Navarro MP, et al.
  PMID 41631553DOI 10.1111/bdi.70080

The 10 most recently updated of 216 ClinicalTrials.gov registrations naming Paliperidone as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Τhe Combination of Pharmacotherapy With RECOVERYTRSGR and RECOVERYTRSBDGR.
  Active not recruiting · Phase 4 · Interventional · 84 enrolled · Dr. Stavroula Rakitzi
  NCT07047651updated 2026-05-01
• Elpipodect (MK-8189) Multiple Dose Study in Healthy Volunteers and Schizophrenia Participants (MK-8189-003)
  Completed · Phase 1 · Interventional · 55 enrolled · Merck Sharp & Dohme LLC
  NCT02181803updated 2026-04-29
• Risk of Breakthrough Symptoms With Long-Acting Injectable Medications
  Completed · Observational · 51 enrolled · Centre for Addiction and Mental Health
  NCT05473741updated 2026-04-14
• "Extended" (Alternate Day) Antipsychotic Dosing
  Recruiting · Phase 4 · Interventional · 120 enrolled · Centre for Addiction and Mental Health
  NCT04478838updated 2026-04-13
• Long-acting Injectable Antipsychotics for Mental Ill-Health in Pregnancy and Postpartum
  Completed · Observational · 168 enrolled · University of Liverpool
  NCT05766007updated 2026-04-07
• Substance Misuse To Psychosis for Stimulants
  Completed · Phase 2 · Phase 3 · Interventional · 165 enrolled · The University of Hong Kong
  NCT03485417updated 2026-03-27
• A Bioequivalence Study of PP3M in Patients With Schizophrenia
  Recruiting · Interventional · 260 enrolled · CSPC Zhongnuo Pharmaceutical (Shijiazhuang) Co., Ltd.
  NCT07493551updated 2026-03-25
• Predictive Validity of the Personal and Social Performance Scale for PANSS Outcomes in Schizophrenia
  Completed · Phase 2 · Interventional · 763 enrolled · Calo Psychiatric Center
  NCT07445217updated 2026-03-03
• An Exploratory Analysis of Immune and Inflammatory Response Associated With Clozapine
  Terminated · Phase 4 · Interventional · 5 enrolled · Ohio State University
  NCT05741502updated 2026-02-25
• Bioequivalence Study of Long-Acting Paliperidone Palmitate in Patients With Schizophrenia
  Completed · Interventional · 256 enrolled · CSPC Zhongnuo Pharmaceutical (Shijiazhuang) Co., Ltd.
  NCT07268430updated 2025-12-05

CPIC-curated drug–gene pairs for Paliperidone. Levels describe the strength of curated evidence and guideline status — never a recommendation to test or to adjust therapy.

• MC4RCPIC C (provisional)ClinPGx 3

Ranked by 2D fingerprint (Tanimoto) similarity over PubChem structures. Structural proximity only — not a claim of therapeutic equivalence.

• RisperidoneAtypical Antipsychotic86%

Frequently asked questions

How does Paliperidone work?

Paliperidone is the major active metabolite of risperidone. The mechanism of action of paliperidone in schizophrenia is unclear.

What is Paliperidone used for?

According to FDA labeling, Paliperidone carries indications including: Paliperidone extended-release tablets are an atypical antipsychotic agent indicated for Treatment of schizophrenia (1.1) Adults: Efficacy was established in three 6-week trials and one maintenance trial. (14.1) Adolescents (ages 12 to 17): Efficacy was established in one 6-week trial.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Paliperidone?

Paliperidone is classified as Other antipsychotics, Atypical Antipsychotic, Unknown Cellular or Molecular Interaction.

What are the brand names for Paliperidone?

Paliperidone is marketed under brand names including Erzofri, Invega.

What are the contraindications for Paliperidone?

Paliperidone labeling lists contraindications including: Paliperidone extended-release tablets are contraindicated in patients with a known hypersensitivity to either paliperidone or risperidone, or to any of the excipients in the paliperidone extended-release tablet formulation. Hypersensitivity reactions, including anaphylactic reactions and angioedema, have been reported in patients treated with risperidone and in patients treated with paliperidone.. Always consult the full prescribing information and a clinician.