Flupentixol

May alter cardiac conduction; life-threatening arrhythmias have occurred with therapeutic doses of antipsychotics (Haddad 2002; Stollberger 2005). Use with caution in susceptible patients (eg, significant bradycardia, recent MI, decompensated HF, arrhythmias). Correct electrolyte abnormalities (eg, hypokalemia, hypomagnesemia prior to use. 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, flupentixol has a low potency of cholinergic blockade.

Antipsychotic use has been associated with agranulocytosis, neutropenia, leukopenia, and granulocytopenia; monitoring of CBC is recommended.

May be sedating in some patients (flupentixol is associated with less sedative effects compared to other antipsychotics), 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).

DKA has been observed in patients with no prior history of hyperglycemia; monitoring of blood glucose and body weight is recommended.

Antipsychotic use has been associated with esophageal dysmotility and aspiration; use with caution in patients at risk of pneumonia (ie, Alzheimer's disease) (Maddalena 2004).

May cause extrapyramidal symptoms, 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.

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

Lens opacity has been reported rarely with use. Similar drugs have been associated with pigmentary retinopathy, corneal and lenticular 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).

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. Disease-related concerns:

Use is contraindicated in patients with severe cardiovascular disease. Use with caution in patients with a history of or at risk for cerebrovascular accident.

Elderly patients with dementia-related psychosis who are 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. Flupentixol is not approved for use in elderly patients with dementia or dementia-related psychosis.

Use with caution in patients with known or suspected glaucoma (avoid use in patients with known or suspected narrow-angle glaucoma); condition may be exacerbated by cholinergic blockade (flupentixol has weak anticholinergic properties compared to other antipsychotics).

Use is contraindicated in patients with liver damage.

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

Use is associated with increased prolactin levels; clinical significance of hyperprolactinemia in patients with breast cancer or other prolactin-dependent tumors is unknown.

Use is contraindicated in patients with renal insufficiency.

Use with caution in patients at risk of seizures, including those with a history of seizures, head trauma, brain damage, alcoholism, or concurrent therapy with medications which may lower seizure threshold. 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:

Surgical patients receiving high-dose flupentixol should be monitored closely for hypotension; dose reduction of anesthetic or CNS depressants may be necessary. Other warnings/precautions:

May mask toxicity of other drugs or conditions (eg, intestinal obstruction, brain tumor) due to antiemetic effects.

Not recommended for use in excitable, overactive, or manic patients.

Avoid abrupt withdrawal in patients receiving maintenance therapy; withdrawal symptoms (eg, n/v, insomnia, restlessness, agitation) may appear 1 to 4 days after discontinuing therapy and subside within 7 to 14 days.