ERZOFRI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ERZOFRI (ERZOFRI).
Erzofri (paliperidone palmitate) is an atypical antipsychotic. Its mechanism of action is not fully understood but is believed to be mediated through a combination of central dopamine type 2 (D2) and serotonin type 2 (5HT2A) receptor antagonism. It also acts as an antagonist at α1 and α2 adrenergic receptors and H1 histaminergic receptors.
| Metabolism | Paliperidone is primarily metabolized by hepatic glucuronidation and to a lesser extent by CYP3A4 and CYP2D6. It is a substrate of P-glycoprotein (P-gp). |
| Excretion | Primarily renal (79% unchanged) and biliary/fecal (15% as metabolites and parent drug); less than 1% in urine as lactam metabolite. |
| Half-life | Terminal elimination half-life approximately 1.5-2 hours. However, due to prolonged inhibition of monoamine oxidase B (MAO-B), clinical effects extend beyond drug presence; enzyme recovery takes several weeks. |
| Protein binding | 90-94% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Approximately 2-5 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral: ≈80% (first-pass metabolism minimal). Transdermal: ≈50% (variable due to skin permeability). |
| Onset of Action | Oral: 1-2 hours for peak effect on MAO-B inhibition; transdermal: approximately 2-4 hours to reach therapeutic levels. |
| Duration of Action | MAO-B inhibition is irreversible, resulting in clinical duration corresponding to enzyme turnover (≈2-4 weeks). Drug elimination half-life does not reflect duration of action. |
| Molecular Weight | 624.7 |
Intermittent IV infusion (over 1-2 hours), 100 mg/m² every 2 weeks, or 200 mg/m² every 3 weeks.
| Dosage form | SUSPENSION, EXTENDED RELEASE |
| Renal impairment | For CrCl 50-80 mL/min: no adjustment. For CrCl 30-49 mL/min: reduce dose by 25%. For CrCl <30 mL/min: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 25%. Child-Pugh C: not recommended. |
| Pediatric use | Weight-based: 1.4 mg/kg IV every 2 weeks, or 2.8 mg/kg IV every 3 weeks (max 200 mg/dose). |
| Geriatric use | Elderly patients (≥65 years) require no specific dose adjustment, but monitor renal function and consider increased susceptibility to myelosuppression. |
| 1st trimester | Avoid; associated with teratogenicity in animal studies and limited human data. |
| 2nd trimester | Avoid; risk of fetal harm outweighs potential benefits. |
| 3rd trimester | Avoid; may cause neonatal toxicity including myelosuppression. |
Clinical note
Comprehensive clinical and safety monograph for ERZOFRI (ERZOFRI).
| Placental transfer | Erzofri crosses the placenta in animal studies; human data suggest significant transfer. |
| Breastfeeding | Excreted into breast milk; potential for serious adverse reactions in nursing infants. Discontinue breastfeeding or discontinue drug. |
| Lactation Rating |
■ FDA Black Box Warning
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Erzofri is not approved for the treatment of patients with dementia-related psychosis.
| Serious Effects |
Hypersensitivity to Erzofri or any componentSevere hepatic impairmentPregnancy
| Precautions | Increased mortality in elderly patients with dementia-related psychosis, Cerebrovascular adverse events (including stroke) in elderly patients with dementia, Neuroleptic malignant syndrome (NMS), QT interval prolongation, Tardive dyskinesia, Hyperglycemia and diabetes mellitus, Weight gain, Orthostatic hypotension and syncope, Seizures, Potential for cognitive and motor impairment, Dysphagia, Priapism, Body temperature regulation disruption, Antiemetic effect masking toxicity |
| Food/Dietary | No significant food interactions. Grapefruit juice has not been shown to interact significantly. Administer without regard to meals. |
Loading safety data…
| L5 - Contraindicated |
| Teratogenic Risk | Pregnancy Category D. First trimester: Associated with congenital malformations including neural tube defects, cardiovascular anomalies, and cleft palate. Second and third trimesters: Risks include preterm labor, low birth weight, and neonatal hemorrhage. Oligohydramnios may occur with late third trimester use. |
| Fetal Monitoring | Monitor complete blood count, hepatic and renal function monthly. Perform fetal ultrasound for growth and amniotic fluid volume every 4 weeks starting at 20 weeks gestation. Nonstress test or biophysical profile weekly after 32 weeks. Monitor for maternal hemorrhage, hypertension, and edema. |
| Fertility Effects | May impair female fertility through disruption of prostaglandin-mediated implantation; reversible upon discontinuation. In males, animal studies show reduced spermatogenesis and fertility index; human data limited. |
| Clinical Pearls | Erzofri (paliperidone palmitate) is a long-acting injectable atypical antipsychotic. Initiate with two loading doses: 150 mg IM on day 1 and 100 mg IM on day 8, both in deltoid muscle. Subsequent monthly maintenance doses can be administered in deltoid or gluteal muscle. Monitor for orthostatic hypotension, QT prolongation, and extrapyramidal symptoms. Avoid concurrent use with strong CYP3A4 inducers or inhibitors. Do not use in patients with severe renal impairment (CrCl <20 mL/min). |
| Patient Advice | This medication is given as an injection once a month. · Do not miss your scheduled injections; if you do, contact your doctor immediately. · You may experience dizziness or lightheadedness when standing up; rise slowly. · Report any involuntary muscle movements, stiffness, or restlessness. · Avoid driving or operating heavy machinery until you know how this drug affects you. · Tell your doctor if you are pregnant, planning to become pregnant, or breastfeeding. · This medication may cause weight gain and increase blood sugar; monitor for increased thirst or urination. · Avoid alcohol while taking this medication. |