Zuclopenthixol

May alter cardiac conduction; life-threatening arrhythmias have occurred with therapeutic doses of antipsychotics. Avoid use in patients with underlying QT prolongation, in those taking medicines that prolong the QT interval, or cause polymorphic ventricular tachycardia; monitor ECG closely for dose-related QT effects. Adverse effects of decanoate may be prolonged.

May cause anticholinergic effects (constipation, xerostomia, blurred vision, urinary retention); use with caution in patients with decreased gastrointestinal motility, paralytic ileus, urinary retention, BPH, xerostomia, or visual problems. Relative to other neuroleptics, zuclopenthixol has a low potency of cholinergic blockade. Advise patients to report onset or worsening of anticholinergic effects.

Leukopenia, neutropenia, granulocytopenia, and agranulocytosis (sometimes fatal) have been reported in clinical trials and postmarketing reports with antipsychotic use. Obtain blood counts prior to initiation and then periodically thereafter.

Antipsychotic use has been associated with esophageal dysmotility and aspiration; use with caution in patients at risk of pneumonia (ie, Alzheimer disease).

May cause extrapyramidal symptoms (EPS), including pseudoparkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesia. Risk of dystonia (and possibly other EPS) may be greater with increased doses, use of conventional antipsychotics, males, and younger patients. Factors associated with greater vulnerability to tardive dyskinesia include older in age, female gender combined with postmenopausal status, Parkinson disease, pseudoparkinsonism symptoms, affective disorders (particularly major depressive disorder), concurrent medical diseases such as diabetes, previous brain damage, alcoholism, poor treatment response, and use of high doses of antipsychotics (APA [Lehman 2004]; Soares-Weiser 2007). Consider therapy discontinuation with signs/symptoms of tardive dyskinesia.

Cases of diabetic ketoacidosis have occurred in patients with no reported history of hyperglycemia. Obtain blood glucose level and body weight prior to initiation and then periodically thereafter.

Use associated with increased prolactin levels; dosage adjustment or therapy discontinuation may be necessary with clinically significant hyperprolactinemia. Use with caution in patients with breast cancer, other prolactin-dependent tumors, and pituitary gland tumors. Prolonged hyperprolactinemia in association with hypogonadism may result in decreased bone mineral density in females and males.

[Canadian Boxed Warning]: NMS has been associated with use of antipsychotic agents, including zuclopenthixol; monitor for mental status changes, fever, muscle rigidity, and/or autonomic instability (risk may be increased in patients with Parkinson's disease or Lewy body dementia). Discontinue treatment immediately with onset of NMS; recurrence has been reported in patients rechallenged with antipsychotic therapy.

Similar drugs have been associated with pigmentary retinopathy, corneal deposits, and photosensitivity.

May cause orthostatic hypotension; use with caution in patients at risk of this effect or in those who would not tolerate transient hypotensive episodes (cerebrovascular disease, cardiovascular disease, hypovolemia, or concurrent medication use which may predispose to hypotension/bradycardia).

May be sedating, use with caution in disorders where CNS depression is a feature; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

Decreased libido, menstrual disorders, erectile dysfunction (including priapism rarely) and ejaculation failure have been reported; significant dysfunction may require dosage adjustment or discontinuation of therapy. Effects are reversible upon discontinuation.

Impaired core body temperature regulation may occur; caution with strenuous exercise, heat exposure, dehydration, and concomitant medication possessing anticholinergic effects.

VTE has been reported with antipsychotics; evaluate VTE risk prior to and during therapy.

Use caution when withdrawing therapy; decrease slowly and monitor for withdrawal symptoms. Abrupt cessation may cause (rarely) acute withdrawal symptoms (eg, nausea, vomiting, or insomnia). Symptoms usually observed within 4 days of withdrawal and subside within 1 to 2 weeks. Disease-related concerns:

Use with caution in patients with cardiovascular disease.

Elderly patients with dementia-related psychosis treated with antipsychotics are at an increased risk of death compared to placebo. Most deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. An increased incidence of cerebrovascular adverse events (including fatalities) has been reported in elderly patients with dementia-related psychosis. Zuclopenthixol is not approved for use in elderly patients with dementia or dementia-related psychosis.

Use is not recommended in patients with narrow-angle glaucoma; condition may be exacerbated by cholinergic blockade.

Use with caution in patients with hepatic impairment; undergoes hepatic metabolism.

Use with caution in patients with Parkinson disease; may be more sensitive to adverse effects.

Use with caution in patients with renal impairment; has not been studied.

Use with caution in patients at risk of seizures. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:

Increased risk for developing tardive dyskinesia, particularly elderly women.