Nitrazepam Tablets 5mg
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Nitrazepam Tablets 5 mg
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 5 mg Nitrazepam.
For excipients, see 6.1.
3 PHARMACEUTICAL FORM
White, flat bevelled edged, scored tablet.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
FOR SHORT TERM (2- 4 weeks only) USE
• Insomnia - but only if severe, disabling or subjecting the individual to extreme distress
• An underlying cause should always be sought (and addressed) before deciding to use benzodiazepines for insomnia.
NOT FOR USE (See also Section 4.3)
• Long term (ie longer than 4 weeks)
• In children (see section 4.3)
• If daytime sedation not acceptable
4.2 Posology and method of administration
Route of administration: oral - taken just before going to bed Treatment to be given
• under close medical supervision
• at the lowest effective dose
• for the shortest possible duration (not exceeding 4 weeks)
Extension of use should not take place without further clinical evaluation
Chronic use not recommended (potential for dependence: limited information on long-term safety and efficacy - see section 4.4).
When treatment is started the patient should be informed that
• treatment will be of limited duration
• the dosage will be progressively decreased
• there is the possibility of rebound phenomena Adults
• 5mg before retiring - if necessary may be increased to 10 mg
• Treatment should not continue at full dose for more than 2 weeks with a 2 week tapering off process. Nitrazepam should not stopped abruptly
Special populations
Elderly and/or debilitated patients
The elderly or patients with impaired renal and/or hepatic function will be particularly susceptible to the adverse effects of nitrazapam. Doses should not exceed half those normally recommended.
Children
Nitrazepam is not for paediatric use Patients with chronic pulmonary insufficiency
• Dose may need to be reduced
• Contraindicated in acute pulmonary insufficiency (see section 4.3) Patients with impaired hepatic or renal function
• Dosage should not exceed half the adult dose and steps should be taken to ensure that there is no accumulation of plasma nitrazepam
• Contraindicated in severe hepatic insufficiency (see section 4.3)
Patients who have taken benzodiazepines for a prolonged time may require a longer period of dosage reduction and specialist help may be appropriate.
4.3 Contraindications
• Hypersensitivity to benzodiazepines or to any of the other ingredients
• Acute pulmonary insufficiency: respiratory depression: sleep apnoea (risk of further respiratory depression)
• Obsessional states (inadequate evidence of safety and efficacy).
• Chronic psychoses (inadequate evidence of safety and efficacy).
• Severe hepatic insufficiency (may precipitate encephalopathy)
• Planning a pregnancy (see section 4.6)
• Pregnancy (unless there are compelling reasons - see section 4.6)
• Myasthenia gravis
Nitrazepam should not be used alone in depression or anxiety with depression (may precipitate suicide).
4.4 Special warnings and precautions for use
Tolerance
Loss of efficacy to the hypnotic effects may develop after repeated use for a few weeks.
Dependence
The risk of dependence (physical or psychological) increases with dose and duration of treatment and is greater in patients with a history of alcohol or drug abuse, or in patients with a marked personality disorder. Therefore
• regular monitoring of such patients is essential
• routine repeat prescriptions should be avoided
• treatment should be withdrawn gradually Withdrawal effects
The duration of treatment should be as short as possible (see section 4.2).
If physical dependence has developed, abrupt termination of treatment results in withdrawal symptoms. These include headache, muscle pain, extreme anxiety, tension, restlessness, confusion and irritability, sleep disturbance, diarrhoea and mood changes. In severe cases the following may occur: a feeling of unreality or of being separated from the body, depersonalisation, confusional states, numbness and tingling of the extremities, hypersensitivity to light, noise and physical contact, psychotic manifestations including hallucinations or epileptic seizures. Withdrawal symptoms will be worse in patients who have been dependent on alcohol or other narcotic drugs in the past, but can occur following abrupt cessation of treatment in patients receiving normal therapeutic doses for a short period of time.
When nitrazepam is being used it is important not to change to a benzodiazepine with a short duration of action, as withdrawal symptoms may be precipitated.
Rebound symptoms
Symptoms including insomnia may occur on withdrawal of treatment. As this is greater after abrupt discontinuation, the dose should be decreased gradually (see section 4.2).
Amnesia
Anterograde amnesia may occur, most often several hours after ingestion. To reduce the risk, patients should ensure that they will be able to have an uninterrupted sleep of 7-8 hours (see also section 4.8).
Bereavement/loss
Psychological adjustment may be inhibited by benzodiazepines Psychiatric and ‘paradoxical’ reactions
Reactions such as restlessness, agitation, irritability, aggressiveness, excitement, confusion, delusions, rage, nightmares, hallucinations, psychoses, inappropriate behaviour and other adverse behavioural effects can occur. These reactions are more likely in children and the elderly, and extreme caution should be used in prescribing benzodiazepines to patients with personality disorders. Should they occur, treatment should be discontinued.
Risk of falls
Due to myorelaxant effect there is a risk of falls and consequently of hip fractures particularly for elderly patients when they get up at night.
Specific Patient Groups
Intolerance to sugars
Nitrazepam should not be given to patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
Patients with depression
Nitrazepam should not be used alone to treat depression or anxiety associated with depression as suicide may be precipitated in such patients.
Patients with a history of alcohol & drug abuse
Nitrazepam should be used with extreme caution in patients with a history of alcohol or drug abuse (risk of abuse/dependence).
Patients with phobias and/or chronic psychoses
Nitrazepam is not recommend (inadequate evidence of efficacy and safety -see also section 4.3)
Patients with glaucoma Nitrazepam is not recommended
4.5 Interaction with other medicinal products and other forms of interaction
Not recommended
Alcohol: Nitrazepam should not be used together with alcohol (enhanced sedative effects: effect the ability to drive or operate machinery - see section 4.7).
Sodium oxybate: avoid concomitant use (enhanced effects of sodium oxybate) Take into account
Centrally acting drugs: Enhancement of the central depressive effect may occur if nitrazepam is combined with drugs such as neuroleptics, antipsychotics, tranquillisers, antidepressants, hypnotics, analgesics, anaesthetics, barbiturates and sedative antihistamines. The elderly may require special supervision.
Anti-epileptic drugs: When used concurrently, side effects and toxicity may be more evident, particularly with hydantoins (eg phenytoin) and/or barbiturates. This requires extra care in adjusting dosage in the initial stages of treatment.
Narcotic analgesics: Enhancement of the euphoria may lead to increased psychological dependence.
Other drugs enhancing the sedative effect of nitrazepam: cisapride, lofexidine, nabilone, disulfiram and the muscle-relaxants baclofen and tizanidine.
Compounds that affect hepatic enzymes (particularly cytochrome P450):
• inhibitors (eg cimetidine) reduce clearance and may potentiate the action of benzodiazepines
• Inducers (eg rifampicin) may increase clearance of benzodiazepines
Antihypertensives, vasodilators& diuretics: Enhanced hypotensive effect with ACE-inhibitors, alpha-blockers, angiotensin-II receptor antagonists, calcium channel blockers adrenergic neurone blockers, beta-blockers, moxonidine, nitrates, hydralazine, minoxidil, sodium nitroprusside and diuretics
Dopaminergics: possible antagonism of the effect of levodopa by nitrazepam
Aluminium hydroxide mixtures: may enhance absorption of nitrazepam
4.6 Fertility, Pregnancy and lactation
Pregnancy
Nitrazepam should only be used during pregnancy if there are compelling reasons (eg no alternative : benefit outweighs risk).
An increased risk of congenital malformations in humans has been associated with its use, particularly in the first and second trimesters. If the product is prescribed to a woman of childbearing potential, she should be warned to contact her physician regarding stopping if she intends to become or suspects she may be pregnant.
If the product is administered at high doses during the late phase of pregnancy or during labour, effects on the neonate such as hypothermia, irregularities in fetal heart rate and hypotonia, poor-sucking and moderate respiratory depression, can be expected. Infants born to mothers who took benzodiazepines chronically during the latter stages of pregnancy may have physical dependence and may be at some risk for withdrawal symptoms in the postnatal period.
Lactation
Use during lactation should be avoided as nitrazepam is found in breast milk.
4.7 Effects on ability to drive and use machines
• Patients should be advised that sedation, amnesia, impaired concentration, dizziness, blurred vision and impaired muscular function may occur and that, if affected, they should not drive or to use machines, or take part in other activities where this would put themselves or others at risk.
• If insufficient sleep duration occurs, the likelihood of impaired alertness may be increased
• Concurrent medication, particularly with CNS depressants, may increase these effects (see section 4.5).
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 a 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, sedation, reduced alertness, lightheadedness, dizziness, fatigue, muscle weakness unsteadiness, double vision and ataxia; these are usually dose-related but, even after a single dose, may persist into the following day. They occur predominantly at the start of therapy and usually disappear with repeated administration. However, the elderly are particularly sensitive to the effects of central depressant drugs and may experience confusion, especially if organic brain changes are present; the dosage of nitrazepam should not exceed one-half that recommended for other adults (see section 4.2).
Other adverse effects include dependence, confusion, restlessness, agitation, irritability, aggressive outbursts, delusion, nightmares, hallucinations, inappropriate behaviour, tremor, dysarthria, salivation changes, incontinence, and thrombocytopenia/other blood disorders. Depression and amnesia can result from high doses (see also below).
Rare adverse effects include numbed emotions, reduced alertness, fatigue, headache, dizziness, grand mal seizures, muscle weakness, vertigo, blurred vision, hypotension, gastrointestinal upsets, skin rashes, visual disturbances, changes in libido, and urinary retention.
Isolated cases of blood dyscrasias and jaundice have also been reported.
Amnesia
Anterograde amnesia may occur at therapeutic doses, with increasing risk at higher doses. This may be associated with inappropriate behaviour (see section 4.4).
Depression
Pre-existing depression may be unmasked by benzodiazepines.
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 benzodiazepine-like agents. They may be quite severe with this product. They are more likely to occur in children and the elderly.
Dependence
Use (even therapeutic doses) may lead to the development of physical dependence: discontinuation of the therapy may result in the withdrawal or rebound phenomena. Psychological dependence may occur. Abuse of benzodiazepines has been reported (see sections 4.2 & 4.4).
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
Benzodiazepines potentiate the effects of other CNS depressants including alcohol (see also section 4.5)
Features
Benzodiazepines commonly cause drowsiness, ataxia, dysarthria and nystagmus. Coma, hypotension and respiratory depression occasionally occur but are seldom serious if these drugs are taken alone. Coma usually lasts a few hours but in the elderly may be more protracted and cyclical. Respiratory depression is more serious in those with severe obstructive airways disease. Patients who are asymptomatic at 4 hours are unlikely to develop symptoms.
Management
• Maintain clear airway and adequate ventilation, if indicated
• The value of gastric decontaminants is uncertain. Consider activated charcoal (50g for an adult: 1g/Kg for a child) within 1 hour of ingestion if more than 1mg/Kg has been taken provided the patient is not too drowsy.
• Gastric lavage - unnecessary if only benzodiazepine taken
• Supportive measures as indicated by the patient’s clinical condition
Rarely flumazenil may be used as an antidote, however it has a short halflife (about 1 hour). It should not be used in mixed overdoses or as a “diagnostic test”.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic Group: Hypnotics and sedatives, benzodiazepine derivatives ATC Code: N05C D02
Nitrazepam is a benzodiazepine hypnotic with actions similar to those of diazepam. It is reported to act in 30 to 60 minutes to produce sleep lasting for 6 to 8 hours. As a hypnotic, the usual dose for adults is 5 to 10 mg at night. The elderly and debilitated patients are generally given half of the usual adult dose.
5.2 Pharmacokinetic properties
Nitrazepam is fairly readily absorbed from the gastro-intestinal tract although there is some individual variation. It has a biphasic half-life probably owing to tissue redistribution, and 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 its 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
There are no pre-clinical data of relevance to the prescriber that are additional to that already included in other sections of the SmPC.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Maize starch Lactose
Pregelatinised starch Magnesium stearate Sodium starch glycollate
6.2 Incompatibilities
None reported.
6.3 Shelf life
3 years for opaque plastic containers.
2 years for aluminium/opaque PVC blister packs.
6.4 Special precautions for storage
Keep out of reach and sight of children. Protect from heat, light and moisture.
6.5 Nature and contents of container
1. Opaque plastic containers for pack sizes of 28, 30, 42, 50, 56, 60, 84, 90, 100, 112, 250, 500 and 1000.
2. Opaque plastic container composed of either high density polypropylene or high density polypropylene or high density polyethylene with a tamper evident or child resistant tamper evident closure composed of high density polyethylene for all pack sizes (28, 30, 42, 50, 56, 60, 84, 90, 100, 112, 250, 500 and 1000) with packaging inclusion of standard polyether foam or polyethylene or polypropylene filler.
3. Blister packs of aluminium/opaque PVC in printed cartons in pack sizes of 28, 30, 42, 56, 60, 84, 90 and 112.
6.6 Special precautions for disposal
None.
7 MARKETING AUTHORISATION HOLDER
Crescent Pharma Ltd
Units 3 and 4, Quidhampton Business Units
Polhampton Lane
Overton
Hampshire
RG25 3ED
United Kingdom
MARKETING AUTHORISATION NUMBER(S)
PL 20416/0228
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DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
22/10/2012
DATE OF REVISION OF THE TEXT
07/04/2014