Nitrazepam 5mg Tablets – Summary of Product Characteristics (SmPC) for healthcare professionals

1 NAME OF THE MEDICINAL PRODUCT

Nitrazepam 5mg Tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 5mg Nitrazepam BP.

Excipient with known effect: contains 395mg of lactose.

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Uncoated Tablets

Creamy white tablets with bevel edge, embossed ‘N/5’ on one face and ‘PV’ on the other.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Insomnia: Nitrazepam is only indicated for the short term treatment of insomnia only when it is severe, disabling or subjecting the individual to extreme distress and where daytime 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

Posology

Adults: 5mg before retiring. This dose may, if necessary, be increased to10mg.

Children: Not recommended for use in children under 12 years of age.

Elderly or debilitated patients: 2.5-5mg before retiring. The elderly or patients with impaired renal and/or hepatic function will be particularly susceptible to the adverse effects of Nitrazepam tablets. Doses should not exceed half those normally recommended. If organic brain changes are present, the dosage of Nitrazepam tablets should not exceed 5 mg in these patients.

Other populations

In patients with chronic pulmonary insufficiency and in patients with chronic renal or

hepatic disease, the dosage may need to be reduced.

Dosage should be adjusted on an individual basis. Treatment should, if possible, be

on an intermittent basis.

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 a maximum of four weeks; including the tapering off process. Patients who have taken benzodiazepines for a prolonged 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.

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. 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 tablets therapy should not be stopped

abruptly, but the dose tapered off.

The product should be taken just before going to bed.

In addition, for long acting benzodiazepines, it must be stated that the patient should be checked regularly at the start of treatment in order to decrease, if necessary, the dose or frequency of administration to prevent overdose due to accumulation.

Method of Administration

For oral administration.

Prior to starting treatment with Nitrazepam, a discussion should be held with patients to put in place a strategy for ending treatment with Nitrazepam in order to minimise the risk of dependence, addiction and drug withdrawal syndrome (see section 4.4).

Treatment should be given for the shortest possible duration. If this medicine is being used for the treatment of epilepsy this medicine should be used for as long as the prescriber considers it necessary.

4.3 Contraindications

Patients with known hypersensitivity to benzodiazepines, nitrazepam or to any of the excipients listed in section 6.1

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

Use of this drug is also contraindicated in patients with acute pulmonary insufficiency; respiratory depression; phobic or obsessional states; chronic psychosis; myasthenia gravis; sleep apnoea syndrome; severe hepatic insufficiency and acute porphyria. Should not be used alone to treat depression, or anxiety associated with depression.

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. Tolerance to their effects develops within 3-14 days of continuous use and hence treatment regimes should be kept to a minimum and repeat prescriptions avoided. Limits of tolerance in patients with organic cerebral changes (particularly resulting from arteriosclerosis) or cardio-respiratory insufficiency may be very wide; care must be taken in adapting the dosage with such patients.

Nitrazepam tablets should not be used alone to treat depression or anxiety associated with depression, since suicide may be precipitated in such patients. Benzodiazepines should be used with extreme caution in patients with a history of alcohol or drug abuse. Benzodiazepines are not recommended for the primary treatment of psychotic illness.

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.

Use of benzodiazepines may lead to the development of physical and psychological dependence upon these products. The risk of dependence increases when high doses are used, especially when given over long periods. This is particularly so in patients with a history of alcoholism 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.

Symptoms such as depression, headaches, muscle weakness, nervousness, extreme anxiety, tension, restlessness, confusion, mood changes, rebound insomnia, irritability, sweating and diarrhoea have been reported following abrupt cessation of treatment in patients receiving even normal therapeutic doses for short periods of time.

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 and 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.

Some loss of efficacy to the hypnotic effects of short-acting benzodiazepines may develop after repeated use for a few weeks.

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. If any of these reactions occur, use of the drug should be discontinued. These reactions may be quite severe and are more likely to occur in children and the elderly.

Benzodiazepines may induce anterograde amnesia. The condition usually occurs 1 to 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 to 8 hours.

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 group: 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 reduced dose. Hypoalbuminaemia (may predispose patient to higher incidence of sedative side effects).Care should be exercised in patients with epilepsy since there have been reports of rare paradoxical exacerbation of seizures in these patients (See section 4.5).

Contains Lactose: Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Drug dependence, tolerance and potential for abuse

Drug addiction comprises behavioural, cognitive and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use and possible tolerance or physical dependence. Physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, which manifests as withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. Addiction and dependence are related but distinct presentations and in discussing these themes, terminology that apportion blame to the individual should be avoided.

For all patients, prolonged use of this product may lead to drug dependence and addiction but can occur with short-term use at recommended therapeutic doses. The risks are increased in individuals with current or past history of substance misuse disorder (including alcohol misuse) or mental health disorder (e.g., major depression).

Additional support and monitoring may be necessary when prescribing for patients at risk of drug misuse.

A comprehensive patient history should be taken to document concomitant medications, including over-the-counter medicines and medicines obtained on-line, and past and present medical and psychiatric conditions.

Patients may find that treatment is less effective with chronic use and express a need to increase the dose to obtain the same level of symptom control as initially experienced. Patients may also supplement their treatment with additional medications to achieve the same effect. These could be signs that the patient is developing tolerance. The risks of developing tolerance should be explained to the patient.

Overuse or misuse may result in overdose and/or death. It is important that patients only use medicines that are prescribed for them at the dose they have been prescribed and do not give this medicine to anyone else.

Patients should be closely monitored for signs of misuse, abuse, or addiction. The clinical need for treatment with Nitrazepam should be reviewed regularly, with frequent assessments of patients being undertaken during the course of their treatment.

Drug withdrawal syndrome

Prior to starting treatment with Nitrazepam, a discussion should be held with patients to explain the risk of dependence, addiction, and drug withdrawal syndrome. A withdrawal strategy for ending treatment with Nitrazepam should also be put in place with the patient before starting treatment (there may be exceptions to this in specific clinical situations such as symptom management in end of life palliative care, and for use in epilepsy).

Drug withdrawal syndrome may occur upon abrupt cessation of therapy or dose reduction. When a patient no longer requires therapy, it is advisable to taper the dose gradually to minimise symptoms of withdrawal. Tapering from a high dose may take in excess of weeks or months. Patients should be informed of this when the medication is first prescribed.

The reduction schedule for a patient should be tailored to the individual and should be modified to allow intolerable withdrawal symptoms to improve before making the next reduction. If using a published withdrawal schedule, apply it flexibly to accommodate the person’s preferences, changes to their circumstances and the response to dose reductions.

Benzodiazepines: Suggest a slow stepwise rate of reduction proportionate to the existing dose, so that decrements become smaller as the dose is lowered, unless clinical risk is such that rapid withdrawal is needed.

If a patient develops withdrawal reactions, consider pausing the taper or increasing the dosage to the previous tapered dosage level.

If women take this drug during pregnancy, there is a risk that their newborn infants will experience neonatal withdrawal syndrome.

4.5 Interaction with other medicinal products and other forms of interaction

If nitrazepam is combined with centrally acting drugs such as neuroleptic, tranquillisers, antidepressant, hypnotics, narcotic analgesics (enhancement of euphoria may also occur, leading to an increase in psychological dependence), sedative antihistamines, anaesthetics, lofexidine, nabilone and alcohol, the sedative effects are likely to be intensified. 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.

Compound which inhibits certain hepatic enzymes (particularly cytochrome P450) may enhance the activity of benzodiazepines. To a lesser degree this also applies to benzodiazepines that are metabolised only by conjugation.

• Dopaminergics (concurrent use with benzodiazepines may decrease the therapeutic effects of levodopa).
• Caffeine and theophylline (concurrent use may result in reduced sedative and anxiolytic effects of nitrazepam).
• Cimetidine, oestrogen-containing contraceptives, disulfiram (these medicines may inhibit hepatic metabolism of nitrazepam).
• Antibacterials (Rifampicin may increase the metabolism of nitrazepam. Isoniazid may inhibit the metabolism of benzodiazepines).
• Antivirals (Ritonavir may inhibit benzodiazepine hepatic metabolism).
• Antihypertensives (enhanced hypotensive effects. Enhances sedative effect with alpha blockers or moxonidine).
• Baclofen and tizanidine (enhanced sedative effect).
• Probenecid (may increase effects and possibility of excessive sedation).

Not recommended: Concomitants 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 machine.

4.6 Fertility, pregnancy and lactation

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.

Do not use during pregnancy, if the product is prescribed to a woman of child bearing potential, she should be warned to contact her physician regarding discontinuance of the product if she intends to become or suspect 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, effect 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 benzodiazepine 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 benzodiazepine are found in the breast milk, benzodiazepine should not be given to breast feeding mothers.

4.7 Effects on ability to drive and use machines

Patients should be advised that, like all medicaments of this type, Nitrazepam tablets may modify patients’ performance at skilled tasks. Sedation, amnesia and impaired muscular function may adversely affect the ability to drive or use machines. If insufficient sleep duration occurs, the likelihood of impaired alertness may be increased. Patients should further be advised that alcohol may intensify any impairment, and should therefore be avoided during treatment.

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:

Not known (cannot

be estimated from

the available data)

Drug

dependence (see section 4.4) and abuse of

benzodiazepines amnesia

(2), depression (3),withdrawal symptoms (1)

Dysarthria

Drug withdrawal symptoms (see 4.4 Special

warnings and precautions)

• Abnormal psychological reactions to benzodiazepines have been reported.

  Behavioural adverse effects include paradoxical aggressive outbursts, excitement, confusion and the uncovering of depression with suicidal tendencies.

• 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 elderly.

(1) 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

(2) Anterograde amnesia may occur at therapeutic dosages, the risk increasing at higher dosages. Amnesiac effects may be associated with inappropriate behaviour.

(3) Pre-existing depression may be unmasked during benzodiazepine use.

(4) These phenomena are dose related and occur predominantly at the start of therapy, they usually disappear with repeated administration. The elderly are particularly sensitive to the effects of centrally-depressant drugs.

Symptoms reported following discontinuation of benzodiazepines include headaches, muscle pain, anxiety, tension, depression, insomnia, restlessness, confusion, irritability, sweating, and the occurrence of “rebound” phenomena whereby the symptoms that led to treatment with benzodiazepines recur in an enhanced form. These symptoms may be difficult to distinguish from the original symptoms for which the drug was prescribed.

In severe cases the following symptoms may occur: derealisation; depersonalisation; hyperacusis; tinnitus; numbness and tingling of the extremities; hypersensitivity to light, noise, and physical contact; involuntary movements; hyperreflexia, tremor, nausea, vomiting; diarrhoea, abdominal cramps, loss of appetite, agitation, palpitations, tachycardia, panic attacks, vertigo, short-term memory loss, hallucinations/delirium; catatonia; hyperthermia, convulsions. Convulsions may be more common in patients with pre-existing seizure disorders or who are taking other drugs that lower the convulsive threshold such as antidepressants.

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 Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose:

When taken alone in over-dosage Nitrazepam tablets presents few problems in management and 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.

Patients should be informed of the signs and symptoms of overdose and to ensure that family and friends are also aware of these signs and to seek immediate medical help if they occur.

Symptoms:

Over-dosage 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, dysarthria and lethargy; in more serious cases, symptoms may include ataxia, hypotonia, hypotension, cardiorespiratory 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. Occasionally a respirator may be required but generally few problems are encountered, although behavioural changes are likely in children.

Special attention should be paid to respiratory, renal and cardiovascular functions and to the maintenance of electrolyte balance 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.

Hypotension should be managed with fluids and if persistent, a positive inotrope such as dobutamine. If excitation occurs, barbiturates should not be used.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Hypnotics and Sedatives, Benzodiazepine derivatives, ATC Code: N05CD02

Nitrazepam tablet 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

Nitrazepam is well absorbed with peak blood levels being achieved within two hours after administration. 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).

The half life of nitrazepam is on 24 hour. Steady state levels are achieved within 5 days. Nitrazepam undergoes biotransformation to a number of metabolites none of which possesses significant clinical activity. After oral administration about 50% to 70% of a dose is excreted in the urine in 120 hours and up to 20% is eliminated in the faeces.

Only a small amount (less than 4%) is excreted as unchanged nitrazepam. It crosses the placental barrier and traces are found in breast milk.

5.3 Preclinical safety data

N/A

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Lactose

Maize Starch

Pregelatinised Starch

Colloidal Silicon Dioxide

Stearic Acid

Magnesium Stearate

6.2 Incompatibilities

None known

6.3 Shelf life

5 years

6.4 Special precautions for storage

Store in a cool dry place away from bright light.

6.5 Nature and contents of container

Plastic securitainer with polypropylene lids with double security closure containing nitrazepam tablets ( material of the container complies to EEC directives for plastic in contact with drugs and food stuff ) in the pack sizes of 28,56,500 and1000.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

none

7 MARKETING AUTHORISATION HOLDER

Pharmvit Limited

77 Bilton Road, Perivale

Greenford, Middlesex,

UB6 7HQ

8 MARKETING AUTHORISATION NUMBER(S)

PL 04556/0001

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

14/10/2025

10 DATE OF REVISION OF THE TEXT

16/01/2026