Nitrazepam Tablets Bp 5mg
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Nitrazepam Tablets BP 5mg
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Nitrazepam, 5mg
3. PHARMACEUTICAL FORM
Tablet
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Nitrazepam tablets are indicated for oral administration in the short term treatment of insomnia (only when it is severe, disabling, or subjecting the individual to extreme distress).
4.2. Posology and method of administration
Treatment should be as short as possible. Generally the duration of treatment should vary from a few days to two weeks with a maximum, including the 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 patient’s status. The product should be taken on retiring or up to 30 minutes before going to bed.
Dose
Adults:
5mg before retiring. This dose may, if necessary, be increased
to 10mg.
Elderly and Dose should not exceed half those normally recommended.
debilitated patients:
Treatment should be started with the lowest recommended dose. The maximum dose should not be exceeded. Patients with impaired liver function should have a reduced dose.
4.3. Contra-indications
Nitrazepam should not be given to patients with a previous history of sensitivity to benzodiazepines or patients with severe respiratory insufficiency.
Nitrazepam is not for use in patients with myasthenia gravis or patients who suffer from sleep apnoea syndrome.
Nitrazepam is not to be used in children or in patients with severe hepatic insufficiency
4.4. Special warnings and precautions for use
Extreme caution should be exercised when using Nitrazepam in patients with a history of alcohol or drug abuse.
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 (suicide may be precipitated in such patients).
As with all benzodiazepines doctors should be aware that long term use may lead to physical and psychological dependence and withdrawal symptoms in certain patients.
All patients taking Nitrazepam should be carefully monitored and routine repeat prescriptions should be avoided.
An underlying cause for insomnia should be sought before deciding upon the use of benzodiazepines for symptomatic relief.
Amnesia may occur and in cases of loss or bereavement psychological adjustment may be inhibited by benzodiazepines. Anterograde amnesia 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 7-8 hours (see also ‘undesirable effects’). Disinhibiting effects may be manifested in various ways. The use of benzodiazepines may release suicidal tendencies in depressed patients. Other rarely reported behavioural effects of benzodiazepines include restlessness, agitation, irritability, delusion, nightmares, psychoses, paradoxical aggressive outbursts, excitement, hallucinations and confusion. Should this occur, use of the product should be discontinued. These reactions are most likely to occur in the elderly.
Treatment in all patients should be withdrawn gradually with careful monitoring and reassessment to minimise possible withdrawal symptoms. Patients who have taken benzodiazepines for a long time may require a longer period during which doses are reduced.
When used at the appropriate recommended dose for short term treatment of insomnia the dependence potential of Nitrazepam is low. However, the risk of dependence increases with higher doses and longer-term use and is further increased in patients with a history of alcoholism, drug abuse or in patients with marked personality disorders.
Symptoms such as anxiety, depression, restlessness, headache, insomnia, tension and sweating have been reported following abrupt discontinuation of benzodiazepines and these symptoms may be difficult to distinguish from the original ones.
Other symptoms such as persistent tinnitus, hyperacusis, involuntary movements, hypersensitivity to light, noise and physical contact, paraesthesia, perceptual changes, de-realisation, depersonalisation, confusion, convulsions, abdominal and muscle cramps and vomiting may be characteristic of benzodiazepine withdrawal syndrome. Rebound insomnia may occur this is a transient syndrome whereby the symptoms that led to treatment with a benzodiazepine recur in an enhanced form , and may occur on withdrawal of hypnotic treatment. 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 is decreased gradually.
Elderly patients or those suffering from cerebral vascular changes such as arteriosclerosis are likely to respond to smaller doses.
4.5. Interaction with other medicinal products and other forms of interaction
Not recommended:
Concomitant intake with alcohol. The sedative effect may be enhanced when the product is used in combination with alcohol. This affects the ability to drive or use machines.
The combination of nitrazepam with CNS depressants can lead to enhancement of the central depressive effect. For example this may occur during concomitant use with antipsychotics (neuroleptics), hypnotics, anxiolytics/sedatives, antidepressant agents, narcotic analgesics, antiepileptic drugs, anaesthetics and sedative antihistamines. In the case of narcotic analgesics enhancement of the euphoria may also occur leading to an increase in psychological dependence.
4.6. Pregnancy and lactation
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.
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 to breast feeding mothers.
4.7 Effects on ability to drive and use machines
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:
o The medicine has been prescribed to treat a medical or dental problem and
o You have taken it according to the instructions given by the prescriber and in the information provided with the medicine and o It was not affecting your ability to drive safely
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
Drowsiness during the day, numbed emotions, reduced alertness, confusion, fatigue, headaches, dizziness, muscle weakness, ataxia, or double vision.
These phenomena occur predominantly at the start of therapy and usually disappear thereafter. Other side effects like gastrointestinal disturbances, changes in libido or skin reactions have been reported occasionally.
Anterograde amnesia may occur using therapeutic dosages, the risk increasing at higher dosages. Amnesia may be associated with inappropriate behaviour. (see ‘warnings and precautions’). Pre-existing depression may be unmasked during benzodiazepine use. 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.
Should this occur, use of the product should be discontinued. These reactions are more likely to occur in children and the elderly. Use (even at therapeutic doses) may lead to the development of physical dependence: discontinuation of therapy may result in withdrawal or rebound phenomena (see ‘warnings and precautions’). Psychological dependence may occur. Abuse has been reported in polydrug abusers.
4.9 Overdose
As with other benzodiazepines, overdosage should not present a threat to life unless combined with other CNS depressants (including alcohol). 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. 3-oh benzodiazepines are, as a rule, not dialysable and their metabolites (glucuronides) only dialysable with difficulty. Special attention should be paid to respiratory and cardiovascular function in intensive care.
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. Flumazenil may be used as an antidote.
5.1 Pharmacodynamic properties
Nitrazepam is a benzodiazepine with more pronounced hypnotic properties than other compounds in this group. It is reported to act in 30 to 60 minutes to produce sleep lasting for 6 to 8 hours.
5.2. Pharmacokinetic properties
Nitrazepam is fairly readily absorbed from the gastro-intestinal tract although there is some individual variation. It is extensively bound to plasma proteins. It is metabolised in the liver, mainly by nitroreduction and acetylation (which is reported to be subject to genetic polymorphism). It is excreted in the urine in the form of metabolites with only small amounts of a dose appearing unchanged. Up to about 20% of an oral dose is found in the faeces. It crosses the placental barrier and traces are found in breast milk.
5.3. Preclinical safety data
Animal studies of acute toxicity carried out, showed Nitrazepam to be moderately toxic by ingestion.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Lactose Monohydrate, Maize starch, Pregelatinised Starch, Magnesium stearate, Purified talc, Colloidal silicon dioxide (aerosil 200).
6.2. Incompatibilities
None.
Shelf life
6.3.
36 months.
6.4. Special precautions for storage
Store in a dry place below 25°C. Protect from light.
6.5. Nature and contents of container
Amber glass bottles with steran wadded cap. Packed in 100, 250, and 500 pack-sizes.
Polypropylene pots with white polyethylene caps and polyethylene ullage filler or PVC aluminium blister packs. Packed in 5, 7, 10, 14, 15, 20, 21, 25, 28, 30, 50, 56, 60, 84, 90, 100, 112, 120, 168, 180, 250 and 500 pack sizes.
6.6 Special precautions for disposal
Not applicable.
7 MARKETING AUTHORISATION HOLDER
Generics [UK] Ltd t/a Mylan
Station Close
Potters Bar
Herts
EN6 1TL
8. MARKETING AUTHORISATION NUMBER
PL 4569/0098
9. DATE OF FIRST AUTHORISATION/RENEWAL OF AUTHORISATION
10 September 1985, 10 September 1990, 7 November 1996
10
DATE OF REVISION OF THE TEXT
23/09/2014