PALIPERIDONE PALMITATE

Clinical safety rating: safe

Strong CYP3A4 or P-gp inducers may decrease levels Can cause QT prolongation and orthostatic hypotension.

How it works

Paliperidone is an atypical antipsychotic with high affinity for serotonin 5-HT2A and dopamine D2 receptors. It also blocks alpha-2 adrenergic and H1 histaminergic receptors.

What the body does with it

Metabolism	Paliperidone is primarily metabolized by CYP3A4 and CYP2D6, but also via dealkylation and hydroxylation. It is a substrate of P-glycoprotein.
Excretion	Renal: 80% as unchanged drug and metabolites; fecal: 11%
Half-life	Terminal elimination half-life: 25-49 days (mean ~30 days) for IM injection; allows monthly dosing
Protein binding	74% bound to albumin and alpha1-acid glycoprotein
Volume of Distribution	Vd: 391-487 L (approx 7-10 L/kg) indicating extensive tissue distribution
Bioavailability	IM: 100% bioavailability via gluteal or deltoid injection
Onset of Action	IM: Onset within 1 week; clinical effect may take 2-4 weeks for full antipsychotic response
Duration of Action	IM: Duration ~4 weeks; therapeutic levels maintained with monthly injections

Classification & Brands

Dosing & administration

Paliperidone palmitate is administered intramuscularly. Initial dose: 150 mg eq. on day 1 and 100 mg eq. on day 8, both in the deltoid muscle. Maintenance dose: 75 mg eq. monthly (range 25–150 mg eq.) administered in the deltoid or gluteal muscle.

Dosage form	INJECTABLE
Renal impairment	For patients with mild renal impairment (CrCl 50 to <80 mL/min): initiate with 100 mg eq. on day 1 and 75 mg eq. on day 8, then 50 mg eq. monthly. For moderate to severe renal impairment (CrCl <50 mL/min): use paliperidone extended-release tablets, not the palmitate injection.
Liver impairment	No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh class A or B). Not studied in severe hepatic impairment (Child-Pugh class C); use with caution.
Pediatric use	Not approved for patients <18 years of age. Safety and efficacy not established.
Geriatric use	Use with caution due to increased sensitivity, risk of orthostatic hypotension, and higher incidence of renal impairment. Consider lower initial doses and slower titration. Monitor renal function and adjust dose accordingly.

Use during pregnancy

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

Clinical note

Strong CYP3A4 or P-gp inducers may decrease levels Can cause QT prolongation and orthostatic hypotension.

FDA category	Animal
Breastfeeding	Paliperidone is excreted in human breast milk; milk-to-plasma ratio is approximately 0.7. Monitor infant for sedation, irritability, and abnormal movements. Risk versus benefit should be considered.
Teratogenic Risk	First trimester: Limited human data; animal studies show no teratogenicity at clinically relevant doses. Second and third trimesters: Antipsychotic use may increase risk of extrapyramidal symptoms and/or withdrawal symptoms in neonates (e.g., agitation, hypertonia, hypotonia, tremor, somnolence). Overall risk of major malformations is not significantly increased.

Warnings & precautions

■ FDA Black Box Warning

Increased mortality in elderly patients with dementia-related psychosis.

Side Effect Profile

Common Effects	Weight gain
Serious Effects

Absolute Contraindications

["Hypersensitivity to paliperidone, risperidone, or any component of the formulation"]

Clinical Precautions

Precautions

["Cerebrovascular adverse events (including stroke) in elderly dementia patients","Neuroleptic malignant syndrome","Tardive dyskinesia","Hyperglycemia/diabetes mellitus","Orthostatic hypotension","Seizures","Potential for cognitive and motor impairment","Priapism","Disruption of body temperature regulation","Dysphagia","Suicide risk"]

Clinical Tips & Counseling

Drug interactions

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PALIPERIDONE PALMITATE

Clinical safety rating: safe

Strong CYP3A4 or P-gp inducers may decrease levels Can cause QT prolongation and orthostatic hypotension.

How it works

Paliperidone is an atypical antipsychotic with high affinity for serotonin 5-HT2A and dopamine D2 receptors. It also blocks alpha-2 adrenergic and H1 histaminergic receptors.

What the body does with it

Metabolism	Paliperidone is primarily metabolized by CYP3A4 and CYP2D6, but also via dealkylation and hydroxylation. It is a substrate of P-glycoprotein.
Excretion	Renal: 80% as unchanged drug and metabolites; fecal: 11%
Half-life	Terminal elimination half-life: 25-49 days (mean ~30 days) for IM injection; allows monthly dosing
Protein binding	74% bound to albumin and alpha1-acid glycoprotein
Volume of Distribution	Vd: 391-487 L (approx 7-10 L/kg) indicating extensive tissue distribution
Bioavailability	IM: 100% bioavailability via gluteal or deltoid injection
Onset of Action	IM: Onset within 1 week; clinical effect may take 2-4 weeks for full antipsychotic response
Duration of Action	IM: Duration ~4 weeks; therapeutic levels maintained with monthly injections

Classification & Brands

Dosing & administration

Dosage form	INJECTABLE
Renal impairment	For patients with mild renal impairment (CrCl 50 to <80 mL/min): initiate with 100 mg eq. on day 1 and 75 mg eq. on day 8, then 50 mg eq. monthly. For moderate to severe renal impairment (CrCl <50 mL/min): use paliperidone extended-release tablets, not the palmitate injection.
Liver impairment	No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh class A or B). Not studied in severe hepatic impairment (Child-Pugh class C); use with caution.
Pediatric use	Not approved for patients <18 years of age. Safety and efficacy not established.
Geriatric use	Use with caution due to increased sensitivity, risk of orthostatic hypotension, and higher incidence of renal impairment. Consider lower initial doses and slower titration. Monitor renal function and adjust dose accordingly.

Use during pregnancy

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

Clinical note

Strong CYP3A4 or P-gp inducers may decrease levels Can cause QT prolongation and orthostatic hypotension.

FDA category	Animal
Breastfeeding	Paliperidone is excreted in human breast milk; milk-to-plasma ratio is approximately 0.7. Monitor infant for sedation, irritability, and abnormal movements. Risk versus benefit should be considered.
Teratogenic Risk	First trimester: Limited human data; animal studies show no teratogenicity at clinically relevant doses. Second and third trimesters: Antipsychotic use may increase risk of extrapyramidal symptoms and/or withdrawal symptoms in neonates (e.g., agitation, hypertonia, hypotonia, tremor, somnolence). Overall risk of major malformations is not significantly increased.

Warnings & precautions

■ FDA Black Box Warning

Increased mortality in elderly patients with dementia-related psychosis.

Side Effect Profile

Common Effects	Weight gain
Serious Effects

Absolute Contraindications

["Hypersensitivity to paliperidone, risperidone, or any component of the formulation"]