CHLORDIAZEPOXIDE

Posology:

Anxiety states: Usual dose 10 mg, 2-3 times a day and up to 30 mg daily in divided doses. For severe symptoms 20 mg, 2-4 times a day. Maximum dose up to 100 mg daily in divided doses. Adjusted on an individual basis. Generally, duration of treatment should not be more than 4 weeks, including a tapering-off process.

Insomnia associated with anxiety: 10 to 30 mg before retiring. Generally, duration of treatment varies from a few days to two weeks, with a maximum including a tapering-off process of four weeks. Symptomatic relief of acute alcohol withdrawal: 25 to 100 mg and repeated if necessary in 2 to 4 hours.

Muscle spasm of varied aetiology: 10 to 30 mg daily in divided doses. Paediatric patients Chlordiazepoxide is not for paediatric use. Special patient groups Elderly or debilitated patients, patients with organic brain damage, respiratory impairment and/or hepatic or renal dysfunction should normally not exceed half of the doses normally recommended.

The lowest dose which can control symptoms should be used. The dosage and duration of treatment should be determined on an individual basis dependent by the patient’s response and severity of the disorder. Given that chlordiazepoxide is a long- acting benzodiazepine, the patient should be monitored regularly at the start of the treatment to decrease, if necessary, the dose or frequency of administration to prevent overdose due to accumulation.

Treatment should be as short as possible. The patient should be reassessed regularly and the need for continued treatment should be evaluated, especially in case the patient is symptom free. Treatment should not be continued at the full dose beyond four 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. Little is known regarding the efficacy or safety of benzodiazepines in long- term use.

Long-term chronic use is not recommended. Treatment should always be tapered off gradually. Patients who have taken benzodiazepines for a prolonged time may require a longer period during which doses are reduced. Specialist help may be appropriate.

Method of administration Chlordiazepoxide capsules are for oral administration and must be taken with water and not be chewed.

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

Should these effects occur, use of the medicinal product should be discontinued. They are more likely to occur in children and the elderly.

Risk from concomitant use of opioids:

Concomitant use of chlordiazepoxide and opioids may result in sedation, respiratory depression, coma and death. Because of these risks, concomitant prescribing of sedative medicines such as benzodiazepines with opioids should be reserved for patients for whom alternative treatment options are not possible.

2). The patients should be followed closely for signs and symptoms of respiratory depression and sedation. 5). 2). A lower dose is also recommended for patients with chronic respiratory insufficiency due to the risk of respiratory depression.

Benzodiazepines are contraindicated to treat patients with severe hepatic insufficiency as they may precipitate encephalopathy and reduced doses should be given to patients with renal or hepatic disease. Benzodiazepines are not recommended for the primary treatment of psychotic illness, phobia or obsessive-compulsive diseases.

Chlordiazepoxide should not be used alone to treat depression or anxiety associated with depression, since it may uncover depression with suicidal tendencies. Extreme caution should be used in prescribing benzodiazepines to patients with personality disorders.

Benzodiazepines should be used with extreme caution in patients with a history of alcohol or drug abuse. In cases of loss or bereavement, psychological adjustment may be inhibited by benzodiazepines. Due to the myorelaxant effect there is a risk of falls and consequently fractures in the elderly.

This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine. 5 Interaction with other medicinal products and other forms of interaction If chlordiazepoxide is combined with centrally-acting drugs such as neuroleptics, tranquilisers, antidepressants, hypnotics, analgesics, anaesthetics, and sedative antihistamines the central depressive effects are likely to be intensified.

In the case of narcotic analgesics, enhancement of the euphoria may also occur leading to an increase in psychic dependence. The elderly require special supervision. Chlordiazepoxide in combination with 4-hydroxybutanoic acid (sodium oxybate) may cause an increased respiratory depression.

Concomitant intake with alcohol should be avoided. The sedative effect may be enhanced when the product is used in combination with alcohol. This adversely affects the ability to drive or use machines. Concurrent treatment with traquilisers may increase the effects of relaxing the muscles – especially elderly patients receiving higher doses ofChlordiazepoxide should be well monitored (higher risk of falling).

When chlordiazepoxide is used in conjunction with antiepileptic drugs, side effects and toxicity may be more evident, particularly with hydantoins or barbiturates or combinations including them. This requires extra caution in adjusting dosage in the initial stages of treatment.

The concomitant use of sedative medicines such as benzodiazepines with opioids increases the risk of sedation, respiratory depression, coma and death because of additive CNS depressant effect. 4). g. cimetidine, omeprazole, macrolide antiobiotics (erythromycin) and disulfiram have been shown to reduce the clearance of benzodiazepines and may potentiate their action.

The same applies to the use of contraceptive agents. g. rifampicin, may increase the clearance of benzodiazepines. In patients receiving long-term treatment with other medicines (such as centrally acting antihypertensive agents, beta receptor blockers, anticoagulant agents and cardiac glycosides), nature and extent of interactions cannot safely be foreseen.

Benzodiazepines possibly antagonise the effect of levodopa. Sedative effects are possibly increased when benzodiazepines are given with moxonidine. Benzodiazepines enhance effects of sodium oxybate. Concomitant use should be avoided. Effects of benzodiazepines are possibly reduced by theophylline.

3), women of childbearing potential should use effective contraceptive measures while being treated with Chlordiazepoxide and for 7 months following completion of treatment. If the patient suspects to be pregnant or intends to become pregnant, she should be warned to contact her physician to discuss discontinuation of Chlordiazepoxide.

Men are recommended to use effective contraceptive measures and to not father a child while receiving Chlordiazepoxide and for 4 months following completion of treatment.

Pregnancy:

Chlordiazepoxide crosses the placenta. There islimited amount of data from the use of chlordiazepoxide in pregnant women. 3). Chlordiazepoxide should not be used during pregnancy, especially during the first and […]

Tolerance Some loss of efficacy to the hypnotic effects of benzodiazepines may develop after repeated use for a few weeks. Dependence and withdrawal The dependent potential of the benzodiazepines is low, particularly when limited to short-term use.

Risk for physical and psychological dependence increases when high doses are used, especially when given over long periods. This is particularly so in patients with a history of alcoholism 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. Symptoms such as headaches, muscle pain, extreme anxiety, restlessness, confusion, depression, nervousness, rebound insomnia, irritability, sweating and diarrhoea have been reported following abrupt cessation of treatment in patients receiving even normal therapeutic doses for short periods of time.

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, psychotic manifestations or epileptic seizures.

Abuse of benzodiazepines has been reported. Rebound insomnia and anxiety This is 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. 2 posology) depending on the indication, but should not exceed 4 weeks, including tapering-off process.

Routine repeat prescriptions should be avoided. 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.

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 Amnesia may occur. Benzodiazepines may induce anterograde amnesia.

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

Should these effects occur, use of the medicinal product should be discontinued. They are more likely to occur in children and the elderly.

Risk from concomitant use of opioids:

Concomitant use of chlordiazepoxide and opioids may result in sedation, respiratory depression, coma and death. Because of these risks, concomitant prescribing of sedative medicines such as benzodiazepines with opioids should be reserved for patients for whom alternative treatment options are not possible.

2). The patients should be followed closely for signs and symptoms of respiratory depression and sedation. 5). 2). A lower dose is also recommended for patients with chronic respiratory insufficiency due to the risk of respiratory depression.

Benzodiazepines are contraindicated to treat patients with severe hepatic insufficiency as they may precipitate encephalopathy and reduced doses should be given to patients with renal or hepatic disease. Benzodiazepines are not recommended for the primary treatment of psychotic illness, phobia or obsessive-compulsive diseases.

Chlordiazepoxide should not be used alone to treat depression or anxiety associated with depression, since it may uncover depression with suicidal tendencies. Extreme caution should be used in prescribing benzodiazepines to patients with personality disorders.

Benzodiazepines should be used with extreme caution in patients with a history of alcohol or drug abuse. In cases of loss or bereavement, psychological adjustment may be inhibited by benzodiazepines. Due to the myorelaxant effect there is a risk of falls and consequently fractures in the elderly.

This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

1 Myasthenia gravis Severe pulmonary insufficiency Respiratory depression Severe hepatic insufficiency Sleep apnoea syndrome Phobic or obsessional states Chronic psychosis Spinal or cerebral ataxia