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Drug Details

DEPIXOL

• Drug Class Description
  Thioxanthenes (antipsychotics).
• Generic Name
  Flupentixol [flupenthixol]
• Presentation
  Round, biconvex, yellow, sugar-coated tablets.
• Description
  3.504 mg flupentixol dihydrochloride corresponding to 3 mg flupentixol base
• Indications
  The treatment of schizophrenia and other psychoses.
• Adult Dosage
  

  Route of administration

  Oral.

  Adults

  1 - 3 tablets twice daily to a maximum of 18 mg (6 tablets) per day. It is recommended that commencement of treatment and increase in dosage should be carried out under close supervision. As with all antipsychotic drugs, the dose of Depixol should be titrated to the needs of each patient.

  When transferring patients from oral to depot antipsychotic treatment, the oral medication should not be discontinued immediately, but gradually withdrawn over a period of several days after administering the first injection.

• Child Dosage
  Not recommended.
• Elderly Dosage
  

  In accordance with standard medical practice, initial dosage may need to be reduced to a quarter or half the normal starting dose in the frail or elderly.

• Contra Indications
  

  Hypersensitivity to the active substance or to any of the excipient.

  Circulatory collapse, depressed level of consciousness due to any cause (e.g. intoxication with alcohol, barbiturates or opiates), coma

  Not recommended for excitable or agitated patients.

• Special Precautions
  

  Caution should be exercised in patients having: liver disease; cardiac disease or arrhythmias; severe respiratory disease; renal failure; epilepsy (and conditions predisposing to epilepsy e.g. alcohol withdrawal or brain damage); Parkinson's disease; narrow angle glaucoma; prostatic hypertrophy; hypothyroidism; hyperthyroidism; myasthenia gravis; phaeochromocytoma and patients who have shown hypersensitivity to thioxanthenes or other antipsychotics.

  The elderly require close supervision because they are specially prone to experience such adverse effects as sedation, hypotension, confusion and temperature changes.

  The possibility of development of neuroleptic malignant syndrome (hyperthermia, muscle rigidity, fluctuating consciousness, instability of the autonomous nervous system) exists with any neuroleptic. The risk is possibly greater with the more potent agents. Patients with pre-existing organic brain syndrome, mental retardation, and opiate and alcohol abuse are over-represented among fatal cases.

  Treatment: Discontinuation of the neuroleptic. Symptomatic treatment and use of general supportive measures. Dantrolene and bromocriptine may be helpful.

  Symptoms may persist for more than a week after oral neuroleptics are discontinued and somewhat longer when associated with the depot forms of the drugs.

  Blood dyscrasias, including thrombocytopenia, have been reported rarely. Blood counts should be carried out if a patient develops signs of persistent infection.

  As described for other psychotropics flupentixol may modify insulin and glucose responses calling for adjustment of the antidiabetic therapy in diabetic patients.

  Acute withdrawal symptoms, including nausea, vomiting, sweating and insomnia have been described after abrupt cessation of antipsychotic drugs. Recurrence of psychotic symptoms may also occur, and the emergence of involuntary movement disorders (such as akathisia, dystonia and dyskinesia) has been reported. Therefore, gradual withdrawal is advisable.

  When transferring patients from oral to depot antipsychotic treatment, the oral medication should not be discontinued immediately, but gradually withdrawn over a period of several days after administering the first injection.

  An approximately 3-fold increased risk of cerebrovascular adverse events have been seen in randomised placebo controlled clinical trials in the dementia population with some atypical antipsychotics. The mechanism for this increased risk is not known. An increased risk cannot be excluded for other antipsychotics or other patient populations.

  Flupentixol should be used with caution in patients with risk factors for stroke.

  As with other drugs belonging to the therapeutic class of antipsychotics, flupentixol may cause QT prolongation. Persistently prolonged QT intervals may increase the risk of malignant arrhythmias. Therefore, flupentixol should be used with caution in susceptible individuals (with hypokalaemia, hypomagnesia or genetic predisposition) and in patients with a history of cardiovascular disorders, e.g. QT prolongation, significant bradycardia (<50 beats per minute), a recent acute myocardial infarction, uncompensated heart failure, or cardiac arrhythmia.

  Concomitant treatment with other antipsychotics should be avoided.

   

  Suicide/suicidal thoughts or clinical worsening

  Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide-related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of suicide may increase in the early stages of recovery.

  Other psychiatric conditions for which Flupentixol is prescribed can also be associated with an increased risk of suicide-related events. In addition, these conditions may be co-morbid with major depressive disorder. The same precautions observed when treating patients with major depressive disorder should therefore be observed when treating patients with other psychiatric disorders.

  Patients with a history of suicide-related events, or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment are known to be at greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment. A meta-analysis of placebo-controlled clinical trials of antidepressant drugs in adult patients with psychiatric disorders showed an increased risk of suicidal behaviour with antidepressants compared to placebo in patients less than 25 years old.

  Close supervision of patients and in particular those at high risk should accompany drug therapy especially in early treatment and following dose changes. Patients (and caregivers of patients) should be alerted about the need to monitor for any clinical worsening, suicidal behaviour or thoughts and unusual changes in behaviour and to seek medical advice immediately if these symptoms present.

• Interactions
  

  In common with other antipsychotics, flupentixol enhances the response to alcohol, the effects of barbiturates and other CNS depressants. Flupentixol may potentiate the effects of general anaesthetics and anticoagulants and prolong the action of neuromuscular blocking agents.

  The anticholinergic effects of atropine or other drugs with anticholinergic properties may be increased. Concomitant use of drugs such as metoclopramide, piperazine or antiparkinson drugs may increase the risk of extrapyramidal effects such as tardive dyskinesia. Combined use of antipsychotics and lithium or sibutramine has been associated with an increased risk of neurotoxicity.

  Antipsychotics may enhance the cardiac depressant effects of quinidine; the absorption of corticosteroids and digoxin. The hypotensive effect of vasodilator antihypertensive agents such as hydralazine and αblockers (e.g. doxazosin), or methyl-dopa may be enhanced.

  Increases in the QT interval related to antipsychotic treatment may be exacerbated by the coadministration of other drugs known to significantly increase the QT interval. Co-administration of such drugs should be avoided. Relevant classes include:

  • class Ia and III antiarrhythmics (e.g. quinidine, amiodarone, sotalol, dofetilide)

  • some antipsychotics (e.g. thioridazine)

  • some macrolides (e.g. erythromycin)

  • some antihistamines (e.g. terfenadine, astemizole)

  • some quinolone antibiotics (e.g. gatifloxacin, moxifloxacin)

  The above list is not exhaustive and other individual drugs known to significantly increase QT interval (e.g. cisapride, lithium) should be avoided.

  Drugs known to cause electrolyte disturbances such as thiazide diuretics (hypokalaemia) and drugs known to increase the plasma concentration of flupentixol should also be used with caution as they may increase the risk of QT prolongation and malignant arrythmias.

  Antipsychotics may antagonise the effects of adrenaline and other sympathomimetic agents, and reverse the antihypertensive effects of guanethidine and similar adrenergic-blocking agents. Antipsychotics may also impair the effect of levodopa, adrenergic drugs and anticonvulsants.

  The metabolism of tricyclic antidepressants may be inhibited and the control of diabetes may be impaired.

• Adverse Drug Reactions
  

  Cases of suicidal ideation and suicidal behaviours have been reported during Flupentixol therapy or early after treatment discontinuation.

  Undesirable effects are for the majority dose dependent. The frequency and severity are most pronounced in the early phase of treatment and decline during continued treatment.

  Extrapyramidal reactions may occur, especially in the early phase of treatment. In most cases these side effects can be satisfactorily controlled by reduction of dosage and/or use of antiparkinson drugs. The routine prophylactic use of antiparkinson drugs is not recommended. Antiparkinson drugs do not alleviate tardive dyskinesia and may aggravate them. Reduction in dosage or, if possible, discontinuation of zuclopenthixol therapy is recommended. In persistent akathisia a benzodiazepine or propranolol may be useful.

  Cardiac disorders	Tachycardia, palpitations.Electrocardiogram QT prolonged.
  Blood and lymphatic system disorders	Thrombocytopenia, neutropenia, leukopenia, agranulocytosis
  Nervous system disorders	Somnolence, akathisia, hyperkinesia, hypokinesia. Tremor, dystonia, dizziness, headache, disturbance in attention.Tardive dyskinesia, dyskinesia, parkinsonism, speech disorder, convulsion.Neuroleptic malignant syndrome.
  Eye disorders	Accommodation disorder, vision abnormal.Oculogyration.
  Respiratory, thoracic and mediastinal disorders	Dyspnoea.
  Gastrointestinal disorders	Dry mouth.Salivary hypersecretion, constipation, vomiting, dyspepsia, diarrhoea.Abdominal pain, nausea, flatulence.
  Renal and urinary disorders	Micturition disorder, urinary retention
  Skin and subcutaneous tissue disorders	Hyperhidrosis, pruritus.Rash, photosensitivity reaction, dermatitis
  Musculoskeletal and connective tissue disorder	Myalgia.Muscle rigidity.
  Endocrine disorder	Hyperprolactinaemia.
  Metabolism and nutrition disorders	Increased appetite, weight increased. Decreased appetite.Hyperglycaemia, glucose tolerance abnormal.
  Vascular disorders	Hypotension, hot flush.
  General disorders and administration site conditions	Asthenia, fatigue.
  Immune system disorders	Hypersensitivity, anaphylactic reaction.
  Hepatobiliary disorders	Liver function test abnormal.Jaundice.
  Reproductive system and breast disorders	Ejaculation failure, erectile dysfunction.Gynaecomastia, galactorrhoea, amenorrhoea.
  Psychiatric disorders	Insomnia, depression, nervousness, agitation, libido decreased. Confusional state.

  As with other drugs belonging to the therapeutic class of antipsychotics, rare cases of QT prolongation, ventricular arrhythmias - ventricular fibrillation, ventricular tachycardia, Torsade de Pointes and sudden unexplained death have been reported for flupentixol.

  Abrupt discontinuation of flupentixol may be accompanied by withdrawal symptoms. The most common symptoms are nausea, vomiting, anorexia, diarrhoea, rhinorrhoea, sweating, myalgias, paraesthesias, insomnia, restlessness, anxiety, and agitation. Patients may also experience vertigo, alternate feelings of warmth and coldness, and tremor. Symptoms generally begin within 1 to 4 days of withdrawal and abate within 7 to 14 days.