Chlordiazepoxide

Concomitant intake of chlordiazepoxide with alcohol should be avoided as the enhanced sedative effect adversely affects the ability to drive or operate machinery.

Enhancement of the euphoria may also occur, leading to an increase in psychological dependence.

When used concurrently, side effects and toxicity may be more evident, particularly with hydantoins (e.g. phenytoin) or barbiturates or combinations including them. This requires extra care in adjusting dosage in the initial stages of treatment.

Enhancement of central depressive effects may occur if chlordiazepoxide is combined with drugs such as neuroleptics, antipsychotics, tranquillisers, antidepressants, hypnotics, analgesics, anaesthetics, barbiturates and sedative antihistamines. The elderly may require special supervision.

Cisapride, lofexidine, nabilone and the muscle relaxants baclofen and tizanidine enhancing the sedative effect of chlordiazepoxide.

Avoid concomitant use administration of chlordiazepoxide with sodium oxybate (enhanced effects of sodium oxybate).

Chlordiazepoxide crosses the placenta.

There is a limited amount of data from the use of chlordiazepoxide in pregnant women.

Studies in animals have shown reproductive toxicity.

There is no evidence as to drug safety in human pregnancy. Do not use during pregnancy, especially during the first and last trimesters, unless there are compelling reasons (e.g. no alternative or benefit outweighs risk).

An increased risk of congenital malformations in humans has been associated with its use, particularly in the first and second trimesters. If the product is prescribed to a woman of childbearing potential, she should be warned to contact her physician regarding stopping if she intends to become or suspects she may be pregnant.

The administration of high doses or prolonged administration of low doses of benzodiazepines during the late phase of pregnancy or during labour has been reported to produces hypothermia, irregularities in fetal heart rate, hypotonia, poor-sucking and moderate respiratory depression, in the neonate. Infants born to mothers who took benzodiazepines chronically during the later stages of pregnancy may have developed physical dependence and may be at some risk for developing withdrawal symptoms in the postnatal period.

Use during lactation should be avoided as chlordiazepoxide is found in breast milk.

Patients should be advised that sedation, amnesia, impaired concentration, dizziness, blurred vision and impaired muscular function may occur and that, if affected, they should not drive or use machines, or take part in other activities where this would put themselves or others at risk. If insufficient sleep duration occurs, the likelihood of impaired alertness may be increased. Patients should further be advised that alcohol may intensify any impairment, and should therefore be avoided during treatment. Other concurrent medication may increase effects.

This medicine can impair cognitive function and can affect a patient’s ability to drive safely. This class of medicine is in the list of drugs included in regulations under 5a of the Road Traffic Act 1988. When prescribing this medicine, patients should be told:

• The medicine is likely to affect your ability to drive.
• Do not drive until you know how the medicine affects you.
• It is an offence to drive while under the influence of this medicine.
• However, you would not be committing an offence (called ‘statutory defence’) if:
  • The medicine has been prescribed to treat a medical or dental problem and
  • You have taken it according to the instructions given by the prescriber and in the information provided with the medicine and
  • It was not affecting your ability to drive safely.

Common adverse effects include light-headedness and drowsiness, sedation, dizziness, somnolence, fatigue, balance disorder, unsteadiness and ataxia; these are usually dose related but, even after a single dose, may persist into the following day. However, these phenomena occur predominantly at the start of therapy and usually disappear with repeated administration. The elderly are particularly sensitive to the effects of central depressant drugs and may experience confusion, especially if organic brain changes are present; the dosage of chlordiazepoxide should not exceed one-half that recommended for other adults.

Evaluation of undesirable effects is based on the following frequency information: 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 (frequency cannot be estimated from available data).

Blood and lymphatic system disorders

Rare: Bone marrow depression (e.g. thrombocytopenia, leukopenia, agranulocytosis, pancytopenia)

Not known: Blood dyscrasias.

Immune system disorders

Very rare: Anaphylactic reaction, angioedema

Frequency not known: Hypersensitivity

Metabolism and nutrition disorders

Frequency not known: Increased appetite

Psychiatric disorders

Frequency not known: Amnesia, hallucinations, dependence, depression, depressed level of consciousness, restlessness, agitation, irritability, aggression, delusion, nightmares, psychotic disorder, abnormal behaviour, emotional disturbances, paradoxical drug reaction (e.g. anxiety, sleep disorders, insomnia, suicide attempt, suicidal ideation) aggressive outbursts and inappropriate behaviour.

Rare: numbed emotions

Nervous system disorders

Common: Sedation, dizziness, confusional states, unsteadiness, somnolence, ataxia, balance disorder, Rare: Headache, vertigo, reduced alertness

Frequency not known: Dysarthria, gait disturbance, extrapyramidal disorder (e.g. tremor, dyskinesia)

Eye disorders

Rare: Visual impairment including diplopia and blurred vision.

Vascular disorders

Rare: Hypotension

Respiratory, thoracic and mediastinal disorders

Frequency not known: Respiratory depression

Gastrointestinal disorders

Rare: Gastrointestinal upsets

Frequency not known: Saliva altered

Hepatobiliary disorders

Frequency not known: Jaundice, blood bilirubin increased, transaminases increased, blood alkaline phosphatase increased

Skin and subcutaneous tissue disorders

Rare: Skin reaction (e.g. rash)

Musculoskeletal and connective tissue disorders

Due to the myorelaxant effect there is a risk of falls and consequently fractures in the elderly.

Frequency not known: Muscle weakness

Renal and urinary disorders

Rare: Urinary retention, incontinence

Reproductive system and breast disorders

Rare: Libido disorders, erectile dysfunction, menstrual disorder

General disorders and administration site conditions

Common: Fatigue

Amnesia

Anterograde amnesia may occur at the therapeutic doses, with increasing risk at higher doses. This may be associated with inappropriate behaviour.

Depression

Pre-existing depression may be unmasked by benzodiazepines.

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 benzodiazepine-like agents. They may be quite severe with this product. They are more likely to occur in children and the elderly.

Dependence

Use (even therapeutic doses) may lead to the development of physical dependence: discontinuation of the therapy may result in the withdrawal or rebound phenomena. Psychological dependence may occur. Abuse of benzodiazepines has been reported.