Nitrazepam 5mg Tablets
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Nitrazepam 5mg Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Nitrazepam 5mg For excipients, see 6.1.
3 PHARMACEUTICAL FORM
Oral tablet
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Tablets containing nitrazepam (a benzodiazepine) should be used to treat insomnia only when it is severe, disabling or subjecting the individual to extreme distress.
4.2 Posology and method of administration
Adults:
5 - 10mg before retiring.
Elderly or debilitated:
2.5 - 5mg before retiring
Hepatic/renal impairment:
A reduction in dose may be required in patients with hepatic or renal impairment.
Children:
Nitrazepam Tablets are not recommended for use in children
Note:
The lowest dose which can control symptoms should be used. It should not be continued beyond four weeks.
Treatment if possible should be intermittent. Long term chronic use is not recommended.
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.
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)
• Porphyria
• Phobic or 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 (increased risk of respiratory depression)
• Head injuries (reduced cerebral perfusion: risk of irreversible neurological damage)
Nitrazepam should not be used alone in depression or anxiety with depression (may precipitate suicide).
4.4 Special warnings and precautions for use
Nitrazepam should be used with caution in patients with renal or hepatic dysfunction, coma, muscle weakness and gout.
Tolerance
Loss of efficacy to the hypnotic effects may develop within 3 to 14 days of continuous use.
Limits of tolerance in patients with organic brain disease (particularly that resulting from arteriosclerosis) and cardio-respiratory insufficiency may be very wide: careful dose selection is required in these patients.
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/other GI disturbances including nausea and vomitting, impaired concentration, dizziness, tinnitus, loss of appetite, tremor, sweating, palpitations, changes in blood pressure and mood changes/depression, tachycardia. 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, perceptual disturbances such as hypersensitivity to light, noise and physical contact and abnormal taste, psychotic manifestations including muscle twitching, hallucinations or epileptic seizures, and a state resembling delirium tremons.
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). Broken sleep with vivid dreams and increased REM sleep may persist for some weeks after withdrawal of benzodiazepines
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). If a patient is woken during the period of maximum drug activity, recall may be impaired.
Complex sleep-related behaviours
Sleep-driving or driving while not fully awake, talking, walking, eating or cooking, with no memory of the event, have been reported in patients taking benzodiazepines, including nitrazepam. Nitrazepam should be discontinued in patients who report any such sleep-related behaviours.
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 (disinhibition may manifest itself as aggressive behaviour towards self and others).
Should they occur, treatment should be discontinued.
Elderly (and debilitated) patients
• Risk of falls: Due to myorelaxant effect there is a risk of falls (and consequent hip fractures) particularly for elderly patients when they get up at night.
• Dementia: Benzodiazepines should be used with caution in the elderly as long term use has been associated with increased risk of dementia
• CNS effects (see also sections 4.2 & 4.8): elderly and debilitated patients more prone to these. Doses should not exceed half those normally recommended.
Patients with epilepsy
Nitrazepam should be used with extreme caution in patients with epilepsy. Benzodiazepines can provoke seizures and occasionally precipitate status epilepticus.
Concurrent use of other medication (see also section 4.5)
• Severe hypotension, collapse, respiratory depression and potentially fatal respiratory arrest, and unconsciousness have been reported in a few patients on benzodiazepines and clozapine.
• Nitrazepam enhances the effects of other CNS depressants - avoid concurrent use
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). Abuse of benzodiazepines has been reported.
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
Alcohol: enhanced sedation or respiratory or CNS depression with concomitant administration of nitrazepam. Concomitant use should be avoided.
CNS depressants:
Enhanced sedation or respiratory and cardiovascular depression may occur if nitrazepam is given with other drugs that have CNS depressant properties, (e.g. antipsychotics, anxiolytics, sedatives, other hypnotics, narcotic analgesics, nabilone, general anaesthetics, Antiepileptics (e.g. sodium valproate), and sedative antihistamines.
Antidepressants: enhanced sedation or respiratory or cardiovascular depression with concomitant administration of antidepressants (e.g. agents such as mirtazapine, fluvoxamine or tricyclic antidepressants).
Antihypertensives: enhanced hypotensive effect with concomitant administration of ACE inhibitors, beta-blockers, calcium-channel blockers, hydralazine. Enhanced sedative effect with alpha blockers and possibly moxonidine.
Diuretics: enhanced hypotensive effect.
Nitrates: enhanced hypotensive effect.
Sodium oxybate: enhanced CNS depression effects of sodium oxybate.
Severe hypotension, collapse, respiratory depression, potentially fatal respiratory arrest and unconsciousness have been reported in a few patients on benzodiazepines and clozapine.
Hepatic enzyme inducers and inhibitors:
Agents that interfere with metabolism by hepatic enzymes (e.g. isoniazid, disulfiram, cimetidine, omeprazole, oral contraceptives, erythromycin, fluvoxamine, probenecid) have been shown to reduce the clearance of benzodiazepines and may potentiate their actions. Known inducers of hepatic enzymes, for example rifampicin, carbamazepine, phenobarbital and phenytoin may increase the clearance of benzodiazepines.
Benzodiazepine metabolism is accelerated by xanthines (e.g. caffeine) and smoking.
Nitrazepam may interact with other hepatically metabolised drugs, causing inhibition (levodopa) or potentiation (muscle relaxants - enhanced sedative effect with baclofen). Serum phenytoin levels may rise, fall or remain unaltered.
4.6 Pregnancy and lactation
There is no evidence regarding the safety of nitrazepam in pregnancy. It should not be used, especially in the first and third trimesters, unless the benefit is considered to outweigh the risk. If nitrazepam is prescribed to a woman of childbearing potential, she should be warned to contact her physician regarding discontinuance if she intends to become or suspects that she is pregnant.
There may be a small increase in the risk of congenital malformation, particularly oral cleft, with the use of benzodiazepines in the first trimester.
If for compelling reasons nitrazepam is given during the late phase of pregnancy or during labour, high single doses or repeated low doses of benzodiazepines can be expected to produce hypothermia, hypotonia, respiratory depression and poor suckling (floppy infant syndrome) in the neonate and irregularities in the foetal heart.
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. A small number of children exposed in utero to benzodiazepines have shown slow development in the early years but by four years of age had developed normally.
Nitrazepam is excreted in the breast milk, and therefore its use during lactation should be avoided.
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) and alcohol, 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 of 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
4.8 Undesirable effects
Elderly or debilitated patients are particularly susceptible to side effects. It is recommended that dosage be limited to the smallest effective dose (see 4.2 Posology and Method of Administration) and increased gradually, if necessary, to decrease the possibility of ataxia, dizziness, and oversedation, which may lead to falls and other accidents.
Development of dependence is common after regular use, even in therapeutic doses for short periods, particularly in patients with a history of drug or alcohol abuse or marked personality disorders. Discontinuation may be associated with withdrawal symptoms (see 4.4 Special Warnings and Precautions for Use).
Psychiatric disorders: Complex sleep-related behaviours (sleep-driving or driving while not fully awake, talking, walking, eating or cooking), with no memory of the event, have been reported in patients taking benzodiazepines, including nitrazepam. Numbed emotions, hallucinations. In susceptible patients, an unnoticed depression may become evident. Paradoxical reactions (including aggressive behaviour, hostility, disinhibition, euphoria, excitation, irritability and increased anxiety) are known to occur with benzodiazepines and are more likely the elderly. Abuse of benzodiazepines has been reported.
Vascular disorders: hypotension with high doses.
Eye disorders: visual disturbances.
Immune system disorders: Rarely, allergic reactions, including skin reactions and anaphylaxis.
Gastrointestinal disorders: salvation changes, including dry mouth or excessive salvation may occur rarely with nitrazepam. Gastrointestinal disturbances, including nausea.
General disorders and administration site conditions: fatigue, hangover effect, reduced alertness, hypothermia, dizziness.
Blood and lymphatic system disorders: blood dyscrasias. Agranulocytosis is a rare side effect of nitrazepam.
Ear and labyrinth disorders: vertigo is a rare side effect of nitrazepam. Hepatobiliary disorders: jaundice
Musculoskeletal and connective tissue disorders: muscle weakness. Muscle aches and cramps.
Nervous system disorders: headaches, convulsions, sedation, drowsiness, confusion, slurred speech, tremor, reduced alertness, anterograde amnesia and extrapyramidal effects may occur rarely. Long term use of benzodiazepines in the elderly may be associated with an increased risk of dementia.
Renal and urinary disorders: Urinary retention, incontinence.
Respiratory, thoracic and mediastinal disorders: Respiratory depression and apnoea in high doses or hepatic impairment.
Reproductive system and breast disorders: changes in libido. May inhibit female orgasm. On rare occasions may increase prolactin levels and cause galactorrhoea.
Overdose
4.9
Benzodiazepines potentiate the effects of other CNS depressants including alcohol (see also section 4.5)
Features
Benzodiazepines commonly cause drowsiness, insomnia, muscular weakness, confusion, 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. Rarely, deep coma or other manifestations of severe depression of brainstem vital functions Respiratory depression is more serious in those with severe obstructive airways disease, while a full-blown withdrawal syndrome, possibly with major convulsions, can occur in patients who have previously been chronic users.,
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 to maintain cardiovascular and respiratory function.
• Rarely flumazenil may used as an antidote, however it has a short half-life (about 1 hour). It should not be used in mixed overdoses or as a “diagnostic test”. Expert advice is essential since adverse effects may occur (e.g. convulsions in patients dependent on benzodiazepines).
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Nitrazepam is a bendodiazepine hypnotic with actions similar to those of diazepam.
5.2 Pharmacokinetic properties
Nitrazepam is fairly readily absorbed from the gastrointestinal 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. It is excreted in the urine and faeces.
5.3 Preclinical safety data
There are no pre-clinical data of relevance to the prescriber which are additional to those already provided in other sections.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Lactose Maize starch Povidone
Magnesium stearate
6.2 Incompatibilities
Not known.
6.3 Shelf life
36 months for amber glass bottles, polypropylene or polyethylene containers and cardboard cartons.
24 months for PVC/aluminium strips.
6.4 Special precautions for storage
Do not store above 25 °C.
Store in the original container.
6.5 Nature and contents of container
Amber glass bottles with a plastic cap and polypropylene/polyethylene containers containing 50, 100, 250, 500 and 1,000 tablets.
Plastic container with liner containing 5,000 tablets.
Lined cardboard carton containing 20,000 tablets.
PVC/aluminium strips in cartons in pack sizes of 10, 14, 20, 28, 30, 40, 50, 56, 60, 70, 80, 84, 90, 100 and 112 tablets.
6.6 Special precautions for disposal
Not applicable.
7 MARKETING AUTHORISATION HOLDER
Wockhardt UK Ltd Ash Road North Wrexham LL13 9UF UK
8 MARKETING AUTHORISATION NUMBER(S)
PL 29831/0151
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
24/08/2007
10 DATE OF REVISION OF THE TEXT
28/04/2014