TRILAFON

Clinical safety rating: caution

Comprehensive clinical and safety monograph for TRILAFON (TRILAFON).

How it works

Perphenazine is a typical antipsychotic that blocks postsynaptic dopamine D2 receptors in the brain, exerting antipsychotic effects. It also has alpha-adrenergic blocking, anticholinergic, and antihistaminic properties.

What the body does with it

Metabolism	Extensively metabolized in the liver via glucuronidation, sulfoxidation, side-chain oxidation, and N-dealkylation. CYP2D6 is a major enzyme involved in metabolism; polymorphisms can lead to poor metabolizer status.
Excretion	Primarily hepatic metabolism; less than 1% excreted unchanged in urine; biliary/fecal elimination of metabolites accounts for the majority of elimination.
Half-life	Terminal elimination half-life is approximately 10–20 hours (mean ~12 hours); supports twice-daily dosing.
Protein binding	90–95% bound, primarily to albumin and alpha-1-acid glycoprotein.
Volume of Distribution	Approximately 10–15 L/kg; large Vd indicates extensive tissue distribution.
Bioavailability	Oral: 40–50% (due to first-pass metabolism); IM: 100% (assumed complete absorption).
Onset of Action	Oral: 30–60 minutes; IM: 10–30 minutes; IV: 5–10 minutes.
Duration of Action	Oral: 6–8 hours; IM/IV: 4–6 hours; clinical effects may persist longer due to active metabolites.

Classification & Brands

Dosing & administration

8-16 mg orally twice daily; maximum 64 mg/day. Also 5-10 mg IM every 4-6 hours, maximum 30 mg/day.

Dosage form	INJECTABLE
Renal impairment	No dosage adjustment required for GFR 10-50 mL/min; use 50% of normal dose if GFR <10 mL/min.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use.
Pediatric use	Not recommended for children under 12 years; for ages 12 and older, 6-12 mg orally 2-3 times daily; maximum 24 mg/day.
Geriatric use	Initiate at 4-8 mg orally daily; increase slowly; monitor for QT prolongation, hypotension, and tardive dyskinesia.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for TRILAFON (TRILAFON).

Breastfeeding	Trilafon (perphenazine) is excreted into human milk in small amounts; M/P ratio unknown. Monitor infant for drowsiness, irritability, or movement disorders. Use with caution during breastfeeding.
Teratogenic Risk	First trimester: Periconceptional use associated with neural tube defects? Limited data; avoid if possible. Second and third trimesters: Risk of extrapyramidal symptoms and/or withdrawal in neonates after late third trimester exposure. Overall, use only if benefit outweighs risk; avoid during organogenesis.

Warnings & precautions

■ FDA Black Box Warning

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Perphenazine is not approved for the treatment of dementia-related psychosis.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to perphenazine or any component of the formulation","Comatose states","CNS depression due to alcohol, barbiturates, or other drugs","Subcortical brain damage","Blood dyscrasias","Bone marrow suppression","Severe hypotension","Known QT prolongation or concurrent use with QT-prolonging drugs"]

Clinical Precautions

Precautions

["Extrapyramidal symptoms (including tardive dyskinesia) may occur","Neuroleptic malignant syndrome (NMS) - potentially fatal","QT prolongation and risk of arrhythmias","Orthostatic hypotension","Seizures (lower seizure threshold)","Leukopenia, neutropenia, and agranulocytosis","Hematologic toxicity","Hyperprolactinemia","Cognitive and motor impairment","Antiemetic effect may mask signs of toxicity or overdose","Use in elderly with dementia not approved"]

Clinical Tips & Counseling

Drug interactions

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TRILAFON

Clinical safety rating: caution

Comprehensive clinical and safety monograph for TRILAFON (TRILAFON).

How it works

What the body does with it

Metabolism	Extensively metabolized in the liver via glucuronidation, sulfoxidation, side-chain oxidation, and N-dealkylation. CYP2D6 is a major enzyme involved in metabolism; polymorphisms can lead to poor metabolizer status.
Excretion	Primarily hepatic metabolism; less than 1% excreted unchanged in urine; biliary/fecal elimination of metabolites accounts for the majority of elimination.
Half-life	Terminal elimination half-life is approximately 10–20 hours (mean ~12 hours); supports twice-daily dosing.
Protein binding	90–95% bound, primarily to albumin and alpha-1-acid glycoprotein.
Volume of Distribution	Approximately 10–15 L/kg; large Vd indicates extensive tissue distribution.
Bioavailability	Oral: 40–50% (due to first-pass metabolism); IM: 100% (assumed complete absorption).
Onset of Action	Oral: 30–60 minutes; IM: 10–30 minutes; IV: 5–10 minutes.
Duration of Action	Oral: 6–8 hours; IM/IV: 4–6 hours; clinical effects may persist longer due to active metabolites.

Classification & Brands

Dosing & administration

8-16 mg orally twice daily; maximum 64 mg/day. Also 5-10 mg IM every 4-6 hours, maximum 30 mg/day.

Dosage form	INJECTABLE
Renal impairment	No dosage adjustment required for GFR 10-50 mL/min; use 50% of normal dose if GFR <10 mL/min.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use.
Pediatric use	Not recommended for children under 12 years; for ages 12 and older, 6-12 mg orally 2-3 times daily; maximum 24 mg/day.
Geriatric use	Initiate at 4-8 mg orally daily; increase slowly; monitor for QT prolongation, hypotension, and tardive dyskinesia.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for TRILAFON (TRILAFON).

Breastfeeding	Trilafon (perphenazine) is excreted into human milk in small amounts; M/P ratio unknown. Monitor infant for drowsiness, irritability, or movement disorders. Use with caution during breastfeeding.
Teratogenic Risk	First trimester: Periconceptional use associated with neural tube defects? Limited data; avoid if possible. Second and third trimesters: Risk of extrapyramidal symptoms and/or withdrawal in neonates after late third trimester exposure. Overall, use only if benefit outweighs risk; avoid during organogenesis.

Warnings & precautions

■ FDA Black Box Warning

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Perphenazine is not approved for the treatment of dementia-related psychosis.