Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2019 Publisher: Mylan Products Ltd, Station Close, Potters Bar, Hertfordshire, EN6 1TL, United Kingdom
Librium is contraindicated for patients with:
Some loss of efficacy to the hypnotic effects of benzodiazepines may develop after repeated use for a few weeks.
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 Routine repeat prescriptions should be avoided and treatment should be withdrawn gradually.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.
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.
The duration of treatment should be as short as possible (see 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 may occur. 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 to 8 hours (see Undesirable effects).
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.
Concomitant use of Librium 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. If a decision is made to prescribe Librium concomitantly with opioids, the lowest effective dose should be used, and the duration of treatment should be as short as possible (see also general dose recommendation in section 4.2).
The patients should be followed closely for signs and symptoms of respiratory depression and sedation. In this respect, it is strongly recommended to inform patients and their caregivers (where applicable) to be aware of these symptoms (see section 4.5).
Elderly patients should be given a reduced dose (see section 4.2). 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.
Librium 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.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take Librium.
If Librium 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.
Librium 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 tranquilisers may increase the effects of relaxing the muscles – especially elderly patients receiving higher doses of Librium should be well monitored (higher risk of falling).
When Librium is used in conjunction with anti-epileptic drugs, side-effects and toxicity may be more evident, particularly with hydantoins or barbiturates or combinations including them. This requires extra care 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. The dosage and duration of concomitant use should be limited (see section 4.4).
Known inhibitors of hepatic enzymes, eg cimetidine, omeprazole, macrolide antibiotics (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. Known inducers of hepatic enzymes, e.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.
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 (see section 5.3).
Librium should not be used during pregnancy, especially during the first and last trimester unless the clinical condition of the woman requires treatment with chlordiazepoxide.
If the product is is prescribed to a woman of childbearing potential, she should be warned to contact her physician to discuss discontinuation of Librium if she intends to become or suspects that she is pregnant.
The administration of high doses or prolonged administration of low doses of benzodiazepines in the last trimester of pregnancy or during labour have been reported to produce irregularities in the foetal heart rate, moderate respiratory depression, hypotonia, poor sucking and hypothermia in the neonate. Moreover, infants born to mothers who chronically took benzodiazepines 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.
Chlordiazepoxide may appear in breast milk. If possible the use of Librium should be avoided during breast-feeding.
Patients should be advised that, like all medicaments of this type, Librium may modify patients' performance at skilled tasks. Sedation, amnesia, impaired concentration and impaired muscle function may adversely affect the ability to drive or use machinery. 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.
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:
Common adverse effects include drowsiness, sedation, dizziness, somnolence, fatigue, balance disorder, unsteadiness and ataxia; these are dose-related and may persist into the following day even after a single dose. 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 centrally-depressant drugs and may experience confusion, especially if organic brain changes are present; and the dosage of Librium 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).
Rare: Bone marrow depression (e.g. thrombocytopenia, leukopenia, agranulocytosis, pancytopenia)
Very rare: Anaphylactic reaction, angioedema
Frequency not known: Hypersensitivity
Frequency not known: Increased appetite
Frequency not known: Amnesia, hallucinations, dependence, depression, restlessness, agitation, irritability, depressed level of consciousness, aggression, delusion, nightmares, psychotic disorder, abnormal behaviour, emotional disturbances, paradoxical drug reaction (e.g. anxiety, sleep disorders, insomnia, suicide attempt, suicidal ideation)
Common: Sedation, dizziness, unsteadiness, somnolence, ataxia, balance disorder, confusional states
Rare: Headache, vertigo
Frequency not known: Dysarthria, gait disturbance, extrapyramidal disorder (e.g. tremor, dyskinesia)
Rare: Visual impairment including diplopia
Rare: Hypotension
Frequency not known: Respiratory depression
Rare: Gastrointestinal upsets
Frequency not known: Jaundice, blood bilirubin increased, transaminases increased, blood alkaline phosphatase increased
Rare: Skin reaction (e.g. rash)
Due to the myorelaxant effect there is a risk of falls and consequently fractures in the elderly
Frequency not known: Muscle weakness
Rare: Urinary retention, incontinence
Rare: Libido disorders, erectile dysfunction, menstrual disorder
Common: Fatigue
Frequency not known: Changes in salivation
Anterograde amnesia may occur at the therapeutic doses, with increasing risk at higher doses. This may be associated with inappropriate behavior (see section 4.4)
Pre-existing depression may be unmasked by benzodiazepines.
Reactions like restlessness, agitation, irritability, aggressiveness, delusion, rages, nightmares, hallucinations, psychoses, inappropriate behavior 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.
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
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. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
Not applicable.
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