Clopixol Tablets 2 mg and 10 mg FC tablets

Symptoms of restlessness, agitation, hostility, aggression, psychomotor excitement and other behavioural disturbances in acute and chronic schizophrenia, manic phase of bipolar affective disorder and mental retardation.

Posology

Adults

Dosage should be individually adjusted according to the condition. In general, small doses should be used initially and increased to the optimal effective level as rapidly as possible based on therapeutic responses. The maintenance dose can usually be given as a single dose at bedtime.

Acute schizophrenia and other acute psychoses. Severe acute states of agitation. Mania. Usually 10 - 50 mg/day. In moderate to severe cases initially 20 mg/day increased, if necessary, by 10 - 20 mg/day every 2 - 3 days to 75 mg.

Chronic schizophrenia and other chronic psychoses. Maintenance dosage usually 20 - 40 mg/day.

Agitation in oligophrenic patients. 6 - 20 mg/day, if necessary increased to 25 - 40 mg daily.

Older patients

Older patients should receive dosages in the lower end of the dosage range.

Hypersensitivity to the active substance or to any of the excipients listed under Composition. Acute alcohol, barbiturate and opiate intoxications, comatose states.

Neuroleptic malignant syndrome may occur. Symptoms may be: hyperthermia, muscle rigidity, fluctuating consciousness, instability of the autonomous nervous system. Treatment:

• Discontinuation of CLOPIXOL
• 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 agents. CLOPIXOL should be used with caution in patients with convulsive disorders or advanced hepatic, renal or cardiovascular disease. CLOPIXOL may modify insulin and glucose responses calling for adjustment of the antidiabetic therapy in diabetic patients. Patients on long-term therapy should be monitored carefully and evaluated periodically to decide whether the maintenance dosage can be lowered. CLOPIXOL may cause QT prolongation. Persistently prolonged QT intervals may increase the risk of cardiac dysrhythmias, resulting in an increased risk of death. Therefore, CLOPIXOL should be used with caution in susceptible individuals (with hypokalaemia, hypomagnesaemia 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 dysrhythmia. Concomitant treatment with other antipsychotics should be avoided (see Interactions). Cases of venous thromboembolism (VTE) have been reported. All possible risk factors for VTE should be identified before and during treatment with CLOPIXOL and preventive measures undertaken.

Combinations requiring precautions for use

CLOPIXOL may enhance the response to alcohol and the effects of barbiturates and other CNS depressants. CLOPIXOL should not be given concomitantly with guanethidine or similar acting compounds, since neuroleptics may block the antihypertensive effect of these compounds. Concomitant use of neuroleptics and lithium increases the risk of neurotoxicity. Tricyclic antidepressants and neuroleptics mutually inhibit the metabolism of one another. CLOPIXOL may lower the effect of levodopa and the effect of adrenergic drugs. Concomitant use of metoclopramide and piperazine increases the risk of extrapyramidal symptoms. Since zuclopenthixol is partly metabolised by CYP2D6 concomitant use of agents known to inhibit this enzyme may lead to decreased clearance of zuclopenthixol.

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

• class Ia and III antidysrhythmics (e.g. quinidine, amiodarone, sotalol, dofetilide)
• some antipsychotics (e.g. thioridazine)
• some macrolides (e.g. erythromycin)
• some antihistamines (e.g. astemizole)
• some quinolone antibiotics (e.g. gatifloxacin, moxifloxacin)

The above list is not exhaustive and other individual agents known to significantly increase QT interval (e.g. cisapride, lithium) should be avoided. Medicines known to cause electrolyte disturbances such as thiazide diuretics (hypokalemia) and medicines known to increase the plasma concentration of zuclopentixol should also be used with caution as they may increase the risk of QT prolongation and cardiac dysrhythmias, resulting in an increased risk of death (see section 4.4).

Pregnancy

CLOPIXOL should not be administered during pregnancy. Neonates exposed to antipsychotics (including CLOPIXOL) during the third trimester of pregnancy are at risk of adverse reactions including extrapyramidal and/or withdrawal symptoms that may vary in severity and duration following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, or feeding disorder. Consequently, newborns should be monitored carefully.

Breastfeeding

Zuclopentixol is excreted into the breast milk. Mothers on treatment with CLOPIXOL should not breastfeed their babies.

Fertility

In humans, adverse events such as hyperprolactinaemia, galactorrhoea, amenorrhoea, erectile dysfunction and ejaculation failure have been reported (see section 4.8). These events may have a negative impact on female and/or male sexual function and fertility. If clinical significant hyperprolactinaemia, galactorrhoea, amenorrhoea or sexual dysfunctions occur, a dose reduction (if possible) or discontinuation should be considered. The effects are reversible on discontinuation. Administration of zuclopenthixol to male and female rats were associated with a slight delay in mating. In an experiment where zuclopenthixol was administered via the diet, impaired mating performance and reduced conception rate was noted.

The ability to drive a car or operate machinery may be affected. Therefore, caution should be exercised initially, until the individualu2019s reaction to treatment is known.

Extrapyramidal reactions may occur, Tardive dyskinesia may develop. In the listing below a Frequent event is defined as either a very common or common event (>1/100); all other events are defined as Less frequent.

Organ class Frequency Preferred term

• Blood and lymphatic system disorders Less frequent Thrombocytopenia, neutropenia, leukopenia, agranulocytosis
• Immune system disorders Less frequent Hypersensitivity, anaphylactic reaction.
• Endocrine disorders Less frequent Hyperprolactinaemia.
• Metabolism and nutritional disorders Frequent Increased appetite, weight increased. Less frequent Decreased appetite. Weight decreased Hyperglycaemia, glucose tolerance impaired, hyperlipidaemia
• Psychiatric disorders Frequent Insomnia, depression, anxiety, nervousness, abnormal dreams, agitation, libido decreased. Less frequent Apathy, nightmare, libido increased, confusional state.
• Nervous system disorders Frequent Somnolence, akathisia, hyperkinesia, hypokinesia. Frequent Tremor, dystonia, hypertonia, dizziness, headache, paraesthesia, disturbance in attention, amnesia, gait abnormal. Less frequent Tardive dyskinesia, hyperreflexia, dyskinesia, parkinsonism, syncope, ataxia, speech disorder, hypotonia, convulsion, migraine.
• Neuroleptic malignant syndrome.
• Eye disorders Frequent Accommodation disorder, vision abnormal. Less frequent Oculogyration, mydriasis
• Ear and labyrinth disorders Frequent Vertigo Less frequent Hyperacusis, tinnitus.
• Cardiac disorders Frequent Tachycardia, palpitations. Less frequent Electrocardiogram QT prolonged.
• Vascular disorders Less frequent Hypotension, hot flush, venous thromboembolism
• Respiratory, thoracic and mediastinal disorders Frequent Nasal congestion, dyspnoea.
• Gastrointestinal disorders Frequent Dry mouth, salivary hypersecretion, constipation, vomiting, dyspepsia, diarrhoea. Less frequent Abdominal pain, nausea, flatulence.
• Hepatobiliary disorders Less frequent Liver function test abnormal, cholestatic hepatitis, jaundice.
• Skin and subcutaneous tissue disorders Frequent Hyperhidrosis, pruritus. Less frequent Rash, photosensitivity reaction, pigmentation disorder, seborrhoea, dermatitis, purpura.
• Musculoskeletal and connective tissue disorder Frequent Myalgia. Less frequent Muscle rigidity, trismus, torticollis.
• Renal and urinary disorders Frequent Micturition disorder, urinary retention, polyuria.
• Pregnancy, puerperium and perinatal conditions Less frequent Drug withdrawal syndrome neonatal (see section 4.6)
• Reproductive system and breast disorders Less frequent Ejaculation failure, erectile dysfunction, female orgasmic disorder, vulvovaginal dryness, gynaecomastia, galactorrhoea, amenorrhoea, priapism.
• General disorders and administration site conditions Frequent Asthenia, fatigue, malaise, pain. Less frequent Thirst, hypothermia, pyrexia.

Cases of QT prolongation, ventricular arrhythmias - ventricular fibrillation, ventricular tachycardia, Torsade de Pointes and sudden unexplained death have been reported for CLOPIXOL (see section 4.4). Abrupt discontinuation CLOPIXOL 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.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reactions Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8

Symptoms

Somnolence, coma, movement disorders, convulsions, shock, hyperthermia/hypothermia. ECG changes, QT prolongation, Torsade de Pointes, cardiac arrest and ventricular arrhythmias have been reported when CLOPIXOL has been taken in overdose together with drugs known to affect the Heart.

Treatment:

Treatment is symptomatic and supportive. Measures to support the respiratory and cardiovascular systems should be instituted. Epinephrine (adrenaline) should not be used as further lowering of blood pressure may result.