Flupenthixol

Pronunciation

(floo pen THIKS ol)


Synonyms

Flupenthixol Decanoate; Flupenthixol Dihydrochloride



Generic Available

No



Canadian Brand Names

Fluanxol®



Use

Maintenance therapy of chronic schizophrenic patients whose main manifestations do include excitement, agitation, or hyperactivity

not

Restrictions

Not available in U.S.



Pregnancy Risk Factor

C (based on similar agents)



Lactation

Enters breast milk/not recommended



Contraindications

Hypersensitivity to flupenthixol, phenothiazines, thioxanthenes, or any component of the formulation; acute intoxication (ethanol, barbiturate, or opioid); severe CNS depression; coma; severely-agitated patients; suspected or established subcortical brain damage; cerebrovascular or renal insufficiency; severe cardiovascular disease/circulatory collapse; blood dyscrasias; pheochromocytoma



Warnings/Precautions

Use with caution in Parkinson's disease. Caution in patients with hemodynamic instability; predisposition to seizures; bone marrow suppression; severe cardiac, hepatic, renal, or respiratory disease. Esophageal dysmotility and aspiration have been associated with antipsychotic use; use with caution in patients at risk of pneumonia (ie, Alzheimer's disease). Caution in breast cancer or other prolactin-dependent tumors (may elevate prolactin levels). May alter temperature regulation or mask toxicity of other drugs due to antiemetic effects. May alter cardiac conduction; life-threatening arrhythmias have occurred with therapeutic doses of neuroleptics. May cause orthostatic hypotension; use with caution in patients at risk of this effect or those who would tolerate transient hypotensive episodes (cerebrovascular disease, cardiovascular disease, or other medications which may predispose). Safety and efficacy have not been established in pediatric patients.

Flupenthixol may be sedating, use with caution in disorders where CNS depression is a feature. May cause anticholinergic effects (confusion, agitation, constipation, dry mouth, blurred vision, urinary retention); therefore, they should be used with caution in patients with decreased gastrointestinal motility, urinary retention, BPH, xerostomia, or visual problems. Conditions which also may be exacerbated by cholinergic blockade include narrow-angle glaucoma (screening is recommended) and worsening of myasthenia gravis. Relative to other neuroleptics, flupenthixol has a low potency of cholinergic blockade.

May cause extrapyramidal reactions, including pseudoparkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesia (risk of these reactions is high relative to other neuroleptics). Antipsychotics may be associated with neuroleptic malignant syndrome (NMS) or pigmentary retinopathy. Because of its antiemetic properties, flupenthixol may mask signs of toxicity due to overdosage of other drugs.

Adverse Reactions

Frequency not defined.

Central nervous system: Extrapyramidal effects (up to 30%; including akathisia, dystonia, pseudoparkinsonism, tardive dyskinesia), anxiety/nervousness, insomnia, headache, dizziness, depression, fatigue

Dermatologic: Rash, pruritus, exfoliative dermatitis, contact dermatitis

Endocrine & metabolic: Weight gain, galactorrhea, gynecomastia, decreased libido, hyperglycemia, glycosuria

Gastrointestinal: Xerostomia, increased salivation, nausea, vomiting

Genitourinary: Micturition disorder

Neuromuscular & skeletal: Hypertonia, tremor, weakness

Ocular: Abnormal accommodation, abnormal vision

Miscellaneous: Diaphoresis increased

Additional adverse events associated with antipsychotics include: Arrhythmias, angioedema, hematologic adverse effects (agranulocytosis, hemolytic anemia, pancytopenia, thrombocytopenia) neuroleptic malignant syndrome (NMS), photosensitivity, seizure

Overdosage/Toxicology

Symptoms of overdose include sedation, frequently preceded by extreme agitation, excitement, and confusion. Extrapyramidal symptoms (EPS) may develop, and respiratory and circulatory collapse may occur. Treatment is symptom-directed and supportive. Severe hypotension requires immediate use of I.V. vasopressor drugs such as norepinephrine bitartrate. Antiparkinsonian medication should be administered only if EPS symptoms develop.



Drug Interactions

Aluminum salts: May decrease the absorption of antipsychotics; monitor

Amphetamines: Efficacy may be diminished by antipsychotics; in addition, amphetamines may increase psychotic symptoms. Avoid concurrent use

Anticholinergics: May inhibit the therapeutic response to antipsychotics and excess anticholinergic effects may occur; includes benztropine, trihexyphenidyl, biperiden, and drugs with significant anticholinergic activity (TCAs, antihistamines, disopyramide)

Antihypertensives: Concurrent use of antipsychotics with an antihypertensive may produce additive hypotensive effects (particularly orthostasis)

Bromocriptine: Antipsychotics inhibit the ability of bromocriptine to lower serum prolactin concentrations

CNS depressants: Sedative effects may be additive with antipsychotics; monitor for increased effect; includes barbiturates, benzodiazepines, narcotic analgesics, ethanol, and other sedative agents

Epinephrine: Chlorpromazine (and possibly other low potency antipsychotics) may diminish the pressor effects of epinephrine

Guanethidine and guanadrel: Antihypertensive effects may be inhibited by antipsychotics

Levodopa: Antipsychotics may inhibit the antiparkinsonian effect of levodopa; avoid this combination

Lithium: Antipsychotics may produce neurotoxicity with lithium; this is a rare effect

Phenytoin: May reduce serum levels of antipsychotics; phenothiazines may increase phenytoin serum levels

Propranolol: Serum concentrations of antipsychotics may be increased; propranolol also increases some antipsychotic concentrations

Polypeptide antibiotics: Rare cases of respiratory paralysis have been reported with concurrent use of antipsychotics

Sulfadoxine/pyrimethamine: May increase antipsychotic concentrations

Tricyclic antidepressants: Concurrent use may produce increased toxicity or altered therapeutic response

Trazodone: Antipsychotics and trazodone may produce additive hypotensive effects

Valproic acid: Serum levels may be increased by antipsychotics

Stability

Solution: Store at room temperature; protect from light.



Mechanism of Action

Flupenthixol is a thioxanthene antipsychotic which blocks postsynaptic dopamine receptors in the CNS, resulting in inhibition of dopamine-mediated effects



Pharmacodynamics/Kinetics

Onset: I.M. depot: 24-72 hours following injection

Duration: I.M. depot: 2-4 weeks

Time to peak:

I.M. depot: 4-7 days

Oral: 3-8 hours

Metabolism: Hepatic

Excretion: Feces (as metabolites); urine (small amounts)

Dosage

I.M. (depot): Flupenthixol is administered by deep I.M. injection, preferably in the gluteus maximus, NOT for I.V. use; maintenance dosages are given at 2- to 3-week intervals

Patients not previously treated with long-acting depot neuroleptics should be given an initial test dose of 5-20 mg. An initial dose of 20 mg is usually well tolerated; however, a 5 mg test dose is recommended in elderly, frail, and cachectic patients, and in patients whose individual or family history suggests a predisposition to extrapyramidal reactions. In the subsequent 5-10 days, the therapeutic response and the appearance of extrapyramidal symptoms should be carefully monitored. Oral neuroleptic drugs may be continued, but dosage should be reduced during this overlapping period and eventually discontinued.

Oral: Initial: 1 mg 3 times/day; dose must be individualized. May be increased by 1 mg every 2-3 days based on tolerance and control of symptoms. Usual maintenance dosage: 3-6 mg/day in divided doses (doses

12 mg/day used in some patients).

Administration

Administer by deep I.M. injection, preferably in the gluteus maximum;

not for I.V. use

Monitoring Parameters

Vital signs; lipid profile, fasting blood glucose/Hgb A1c; BMI; mental status, abnormal involuntary movement scale (AIMS), extrapyramidal symptoms (EPS)



Additional Information

Not available in U.S.



Dental Health: Effects on Dental Treatment

No significant effects or complications reported



Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions



Dosage Forms

Injection, solution, as decanoate [depot]: 20 mg/mL (10 mL); 100 mg/mL (2 mL)

Tablet, as dihydrochloride: 0.5 mg, 3 mg

International Brand Names

Fluanxol® (CA)



Review Date: 1969-12-31 Reviewed By: Keywords: ,
Adam Data Copyright The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only--they do not constitute endorsements of those other sites. © 1997- 2010 A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited.

For information 410.787.4000

© 2013 UM Baltimore Washington Medical Center.  All rights reserved.

301 Hospital Drive, Glen Burnie, MD 21061 | 410-787-4000 | TTY 410-787-4498