ZACCO

4). Treatment should be given for the shortest possible duration. If this medicine is being used for the treatment of epilepsy this medicine should be used for as long as the prescriber considers it necessary.

Treatment of anxiety:

Treatment should be as short as possible. The patient must be re-assessed after a period not exceeding 4 weeks and regularly thereafter in order to evaluate the need for continued treatment, especially where the patient is free of symptoms.

e. including tapering-off process) must not exceed 8 to 12 weeks. In certain cases extension beyond the maximum treatment period may be necessary; if so it should not take place without re-evaluation of the patient’s status with special expertise.

It is strongly recommended that prolonged periods of uninterrupted treatment be avoided, since they may lead to dependence.

Adults:

The usual anxiolytic dose for adults is 20-30mg daily in divided doses or as a single dose given at night. Doses up to 60mg daily have been used in the treatment of adult in-patients with severe anxiety. The lowest dose that can control symptoms should be used.

After improvement of the symptoms, the dose may be reduced. It should not be used for longer than 4 weeks. Due regard must be paid to the possibility of interference with alertness and reaction time. Long term chronic use as an anxiolytic is not recommended.

In certain cases, extension beyond the maximum treatment period may be necessary; treatment must not be extended without re- evaluation of the patient's status using special expertise. It is strongly recommended that prolonged periods of uninterrupted treatment be avoided, since they may lead to dependence.

Treatment should always be withdrawn gradually. Patients who have taken Zacco for a long time may require a longer period during which doses are reduced.

Elderly:

Doses of 10-20mg daily in anxiety may be used in the elderly, who are more sensitive to the effects of psychoactive agents. Treatment requires low initial doses and gradual dose increments under careful observation. Treatment of epilepsy in association with one or more other anticonvulsants Adults: In epilepsy a starting dose of 5-15mg/day is recommended with increases of 10mg increments, increasing as necessary up to maximum of 60mg daily.

Elderly:

In elderly patients in the management of epilepsy with clobazam increased response and increased susceptibility to adverse reactions may occur. These patients require low initial doses with gradual increases under careful observation.

Paediatric population aged 2 years and above:

Zacco doses should be adapted individually. Doses can be taken once a day, or as 2 to 3 divided doses, keeping the total daily dose the same. When prescribed for children, treatment requires low initial doses and gradual dose increments under careful observation.

1 mg/kg/day for younger patients. 2 mg/kg/day at 7 days intervals, until the required clinical effect is achieved or side effects occur. 2mg/kg every week up to the target dose. 3 to 1mg/kg body weight daily is usually sufficient.

Paediatric population aged 1 month -2 years:

There is a lack of data regarding the use of the product in patients under 2 years old Zacco should not be used as an anticonvulsant treatment in children from 1 months to 2 years old unless under exceptional situations when there is a clear epilepsy indication.

1mg/kg/day as in this population the metabolic pathways for clobazam may not be fully mature. Up-to-date no precise dosage recommendations can be made for this population. During adjunctive therapy in epilepsy, in adults and children aged two years and above, the patient must be re-assessed after a period not exceeding 4 weeks and every 4 weeks thereafter in order to evaluate the need for continued treatment.

A break in therapy may be beneficial if drug exhaustion develops, recommencing therapy at a low dose. At the end of treatment (including in poor-responding patients), it is recommended to gradually decrease the dosage since the risk of withdrawal phenomena/rebound phenomena is greater after abrupt discontinuation of treatment.

Hepatic and renal impairment (all indications):

Increased responsiveness and higher susceptibility to adverse effects may be present in these patients and require low initial doses and gradual dose increments under careful observation. The maximum dose should not be exceeded. Zacco Oral Suspension is particularly recommended for children and adults with swallowing difficulties as it allows a secure and precise dosage.

The patient should be checked regularly at the start of the treatment in order to decrease if necessary, the dose or frequency of administration to prevent overdose due to accumulation. Method of administration For oral use only. Zacco can be given with or without food.

This product may settle during storage. Shake the bottle well before use.

g. 4 Warnings and Precautions) Gastrointestinal disorders Common: dry mouth, nausea, constipation Skin and subcutaneous tissue disorders Uncommon: rash Not known: urticaria; Steven-Johnson syndrome, toxic epidermal necrolysis (including some cases with fatal outcome); Musculoskeletal and connective tissue disorders Not known: muscle spasms, muscle weakness General disorders and administration site conditions Very common: fatigue, especially at the beginning of treatment and when higher doses are used Not known: slow response to stimuli, hypothermia Symptoms reported following discontinuation of benzodiazepines include headaches, muscle pain, anxiety, tension, depression, insomnia, restlessness, confusion, irritability, sweating, and the occurrence of “rebound” phenomena whereby the symptoms that led to treatment with benzodiazepines recur in an enhanced form.

These symptoms may be difficult to distinguish from the original symptoms for which the drug was prescribed. In severe cases the following symptoms may occur: derealisation; depersonalisation; hyperacusis; tinnitus; numbness and tingling of the extremities; hypersensitivity to light, noise, and physical contact; involuntary movements; hyperreflexia, tremor, nausea, vomiting; diarrhoea, abdominal cramps, loss of appetite, agitation, palpitations, tachycardia, panic attacks, vertigo, short-term memory loss, hallucinations/delirium; catatonia; hyperthermia, convulsions.

Convulsions may be more common in patients with pre-existing seizure disorders or who are taking other drugs that lower the convulsive threshold such as antidepressants. Investigations Uncommon: weight increased (particularly with high doses or in long-term treatment) Injury poisoning and procedural complications Uncommon: fall Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Switching between formulations In some individuals taking Zacco, clobazam reaches higher plasma levels than the same dose taken as a tablet. This may lead to an increased risk of respiratory depression and sedation, which may be most noticeable when switching to this medicine from tablets.

Therefore, caution must be taken when switching between clobazam products. Children under 2 years There is a lack of data regarding the use of the product in patients under 2 years old. For this reason, careful assessment and monitoring is required by the treating physician for use in children under 2 years for anticonvulsant treatment.

Amnesia Benzodiazepines may induce anterograde amnesia. The condition occurs most often several hours after ingesting the product and therefore to reduce the risk patients should ensure that they will be able to have an uninterrupted sleep of 7-8 hours (see also Undesirable Effects).

Muscle weakness Clobazam can cause muscle weakness. Therefore, in patients with pre-existing muscle weakness or spinal or cerebellar ataxia or sleep apnoea, special observation is required and a dose reduction may be necessary. Clobazam is contraindicated in patients with myasthenia gravis.

Duration of treatment The duration of treatment should be as short as possible (see Posology). Extension beyond these periods should not take place without revaluation of the situation. It may be useful to inform the patient when treatment is started that it will be of limited duration and to explain precisely how the dosage will be progressively decreased.

Moreover it is important that the patient should be aware of the possibility of rebound phenomena, thereby minimising anxiety over such symptoms should they occur while the medicinal product is being discontinued. There are indications that, in the case of benzodiazepines with a short duration of action, withdrawal phenomena can become manifest within the dosage interval, especially when the dosage is high.

When benzodiazepines with a long duration of action are being used (for example Zacco) it is important to warn against changing to a benzodiazepine with a short duration of action, as withdrawal symptoms may develop. Depression and personality disorders Disinhibiting effects may be manifested in various ways.

Suicide may be precipitated in patients who are depressed and aggressive behaviour towards self and others may be precipitated. Extreme caution should therefore be used in prescribing benzodiazepines in patients with personality disorders.

Before treatment of anxiety states associated with affective disorders, it must first be determined whether the patient suffers from a depressive disorder requiring adjunctive or different treatment. In patients with anxiety associated with depression, clobazam must be used only in conjunction with adequate treatments for the underlying disorder.

Use of benzodiazepine (such as clobazam) alone, can precipitate suicide in such patients. Patients with schizophrenic or other psychotic illnesses Benzodiazepines are not recommended for the primary treatment of patients with schizophrenic or other psychotic illnesses.

Psychiatric and paradoxical reactions Reactions like restlessness, agitation, irritability, aggressiveness, delusion, rages, nightmares, hallucinations, psychoses, inappropriate behaviour and other adverse behavioural effects are known to occur when using benzodiazepines.

8). They are more likely to occur in children and the elderly. Should this occur, use of the medicinal product should be discontinued. Suicidal ideation/suicide attempt/ suicide and depression Suicidal ideation and behaviour have been reported in patients treated with antiepileptic agents in several indications.

A meta-analysis of randomised placebo controlled trials of anti-epileptic drugs has also shown a small increased risk of suicidal ideation and behaviour. The mechanism of this risk is not known and the available data do not exclude the possibility of an increased risk for clobazam.

Therefore patients should be monitored for signs of suicidal ideation and behaviours and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge.

Some epidemiological studies suggest an increased incidence of suicidal ideation, suicide attempt and suicide in patients with or without depression, and treated with benzodiazepines and other hypnotics, including clobazam. 8). Drug dependence, tolerance and potential for abuse Drug addiction comprises behavioural, cognitive and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use and possible tolerance or physical dependence.

Physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, which manifests as withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug.

Addiction and dependence are related but distinct presentations and in discussing these themes, terminology that apportion blame to the individual should be avoided. For all patients, prolonged use of this product may lead to drug dependence and addiction but can occur with short-term use at recommended therapeutic doses.

, major depression). Additional support and monitoring may be necessary when prescribing for patients at risk of drug misuse. A comprehensive patient history should be taken to document concomitant medications, including over-the-counter medicines and medicines obtained on-line, and past and present medical and psychiatric conditions.

Patients may find that treatment is less effective with chronic use and express a […]

1. • In patients with any history of drug or alcohol dependence (increased risk of development of dependence). • In patients with myasthenia gravis (risk of aggravation of muscle weakness). • In patients with severe respiratory insufficiency (risk of deterioration).

• In patients with sleep apnoea syndrome (risk of deterioration). • In patients with severe hepatic insufficiencies (risk of precipitating encephalopathy). • In breast-feeding women. Benzodiazepines must not be given to children without careful assessment of the need for their use.

Zacco should not be used in children from 1 month to 2 years old unless under exceptional situations as an anticonvulsant treatment where there is a clear epilepsy indication.