TRILAFON
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TRILAFON (TRILAFON).
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.
| 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. |
| Molecular Weight | 403.97 |
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. |
| 1st trimester | Avoid; animal studies show fetal abnormalities and risk of extrapyramidal effects in neonates. |
| 2nd trimester | Avoid; potential for maternal hypotension and decreased placental perfusion. |
| 3rd trimester | Avoid; risk of neonatal extrapyramidal symptoms, jaundice, and prolonged QT interval. |
Clinical note
Comprehensive clinical and safety monograph for TRILAFON (TRILAFON).
| Placental transfer | Crosses placenta readily; detected in fetal plasma at concentrations similar to maternal levels. |
| Breastfeeding | Excreted into breast milk in small amounts; monitor infant for sedation, extrapyramidal symptoms, and poor feeding. Use only if clearly needed. |
| Lactation Rating |
■ 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.
| Serious Effects |
ComaSevere CNS depressionBlood dyscrasiasKnown hypersensitivity to phenothiazinesConcurrent use of high-dose CNS depressants
| 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 |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they may increase perphenazine levels. Limit caffeine intake as it may worsen side effects like restlessness. Taking with food may reduce GI upset but avoid high-fat meals which can affect absorption. |
Loading safety data…
| L3 (Moderately Safe) |
| 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. |
| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and signs of extrapyramidal symptoms. In neonates, observe for dystonia, tremors, or sedation especially if used near term. |
| Fertility Effects | May cause hyperprolactinemia leading to menstrual irregularity, galactorrhea, or reduced fertility due to hypothalamic-pituitary-gonadal axis suppression. Effects are reversible upon discontinuation. |
| Clinical Pearls | TRILAFON (perphenazine) is a typical antipsychotic with potent antiemetic properties. Monitor for extrapyramidal symptoms (EPS), especially akathisia and dystonia. Avoid use in patients with CNS depression or bone marrow suppression. May lower seizure threshold; use cautiously in epilepsy. QT prolongation risk requires ECG monitoring. Taper dose when discontinuing to avoid withdrawal dyskinesias. |
| Patient Advice | Avoid alcohol and other CNS depressants. · Report any involuntary muscle movements, stiffness, or restlessness immediately. · May cause drowsiness; avoid driving until you know how the medication affects you. · Rise slowly from sitting or lying to prevent dizziness. · Use sun protection as this drug may increase sensitivity to sunlight. · Do not stop taking abruptly without consulting your doctor. · Inform all healthcare providers that you are taking this medication. |