INVEGA SUSTENNA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for INVEGA SUSTENNA (INVEGA SUSTENNA).
Paliperidone is an atypical antipsychotic that acts primarily as a central dopamine type 2 (D2) receptor antagonist and serotonin type 2A (5-HT2A) receptor antagonist. It also blocks α1- and α2-adrenergic receptors and H1 histamine receptors.
| Metabolism | Paliperidone is primarily metabolized by the liver via CYP3A4 and CYP2D6 enzymes, with minor contribution from other pathways. It is a substrate of P-glycoprotein. The major metabolites are inactive. |
| Excretion | Renal: approximately 59-80% as unchanged drug and metabolites, with about 1% unchanged; biliary/fecal: approximately 20-41% primarily as metabolites. |
| Half-life | Terminal elimination half-life ranges from 25 to 49 days (mean ~38 days) for deltoid injection and 30 to 50 days (mean ~45 days) for gluteal injection, supporting monthly dosing. |
| Protein binding | Paliperidone is approximately 74% bound to plasma proteins, primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution (Vd) for paliperidone is approximately 487 L (range 395-701 L; equivalent to ~6-10 L/kg for a 70 kg individual), indicating extensive extravascular distribution. |
| Bioavailability | IM: Absolute bioavailability of INVEGA SUSTENNA (paliperidone palmitate) is 100% relative to the marketed oral formulation but with controlled release; oral bioavailability of paliperidone is approximately 28%. |
| Onset of Action | IM: Clinical effect (e.g., reduction in psychotic symptoms) typically observed within the first week, with full effect achieved after several doses over the first month. |
| Duration of Action | IM: Therapeutic effect persists for approximately 4 weeks after each monthly injection, consistent with the dosing interval. |
| Molecular Weight | 427.5 |
| Action Class | Atypical Antipsychotics |
Initiate with 234 mg intramuscular injection on day 1, then 156 mg on day 8, both deltoid. Maintenance: 117 mg monthly (range 39-234 mg) via deltoid or gluteal injection. Dosing based on paliperidone palmitate.
| Dosage form | SUSPENSION, EXTENDED RELEASE |
| Renal impairment | Creatinine clearance (CrCl) ≥50 mL/min: no adjustment. CrCl 30-49 mL/min: 156 mg on day 1, 78 mg on day 8, then 39-78 mg monthly. CrCl <30 mL/min: not recommended. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A and B). Not studied in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Not approved for patients <18 years of age. Safety and efficacy not established. |
| Geriatric use | No specific dose adjustment for age alone, but renal function should be assessed. Use cautiously due to increased sensitivity and risk of adverse effects. For CrCl ≥50 mL/min, follow standard adult dosing. |
| 1st trimester | Avoid. Antipsychotic use in first trimester associated with increased risk of congenital malformations, though data for paliperidone are limited. |
| 2nd trimester | Use only if benefit outweighs risk. Monitor for gestational diabetes and excessive weight gain. |
| 3rd trimester | Use with caution. Risk of extrapyramidal symptoms and withdrawal in neonate. Consider tapering before delivery. |
Clinical note
Comprehensive clinical and safety monograph for INVEGA SUSTENNA (INVEGA SUSTENNA).
| Placental transfer | Paliperidone crosses the placenta. In vitro data suggest moderate transfer; clinical significance unknown. |
| Breastfeeding | Paliperidone is excreted in breast milk. Monitor infant for sedation, poor feeding, and extrapyramidal symptoms. Use lowest effective dose if necessary. |
■ FDA Black Box Warning
Increased mortality in elderly patients with dementia-related psychosis. Antipsychotic drugs are not approved for the treatment of dementia-related psychosis.
| Serious Effects | Increased mortality in elderly patients with dementia-related psychosis, Cerebrovascular adverse events (e.g., stroke) in elderly patients with dementia, Neuroleptic malignant syndrome (NMS), Tardive dyskinesia, QT interval prolongation, Hyperglycemia and diabetes mellitus, Hyperprolactinemia, Orthostatic hypotension and syncope, Seizures, Leukopenia, neutropenia, and agranulocytosis, Priapism, Thrombotic thrombocytopenic purpura (TTP) |
Hypersensitivity to paliperidone or risperidone
| Precautions | Cerebrovascular adverse events (including stroke) in elderly dementia patients, Neuroleptic Malignant Syndrome (NMS), Tardive dyskinesia, Metabolic changes: hyperglycemia, diabetes, weight gain, dyslipidemia, Orthostatic hypotension due to alpha-blockade, Leukopenia, neutropenia, and agranulocytosis, Seizure risk, Potential for cognitive and motor impairment, Suicide risk, Hyperprolactinemia, Priapism, QT interval prolongation |
| Food/Dietary |
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| Lactation Rating |
| L3 (Moderately Safe) |
| Teratogenic Risk | Paliperidone, the active metabolite of INVEGA SUSTENNA, is not associated with major malformations in first trimester exposure based on limited data, but infants exposed during the third trimester are at risk for extrapyramidal symptoms and withdrawal after delivery. Risk cannot be excluded. |
| Fetal Monitoring | Monitor for maternal hypotension, sedation, EPS, and glycemic control. Assess fetal growth and movement. Neonates should be observed for extrapyramidal symptoms, respiratory distress, and feeding difficulties for at least 4 days after delivery. |
| Fertility Effects | Paliperidone may increase serum prolactin levels, which can lead to menstrual irregularities, galactorrhea, and reversible suppression of ovulation. Effects on fertility are dose-dependent and normalize after dose reduction or discontinuation. |
| Avoid grapefruit juice as it may increase drug levels. Alcohol can potentiate CNS depression; avoid concurrent use. |
| Clinical Pearls | Administer intramuscularly into the deltoid or gluteal muscle; do not administer intravenously. First dose should be followed by a second dose one week later to achieve therapeutic levels. Do not use if particulate matter or discoloration is present. Priming of the syringe is not required. Rotate injection sites between deltoid and gluteal regions. Monitor for orthostatic hypotension, especially during dose titration. Tardive dyskinesia may occur with long-term use. |
| Patient Advice | This medication is given as an injection every month by a healthcare professional. · It is important to keep all appointments for your injections; missing a dose may cause your symptoms to return. · You may experience dizziness or lightheadedness when standing up; rise slowly from sitting or lying positions. · Report any unusual muscle movements, especially of the face or tongue, to your doctor immediately. · Avoid alcohol and grapefruit juice while on this medication. · Do not drive or operate heavy machinery until you know how this medication affects you. |