ERZOFRI

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ERZOFRI (ERZOFRI).

How it works

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.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for ERZOFRI (ERZOFRI).

Breastfeeding	Excreted into breast milk; M/P ratio not established. Use contraindicated due to potential for serious adverse effects in nursing infants.
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

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to paliperidone, risperidone, or any formulation components"]

Clinical Precautions

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"]

Clinical Tips & Counseling

Drug interactions

Loading safety data…

ERZOFRI

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ERZOFRI (ERZOFRI).

How it works

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for ERZOFRI (ERZOFRI).

Breastfeeding	Excreted into breast milk; M/P ratio not established. Use contraindicated due to potential for serious adverse effects in nursing infants.
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

Warnings & precautions

■ FDA Black Box Warning

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to paliperidone, risperidone, or any formulation components"]