Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2020 Publisher: Mylan Products Ltd, Station Close, Potters Bar, Hertfordshire, EN6 1TL, United Kingdom
Dalmane is contraindicated in:
Dalmane should not be used alone to treat depression or anxiety associated with depression, since suicide may be precipitated in such patients.
Benzodiazepines should be used in extreme caution in patients with a history of alcohol or drug abuse.
Benzodiazepines are not recommended for the primary treatment of psychotic illness.
In cases of loss or bereavement, psychological adjustment may be inhibited by benzodiazepines.
Dalmane is not indicated in patients with spinal and cerebellar ataxia.
Elderly patients should be given a reduced dose (see section 4.2 Posology). Due to the myorelaxant effect there is a risk of falls and consequently fractures in the elderly.
A lower dose is also recommended for patient 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 and reduced doses should be given to patients with renal or hepatic disease.
Dalmane should not be given in acute intoxication with alcohol, sedative agents, hypnotic agents, analgesics or psychotropic agents (neuroleptic agents, antidepressants, lithium).
Dalmane is not indicated for children. If necessary for compelling reasons, benzodiazepines should be prescribed for children and adolescents after careful appraisal of the risk-benefit ratio only.
Concomitant use of Dalmane 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 Dalmane with opioids should be reserved for patients for whom alternative treatment options are not possible. If a decision is made to prescribe Dalmane 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).
Some loss of efficacy to the hypnotic effects of benzodiazepines may develop after repeated use for a few weeks.
Use of benzodiazepines may lead to the development of physical and psychological dependence. The dependence potential of the benzodiazepines is low, particularly when limited to short-term use, but this 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 depression, nervousness, extreme anxiety, tension, restlessness, confusion, mood changes, rebound insomnia, irritability, sweating, diarrhoea, headaches and muscle pain 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 and hallucinations or epileptic seizures. In rare instances, withdrawal following excessive dosages may produce confusional states, psychotic manifestations and convulsions. Abuse of the 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.
Abnormal psychological reactions to benzodiazepines have been reported. Rare behavioural effects include paradoxical aggressive outbursts, excitement, confusion, restlessness, agitation, irritability, delusion, rages, nightmares, hallucinations, psychoses, inappropriate behaviour and the uncovering of depression with suicidal tendencies. Extreme caution should therefore be used in prescribing benzodiazepines to patients with personality disorders. If any of these reactions occur, use of the drug should be discontinued. These reactions may be quite severe and are more likely to occur in children and the elderly.
Benzodiazepines may induce anterograde amnesia. The condition usually occurs 1-2 hours after ingesting the product and may last up to several hours. Therefore, to reduce the risk, patients should ensure that they will be able to have an uninterrupted sleep of 7 to 8 hours.
If the patient is awoken during the period of maximum drug activity, recall may be impaired.
The duration of treatment should be as short as possible (see section 4.2 Posology) depending on the indication, but should not exceed 4 weeks, including 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.
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.
Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.
The benzodiazepines, including flurazepam, produce additive CNS depressant effects when co-administered with other CNS drugs such as barbiturates, antipsychotics, sedative/hypnotics, anxiolytics, antidepressants, narcotic analgesics, sedative antihistamines, anticonvulsants, anaesthetics, antihypertensives and beta (receptor) blockers.
Administration of theophylline or aminophylline may reduce the sedative effects of benzodiazepines. In case of narcotic analgesics enhancement of the euphoria may also occur leading to an increase in psychological dependence.
The elderly require special supervision.
The concomitant use of sedative medicines such as benzodiazepines or related drugs such as Dalmane 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).
When Dalmane 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.
Concomitant intake with muscle relaxants may increase the relaxant effect of flurazepam.
Known inhibitors of hepatic enzymes, eg cimetidine, omeprazole and disulfuram, have been shown to reduce the clearance of benzodiazepines and may potentiate their action and known inducers of hepatic enzymes, eg rifampicin, may increase the clearance of benzodiazepines.
Concomitant intake with alcohol should be avoided. The sedative effect of Dalmane may be modified and enhanced in an unpredictable way if the product is used in combination with alcohol. This adversely affects the ability to drive or use machines.
There is no evidence as to drug safety in human pregnancy, nor is there evidence from animal work that it is free from hazard. Do not use during pregnancy, especially during the first and last trimesters, unless there are compelling reasons.
If the product is prescribed to a woman of childbearing potential, she should be warned to contact her physician regarding discontinuance of the product if she intends to become or suspects that she is pregnant.
Administration of benzodiazepines in the last trimester of pregnancy or during labour has been reported to produce irregularities in the foetal heart rate, and hypotonia, poor sucking and hypothermia and moderate respiratory depression in the neonate.
Moreover, infants born to mothers who took benzodiazepines chronically during the latter stages of pregnancy may have developed physical dependence and may be at some risk of developing withdrawal symptoms in the postnatal period.
There is insufficient information on the excretion of flurazepam and/or metabolites into human milk. However, in common with other benzodiazepines, its passage into breast milk might be expected. The use of Dalmane in mothers who are breast-feeding is not recommended.
Patients should be advised that, like all medicaments of this type, Dalmane might modify patients' performance at skilled tasks (driving, operating machinery, etc) to a varying degree depending upon dosage, administration, and sleep pattern and individual susceptibility. 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 somnolence during the day, emotional poverty, reduced alertness, confusional state, fatigue, headache, dizziness, muscle weakness, ataxia and diplopia. These phenomena are dose-related and are likely to be uncommon with the recommended dosage; they occur predominantly at the start of therapy and usually disappear with repeated administration or after dose adjustment. The elderly are particularly sensitive to the effects of centrally depressant drugs.
Within the system organ classes, adverse reactions are listed under headings of frequency (number of patients expected to experience the reaction), using the following categories: 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), Frequency not known (cannot be estimated from the available data).
Frequency not known: blood disorders (e.g. thrombocytopenia, leukopenia, agranulocytosis, pancytopenia).
Rare: Hypersensitivity (e.g. angioedema).
Uncommon: Emotional poverty.
Frequency not known: Confusional state, hallucinations, dependence, withdrawal syndrome, rebound effect, depression, paradoxical drug reactions (e.g. anxiety, sleep disorders, insomnia, nightmares, restlessness, agitation, irritability, aggression, delusion, psychotic disorder, abnormal behaviour, emotional disturbances, suicide attempt, suicidal ideation).
Common: Somnolence, reduced alertness, ataxia, dizziness, headache, dysgeusia.
Frequency not known: Extrapyrimidal disorder, anterograde amnesia.
Rare: Visual impairment (e.g. diplopia).
Rare: Vertigo.
Rare: Hypotension.
Rare: Respiratory depression (particularly at night).
Rare: Abdominal discomfort, nausea.
Very rare: Jaundice, hepatic enzyme increase.
Rare: Skin reactions (e.g. rash).
Common: Muscle weakness. Due to the myorelaxant effect there is a risk of falls and consequently fractures in the elderly.
Rare: Urinary retention.
Rare: Libido disorder.
Uncommon: Fatigue.
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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