Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2020 Publisher: Accord-UK Ltd (Trading style: Accord), Whiddon Valley, Barnstaple, Devon, EX32 8NS
In patients with chronic pulmonary insufficiency, and in patients with chronic renal or hepatic disease, dosage may need to be reduced. Benzodiazepines are contraindicated in patients with severe hepatic insufficiency.
Nitrazepam tablets 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 with extreme caution in patients with a history of alcohol or drug abuse. Benzodiazepines are not recommended for the primary treatment of psychotic illness.
Concomitant use of nitrazepam 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 nitrazepam with opioids should be reserved for patients for whom alternative treatment options are not possible. If a decision is made to prescribe nitrazepam 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).
If the patient is awoken during the period of maximum drug activity, recall may be impaired.
In cases of loss or bereavement, psychological adjustment may be inhibited by benzodiazepines.
Use of benzodiazepines may lead to the development of physical and psychological dependence upon these products. The risk of 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monitoring in such patients is essential; routine repeat prescriptions should be avoided and treatment should be withdrawn gradually.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 depression, headaches, muscle weakness, nervousness, extreme anxiety, tension, restlessness, confusion, mood changes, 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.
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.
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 and psychotic manifestations and convulsions. Abuse of the benzodiazepines has been reported.
Some loss of efficacy to the hypnotic effects of short-acting benzodiazepines may develop after repeated use for a few weeks.
Tolerance to their effects develops within 3-14 days of continuous use and hence treatment regimes should be kept to a minimum and repeat prescriptions avoided. Limits of tolerance in patients with organic cerebral changes (particularly resulting from arteriosclerosis) or cardiorespiratory insufficiency may be very wide; care must be taken in adapting the dosage with such patients.
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 the elderly.
Benzodiazepines may induce anterograde amnesia. The condition usually occurs 1 to 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.
Due to the myorelaxant effect there is a risk of falls and consequently of hip fractures particularly for elderly patients when they get up at night.
Hypoalbuminaemia (may predispose patient to higher incidence of sedative side effects).
Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Enhancement of the central depressive effect may occur if benzodiazepines are combined with centrally-acting drugs such as neuroleptics, tranquillisers, antidepressants, hypnotics, analgesics and anaesthetics, anti-epileptics, sedative antihistamines, lofexidine and nabilone. In the 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 nitrazepam 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 nitrazepam 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.
Known inhibitors of hepatic enzymes, particularly cythochrome P450 have been shown to reduce the clearance of benzodiazepines and may potentiate their action and known inducers of hepatic enzymes, e.g. rifampicin, may increase the clearance of benzodiazepines.
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.
Enhances sedative effect with moxonidine.
Baclofen and tizanidine (enhanced sedative effect).
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, hypothermia and moderate respiratory depression in the neonate.
Infants born to mothers who took benzodiazepines chronically in the latter stages of pregnancy may have developed physical dependence and may be at some risk for developing withdrawal symptoms in the postnatal period.
Since benzodiazepines are found in the breast milk, the use of nitrazepam in mothers who are breast-feeding should be avoided.
Patients should be advised that, like all medicaments of this type, Nitrazepam Tablets 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 during the day, numbed emotions, reduced alertness, confusion, fatigue, headache, dizziness, muscle weakness, ataxia and double vision. These phenomena are dose related and occur predominantly at the start of therapy, they usually disappear with repeated administration. The elderly are particularly sensitive to the effects of centrally-depressant drugs.
The following undesirable effects have been divided into 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, not known (cannot be estimated from the available data).
Rare: Blood dyscrasias
Very rare: Hypersensitivity reactions (anaphylaxia and angiooedema)
Uncommon: Sleeping disorders, including insomnia.
Rare: Psychiatric and paradoxical reactions4, Muscular cramps, libido fluctuations
Not known: Dependence and abuse of benzo-diazepines, amnesia2, depression3, withdrawal symptoms1
Common: Dizziness, ataxia, drowsiness
Uncommon: Tremor
Not known: Dysarthria
Rare: Visual disturbances
Rare: Vertigo
Rare: Hypotension
Rare: Respiratory depression
Rare: Nausea, gastrointestinal upsets
Rare: Jaundice
Rare: Rash and other allergic skin reactionsStevens-Johnson syndrome
Rare: Urinary retention
Uncommon: Muscular weakness
1 Use (even at therapeutic doses) may lead to the development of physical and psychological dependence: discontinuation of the therapy may result in withdrawal or rebound phenomena, a transient syndrome whereby the symptoms that led to treatment with benzodiazepine or benzodiazepine-like agent recur in an enhanced form. It may be accompanied by other reactions including mood changes, anxiety and restlessness. Since the risk of withdrawal phenomena/rebound phenomena is greater after abrupt discontinuation of treatment, it is recommended that the dosage be decreased gradually.
2 Anterograde amnesia may occur during the use of therapeutic doses since the risk is increased at higher doses. Amnesia may be combined with behavioural problems.
3 Pre-existing depression may be revealed during the use of benzodiazepins.
4 Reactions such as restlessness, excitation, irritability, aggressiveness, delusions, rage, nightmares, hallucinations, psychoses, inappropriate behaviour and other behavioural side effects may occur during benzodiazepine treatment. They can be very serious with this product. These side effects are observed more frequently in children and elderly patients.
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; website: 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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