Section 4.3 Contraindications
Amended to:
Hypersensitivity to the active substance or to any of the excipients (see section 6.1).
Circulatory collapse, depressed level of consciousness due to any cause (e.g. intoxication with alcohol, barbiturates or opiates), coma.
Section 4.4 Special warnings and precaution for use
Addition of:
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.
Like other neuroleptics, zuclopenthixol should be used with caution in patients with organic brain syndrome, convulsions or advanced hepatic disease.
Blood dyscrasias have been reported rarely. Blood counts should be carried out if a patient develops signs of persistent infection.
As described for other psychotropics zuclopenthixol may modify insulin and glucose responses calling for adjustment of the antidiabetic therapy in diabetic patients.
Section 4.5 Interaction with other medicinal products and other forms of interaction
Sub-section related to co-administration and increase in QT interval amended to: 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
· some quinolone antibiotics (e.g. 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 (hypokalemia) and drugs known to increase the plasma concentration of zuclopenthixol should also be used with caution as they may increase the risk of QT prolongation and malignant arrhythmias (see section 4.4).
Addition of: Since zuclopenthixol is partly metabolised by CYP2D6 concomitant use of drugs known to inhibit this enzyme may lead to higher than expected plasma concentrations of zuclopenthixol, increasing the risk of adverse effects and cardiotoxicity.
Section 4.8 Undesirable effects
Amended to: 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 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.
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Cardiac disorders
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Tachycardia, palpitations.
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Electrocardiogram QT prolonged.
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Blood and lymphatic system disorders
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Thrombocytopenia, neutropenia, leukopenia, agranulocytosis.
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Nervous system disorders
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Somnolence, akathisia, hyperkinesia, hypokinesia.
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Tremor, dystonia, hypertonia, dizziness, headache, paraesthesia, disturbance in attention, amnesia, gait abnormal.
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Tardive dyskinesia, hyperreflexia, dyskinesia, parkinsonism, syncope, ataxia, speech disorder, hypotonia, convulsion, migraine.
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Neuroleptic malignant syndrome.
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Eye disorders
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Accommodation disorder, vision abnormal.
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Oculogyration, mydriasis.
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Ear and labyrinth disorders
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Vertigo.
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Hyperacusis, tinnitus.
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Respiratory, thoracic and medistianal disorders
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Nasal congestion, dyspnoea.
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Gastrointestinal disorders
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Dry mouth.
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Salivary hypersecretion, constipation, vomiting, dyspepsia, diarrhoea.
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Abdominal pain, nausea, flatulence.
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Renal and urinary disorders
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Micturition disorder, urinary retention, polyuria.
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Skin and subcutaneous tissue disorders
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Hyperhidrosis, pruritus.
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Rash, photosensitivity reaction, pigmentation disorder, seborrhoea, dermatitis, purpura.
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Musculoskeletal and connective tissue disorder
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Myalgia.
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Muscle rigidity, trismus, torticollis.
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Endocrine disorders
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Hyperprolactinaemia.
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Metabolism and nutrition disorders
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Increased appetite, weight increased .
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Decreased appetite, weight decreased.
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Hyperglycaemia, glucose tolerance impaired, hyperlipidaemia.
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Vascular disorders
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Hypotension, hot flush.
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General disorders and administration site conditions
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Asthenia, fatigue, malaise, pain.
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Thirst, hypothermia, pyrexia.
Injection site reaction
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Immune system disorders
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Hypersensitivity, anaphylactic reaction.
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Hepato-biliary disorders
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Liver function test abnormal.
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Cholestatic hepatitis, jaundice.
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Reproductive system and breast disorders
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Ejaculation failure, erectile dysfunction, female orgasmic disorder, vulvovaginal dryness.
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Gynaecomastia, galactorrhoea, amenorrhoea, priapism.
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Psychiatric disorders
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Insomnia, depression, anxiety, nervousness, abnormal dreams, agitation, libido decreased.
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Apathy, nightmare, libido increased, confusional state.
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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 zuclopenthixol (see section 4.4).
Abrupt discontinuation of zuclopenthixol 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.
For further information contact:
Lundbeck Medical Information, email: ukmedicalinformation@lundbeck.com
Tel: 01908 638972.