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Drugs List
Therapeutic Indications
Dosage
Administration
Contraindications
Precautions and Warnings
Pregnancy and Lactation
Side Effects
Monograph

Precautions and Warnings

Hepatic impairment (see Dosage - Hepatic Impairment )

Renal impairment (see Dosage - Renal Impairment )

Psychological or personality disorders

Respiratory disease

Muscle weakness

Pregnancy (see Pregnancy )

Elderly and debilitated patients are particularly susceptible to adverse effects.

Undesirable effects such as drowsiness may persist into the next day due to nitrazepam's long half life.

Sedation, amnesia, impaired concentration and impaired muscle function may occur, modifying patients' performance at skilled tasks. If affected, patients should not drive or operate machinery.

Duration of treatment should be as short as possible, depending on the indication, but should not exceed 4 weeks including any dose-tapering period for insomnia. Extension beyond this maximum time period should not take place without re-evaluation of the patient's status.

Alcohol may intensify impaired alertness, and should therefore be avoided during treatment.

Tolerance to the hypnotic effects of benzodiazepines may develop after repeated use for a few weeks.

The risk of development of physical and psychic dependence on benzodiazepines increases with dose and duration of treatment. The lowest possible dose necessary to control symptoms should therefore be used for the shortest period of time, ideally intermittently.
Patients with a history of alcohol or drug abuse are also at greater risk of dependence.

Dosage should be decreased gradually to avoid withdrawal symptoms. These are more likely if physical dependence has developed during usage.

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. The risk of this is greater after abrupt discontinuation; therefore gradual withdrawal is recommended.

Patients should be informed upon commencing treatment that it will be of limited duration, and that the dosage will be decreased progressively. Patients should also be warned of the risk of withdrawal symptoms if a change to a short-acting benzodiazepine is made.

Benzodiazepines may induce anterograde amnesia, occurring most often several hours after ingesting the product. Patients should therefore ensure they are able to devote 7-8 hours to sleep before taking nitrazepam.

Discontinue nitrazepam if psychiatric and paradoxical reactions occur. These may be severe and are more likely in children and elderly.

Psychological adjustment may be inhibited by benzodiazepines in cases of loss or bereavement.

Risk of falls and consequently hip fractures, particularly for elderly patients when they get up at night, due to myorelaxant effect.

Patients with chronic kidney disease (CKD) of stage 5 status will be more susceptible to adverse side effects.

Some formulations contain lactose and should be used with caution in patients with galactosaemia, glucose and galactose malabsorption syndrome and lactose intolerance.

Some formulations contain sucrose and should be used with caution in patients with hereditary fructose intolerance and glucose and galactose malabsorption syndrome.

CSM Warnings

Benzodiazepines are indicated for the short-term relief (two to four weeks only) of anxiety that is severe, disabling or subjecting the individual to unacceptable distress, occurring alone or in association with insomnia or short-term psychosomatic, organic or psychotic illness.

The use of benzodiazepines to treat short-term 'mild' anxiety is inappropriate and unsuitable.

Benzodiazepines should be used to treat insomnia only when it is severe, disabling, or subjecting the individual to extreme distress.

Use in Porphyria

Nitrazepam has been associated with acute attacks of porphyria and is considered unsafe in porphyric patients.

Pregnancy and Lactation

Pregnancy

Nitrazepam is not recommended during pregnancy.

Benzodiazepines cross the placenta, and accumulation may occur in the neonate due to a low rate of metabolism. Some studies suggest a risk of malformations after exposure to benzodiazepines in the first trimester, such as cardiac malformations, facial clefts, intestinal atresia, and microcephaly. Administration during the late phase of pregnancy, or during labour at high doses, may cause 'floppy infant syndrome' (hypothermia, hypotonia, sedation, sucking problems, apnoea and cyanosis). Neonatal dependence and withdrawal symptoms which may include hypertonia, hyperreflexia, restlessness, sleeping disorders and tremors, may also occur in infants of mothers who took benzodiazepines chronically during the latter stages of pregnancy.

Data on the long-term effects of foetal exposure to benzodiazepines are scarce.

However, benzodiazepines are among the drugs of first choice for the treatment of anxiety and sleeping disorders during pregnancy (Schaefer et al, 2007). They should be given at the lowest possible dose for the shortest time, and long-acting benzodiazepines should be avoided. Observe the neonate for respiratory depression, withdrawal symptoms or adaption problems, particularly when benzodiazepines have been used up to delivery.

If prescribed to a woman of child bearing potential, she should be warned to contact her doctor if she becomes, or intends to become pregnant.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password at ( https://www.toxbase.org/ ) or if this is unavailable at the backup site ( https://www.TOXBASEbackup.org/ ).

Licensed in pregnancy? - No

Recommended for use in pregnancy? - No

Crosses placenta? - Yes

Effects on foetus - Possibility of malformations, 'floppy infant syndrome', neonatal withdrawal and dependence.

Other information - Benzodiazepines are drugs of choice for anxiety and sleeping disorders, but should be used at the lowest possible dose for the shortest duration. Long acting benzodiazepines should be avoided.

Lactation

Nitrazepam is not recommended during breast feeding.

Benzodiazepines are excreted in breast milk, and may result in lethargy and poor feeding. The elimination capacity for newborns develops within the first few weeks of life. The UK Drugs in Lactation Advisory Service advises that low doses (equivalent to <10mg diazepam/day) may be administered to nursing mothers, but high doses (equivalent to >10mg diazepam/day) should only be administered when the mother and infant can be monitored, as minor adverse effects have been described.

Diphenhydramine is the drug of choice for sleep disturbances during lactation, and short-acting benzodiazepines are preferred if their use is unavoidable. Single doses of benzodiazepines do not require any limitation of breastfeeding (Schaefer et al 2007). There is insufficient experience on the long-term effects on breastfed children as a result of ongoing therapy in their mothers. Long term use of benzodiazepines in nursing mothers could conceivably alter CNS function in the infant and should therefore be avoided, and the CSM has recommended that they should not be given to breastfeeding mothers.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Drug excreted in breast milk? - Yes

Considered suitable or recommended by manufacturer? - No, contraindicated.

UK Drugs in Lactation Advisory Service Classification - High doses equivalent to > 10 mg diazepam daily carry a minor level of risk of side effects. Low doses (equiv. < 10mg diazepam daily) give very low levels in infants and are considered safe. (5 mg of Nitrazepam is equiv. to 5 mg of Diazepam for example.)

Drug substance licensed in infants? - No

Presentation

Tablets containing 5mg nitrazepam
Oral suspension containing nitrazepam 2.5mg per 5ml

Drugs List

MOGADON 5mg tablets

nitrazepam 2.5mg/5ml suspension

nitrazepam 5mg tablets

Therapeutic Indications

Uses

Short term treatment for insomnia where daytime sedation is acceptable. Only for use when insomnia is severe or disabling, or subjecting the individual to extreme distress.

Unlicensed Uses

Infantile spasms

Dosage

The lowest dose which can control the symptoms should be used, as nitrazepam is a long acting benzodiazepine. If possible, treatment should be intermittent. The maximum dose should not be exceeded.

Adults

5mg before retiring to bed. May be increased to 10mg if necessary.

Elderly

2.5mg before retiring to bed. May be increased to 5mg if necessary.

Patients with Renal Impairment

Use with caution and reduce dose

2.5mg before retiring to bed. May be increased to 5mg if necessary.

Start with small doses in patients with glomerular filtration rate <10ml/min.

Patients with Hepatic Impairment

Avoid in severe hepatic impairment.

Mild to moderate impairment: 2.5mg before retiring to bed. May be increased to 5mg if necessary.

May precipitate coma.

Additional Dosage Information

Dosage should not exceed 5mg in patients with organic brain changes.

Dosage may need to be reduced in patients with chronic pulmonary insufficiency.

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 chronically may require a longer tapering off period. Extension beyond the maximum treatment period may be necessary but should not take place without re-evaluation of the patient's status.

The patient should be checked regularly at the start of treatment in order to decrease the dose or frequency of administration if necessary, in order to prevent overdose due to accumulation.

Administration

For oral administration

Contraindications

Children under 1 month

Acute pulmonary insufficiency

Respiratory depression

Phobic or obsessional states

Chronic psychoses

Severe hepatic impairment

Porphyria

Sleep apnoea

Marked neuromuscular weakness

Myasthenia gravis

Lactation (see Lactation )

Not for use to treat depression, anxiety associated with depression or chronic psychoses with benzodiazepine alone, due to precipitated risk of suicide.