PALIPERIDONE PALMITATE
Clinical safety rating: safe
Strong CYP3A4 or P-gp inducers may decrease levels Can cause QT prolongation and orthostatic hypotension.
Paliperidone is an atypical antipsychotic with high affinity for serotonin 5-HT2A and dopamine D2 receptors. It also blocks alpha-2 adrenergic and H1 histaminergic receptors.
| Metabolism | Paliperidone is primarily metabolized by CYP3A4 and CYP2D6, but also via dealkylation and hydroxylation. It is a substrate of P-glycoprotein. |
| Excretion | Renal: 80% as unchanged drug and metabolites; fecal: 11% |
| Half-life | Terminal elimination half-life: 25-49 days (mean ~30 days) for IM injection; allows monthly dosing |
| Protein binding | 74% bound to albumin and alpha1-acid glycoprotein |
| Volume of Distribution | Vd: 391-487 L (approx 7-10 L/kg) indicating extensive tissue distribution |
| Bioavailability | IM: 100% bioavailability via gluteal or deltoid injection |
| Onset of Action | IM: Onset within 1 week; clinical effect may take 2-4 weeks for full antipsychotic response |
| Duration of Action | IM: Duration ~4 weeks; therapeutic levels maintained with monthly injections |
| Molecular Weight | 426.48 |
| Action Class | Atypical Antipsychotic (Long-acting injectable) |
Paliperidone palmitate is administered intramuscularly. Initial dose: 150 mg eq. on day 1 and 100 mg eq. on day 8, both in the deltoid muscle. Maintenance dose: 75 mg eq. monthly (range 25–150 mg eq.) administered in the deltoid or gluteal muscle.
| Dosage form | INJECTABLE |
| Renal impairment | For patients with mild renal impairment (CrCl 50 to <80 mL/min): initiate with 100 mg eq. on day 1 and 75 mg eq. on day 8, then 50 mg eq. monthly. For moderate to severe renal impairment (CrCl <50 mL/min): use paliperidone extended-release tablets, not the palmitate injection. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh class A or B). Not studied in severe hepatic impairment (Child-Pugh class C); use with caution. |
| Pediatric use | Not approved for patients <18 years of age. Safety and efficacy not established. |
| Geriatric use | Use with caution due to increased sensitivity, risk of orthostatic hypotension, and higher incidence of renal impairment. Consider lower initial doses and slower titration. Monitor renal function and adjust dose accordingly. |
| 1st trimester | Paliperidone palmitate is not recommended during first trimester due to limited safety data and potential risk of extrapyramidal effects. Consider fetal risk based on animal studies. |
| 2nd trimester | Use only if maternal benefit outweighs fetal risk. Monitor for gestational diabetes and weight gain. Consider dose adjustment. |
| 3rd trimester | Use with caution; risk of extrapyramidal symptoms and withdrawal in neonate. Monitor for neonatal sedation, respiratory distress, and feeding difficulties. |
Clinical note
Strong CYP3A4 or P-gp inducers may decrease levels Can cause QT prolongation and orthostatic hypotension.
| FDA category | Animal |
| Placental transfer | Paliperidone crosses the placenta; drug concentration in fetal plasma is approximately 50% of maternal plasma concentration. |
■ FDA Black Box Warning
Increased mortality in elderly patients with dementia-related psychosis.
| Common Effects | Weight gain |
| Serious Effects | Tardive dyskinesia, Neuroleptic malignant syndrome (NMS), QT interval prolongation, Stroke and transient ischemic attacks in elderly patients with dementia-related psychosis, Increased mortality in elderly patients with dementia-related psychosis, Orthostatic hypotension and syncope, Seizures, Leukopenia, neutropenia, and agranulocytosis, Hyperprolactinemia, Metabolic changes: hyperglycemia, diabetes mellitus, dyslipidemia, weight gain |
Hypersensitivity to paliperidone or risperidoneQTc interval >500 msecCurrent neuroleptic malignant syndrome (NMS)
| Precautions | Cerebrovascular adverse events (including stroke) in elderly dementia patients, Neuroleptic malignant syndrome, Tardive dyskinesia, Hyperglycemia/diabetes mellitus, Orthostatic hypotension, Seizures, Potential for cognitive and motor impairment, Priapism, Disruption of body temperature regulation, Dysphagia, Suicide risk |
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| Breastfeeding |
| Paliperidone is excreted into human breast milk, but data are limited. The American Academy of Pediatrics considers it compatible with breastfeeding. Monitor infant for drowsiness, irritability, and poor feeding. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Limited human data; animal studies show no teratogenicity at clinically relevant doses. Second and third trimesters: Antipsychotic use may increase risk of extrapyramidal symptoms and/or withdrawal symptoms in neonates (e.g., agitation, hypertonia, hypotonia, tremor, somnolence). Overall risk of major malformations is not significantly increased. |
| Fetal Monitoring | Monitor maternal blood pressure, weight gain, glucose tolerance, and psychiatric stability. Fetal monitoring: ultrasound for growth and anatomy; neonatal monitoring for extrapyramidal symptoms, sedation, and withdrawal after delivery. |
| Fertility Effects | Paliperidone may elevate prolactin levels, potentially leading to menstrual irregularities, galactorrhea, and reversible reduction in fertility. Effects on male fertility are not well studied but may include decreased libido and erectile dysfunction. |
| Food/Dietary | Avoid grapefruit juice as it may increase paliperidone exposure. Alcohol can exacerbate CNS depression and orthostatic hypotension. No specific food restrictions, but advise maintaining a balanced diet to manage weight gain. |
| Clinical Pearls | Paliperidone palmitate is a long-acting injectable antipsychotic for schizophrenia. Requires 2-day oral tolerability test with paliperidone ER or risperidone before first injection. Administer deltoid for initial doses (Days 1 and 8) to achieve therapeutic levels rapidly; maintenance doses can be gluteal. Do not use in patients with known PKP2 gene mutations due to increased risk of QT prolongation. Monitor for extrapyramidal symptoms, tardive dyskinesia, and weight gain. Avoid in patients with severe renal impairment (CrCl <20 mL/min). |
| Patient Advice | This is a long-acting injection given every 3 months after initial doses. · Do not stop or change dose without consulting your doctor. · May cause drowsiness, dizziness, or weight gain; avoid driving until you know how it affects you. · Report any uncontrollable muscle movements, fever, or stiff muscles immediately. · Avoid alcohol and grapefruit juice as they may increase side effects. · Keep all appointments for injections; if a dose is missed, contact your doctor. |