Clopixol Acuphase50 mg/ml

Clopixol Acuphase is a typical (first-generation) antipsychotic of the thioxanthene class. Its approved and evidence-supported uses differ by formulation and are classified below by strength of evidence.

Established / guideline-supported uses

• Schizophrenia and other psychotic disorders (e.g. paranoid psychosis): Clopixol Acuphase tablets and short-acting injection are used for acute exacerbations, particularly when accompanied by agitation, aggression, or hostility.
• Maintenance treatment of schizophrenia: the long-acting depot (decanoate) injectable form of Clopixol Acuphase is used for maintenance therapy in patients with chronic psychotic illness, especially where adherence to daily oral treatment is a concern.
• Acute psychomotor agitation associated with psychosis: the short-acting depot preparation ("acuphase") form of Clopixol Acuphase provides several days of antipsychotic and sedative effect from a single intramuscular injection, used for rapid control of acute psychotic agitation.

Off-label / historically described use

• Low-dose oral Clopixol Acuphase has historically been described for short-term management of severe anxiety or agitation unresponsive to other treatments in some markets; this is not a primary approved indication and is not generally recommended given the availability of better-studied alternatives.

Clopixol Acuphase is not approved for the treatment of dementia-related behavioural disturbances in elderly patients (see Precautions and Warnings).

Zuclopenthixol is available in Bangladesh in the following forms and strengths (brand names vary by manufacturer):

• Zuclopenthixol tablets/coated tablets: commonly 2 mg, 10 mg, and 25 mg
• Zuclopenthixol acuphase (short-acting) injection: 50 mg/mL
• Zuclopenthixol decanoate (long-acting depot) injection: 200 mg/mL

Clopixol Acuphase is a typical (first-generation) antipsychotic medicine belonging to the thioxanthene chemical class. It is used mainly for the treatment of schizophrenia and other psychotic disorders, and is particularly useful in patients whose psychosis is accompanied by agitation, aggression, or hostility because of its combined antipsychotic and sedative properties.

Clopixol Acuphase is marketed in three main formulations: standard oral tablets for day-to-day treatment, a short-acting intramuscular injection ("acuphase") for rapid control of acute agitated psychotic episodes, and a long-acting depot ("decanoate") intramuscular injection given every one to four weeks for maintenance treatment. The depot formulations release the drug slowly over days to weeks, which is an important difference from the oral form when counselling patients about the onset and offset of effects and side effects.

Typical (first-generation) antipsychotic – Thioxanthene derivative (Clopixol Acuphase)

Zuclopenthixol is a thioxanthene-derivative antipsychotic. Its principal mechanism of action is potent antagonism of central dopamine D1 and D2 receptors, which is believed to underlie its antipsychotic effect by reducing dopaminergic overactivity in mesolimbic pathways.

Zuclopenthixol also has significant affinity for alpha-1 adrenergic receptors and serotonin 5-HT2 receptors, contributing to sedative effects and some mood-elevating properties at lower doses, along with weaker affinity for histamine H1 receptors. It has relatively low affinity for cholinergic and alpha-2 adrenergic receptors, resulting in fewer anticholinergic effects compared with some other typical antipsychotics, but dopamine D2 blockade in the nigrostriatal pathway accounts for its notable propensity to cause extrapyramidal symptoms.

Following oral administration, Zuclopenthixol is absorbed from the gastrointestinal tract and undergoes hepatic metabolism (partly via CYP2D6) with a plasma half-life of roughly 20 hours. The decanoate ester (depot) formulation is hydrolysed slowly after intramuscular injection, releasing active Zuclopenthixol over 1–4 weeks and producing a marked delay before peak effect and before adverse effects appear or resolve compared with oral dosing.

• Clopixol Acuphase tablets may be taken with or without food, generally at the same time(s) each day; do not stop or change the dose without consulting a physician.
• Clopixol Acuphase injections (acuphase and decanoate) must be given by deep intramuscular injection, typically into the upper outer buttock (gluteal muscle) or lateral thigh, by a trained healthcare professional. They must not be given intravenously.
• Injection volumes exceeding 2 mL should be divided between two separate injection sites.
• Injection sites should be rotated to reduce local irritation.

Clopixol Acuphase has several clinically significant drug interactions:

• Other CNS depressants (alcohol, sedatives, hypnotics, opioids, general anaesthetics): additive sedation and respiratory depression when combined with Clopixol Acuphase.
• Other QT-prolonging drugs (e.g. certain antiarrhythmics, macrolide antibiotics, some other antipsychotics): additive risk of QT prolongation and ventricular arrhythmia when combined with Clopixol Acuphase.
• Antihypertensive agents: Clopixol Acuphase can enhance the hypotensive effect, increasing risk of orthostatic hypotension.
• Levodopa and dopamine agonists: Clopixol Acuphase antagonises dopamine receptors and may reduce the effectiveness of these Parkinson's disease treatments; conversely, dopamine agonists may worsen psychosis.
• Metoclopramide and other dopamine-antagonist antiemetics: additive risk of extrapyramidal symptoms when used with Clopixol Acuphase.
• CYP2D6 inhibitors (e.g. fluoxetine, paroxetine): may increase plasma levels of Clopixol Acuphase, increasing risk of adverse effects; dose adjustment of Clopixol Acuphase may be needed.
• Lithium: rare reports of neurotoxicity (confusion, extrapyramidal symptoms) when combined with Clopixol Acuphase; combination should be monitored closely.

Common side effects of Clopixol Acuphase include:

• Sedation/drowsiness
• Extrapyramidal symptoms (tremor, rigidity, akathisia, dystonia)
• Dry mouth
• Orthostatic hypotension, tachycardia, palpitations
• Hyperprolactinemia (which may cause menstrual disturbances, galactorrhea, or sexual dysfunction)
• Weight gain

Serious but less common effects of Clopixol Acuphase include:

• Neuroleptic malignant syndrome (fever, severe muscle rigidity, autonomic instability, altered consciousness) – requires immediate medical attention
• Tardive dyskinesia (involuntary, potentially irreversible movements), with risk increasing with duration of Clopixol Acuphase use
• QT-interval prolongation and, rarely, ventricular arrhythmia
• Seizures (lowered seizure threshold)
• Agranulocytosis/blood dyscrasias (rare)

With the depot forms of Clopixol Acuphase, adverse effects may take longer to appear and longer to resolve after stopping treatment compared with the oral form, because the drug continues to be released from the injection site for days to weeks.

Pregnancy: The safety of Clopixol Acuphase in human pregnancy has not been formally established. Clopixol Acuphase should be used during pregnancy only if clearly needed and if the potential benefit to the mother justifies the potential risk to the fetus; a physician should always be consulted before use in pregnancy. Neonates exposed to antipsychotics including Clopixol Acuphase late in the third trimester are at risk of extrapyramidal and/or withdrawal symptoms after birth (agitation, abnormal muscle tone, tremor, feeding difficulty, respiratory distress); newborns should be monitored if Clopixol Acuphase was used in late pregnancy.

Lactation: Clopixol Acuphase is excreted in breast milk. Breastfeeding may generally be continued during treatment with Clopixol Acuphase, but the infant should be monitored for sedation and other adverse effects; a physician should be consulted to weigh the benefits of breastfeeding against potential infant exposure.

Boxed warning (antipsychotic class effect)

Elderly patients with dementia-related psychosis treated with antipsychotic drugs, including Clopixol Acuphase, are at increased risk of death, largely from cardiovascular or infectious causes. Clopixol Acuphase is not approved for the treatment of dementia-related psychosis in elderly patients.

Other precautions

• Neuroleptic malignant syndrome: a rare but potentially fatal reaction; Clopixol Acuphase should be discontinued immediately if it occurs, with supportive medical care.
• Tardive dyskinesia: risk increases with total dose and duration of Clopixol Acuphase treatment; use the lowest effective dose for the shortest necessary duration and monitor regularly.
• QT prolongation/cardiac disease: use Clopixol Acuphase with caution in patients with cardiac disease, electrolyte disturbances, or other risk factors for QT prolongation; avoid in severe cardiac disease.
• Extrapyramidal symptoms and seizure threshold: Clopixol Acuphase can cause extrapyramidal reactions and can lower the seizure threshold; use with caution in patients with a history of epilepsy or Parkinson's disease.
• Hepatic, renal disease, and older adults: use lower starting doses and monitor closely (see Use in Special Populations).
• Narrow-angle glaucoma, prostatic hypertrophy: use Clopixol Acuphase with caution due to mild anticholinergic-type effects.
• Driving and operating machinery: Clopixol Acuphase may cause sedation and impair alertness; patients should be advised accordingly.

Overdose of Clopixol Acuphase may cause deep sedation, coma, severe extrapyramidal symptoms, hypotension, and cardiac arrhythmia (including QT prolongation). Suspected overdose of Clopixol Acuphase is a medical emergency: seek immediate medical attention or contact emergency services / a poison control center right away. Do not attempt to treat an overdose at home. Management in hospital is supportive (airway protection, cardiac monitoring, and treatment of specific complications); there is no specific antidote for Clopixol Acuphase.

Store at room temperature (below 30°C), protected from light and moisture. Do not freeze injectable forms. Keep out of reach of children.

• Elderly: increased sensitivity to sedative, hypotensive, and extrapyramidal effects of Clopixol Acuphase; use lower doses and titrate cautiously. Clopixol Acuphase is not approved for dementia-related psychosis in the elderly (see Precautions and Warnings).
• Renal impairment: use Clopixol Acuphase with caution; monitor clinical status, as formal dose-adjustment data are limited.
• Hepatic impairment: start with a lower dose of Clopixol Acuphase and titrate slowly, given predominantly hepatic metabolism.
• Children and adolescents: safety and efficacy of Clopixol Acuphase have not been established; not recommended for use in this age group.
• Pregnancy and breastfeeding: see Pregnancy and Lactation.

Duration of Clopixol Acuphase therapy is individualized based on diagnosis, severity, and response. Acute psychotic episodes are typically treated for days to a few weeks before reassessment, after which many patients continue on lower maintenance doses of oral or depot Clopixol Acuphase for an extended period, sometimes long-term, to prevent relapse. The lowest effective dose should be used, and the ongoing need for Clopixol Acuphase should be reviewed periodically by the prescriber. When given as the decanoate depot, Clopixol Acuphase is typically administered every 1 to 4 weeks; the interval and total duration are determined by the treating physician based on clinical response.

Antipsychotics (typical/first-generation); Thioxanthene derivatives (Zuclopenthixol)

Zuclopenthixol works mainly by blocking dopamine D1 and D2 receptors in the brain, along with alpha-1 adrenergic and serotonin 5-HT2 receptors, which reduces the excessive dopaminergic activity thought to underlie psychotic symptoms and also produces sedative effects.

The safety and efficacy of Clopixol Acuphase in children and adolescents have not been established. Clopixol Acuphase is not recommended for use in pediatric patients outside of specialist clinical settings, and alternative, better-studied treatments should generally be considered first for this age group.