Zuclopenthixol

From Drugs Prescribing Information
(Redirected from Acuphase)
Jump to: navigation, search

Click on "►" to expand:

Contents

[edit] BRAND NAMES

[edit] STRUCTURE

Zuclopenthixol.jpg

[edit] MECHANISM OF ACTION

Zuclopenthixol is a potent neuroleptic (typical antipsychotic) of the thioxanthene series.

The antipsychotic effect of neuroleptics is related to their dopamine receptor blocking activity.

The thioxanthenes have high affinity for both the adenylate cyclase-coupled dopamine D1 receptors and for the dopamine D2 receptors; in the phenothiazine group the affinity for D1 receptors is much lower than for D2 receptors, whereas butyrophenones, diphenylbutylpiperidines and benzamides only have affinity for D2 receptors.

[edit] INDICATIONS

  • Acute (Zuclopenthixol Acetate, Zuclopenthixol decanoate and Zuclopenthixol dihydrochloride) and chronic (Zuclopenthixol decanoate and Zuclopenthixol dihydrochloride) schizophrenia and other psychoses (including bipolar), especially those with symptoms such as hallucinations, delusions, thought disturbances, agitation, restlessness, hostility or aggressiveness.

[edit] DOSAGE FORMS

  • zuclopenthixol decanoate (long acting intramuscular injection given every two or three weeks)
  • zuclopenthixol acetate (short acting intramuscular injection used in the acute sedation: duration of action is 2–3 days)
  • zuclopenthixol dihydrochloride (tablets)

[edit] DOSAGE

  • zuclopenthixol dihydrochloride (tablets): 20–60 mg daily.
  • zuclopenthixol decanoate: 200-400 mg should be given intramuscularly and repeated every 2nd week. Higher doses or shorter intervals may be needed.
  • zuclopenthixol acetate (Acute phase): The dose range would normally be 50-150 mg i.m., repeated if necessary, preferably with a time interval of 2 to 3 days. In a few patients an additional injection may be needed 24 to 48 hours following the first injection.

[edit] CONTRAINDICATIONS

[edit] WARNINGS AND PRECAUTIONS

Neuroleptic malignant syndrome (NMS) is a rare, sometimes fatal, neurological disorder that has been reported in association with antipsychotic drugs including zuclopenthixol

[edit] INTERACTIONS

Combinations requiring precautions for use

  • Zuclopenthixol acetate may enhance the sedative effect of alcohol and the effects of barbiturates and other CNS depressants.
  • Concomitant use of neuroleptics and lithium increases the risk of neurotoxicity.
  • Tricyclic antidepressants and neuroleptics mutually inhibit the metabolism of each other.
  • Zuclopenthixol may reduce the effect of levodopa and the effect of adrenergic drugs.
  • Concomitant use of metoclopramide and piperazine increases the risk of extrapyramidal disorder.
  • Since zuclopenthixol is partly metabolised by CYP2D6 concomitant use of drugs known to inhibit this enzyme may lead to decreased clearance of zuclopenthixol.


QT interval: Increases in the QT interval related to antipsychotic treatment may be exacerbated by the co administration 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 thiazidediuretica (hypokalemia) and drugs known to increase the plasma concentration of zuclopenthixol acetate should also be used with caution as they may increase the risk of QT prolongation and malignant arrhythmias

[edit] PREGNANCY AND LACTATION

Pregnancy: Zuclopenthixol acetate should not be administered during pregnancy unless the expected benefit to the patient outweighs the theoretical risk to the foetus. The newborns of mothers treated with neuroleptics in late pregnancy, or labour, may show signs of intoxication such as lethargy, tremor and hyperexcitability and have a low apgar score. Animal-reproduction studies on zuclopenthixol have not given evidence of an increased incidence of foetal damage or other deleterious effects on the reproduction process.

Lactation: As zuclopenthixol is found in breast milk in low concentrations it is not likely to affect the infant when therapeutic doses are used. The dose ingested by the infant is less than 1% of the weight related maternal dose (in mg/kg). Breast-feeding can be continued during zuclopenthixol acetate therapy if considered of clinical importance but observation of the infant is recommended, particularly in the first 4 weeks after giving birth.

[edit] SIDE EFFECTS

  • Extrapyramidal symptoms as a result of dopamine blockade: these symptoms are similar to those seen in Parkinsons Disease and include a restlessness and inability to sit still known as akathisia, a slow tremor and stiffness of the limbs. they may occur especially during the first few days after an injection and in the early phase of treatment. In most cases these side effects can be satisfactorily controlled by reduction of dosage and/or use of antiparkinsonian drugs. The routine prophylactic use of antiparkinsonian drugs is not recommended.

Antiparkinsonian 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

  • Elevation in prolactin levels: Like most other neuroleptics zuclopenthixol increases the serum prolactin level, this may occasionally result in amenorrhoea or galactorrhoea and very rarely in the development of neuroleptic malignant syndrome (hyperthermia, muscle rigidity, fluctuating consciousness, instability of the autonomous nervous system).

Very common (Frequency ≥1/10) side effects are:

  • Somnolence, akathisia, hyperkinesia, hypokinesia and Dry mouth.

Common (Frequency ≥1/100 to <1/10) side effects are:

  • Tachycardia, palpitations
  • Tremor, dystonia, hypertonia, dizziness, headache, paraesthesia, disturbance in attention, amnesia, gait abnormal
  • Accommodation disorder, vision abnormal
  • Vertigo.
  • Nasal congestion, dyspnoea
  • Salivary hypersecretion, constipation, vomiting, dyspepsia, diarrhoea.
  • Micturition disorder, urinary retention, polyuria
  • Hyperhidrosis, pruritus.
  • Myalgia.
  • Increased appetite, weight increased.
  • Asthenia, fatigue, malaise, pain.
  • Insomnia, depression, anxiety, nervousness, abnormal dreams, agitation, libido decreased.


Uncommon (Frequency ≥1/1000 to <1/100) side effects are:

  • Oculogyration, mydriasis.
  • Hyperacusis, tinnitus.
  • Abdominal pain, nausea, flatulence.
  • Rash, photosensitivity reaction, pigmentation disorder, seborrhoea, dermatitis, purpura.
  • Muscle rigidity, trismus, torticollis.
  • Decreased appetite, weight decreased.
  • Hypotension, hot flush.
  • Thirst, injection site reaction, hypothermia, pyrexia.
  • Liver function test abnormal
  • Ejaculation failure, erectile dysfunction, female orgasmic disorder, vulvovaginal dryness
  • Apathy, nightmare, libido increased, confusional state.


Uncommon to Rare:

  • Tardive dyskinesia, hyperreflexia, dyskinesia, parkinsonism, syncope, ataxia, speech disorder, hypotonia, convulsion, migraine.


Rare (Frequency ≥1/10000 to <1/1000) side effects are:

  • Electrocardiogram QT prolonged
  • Thrombocytopenia, neutropenia, leukopenia, agranulocytosis.
  • Hyperprolactinaemia.
  • Hyperglycaemia, glucose tolerance impaired, hyperlipidaemia
  • Hypersensitivity, anaphylactic reaction.
  • Gynaecomastia, galactorrhoea, amenorrhoea, priapism.


Very rare (Frequency <1/10000) side effects are:

  • Neuroleptic malignant syndrome.
  • Venous thromboembolism
  • Cholestatic hepatitis, jaundice.

[edit] RELATED LINKS

Antipsychotics (Typical and Atypical): pharmacology, indications and adverse effects

[edit] BIBLIOGRAPHY

Clopixol Acuphase leafelt

[edit] REFERENCES