Nitrazepam 5mg Tablets Bp
Out of date information, search another1 NAME OF THE MEDICINAL PRODUCT
Nitrazepam 5mg Tablets BP
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 5mg of Nitrazepam
3 PHARMACEUTICAL FORM
Tablets.
Uncoated white flat bevel edged tablets with breakline on one face and stamped “SPN5” on the other.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Nitrazepam tablets should be used to treat insomnia only when severe, disabling, or subjecting the individual to extreme distress.
An underlying cause for insomnia should be sought before deciding upon the use of benzodiazepines for symptomatic relief.
Benzodiazepines are not recommended for the primary treatment of psychotic illness.
4.2 Posology and method of administration
Method of Administration:
Tablets are to be taken orally with a drink of water.
Posology:
The product should be taken just before going to bed.
Adults: 5mg before retiring. This dose may, if necessary, be increased to 10mg. Paediatric Population: Not recommended for use in children under 12 years of age.
Elderly: The older patients with impaired renal and/or hepatic function will be particularly suspectible to the adverse effects of Nitrazepam. Dose should not exceed half those normally recommended for adults.
If organic brain changes are present, the dosage of Nitrazepam should not exceed 5mg in these patients.
Other Populations
In patients with chronic pulmonary insufficiency, and in patients with chronic renal or hepatic disease, dosage may need to be reduced.
Benzodiazepines are not indicated to treat patients with severe hepatic insufficiency as they may precipitate encephalopathy.
The lowest dose which can control symptoms should be used. It should not be continued beyond 4 weeks.
Long term chronic use is not recommended. 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 decreased. Moreover, it is important that the patient should be aware of the possibility of rebound phenomena (see Undesirable Effects) thereby minimising anxiety over such symptoms should they occur while the medicinal product is being discontinued. Nitrazepam therapy should not be stopped abruptly, but the dose tapered off.
Treatment should be as short as possible and should be started with the lowest recommended dose. The maximum dose should not be exceeded. Generally the duration of treatment varies from a few days to two weeks with maximum, including tapering off process of 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 patients status.
The patient should be checked regularly at the start of the treatment in order to decrease if necessary, the dose or frequency of administration to prevent overdose due to accumulation.
Patients who have taken Benzodiazepines for a long time may require a longer period during which doses are reduced. Specialist help may be appropriate. Little is known regarding the efficacy or safety of benzodiazepines in long-term use.
Dosage should be adjusted on an individual basis. Treatment should, if possible be on an intermittent basis.
4.3 Contraindications
Patients with hypersensitivity to benzodiazepines, nitrazepam or to any of the excipients listed in section 6.1
Use of this drug is also contraindicated in patients with severe respiratory insufficiency; respiratory depression; porphyria; myasthenia gravis; sleep apnoea syndrome; severe hepatic insufficiency;use in children.
Not for use in phobic or obsessional states (inadequate evidence of efficacy and safety).
Should not be used alone to treat depression, or anxiety associated with depression (suicide may be precipitated in such patients).
Should not be used for the treatment of chronic psychosis.
4.4 Special warnings and precautions for use
Tolerance
Some loss of efficacy to the hypnotic effects of Benzodiazepines may develop after repeated use for a few weeks.
Dependence
Use of Benzodiazepines may lead to the development of physical and psychologicaldependence upon these products. The risk of dependence increases with higher doses andwhen given over long periods; it is also greater in patients with a history of alcohol or drug abuse or in patients with marked personality disorders. Regular monitoring of such patients is essential.
Routine repeat prescriptions should be avoided and treatment should be withdrawn gradually. Once physical dependence has developed, abrupt termination of treatment will be accompanied by withdrawal symptoms. These may consist of headaches, muscle weakness, extreme anxiety, tension, mood changes, sleep disturbances, rebound insomnia, restlessness, confusion, irritability, depression, sweating and diarrhoea. 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 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.
Duration of Treatment
The duration of treatment should be as short as possible (see Posology) depending on the indication, but should not exceed 4 weeks for insomnia, 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.
There are indications that, in the case of benzodiazepines with a short duration of action, withdrawal phenomena can become manifest within the dosage interval, especially when the dosage is high.
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
Benzodiazepines may induce anterograde amnesia. The condition usually occurs 1 to 2 hours most often several 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 7-8 hours (see also Undesirable Effects)
Psychiatric and paradoxical reactions
Reactions like restlessness, agitation, irritability, excitement, consfusion, aggressiveness, delusion, rages, nightmares, hallucinations, psychoses, inappropriate behaviour, the uncovering of depression with suicidal tendencies and other adverse behavioural effects are known to occur when using benzodiazepines. Extreme caution should therefore be used in prescribing benzodiazepines to patients with personality disorders. Should this occur, use of the medicinal product should be discontinued.
They are more likely to occur in children and the elderly. 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.
Insomnia
An underlying cause for insomnia should be sought before deciding upon the use of benzodiazepines for symptomatic relief.
Specific patient groups
Benzodiazepines should not be given to children without careful assessment of the need to do so; the duration of treatment must be kept to a minimum. Elderly should be given a reduced dose (see Posology). A lower dose is also recommended for patients 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.
In patients with chronic pulmonary insufficiency, and in patients with chronic renal or hepatic disease, dosage may need to be reduced.
Benzodiazepines are not recommended for the primary treatment of psychotic illness.
Benzodiazepines should not be used alone to treat depression or anxiety associated with depression.
Disinhibiting effects may be manifested in various ways, suicide may be precipitated in patients who are depressed and aggressive behaviour toward self and others may be precipitated. Extreme caution should therefore be used in prescribing benzodiazepines in patients with personality disorders and in patients with a history of alcohol or drug abuse. In cases of loss or bereavement psychological adjustment may be inhibited by benzodiazepines.
4.5 Interaction with other medicinal products and other forms of interaction
Not recommended: Concomitant intake with alcohol.
The sedative effects may be enhanced when the product is used in combination with alcohol.
This affects the ability to drive or use machines.
Enhancement of the central depressive effect may occur in cases of concomitant use with antipsychotics (neuroleptics), hypnotics, anxiolytics/sedatives, antidepressant agents, narcotic analgesics, anti-epileptic products, anaesthetics and sedative antihistamines.
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.
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.
The clearance of benzodiazepines may be reduced by inhibitors of hepatic enzymes e.g. cimetidine and increased by inducers of hepatic enzymes such as rifampicin.
4.6 Fertility, Pregnancy and lactation
Pregnancy
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.
If, for compelling medical reasons, the product is administered during the late phase of pregnancy, or during labour at high doses, effects on the neonate, such as hypothermia, hypotonia and moderate respiratory depression, can be expected, due to the pharmacological action of the compound. Irregularities to foetal heart and poor sucking in the neonate have also been reported.
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 for developing withdrawal symptoms in the postnatal period.
Since benzodiazepines are found in the breast milk, benzodiazepines should not be given breast feeding mothers.
4.7 Effects on ability to drive and use machines
Sedation, amnesia, impaired concentration and impaired muscular function may adversely affect the ability to drive or to use machines. If insufficient sleep duration occurs, the likelihood of impaired alertness may be increased (see also Interactions).
4.8 Undesirable effects
Common adverse effects include drowsiness during the day, numbed emotions, reduced alertness, confusion, fatigue, headache, dizziness, muscle weakness, ataxia or double vision. 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. Other adverse reactions like gastrointestinal disturbances, changes in libido or skin reactions, vertigo have been reported occasionally. Rare adverse effects include hypotension and urinary retention, with isolated cases of blood dyscrasias and jaundice also reported.
Amnesia
Anterograde amnesia may occur using therapeutic dosages, the risk increasing at higher dosages.
Amnesiac effects may be associated with inappropriate behaviour.
Depression
Pre-existing depression may be unmasked during benzodiazepine use.
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 benzodiazepines or benzodiazepinelike agents. They may be quite severe with this product. They are more likely to occur in children and the elderly.
Dependence
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. Since the risk of withdrawal phenomena/rebound phenomena is greater after abrupt discontinuation of treatment, it is recommended that the dosage be decreased gradually. Abuse of benzodiazepines has been reported.
Reporting of side effects
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.
4.9 Overdose
When taken alone, overdose should not present a threat to life unless combined with other CNS depressants (including alcohol).
Management:
In the management of overdose with any medicinal product, it should be borne in mind that multiple agents may have been taken.
Following overdose with oral benzodiazepines, vomiting should be induced (within one hour) if the patient is conscious or gastric lavage undertaken with the airway protected if the patient is unconscious. If there is no advantage in emptying the stomach, activated charcoal should be given to reduce absorption. Special attention should be paid to respiratory and cardiovascular functions in intensive care. The value of dialysis has not been determined. Flumazenil is a specific IV antidote for use in emergency situations. Patients requiring such intervention should be monitored closely in hospital (see separate prescribing information). The benzodiazepine antagonist flumazenil is not indicated in patients with epilepsy who have been treated with benzodiazepines. Antagonism of the benzodiazepine effect in such patients may trigger seizures.
If excitation occurs, barbiturates should not be used.
Overdose of benzodiazepines is usually manifested by degrees of central nervous system depression ranging from drowsiness to coma. In mild cases, symptoms include drowsiness, mental confusion and lethargy, in more serious cases, symptoms may include ataxia, hypotonia, hypotension, respiratory depression, rarely coma and very rarely death.
PHARMACOLOGICAL PROPERTIES
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5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Hypnotics and Sedatives, Benzodiazepine derivatives, ATC Code: N05CD02
Nitrazepam is a benzodiazepine compound with sedative properties. It acts in 30 to 60 minutes to produce sleep lasting 6 to 8 hours.
5.2 Pharmacokinetic properties
Absorption:
Nitrazepam is well absorbed with peak blood levels being achieved within two hours after administration. Two hours after administration, the concentration of nitrazepam in the cerebrospinal fluid is about 8% and after 36 hours approximately 16% of the concentration in the plasma. The cerebrospinal fluid concentration thus corresponds to the non-protein-bound fraction of active ingredient in the plasma. Steady-state levels are achieved within 5 days.
Distribution:
In younger persons the volume of distribution is 2L/kg, in elderly patients the volume of distribution is greater and the mean elimination half-life rises to 40 hours.
Biotransformation:
Nitrazepam undergoes biotransformation to a number of metabolites, none of which possess significant clinical activity.
Elimination:
About 5% of the metabolites are excreted unchanged in the urine together with less than 10% each of the 7-amino- and 7-acetylamino- metabolites in the first 48 hours. In younger persons the volume of distribution is 2L/kg, in elderly patients the volume of distribution is greater and the mean elimination half-life rises to 40 hours.
The half-life is on average 24 hours.
Pharmacokinetic/Pharmacodynamic relationship:
No clear correlation has been demonstrated between the blood levels of nitrazepam and its clinical effects.
After oral administration about 50 to 70 per cent of a dose is excreted in the urine in 120 hours and up to 20 per cent is eliminated in the faeces. Nitrazepam has been detected in breast milk.
5.3
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6.1
6.2
6.3
6.4
6.5
Preclinical safety data
There is no-pre-clinical data of relevance to a prescriber, which is additional to that already included in other sections of the Summary of Product Characteristics
Nature and contents of container
The product is available in packs of 50, 500, and 1000 tablets in Securitainers.
The container is made up of High Density Polypropylene body and Low Density Polyethylene cap.
6.6 Special precautions for disposal
No special instructions necessary.
7 MARKETING AUTHORISATION HOLDER
Bristol Laboratories Ltd.
Unit 3, Canalside,
Northbridge Road Berkhamsted, Hertfordshire,
HP4 1EG
8 MARKETING AUTHORISATION NUMBER(S)
PL 17907/0355
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
15/11/2012
10 DATE OF REVISION OF THE TEXT
03/06/2014