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NITRAZEPAM TABLETS B.P. 5 MG

Active substance(s): NITRAZEPAM / NITRAZEPAM / NITRAZEPAM

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SUMMARY OF PRODUCT CHARACTERISTICS
1

NAME OF THE MEDICINAL PRODUCT
Nitrazepam Tablets BP 5mg

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Nitrazepam BP 5.0mg
Excipient(s) with known effect:
For the full list of excipients, see section 6.1
Each tablet contains 443mg lactose.

3

PHARMACEUTICAL FORM
Tablet
White, circular tablets, breakline on one side, RN5 on the other.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
Insomnia
Nitrazepam is a Benzodiazepine with sedative properties. Benzodiazepines
should be used in the short term treatment of insomnia when it is severe,
disabling or subjecting the individual to unacceptable distress, where day time
sedation is acceptable.
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
Insomnia
Adult dosage:
The dosage for adults is 5mg before retiring. This dose may be increased if
necessary, to 10mg.
Older people and debilitated patients dosage:
The older people or patients with impaired renal and/or hepatic function will
be particularly susceptible to adverse effects of Nitrazepam. Doses should not
exceed half those normally recommended e.g. 2.5mg before retiring. This
dose may be increased, if necessary to 5mg. Doses should be adjusted on an
individual basis.
If organic brain changes are present, the dosage of Nitrazepam should not
exceed 5mg in these patients.
Paediatric population
Nitrazepam Tablets are contraindicated for use in children.
Other populations:
In patients with chronic pulmonary insufficiency and in patients with chronic
renal or hepatic disease, dosage may need to be reduced.
Treatment should be as short as possible and the lowest dose which can
control symptoms should be used. The maximum dose should not be
exceeded. Generally the duration of treatment varies from a few days to two
weeks with a maximum of four weeks; including tapering off process..
Treatment should always be tapered off gradually. Patients who have taken
Benzodiazepines for a long time may require a longer period during which
doses are reduced. Specialist help may be needed. Long term chronic use is
not recommended.
Little is known regarding the efficacy or safety of
benzodiazepines in long-term use.
In certain cases, extension beyond the maximum treatment period may be
necessary; if so, it should not take place without a re-evaluation of the patient's
status. 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 minimizing 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.
Method of administration
Nitrazepam tablets are for oral administration.

The product should be taken just before going to bed. 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.
4.3

Contraindications











Known sensitivity to benzodiazepines, hypersensitivity to any of the
excipients as listed in section 6.1
Acute pulmonary insufficiency;
Severe respiratory depression;
Phobic or obsessional states;
Chronic psychosis.
Patients with neuromuscular disease e.g. myasthenia gravis,
Closed angle glaucoma,
Sleep aponea syndrome
Severe hepatic insufficiency
Use in children

Hypersensitivity reactions with the benzodiazepines including rash, angioedema and
hypertension have been reported on rare occasions in susceptible patients.

4.4

Special warnings and precautions for use
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.
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.
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
psychological dependence upon these products. The risk of dependence
increases with dose and duration of treatment; it is also greater in patients with
a history of alcohol 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.
Once physical dependence has developed, abrupt termination of treatment will
be accompanied by withdrawal symptoms.

Symptoms such as depression, nervousness, mood changes, rebound insomnia,
sweating, diarrhoea, headaches, muscle pain, extreme anxiety, tension,
restlessness, confusion and irritability have been reported following abrupt
cessation of treatment in patients receiving even normal therapeutic doses for
short periods of time. 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.
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.
Rebound insomnia and anxiety: 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.
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 revaluation 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.
Amnesia
Benzodiazepines may induce anterograde amnesia. The condition 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 7-8 hours (see also 4.8).
Psychiatric and paradoxical reactions:

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.
Should this occur, use of the medicinal product should be discontinued.
They are more likely to occur in children and older people.
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. Older
people should be given a reduced dose (see Posology). Due to myorelaxant
effect there is a risk of falls and consequently of hip fractures particularly for
older patients when they get up at night.
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.
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).
Benzodiazepines should be used with extreme caution in patients with a
history of alcohol or drug abuse.
Lactose intolerance
Nitrazepam tablets contain lactose. Patients with rare hereditary problems of
galactose intolerance, the Lapp lactase deficiency or glucose-galactose
malabsorption should not take this medicine.
4.5

Interaction with other medicinal products and other forms of interaction
Concomitant intake with alcohol is not recommended. The sedative effect 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), tranquillisers, 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 psychological dependence. The older people 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.
Known inhibitors of hepatic enzymes (particularly cytochrome P450) have been
shown to reduce the clearance of benzodiazepines and may enhance the activity of
benzodiazepines and known inducers of hepatic enzymes, e.g. rifampicin, may
increase the clearance of benzodiazepines. To a lesser degree this also applies to
benzodiazepines that are metabolised only by conjugation.
Administration with Cimetidine can cause potentiation due to decreased hepatic
metabolism.
Metabolism may be inhibited by Disfulfiram Isoniazid and contraceptives while
Rifampin may increase the metabolism of nitrazepam.

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
trimester of pregnancy, or during labour , effects on the neonate have been
reported; hypothermia, hypotonia, poor sucking, irregularities in the foetal
heart rate and moderate respiratory depression 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 more risk for developing withdrawal symptoms in the postnatal
period.
Breastfeeding
Since benzodiazepines are found in breast milk, benzodiazepines should not be
given to breast feeding mothers.

4.7

Effects on ability to drive and use machines
Sedation, amnesia, impaired concentration and impaired muscular function are
possible undesirable effects that may affect your ability to drive or operate
machinery. If insufficient sleep duration occurs, the likelihood of impaired
alertness may be increased (see also 4.5).
Patients should be further advised that alcohol might intensify any impairment
and should therefore be avoided during treatment. If patient is awoken during
maximum period of activity of the drug, recall may be impaired.
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:
- The medicine has been prescribed to treat medical or dental
problem and
- You have taken it according to the instructions given by the
prescriber and in the information provided with the medicine and
- It was not affecting your ability to drive safely

4.8

Undesirable effects
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 older patients are particularly sensitive to the effect of
centrally-depressant drugs.
Amnesia:
Anterograde amnesia may occur using therapeutic dosages, the risk increasing
at higher dosages. Amnestic effects may be associated with inappropriate
behaviour (see 4.4).
Pre-existing depression may be unmasked during benzodiazepine use.
Other adverse effects are rare and include vertigo, hypotension, gastrointestinal upsets, skin rashes, visual disturbances, changes in libido, and
urinary retention. Isolated cases of blood dyscrasias and jaundice have also
been reported.

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. 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.
Abuse of benzodiazepines have been reported.
Reporting of suspected adverse reactions
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
As with other benzodiazepines, overdose should not present a threat to life unless
combined with other CNS depressants (including alcohol).
In the management of overdose with any medicinal product, it should be borne in
mind that multiple agents may have been taken.
Symptoms:
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.
Management:
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. Anexate (Flumazenil) is a specific IV
antidote to Nitrazepam and Benzodiazepines for use in emergency situations.
Patients requiring such an 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.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Pharmacotherapeutic group: Hypnotics and Sedatives, Benzodiazepine
derivatives,
ATC Code: NO5C D02
The effect of Benzodiazepines like Nitrazepam result from action on the CNS
even when lethal doses are taken. The most prominent of these effects are
sedation hypnosis, decreased anxiety, muscle relaxation.
In man, as the dose of Benzodiazepine like Nitrazepam is increased, sedation
progresses to hypnosis an hypnosis to stupor as expected of a general CNS
depressant.
The Benzodiazepine drugs, including Nitrazepam, have only slight effect on
respiration; hypnotic doses are without effect in normal subjects. The
cardiovascular effects of Benzodiazepines (Nitrazepam included) are minor,
expect in severe intoxication.

5.2

Pharmacokinetic properties
Nitrazepam is well absorbed after oral administration. It has a half life
ranging from 17 to 28 hours. It is approximately 85% bound to plasma
proteins.
After an oral dose of 10mg, peak plasma concentrations of 70-110ng/ml are
attained in two hours; during therapy with 5mg daily, steady state plasma
concentrations of about 40mg/ml are attained in 4 hours.
Metabolism is principally by reduction of the nitro group to produce inactive
7-amino derivatives. Less than 1% is excreted in the urine unchanged.
After oral administration 65-71% of a dose is excreted in the urine with 1420% excreted in the faeces.

5.3

Preclinical safety data
There are no pre-clinical data of relevance to the prescriber which are
additional to that already included in other sections of the SPC.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Lactose 200#
Starch (Maize)
Povidone
Purified Water
Magnesium Stearate
Sodium Starch Glycollate
Colloidal Anhydrous Silica

6.2

Incompatibilities
None applicable

6.3

Shelf life
Polypropylene containers and amber glass bottle: 3 years
Blister strips: 2 years

6.4

Special precautions for storage
Keep tightly closed,
Store below 25°C.
Protect from light.

6.5

Nature and contents of container
Opaque polypropylene containers having snap on polythene lids, with integral
tear off security seals OR amber glass bottle with screw cap and sternan faced
liner: 5000, 1000, 500, 100, 84, 70, 56, 50, 42, 28, 25, 21, 15, 14 or 7 tablets.
Blister Strips: 84, 70, 56, 42, 28, 21, 14 or 7 tablets.

6.6

Special precautions for disposal
Not applicable.

7

MARKETING AUTHORISATION HOLDER
Ranbaxy Ireland Ltd.,
Spafield, Cork Road,
Cashel, Co. Tipperary,
Ireland.

8

MARKETING AUTHORISATION NUMBER(S)
PL 06809/0042

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
27th July 1990

10

DATE OF REVISION OF THE TEXT
31/03/2015

Expand Transcript

Source: Medicines and Healthcare Products Regulatory Agency

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