INVEGA TRINZA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for INVEGA TRINZA (INVEGA TRINZA).
Paliperidone is the major active metabolite of risperidone. It is a benzisoxazole derivative antipsychotic that antagonizes central dopamine type 2 (D2) and serotonin type 2 (5-HT2A) receptors. It also antagonizes alpha-1 and alpha-2 adrenergic, and histamine H1 receptors.
| Metabolism | Paliperidone is predominantly metabolized by dealkylation, hydroxylation, and dehydrogenation, with minor contribution from CYP2D6 and CYP3A4. It is also a substrate of P-glycoprotein (P-gp). |
| Excretion | Renal: 59-80% as unchanged drug and metabolites; fecal: 6-15%; biliary: minimal. |
| Half-life | Terminal elimination half-life: 3 to 6 months (mean 118 days) due to slow dissolution from intramuscular depot; clinical context: steady state reached after 3 injections every 3 months. |
| Protein binding | 74-84% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Vd: 2-4 L/kg (extensive tissue distribution); clinical meaning: high Vd indicates extensive peripheral binding, supporting long duration. |
| Bioavailability | Intramuscular: 100% (absolute bioavailability after injection). |
| Onset of Action | Intramuscular: 3-4 months (therapeutic effect); due to long-acting formulation, initial loading with oral or shorter-acting injectable required. |
| Duration of Action | Intramuscular: 3 months (dosing interval); clinical note: maintains therapeutic levels for 3 months with minimal fluctuations. |
| Molecular Weight | 426.49 |
| Action Class | Atypical Antipsychotic (Long-acting injectable) |
Administered intramuscularly (gluteal or deltoid) at 3-month intervals. Starting dose: 350 mg, 525 mg, or 700 mg based on prior stabilization dose of oral paliperidone or INVEGA SUSTENNA. Maximum dose: 700 mg.
| Dosage form | SUSPENSION, EXTENDED RELEASE |
| Renal impairment | Contraindicated in eGFR <15 mL/min/1.73m². For eGFR 15-29 mL/min/1.73m²: 350 mg initially, then 350 mg every 3 months. For eGFR 30-49 mL/min/1.73m²: 350 mg initially, then 350 mg every 3 months. For eGFR ≥50 mL/min/1.73m²: no adjustment. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh Class A and B). Not studied in severe impairment (Child-Pugh Class C). |
| Pediatric use | Not approved for use in pediatric patients. Safety and efficacy not established in patients <18 years. |
| Geriatric use | No specific dose adjustment recommended, but elderly patients may have reduced renal function; assess renal function (eGFR) and adjust accordingly. Use lowest effective dose and monitor for orthostatic hypotension, sedation, and extrapyramidal symptoms. |
| 1st trimester | Insufficient human data; animal studies show fetal risk. Avoid unless benefit outweighs risk. |
| 2nd trimester | Insufficient human data; animal studies show fetal risk. Avoid unless benefit outweighs risk. |
| 3rd trimester | Risk of extrapyramidal symptoms and/or withdrawal in neonates after delivery. Avoid unless benefit outweighs risk. |
Clinical note
Comprehensive clinical and safety monograph for INVEGA TRINZA (INVEGA TRINZA).
| Placental transfer | Paliperidone crosses the placenta. The estimated cord blood concentration is approximately 50-100% of maternal plasma concentration. |
| Breastfeeding | Paliperidone is excreted in human milk. The relative infant dose is estimated to be about 5-8% of the maternal weight-adjusted dose. Monitor infant for sedation, irritability, and feeding problems. Use with caution. |
■ FDA Black Box Warning
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. INVEGA TRINZA is not approved for use in patients with dementia-related psychosis.
| Common Effects | Injection site reactions (pain, swelling, redness), Extrapyramidal symptoms (e.g., akathisia, parkinsonism, dystonia), Somnolence/sedation, Headache, Dizziness, Weight gain, Increased appetite, Nausea, vomiting, constipation, Dry mouth, Fatigue, Insomnia, Anxiety, Nasopharyngitis, Upper respiratory tract infection, Urinary tract infection, Tachycardia, Hypertension, Prolactin elevation (galactorrhea, gynecomastia, menstrual irregularities) |
| Serious Effects | Increased mortality in elderly patients with dementia-related psychosis, Cerebrovascular adverse events (e.g., stroke, transient ischemic attack) in elderly dementia patients, Neuroleptic malignant syndrome (NMS), Tardive dyskinesia, QT interval prolongation, Seizures, Hyperprolactinemia, Orthostatic hypotension and syncope, Leukopenia, neutropenia, and agranulocytosis, Dysphagia and aspiration, Priapism, Thrombotic thrombocytopenic purpura (TTP) |
Hypersensitivity to paliperidone or any excipientsConcurrent use with drugs that prolong QT interval (e.g., Class IA/III antiarrhythmics)
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | INVEGA TRINZA (paliperidone palmitate) is a Pregnancy Category C drug. First trimester: Limited human data; animal studies show increased fetal resorptions and skeletal delays at high doses. Second and third trimesters: Risk for extrapyramidal and withdrawal symptoms in neonates after in utero exposure (e.g., agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress). Antipsychotic use near term may increase risk for neonatal extrapyramidal symptoms. Overall, risk-benefit analysis required. |
| Fetal Monitoring | Monitor maternal body weight, blood glucose, lipid profile, and prolactin levels. Assess for extrapyramidal symptoms and orthostatic hypotension. Fetal monitoring: routine prenatal care; third-trimester ultrasound for fetal growth if indicated. Neonatal monitoring after delivery: observe for extrapyramidal symptoms, sedation, withdrawal, and respiratory status for at least 48-72 hours. |
| Fertility Effects | Paliperidone may elevate serum prolactin levels, potentially causing galactorrhea, amenorrhea, and anovulation, thereby impairing fertility. The effect is dose-dependent and reversible upon discontinuation. In males, hyperprolactinemia may reduce libido and spermatogenesis. No formal fertility studies in humans; animal studies show no direct impairment. |
| Precautions |
| Increased mortality in elderly patients with dementia-related psychosis, Cerebrovascular adverse events (e.g., stroke, transient ischemic attack) in elderly patients with dementia-related psychosis, Neuroleptic malignant syndrome (NMS), Tardive dyskinesia (TD), Metabolic changes (hyperglycemia, diabetes mellitus, dyslipidemia, weight gain), Hyperprolactinemia, Orthostatic hypotension and syncope, Leukopenia, neutropenia, and agranulocytosis, Seizures, Potential for cognitive and motor impairment, Dysphagia, Priapism, Body temperature regulation disruption, Suicide risk, Administration errors (not interchangeable with other formulations of paliperidone) |
| Food/Dietary | Avoid grapefruit juice as it may increase paliperidone levels. No significant food interactions otherwise. Advise moderation of alcohol as it may exacerbate CNS depression. |
| Clinical Pearls | INVEGA TRINZA is a long-acting injectable paliperidone palmitate formulation administered every 3 months. It requires 2 loading doses of the monthly formulation (INVEGA SUSTENNA) prior to initiation. The dose should be adjusted based on renal function, and it is contraindicated in patients with severe renal impairment (eGFR < 15 mL/min/1.73m2). Administer only intramuscularly into the deltoid or gluteal muscle; do not administer intravenously or subcutaneously. Use with caution in patients with known risk factors for QT prolongation, significant leukocyte/neutrophil count abnormalities, or a history of neuroleptic malignant syndrome. Monitor for orthostatic hypotension, especially during dose titration. |
| Patient Advice | This medication is given as an injection once every 3 months by a healthcare professional. · Do not attempt to self-administer; it must be given by a doctor or nurse. · You must first receive two doses of the monthly injection (Invega Sustenna) before starting this medication. · Common side effects include injection site pain, sleepiness, dizziness, weight gain, and increased prolactin levels. · Avoid alcohol and grapefruit juice as they may increase side effects. · Seek emergency medical attention if you experience severe muscle stiffness, fever, confusion, or irregular heartbeat. · Inform your doctor if you are pregnant, breastfeeding, or planning to become pregnant. · Do not drive or operate heavy machinery until you know how this medication affects you. |