INVEGA SUSTENNA

Clinical safety rating: caution

Comprehensive clinical and safety monograph for INVEGA SUSTENNA (INVEGA SUSTENNA).

How it works

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.

What the body does with it

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.

Classification & Brands

Action Class

Atypical Antipsychotics

Dosing & administration

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.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for INVEGA SUSTENNA (INVEGA SUSTENNA).

Breastfeeding	Paliperidone is excreted in human breast milk. The milk-to-plasma ratio is unknown. Due to potential for adverse effects in the nursing infant, caution is advised. Consider risk versus benefit and monitor infant for sedation, extrapyramidal symptoms, and weight changes.
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.

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to paliperidone or risperidone","Concurrent use with other drugs that prolong QT interval"]

Clinical Precautions

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"]

Clinical Tips & Counseling

Drug interactions

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INVEGA SUSTENNA

Clinical safety rating: caution

Comprehensive clinical and safety monograph for INVEGA SUSTENNA (INVEGA SUSTENNA).

How it works

What the body does with it

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.

Classification & Brands

Action Class

Atypical Antipsychotics

Dosing & administration

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.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for INVEGA SUSTENNA (INVEGA SUSTENNA).

Breastfeeding	Paliperidone is excreted in human breast milk. The milk-to-plasma ratio is unknown. Due to potential for adverse effects in the nursing infant, caution is advised. Consider risk versus benefit and monitor infant for sedation, extrapyramidal symptoms, and weight changes.
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.

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to paliperidone or risperidone","Concurrent use with other drugs that prolong QT interval"]