Paliperidone Palmitate Once-Monthly (PP1M)

Drug information

Drug's link(s)

https://go.drugbank.com/salts/DBSALT001464

Generic name

Paliperidone Palmitate Once-Monthly (PP1M)

Brand names

INVEGA SUSTENNA®, XEPLION®, Niapelf

Compound type

Small molecule

Drug class/category

Central Dopamine (D2) type 2 and serotonin (5HT2A) type 2 Receptor Antagonist

Summary

Paliperidone palmitate administered as a once monthly long-acting injectable (PP1M) is indicated for the maintenance treatment of schizophrenia and schizoaffective disorder. INVEGA SUSTENNA® and XEPLION® are manufactured by Janssen Pharmaceuticals and available in dosage strengths of 25mg, 50mg, 100mg, and 150mg. Prior to the initiation of treatment, oral-lead periods to establish tolerability are required for patients naïve to either oral paliperidone or oral or injectable risperidone. Due to its extremely low water solubility, PP1M dissolves slowly following intramuscular injection, prior to being hydrolysed to paliperidone and subsequent absorption. Release of the active paliperidone substance lasts up to 4 months, with maximum plasma concentrations achieved after 13 days (median Tmax).

Approval status

PP1M has been approved under the trade name of INVEGA SUSTENNA® (Janssen-Cilag Ltd) by the US Food and Drug Administration for the treatment of schizophrenia (approved Aug 2009) & schizoaffective disorder (approved Nov 2015) as monotherapy and as an adjunct to mood stabilisers or antidepressants. The safety and effectiveness of INVEGA SUSTENNA® in patients < 18 years of age have not been established. PP1M is approved by the European Medicines Agency (EMA) under the trade name XEPLION® (Janssen-Cilag Ltd) for the maintenance treatment of schizophrenia in adults whose disease has already been stabilised on treatment with paliperidone or risperidone. The European Commission granted a marketing authorisation valid throughout the European Union for XEPLION® on 4 March 2011.

Regulatory authorities

PP1M is authorised in 102 countries/territories worldwide as of December 6th 2022.

Therapeutic area(s)

Mental Health Disorders (incl. schizophrenia, bipolar disorders, Schiz. Aff. Dis.) : "Schizophrenia (naive and previously treated) , Psychotic or manic symptoms of schizoaffective disorde"

Use case(s)

Treatment

Administration route

Intramuscular

Associated long-acting platforms

Aqueous drug particle suspension, Lipid Prodrug Depot - Nanocrystal technology

Use of drug

Ease of administration

Administered by a nurse
Administered by a specialty health worker
Administered by a community health worker

Frequency of administration

Monthly

User acceptance

Not provided

Dosage

Available dose and strength

39 mg, 78 mg, 156 mg, and 234 mg

Maximum dose

234 mg

Recommended dosing regimen

1. For both schizophrenia and schizoaffective disorder, the initiation regimen is the same: (i) Day 1: 234 mg (administered in the deltoid muscle) IM (ii) Day 8: 156 mg (administered in the deltoid muscle) IM 2. Maintenance: (i) Schizophrenia: 39 mg to 234 mg monthly - Recommended maintenance dose: 117 mg monthly (ii) Schizoaffective disorder: 78 mg to 234 mg monthly

Additional comments

Contraindicated: Cerebrovascular ADRs, Neuroleptic malignant syndrome, QT Prolongation, Tardive dyskinesia, Metabolic changes, Orthostatic hypotension and syncope, Hyperprolactinemia, Cognitive impairment, and Seizures.

Dosage link(s)

https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022264s023lbl.pdf

Associated compounds, formulations and regimens

Not provided

Associated technologies

Not provided

Additional information

Three bioequivalence studies were conducted to compare Niapelf (a generic paliperidone palmitate prolonged-release injectable suspension) to the reference PP1M product. Two pivotal studies (TOL3033D and TOL3033B) demonstrated bioequivalence through 90% CIs for geometric LS mean ratio of test vs. reference within the acceptance range of 80.00%-125.00% for PK parameters (e.g. AUC0-∞, AUC0-τ, Cmax,ss and Cτ,ss). The TOL3033A study was considered supportive due to a lack of statistical power after excluding a significant number of subjects following methodological deficiencies and GCP non-compliance. Notably, the test product (Niapelf) exhibits consistently lower exposure across all three BE studies (TOL3033D, TOL3033B, TOL3033A), however it was considered unlikely to be of clinical relevance.

Developer(s)

Originator

Belgium

Johnson & Johnson

Janssen Pharmaceuticals is a subsidiary company of Johnson & Johnson headquartered in Beerse, Belgium. They focus on manufacturing and developing pharmaceutical products for use in areas such as, Immunology, Infectious Diseases & Vaccines, Pulmonary Hypertension, Cardiovascular & Metabolism, Oncology, and Neuroscience.

Generic

Spain & Germany

Neuraxpharm

Neruaxpharm is a European biopharmaceutical company headquartered in both Barcelona, Spain and Langenfeld, Germany. Neuraxpharm specialises in developing medicines and generics for diseases of the central nervous system (CNS). Their portfolio consists of more than 120 molecules for the treatment of Anxiety, Depression, Schizophrenia, Epilepsy, Alzheimer’s, Parkinson’s and other CNS disorders.

Drug structure

Scale-up and manufacturing prospects

Scale-up prospects

PP1M is commercially manufactured.

Tentative equipment list for manufacturing

NanoCrystal® Colloidal Dispersion Nanomill™ apparatus.

Manufacturing

NanoCrystal technology enables intrinsically high loading of insoluble drugs as dosage forms consist mostly of pure API packed as a solid crystal, which is the most efficient form possible in relation to weight-to-volume. Paliperidone palmitate particles are dispersed in an aqueous suspension and transformed into smaller nanocrystals through particle-size reduction. These nanocrystals have a greater surface area than the larger original particles, resulting in increased water solubility. This medicinal product does not require any special storage conditions and has a shelf life of two years.

Specific analytical instrument required for characterization of formulation

Digital microscope and scanning electron microscopy (SEM) to determine shape of the particles. Differential scanning calorimetric (DSC) and Fourier transforms infrared spectroscopy (FTIR) for quality control.

Excipients & delivery device(s)

Proprietary excipients used

No proprietary excipient used

Novel excipients or existing excipients at a concentration above Inactive Ingredient Database (IID) for the specified route of administration

No novel excipient or existing excipient used

Residual solvents used

No residual solvent used

Delivery device(s)

No delivery device

Safety, Efficacy and Evidence Summary

Safety

Not provided

Efficacy

Not provided

Evidence Summary

Not provided

References and relevant studies

Not provided