Trifluoperazine

Trifluoperazine is a high-potency piperazine phenothiazine used for schizophrenia, short-term management of non-psychotic anxiety and, in some regions, severe nausea and vomiting. It produces moderate sedation, frequent extrapyramidal effects and little hypotension. Availability is limited in many regions.

Classification. First-generation (typical) antipsychotic, piperazine phenothiazine.

Mechanism. Potent dopamine D2 antagonism, with weak antimuscarinic and antihistamine effects.

Pharmacokinetics. Absorption is erratic; extensive first-pass metabolism. Half-life about 12 hours (reports range from 10 to 20 hours).

All regimens are oral with no loading dose.

Schizophrenia, adults.

• Start 5 mg twice daily (2 to 5 mg twice daily in some labels).
• Titration: after 1 week increase to 15 mg daily; then by 5 mg every few days based on response and extrapyramidal effects.
• Usual 15 to 20 mg daily; maximum 40 mg daily (higher doses only under specialist care).
• Duration: at least 12 months after a first episode.

Non-psychotic anxiety, short term only. 1 to 2 mg twice daily. Maximum 6 mg daily for no more than 12 weeks.

Severe nausea and vomiting (licensed in some regions). 2 to 4 mg daily in divided doses; maximum 6 mg daily.

Children (specialist use only). Aged 6 to 12 years: 1 mg once or twice daily, increased gradually; maximum 15 mg daily.

Older adults. Start 1 to 2.5 mg daily and increase slowly.

Contraindications. Coma or severe CNS depression, bone marrow suppression, liver impairment, phaeochromocytoma, known QT prolongation, hypersensitivity. Boxed-warning-level increase in mortality in older adults with dementia-related psychosis.

Serious adverse effects. Neuroleptic malignant syndrome, acute dystonia, parkinsonism, akathisia, tardive dyskinesia, torsades de pointes, seizures, agranulocytosis (rare), cholestatic jaundice (rare).

Common adverse effects. Extrapyramidal symptoms, restlessness, dry mouth, drowsiness, constipation, blurred vision, galactorrhoea.

Interactions. Anticholinergics, alcohol and sedatives add effects. QT-prolonging drugs (macrolides, quinolones, quinine, artemether-lumefantrine, chloroquine, ondansetron) add risk. Antacids reduce absorption. Levodopa is antagonised. Carbamazepine lowers levels. It lowers the seizure threshold.

Common prescribing errors. Continuing anxiety treatment beyond 12 weeks; using it as a first-line anxiolytic; escalating quickly without checking for extrapyramidal symptoms.

Special groups.

• Pregnancy: use only if benefit outweighs risk; third-trimester exposure can cause neonatal extrapyramidal symptoms and withdrawal.
• Breastfeeding: excreted in milk; avoid or use with infant monitoring.
• Children: specialist use only; aged 6 to 12 years 1 mg once or twice daily, maximum 15 mg daily.
• Older adults: lower doses; high risk of parkinsonism and falls; mortality in dementia.
• Kidney impairment: start low.
• Liver impairment: contraindicated.

Formulations. Tablets 1 mg, 2 mg, 5 mg and 10 mg; oral liquid in some regions. Give twice daily with or without food.

Baseline. ECG, potassium and magnesium, weight, blood pressure, fasting glucose or HbA1c, lipids, full blood count, liver tests, and a baseline rating of extrapyramidal symptoms.

Monitoring. Weight and waist at baseline, 4, 8 and 12 weeks, then annually; fasting glucose or HbA1c and lipids at baseline, 12 weeks, then annually. Check extrapyramidal symptoms at each review and rate abnormal movements every 6 to 12 months. Repeat the ECG after dose increases; stop or reduce if QTc is over 500 ms.

Stopping. Reduce gradually over several weeks to limit relapse and withdrawal dyskinesia.

Referral and escalation. Refer to psychiatry for first-episode psychosis, treatment resistance or persistent extrapyramidal symptoms. Fever with rigidity, jaundice, syncope or QTc over 500 ms needs emergency care.