Paliperidone Palmitate is an atypical antipsychotic indicated for:

• Treatment of schizophrenia in adults.
• Treatment of schizoaffective disorder in adults as monotherapy or as an adjunct to mood stabilizers or antidepressants.

Paliperidone palmitate is hydrolyzed to paliperidone. Paliperidone is the major active metabolite of risperidone. The exact mechanism of action is not fully understood. However, its therapeutic effect in schizophrenia is believed to be mediated through combined central dopamine Type 2 (D2) and serotonin Type 2 (5HT2A) receptor antagonism.

In vitro, paliperidone acts as an antagonist at central dopamine Type 2 (D2) and serotonin Type 2 (5HT2A) receptors with binding affinities (Ki values) of 1.6–2.8 nM for D2 and 0.8–1.2 nM for 5HT2A receptors. It also antagonizes α1 and α2 adrenergic receptors and H1 histaminergic receptors, which may explain additional drug effects. Paliperidone has no affinity for cholinergic muscarinic receptors or β1 and β2 adrenergic receptors. The pharmacological activity of the (+)- and (–)-paliperidone enantiomers is qualitatively and quantitatively similar in vitro.

Schizophrenia:

• Initiation Dosing: Day 1–234 mg and Day 8–156 mg
• Monthly Maintenance Dose: 39–234 mg
• Maximum Monthly Dose: 234 mg

Schizoaffective disorder:

• Initiation Dosing: Day 1–234 mg and Day 8–156 mg
• Monthly Maintenance Dose: 78–234 mg
• Maximum Monthly Dose: 234 mg

Administered 5 weeks after the first injection. The recommended maintenance dose for treatment of schizophrenia is 117 mg. Some patients may benefit from lower or higher maintenance doses within the additional available strengths (39 mg, 78 mg, 156 mg, and 234 mg). Adjust dose based on tolerability and/or efficacy using available strengths. The 39 mg strength was not studied in the long-term schizoaffective disorder study.

For intramuscular injection only. Each injection must be administered only by a healthcare professional. For deltoid injection, use 1-inch 23G needle for patients weighing less than 90 kg or 1 ½-inch 22G needle for patients weighing 90 kg or more. For gluteal injection, use 1 ½-inch 22G needle regardless of patient weight.

Drugs that may cause orthostatic hypotension: An additive hypotensive effect may occur when co-administered with Paliperidone Palmitate.

Strong CYP3A4/P-glycoprotein (P-gp) inducers: Avoid concomitant use of strong CYP3A4 and/or P-gp inducers (e.g., carbamazepine, rifampin, St. John’s Wort) during a dosing interval of Paliperidone Palmitate. If use of a strong inducer is necessary, consider switching to paliperidone extended-release tablets for management.

Known hypersensitivity to paliperidone, risperidone, or any excipients in Paliperidone Palmitate.

The most common adverse reactions (≥5% and at least twice placebo) include injection site reactions, somnolence/sedation, dizziness, akathisia, and extrapyramidal symptoms.

Limited data show the presence of paliperidone in human breast milk. There is insufficient information regarding effects on the breastfed infant or milk production.

Cerebrovascular adverse reactions: Increased risk of stroke and transient ischemic attack in elderly patients with dementia-related psychosis.

Neuroleptic Malignant Syndrome: Immediate discontinuation and close monitoring required.

QT prolongation: Avoid in patients with QT prolongation risk or with drugs that prolong QT interval.

Tardive Dyskinesia: Discontinue if clinically appropriate.

Metabolic changes: Monitor for hyperglycemia, diabetes, dyslipidemia, and weight gain.

Orthostatic hypotension and syncope: Monitor blood pressure and heart rate; caution in cardiovascular or cerebrovascular disease and dehydration risk.

Leukopenia/Neutropenia/Agranulocytosis: Monitor CBC in at-risk patients; discontinue if significant WBC drop occurs.

Hyperprolactinemia: May persist during long-term use.

Cognitive and motor impairment: Use caution when operating machinery.

Seizures: Use cautiously in patients with seizure history or lowered seizure threshold.

Pediatric Use: Safety and efficacy in patients under 18 years have not been established.

Renal Impairment: Not recommended in moderate or severe renal impairment.

Hepatic Impairment: Not studied; based on oral data, no dose adjustment is needed in mild to moderate hepatic impairment.

Atypical neuroleptic drugs

Store at room temperature (15°C–30°C). Do not mix with any other product or diluent.