Drug information of Zuclopenthixol

Zuclopenthixol is a typical antipsychotic neuroleptic drug of the thioxanthene class. It mainly acts by antagonism of D1 and D2 dopamine receptors. Zuclopenthixol also has high affinity for alpha1-adrenergic and 5-HT2 receptors. It has weaker histamine H1 receptor blocking activity, and even lower affinity for muscarinic cholinergic and alpha2-adrenergic receptors

Zuclopenthixol is a thioxanthene with therapeutic actions similar to the phenothiazine antipsychotics. It is an antagonist at D1 and D2 dopamine receptors

:Absorption
Upon reaching the body water phase, the decanoate ester is slowly released from the oil depot, which is resultantly hydrolyzed to the active substance, zuclopenthixol. The decanoate ester provides a means of slow release since zuclopenthixol itself is a short-acting drug

:Distribution
Vd: 20 L/Kg
PB: 98-99%

:Metabolism
The metabolism of zuclopenthixol is mainly by sulphoxidation, side chain N-dealkylation and glucuronic acid conjugation. The metabolites are devoid of pharmacological activity

:Elimination
Half-life: 20 hours (range 12-28 hours) for the tablet form, 19 days for the depot form
Clearance: approximately 0.9 L/min

:Excretion
Primarily in the feces with approximately 10% in the urine

:Acute psychosis
ORAL
Initial:10 to 50 mg/day in 2 to 3 devided doses, may titrate dose upward by 10 to 20 mg every 2 to 3 days, usual therapeutic range: 20-40 mg/day, maximum dose: 100 mg/day
Maintenance therapy: maintain lowest effective dose, usual maintenace dose: 20-40 mg/day, may be given as a single dose

:IM
50-150mg, may be repeated in 2-3 days
Max: 400 mg or 4 injections and the duration of treatment: 2 weeks

Transfer of patients from IM to ORAL tablets: Allow 2-3 days after final injection before initiating oral therapy
50mg of acetate injection every 2-3 days = 20mg daily of oral tablets
100mg of acetate injection every 2-3 days = 40mg daily of oral tablets
150mg of acetate injection every 2-3 days = 60mg daily of oral tablets

Neuroleptic Malignant Syndrome: NMS has been associated with use of antipsychotic agents, including zuclopenthixol

:Adverse Effects
CNS: drowsiness, hypertonia, anxiety, insomnia, akathisia, extrapyramidal reaction, dizziness, dystonia, agitation, depression. lack of concentration, headache, vertigo, amnesia, apathy, confusion, hallucination, tardive dyskinesia, abnormal dreams, abnormal gait, malaise, pain, paresthesia, anorgasmia in females

Gastrointestinal: xerostomia, constipation, sialorrhea, anorexia, vomiting, nausea, increased appetite, diarrhea, dyspepsia

Neuromuscular & skeletal: tremor, weakness, hypokinesia, myalgia

Ophthalmic: accommodation disturbance, visual disturbance

CVD: tachycardia, orthostatic hypotention, hypotention, palpitaions. syncope

Dermatologic: diaphoresis, seborrhea, pruritus

Endocrine & Metabolic: weight gain, decreased libido, weight loss, menstrual disease, increased thirst

Genitourinary: urination disorder, ejaculatory disorder

:Contraindications
Hypersensitivity to zuclopenthixol. thoxanthenes or any component of the formulation
Acute intoxication  » ethanol, barbiturate or opiood
Coma
Suspected or established subcortical brain damage
Circulatory collapse

Adverse events were observed in animal reproduction studies. Antipsychotic use during the third trimester of pregnancy has a risk for abnormal muscle movements (Extrapymidal Syndroms/EPS) and withdrawal symptoms in newborns following delivery. Symptoms in the newborn may include agitation, feeding disorder, hypertonia, hypotonia, respiratory distress, somnollence and tremor. these effects may be self-limiting or require hospitalization