Sentix

Approved Indications:

• Schizophrenia: For the treatment of schizophrenia, especially with predominant positive symptoms (delusions, hallucinations, thought disorder).
• Paranoid Psychoses: Used in chronic psychotic disorders with paranoid features.
• Acute Psychotic Episodes: Effective in managing acute exacerbations of psychosis.
• Delusional Disorders: Treatment of persistent delusional disorder with paranoid components.

Off-Label / Clinically Accepted Uses:

• Agitation in Dementia (in some regions, under specialist supervision)
• Aggressive Behavior and Psychomotor Agitation in severely mentally ill patients
• Treatment-resistant Depression (as augmentation in psychotic depression; usually in combination with antidepressants)
• Bipolar Mania (less commonly, used for controlling psychotic manic symptoms)

Dosage should be individualized.

Adults:

• Oral:
• Initial dose: 1–2 mg/day, usually given in divided doses.
• Maintenance: 3–6 mg/day.
• Maximum: 9 mg/day.
• Parenteral (Depot Flupentixol decanoate is used; not Flupentixol dihydrochloride): Not applicable here.

Elderly:

• Start at lower doses (e.g., 0.5 mg/day), titrate cautiously.
• Maintenance dose usually 1–4 mg/day.

Pediatric Use:

• Not recommended due to insufficient safety and efficacy data.

Renal Impairment:

• Use with caution. Start with lowest possible dose and monitor for adverse effects.
• No specific dosing guideline—clinical judgment required.

Hepatic Impairment:

• Use with caution. Start at lower doses with close monitoring.
• Monitor liver function periodically.

Administration:

• Administer orally with or without food.
• Can be taken once or twice daily depending on tolerance and clinical response.

Flupentixol dihydrochloride is a typical antipsychotic of the thioxanthene class. It primarily acts by antagonizing dopamine D1 and D2 receptors in the mesolimbic and mesocortical pathways of the brain, reducing dopaminergic overactivity responsible for psychotic symptoms such as hallucinations and delusions. It also exhibits some affinity for alpha-adrenergic and serotonin 5-HT2 receptors, contributing to its anxiolytic and mood-stabilizing effects. The antipsychotic activity is mainly attributed to its dopamine receptor blockade, while extrapyramidal side effects arise from dopamine blockade in the nigrostriatal pathway.

• Absorption: Well absorbed orally; peak plasma concentration occurs in 2–5 hours.
• Bioavailability: Approximately 40–55% due to first-pass hepatic metabolism.
• Distribution: Widely distributed in body tissues; crosses the blood-brain barrier and placenta; high protein binding (~99%).
• Metabolism: Primarily hepatic via oxidative pathways (CYP2D6 involvement suspected).
• Half-life: 35–40 hours (enabling once-daily dosing in some cases).
• Excretion: Mainly via urine and feces, both as unchanged drug and metabolites.
• Steady-state: Reached within 5–7 days of daily dosing.

• Pregnancy: Not assigned a specific FDA category.
• Use only if clearly needed.
• Animal studies have shown adverse fetal effects; human data are limited.
• Risk of extrapyramidal and withdrawal symptoms in neonates when used during third trimester.
• Lactation:
• Excreted in human breast milk in small amounts.
• Use caution—possible effects on the infant include sedation, poor feeding, or extrapyramidal signs.
• Monitor breastfed infants closely or consider alternative feeding.

• Primary Class: Typical Antipsychotic
• Subclass: Thioxanthene derivative
• Generation: First-generation antipsychotic (FGA)

• Hypersensitivity to flupentixol or any excipients
• Acute alcohol, barbiturate, or opioid intoxication
• Comatose states
• CNS depression
• Pheochromocytoma (due to possible hypertensive crisis)
• Parkinson’s disease
• History of bone marrow suppression or blood dyscrasias

• Extrapyramidal symptoms (EPS): High risk; monitor for dystonia, akathisia, and parkinsonism.
• Tardive Dyskinesia: May develop with prolonged use; often irreversible.
• Neuroleptic Malignant Syndrome (NMS): Rare but life-threatening; discontinue immediately if suspected.
• QT Prolongation: Use caution in patients with cardiac disease or on QT-prolonging agents.
• Seizure Risk: Dose-dependent risk; caution in epilepsy.
• Hepatic Impairment: Monitor liver function tests.
• Elderly with Dementia-Related Psychosis: Increased mortality risk—not recommended for this population.
• Suicidal Ideation: Monitor patients with depression closely, especially during dose changes.
• Orthostatic Hypotension: Monitor blood pressure in elderly or cardiovascular-compromised patients.

Common Adverse Effects:

• Neurological: Extrapyramidal symptoms (tremor, rigidity, bradykinesia), sedation, akathisia
• Psychiatric: Insomnia, agitation, anxiety
• Gastrointestinal: Dry mouth, constipation, nausea
• Autonomic: Blurred vision, urinary retention, sweating
• Cardiovascular: Orthostatic hypotension, tachycardia

Serious or Rare Effects:

• Tardive dyskinesia (chronic use)
• Neuroleptic malignant syndrome
• QT prolongation, arrhythmias
• Agranulocytosis or leukopenia (rare)
• Seizures
• Jaundice or liver enzyme elevation

Onset:

• EPS typically develop within days to weeks of initiation.
• Tardive dyskinesia may appear after months/years.
• Sedation often improves after the first few weeks.

Major Interactions:

• CNS Depressants (e.g., benzodiazepines, opioids, alcohol): Increased sedation and respiratory depression.
• QT-Prolonging Drugs (e.g., amiodarone, erythromycin): Additive risk of arrhythmias.
• Antihypertensives: Potentiation of hypotensive effects.
• Levodopa/Dopaminergic Agents: Antagonism of therapeutic effects.
• Metoclopramide: Increased risk of EPS.
• CYP2D6 inhibitors (e.g., fluoxetine, paroxetine): May increase flupentixol levels.
• MAO Inhibitors: Increased risk of hypertensive crisis or serotonin syndrome.

Food & Alcohol:

• Avoid alcohol due to enhanced CNS depression.
• Food does not significantly affect absorption.

• No major changes in FDA/EMA labeling in the last 2 years.
• Recent antipsychotic prescribing guidelines emphasize lower initial doses and caution in elderly populations.
• WHO Essential Medicines List: Flupentixol is included as a typical antipsychotic in certain regional formularies.
• Emphasis on monitoring for tardive dyskinesia and cardiovascular risks in long-term use.

• Temperature: Store below 30°C (86°F).
• Humidity: Protect from excessive moisture.
• Light: Store in original packaging to protect from light.
• Handling: Keep tightly closed.
• Reconstitution/Refrigeration: Not applicable for oral tablets.
• Shelf-life: Refer to manufacturer label; generally 2–3 years unopened.