DIAZEPAM

Posology Sensitivity to diazepam varies with age. 25 mg/kg body weight A maximum dose of 30mg diazepam is recommended, unless adequate medical supervision and monitoring are available. 5 mg/kg body weight

During the first week of administration or when high doses are used they may have a sedative effect and cause some degree of drowsiness. In such cases there is an advantage in administering half the total daily intake at night, the remainder being given in divided doses during the day.

The elderly and debilitated are particularly sensitive to the effects of central depressant drugs and may experience confusion, especially if organic brain changes are present; the dosage of diazepam should not exceed one-half that recommended for other adults.

Increased salivary and bronchial secretion has been reported, in particular in children. Amnesia Anterograde amnesia may occur using therapeutic dosages, the risk increasing at higher dosages. 4). 4). Abuse of benzodiazepines has been reported.

The frequencies of adverse events are ranked according to the following:

Very common (≥1/10) Common (≥1/100 to <1/10) Uncommon (≥1/1,000 to <1/100) Rare (≥1/10,000 to <1/1,000) Very rare (<1/10,000) Not known (cannot be estimated from the available data). System organ class Frequency Undesirable effects Blood and lymphatic system disorders Very rare Leukopenia Rare Blood dyscrasias Immune system disorders Very rare Anaphylaxis.

Psychiatric disorders Common Confusion. 4). Abuse of benzodiazepines Nervous system disorders Very common Drowsiness. Common Sedation, unsteadiness, ataxia (these effects are dose-related and may persist into the following day even after a single dose), impaired motor ability, tremor.

c Concentration difficulties, balance disorders, dizziness, headache, slurred speech. Rare Unconsciousness, insomnia, dysarthria, light headedness, vertigo, dystonic effects Eye disorders Not known Reversible disorders of vision: blurred vision, diplopia, nystagmus.

Cardiac disorders Rare Bradycardia, heart failure including cardiac arrest. Vascular disorders Rare Hypotension, syncope. Respiratory, thoracic and mediastinal disorders Uncommon Respiratory depression. Rare Respiratory arrest, increased bronchial secretion.

Not known Apnoea Gastrointestinal disorders Uncommon Gastrointestinal disorders (nausea, vomiting, constipation, diarrhoea), increased salivary secretion. Rare Dry mouth, increased appetite. Hepatobiliary disorders Rare Jaundice, changes of hepatic parameters (elevation of ALT, AST, alkaline phosphatase).

Skin and subcutaneous tissue disorders Uncommon Allergic skin reactions (itching, erythema, rash). Musculoskeletal and connective tissue disorders Uncommon Myasthenia. Renal and urinary disorders Rare Urinary retention, incontinence.

Reproductive system and breast disorders Rare Gynaecomastia, impotence, increased or reduced libido or libido fluctuations. d Investigations Very rare Elevation of transaminases. a Known to occur when using benzodiazepines or benzodiazepine-like agents.

These reactions may be quite severe. They are more likely to occur in children and the elderly. 4). b Pre-existing depression may be unmasked during benzodiazepine use. c May occur using therapeutic dosages, the risk increasing at higher dosages.

4). d The likelihood and degree of severity of withdrawal symptoms is dependent on the duration of treatment, dose level and degree of dependency. 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.

Tolerance Some loss of efficacy to the hypnotic effects of diazepam may develop after repeated use for a few weeks. Dependence Use of benzodiazepines may lead to development of physical and psychic dependence upon these products. The risk of dependence increases with dose and duration of treatment; it is also greater in patients with a history of alcohol or drug abuse or in patients with marked personality disorders.

Regular monitoring in such patients is essential, routine repeat prescriptions should be avoided and treatment should be withdrawn gradually. Withdrawal Once physical dependence has developed, abrupt termination of treatment will be accompanied by withdrawal symptoms.

These may consist of headaches, muscle pain, extreme anxiety, tension, restlessness, confusion and irritability. In severe cases the following symptoms may occur: derealisation, depersonalisation, hyperacusis, numbness and tingling of the extremities, hypersensitivity to light, noise and physical contact, hallucinations or epileptic seizures.

Sudden discontinuation of treatment with diazepam in patients with epilepsy or other patients who have had a history of seizures can result in convulsions or epileptic status. Convulsions can also be seen following sudden discontinuation in individuals with alcohol or drug abuse.

Discontinuation should be gradual in order to minimise the risk of withdrawal symptoms. Rebound insomnia and anxiety: a transient syndrome whereby the symptoms that led to treatment with a benzodiazepine recur in an enhanced form may occur on withdrawal of treatment.

It may be accompanied by other reactions including mood changes, anxiety or sleep disturbances and restlessness. Since the risk of withdrawal phenomena/rebound phenomena is greater after abrupt discontinuation of treatment, it is recommended that the dosage is decreased gradually.

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

Should this occur, use of the medicinal product should be discontinued. They are more likely to occur in children and the elderly. 2) depending on the indication. The patient must be evaluated after a period of no more than 4 weeks and then regularly thereafter in order to assess the need for continued treatment, especially if the patient is free of symptoms.

In general, treatment must not last any longer than 8-12 weeks, including the tapering off process. Extension beyond these periods should not take place without re- evaluation 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 it is important to warn against changing to a benzodiazepine with a short duration of action, as withdrawal symptoms may develop. Amnesia Diazepam may induce anterograde amnesia.

The condition occurs most often several hours after administering the product and therefore to reduce the risk patients should ensure that they will be able to have uninterrupted sleep of 7-8 hours. Anterograde amnesia may occur using therapeutic doses, the risk increases with higher doses.

Specific patient groups Paediatric population Benzodiazepines should not be given to children without careful assessment of the need to do so; the duration of treatment must be kept to a minimum. Safety and effectiveness of diazepam in paediatric patients below the age of 6 months have not been established.

Elderly should be given a reduced dose (see posology). Due to the myorelaxant effect there is a risk of falls and consequently hip fractures in the elderly. A lower dose is also recommended for patients with chronic respiratory insufficiency due to the risk of respiratory depression.

Benzodiazepines are not indicated to treat patients with severe hepatic insufficiency as they may precipitate encephalopathy. In patients with chronic hepatic disease dosage may need to be reduced. The usual precautions in treating patients with impaired renal function should be observed.

In renal failure, the half-life of diazepam is not clinically significantly changed, and dose adjustment is usually not necessary. Benzodiazepines are not recommended for the primary treatment of psychotic illness. Benzodiazepines should not be used alone to treat depression or anxiety associated with depression (suicide may be precipitated in such patients).

In common with other benzodiazepines, the use of diazepam may be associated with amnesia and should not be used in cases of loss or bereavement as psychological adjustment may be inhibited. This medicine should not be used in phobic or obsessional states, as there is insufficient evidence of efficacy and safety in such conditions.

Benzodiazepines should be used with extreme caution in patients with a history of alcohol or drug abuse. Potentially suicidal individuals should not have access to large amounts of diazepam due to the risk of overdosing.

Risk from concomitant use of opioids:

Concomitant use of diazepam and opioids may result in sedation, respiratory depression, coma and death. Because of these risks, concomitant prescribing of sedative medicines such as benzodiazepines or related drugs such as diazepam with opioids […]

1 • Phobic or obsessional states; chronic psychosis, hyperkinesis (paradoxical reactions may occur) • Acute pulmonary insufficiency; respiratory depression, acute or chronic severe respiratory insufficiency (ventilatory failure may be exacerbated) • Myasthenia gravis (condition may be exacerbated) • Sleep apnoea (condition may be exacerbated) • Severe hepatic insufficiency (elimination half-life of diazepam may be prolonged) • Acute porphyria • Diazepam should not be used as monotherapy in patients with depression or those with anxiety and depression as suicide may be precipitated in such patients.

6). 6).