Drugs List

Therapeutic Indications

Uses

Insomnia (short-term treatment)

Contraindications

Children under 18 years
Acute respiratory impairment
Chronic psychosis
Myasthenia gravis
Neuromuscular disorder
Obsessional states
Phobic states
Respiratory depression
Severe hepatic impairment
Sleep apnoea

Precautions and Warnings

Debilitation
Elderly
Females of childbearing potential
Hypoalbuminaemia
Breastfeeding
Chronic respiratory impairment
Hepatic impairment
History of alcohol abuse
History of drug misuse
Muscle weakness
Personality disorder
Porphyria
Pregnancy
Psychiatric disorder
Renal impairment
Respiratory disease

Reduce dose in patients with hepatic impairment
Reduce dose in patients with renal impairment
Advise ability to drive/operate machinery may be affected by side effects
Advise patient not to drive until they know how the medicine affects them
Advise patient this medicine may be subject to driving restrictions
Not suitable as sole treatment of depression or anxiety with depression
Neonate exposed in utero: Monitor for neonatal withdrawal syndrome
Tolerance and dependence may occur
Amnesia may occur
Discontinue if psychiatric disturbances develop
May cause paradoxical behaviour
Psychological adjustment may be impaired in loss or bereavement
Do not withdraw this drug suddenly
Withdraw gradually after long-term use
Discontinue if paradoxical reactions occur
Maintain treatment at the lowest effective dose
Reduce dose in debilitated patients
Reduce dose in elderly
Avoid long term continuous therapy
Only recommended for short term use
Advise patient to avoid alcohol during treatment
Advise patient to ensure 7- 8 hours of uninterrupted sleep/rest post dose

The patient may experience impaired recall if woken during the period of maximum drug activity (1 to 2 hours after ingesting and lasting several hours). Therefore, patients should ensure they have 7 to 8 hours uninterrupted sleep.

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. Monitor these patients regularly, avoid routine repeat prescriptions, and withdraw treatment gradually.

Flurazepam should not be the sole treatment of depression, since suicide may be precipitated in such patients.

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.

Pregnancy and Lactation

Pregnancy

Use flurazepam with caution in pregnancy.

It is not known whether flurazepam crosses the placenta, but the molecular weight, and the fact that other benzodiazepines do, suggests that it is likely. Certainly, manufacturer data indicate that its active metabolite crosses the placenta, and may adversely affect the neonate, causing lethargy. However, other studies do not support an association between flurazepam and congenital defects. No teratogenic or other adverse foetal or postnatal effects have been observed in studies with rats or rabbits, and no reports of congenital abnormalities have been located following human exposure (Briggs, 2011).

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 and facial clefts. 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 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 when strictly indicated (Schaefer, 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.

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 to 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 on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Use flurazepam with caution in pregnancy.

There are currently no studies into the excretion of flurazepam into breast milk, but it should be expected based on data for other benzodiazepines, 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 or less than 10 mg diazepam/day) may be administered to nursing mothers, but high doses (equivalent to or greater than 10 mg 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. The CSM has recommended that benzodiazepines 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

Side Effects

Agitation
Amnesia
Ataxia
Bitter taste
Blood disorders
Changes in libido
Confusion
Delusions
Dependence
Depression
Dizziness
Double vision
Drowsiness and light-headedness (next day)
Excitement
Fatigue
Gastro-intestinal symptoms
Hallucinations
Headache
Hypotension
Increased hostility and aggression (paradoxical)
Irritability
Jaundice
Muscle weakness
Nightmares
Numbed emotions
Psychological changes
Psychosis
Rages
Rash
Reduced alertness
Restlessness
Suicidal tendencies
Urinary retention
Vertigo
Visual disturbances

Presentation

Oral formulations of flurazepam

Drugs List

Therapeutic Indications

Uses

Insomnia (short-term treatment)

Dosage

An underlying cause for insomnia should be sought before deciding upon the use of benzodiazepines for symptomatic relief.

The dosage should be determined on an individual basis, taking into account the severity of insomnia, and the patient's response to the treatment.

The lowest dose which can control the symptoms should be used, and the maximum dose should not be exceeded.

Adults

Elderly

Additional Dosage Information

Contraindications

Children under 18 years
Acute respiratory impairment
Chronic psychosis
Myasthenia gravis
Neuromuscular disorder
Obsessional states
Phobic states
Respiratory depression
Severe hepatic impairment
Sleep apnoea

Precautions and Warnings

Debilitation
Elderly
Females of childbearing potential
Hypoalbuminaemia
Breastfeeding
Chronic respiratory impairment
Hepatic impairment
History of alcohol abuse
History of drug misuse
Muscle weakness
Personality disorder
Porphyria
Pregnancy
Psychiatric disorder
Renal impairment
Respiratory disease

Reduce dose in patients with hepatic impairment
Reduce dose in patients with renal impairment
Advise ability to drive/operate machinery may be affected by side effects
Advise patient not to drive until they know how the medicine affects them
Advise patient this medicine may be subject to driving restrictions
Not suitable as sole treatment of depression or anxiety with depression
Neonate exposed in utero: Monitor for neonatal withdrawal syndrome
Tolerance and dependence may occur
Amnesia may occur
Discontinue if psychiatric disturbances develop
May cause paradoxical behaviour
Psychological adjustment may be impaired in loss or bereavement
Do not withdraw this drug suddenly
Withdraw gradually after long-term use
Discontinue if paradoxical reactions occur
Maintain treatment at the lowest effective dose
Reduce dose in debilitated patients
Reduce dose in elderly
Avoid long term continuous therapy
Only recommended for short term use
Advise patient to avoid alcohol during treatment
Advise patient to ensure 7- 8 hours of uninterrupted sleep/rest post dose

The patient may experience impaired recall if woken during the period of maximum drug activity (1 to 2 hours after ingesting and lasting several hours). Therefore, patients should ensure they have 7 to 8 hours uninterrupted sleep.

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. Monitor these patients regularly, avoid routine repeat prescriptions, and withdraw treatment gradually.

Flurazepam should not be the sole treatment of depression, since suicide may be precipitated in such patients.

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.

Pregnancy and Lactation

Pregnancy

Use flurazepam with caution in pregnancy.

It is not known whether flurazepam crosses the placenta, but the molecular weight, and the fact that other benzodiazepines do, suggests that it is likely. Certainly, manufacturer data indicate that its active metabolite crosses the placenta, and may adversely affect the neonate, causing lethargy. However, other studies do not support an association between flurazepam and congenital defects. No teratogenic or other adverse foetal or postnatal effects have been observed in studies with rats or rabbits, and no reports of congenital abnormalities have been located following human exposure (Briggs, 2011).

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 and facial clefts. 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 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 when strictly indicated (Schaefer, 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.

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 to 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 on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Use flurazepam with caution in pregnancy.

There are currently no studies into the excretion of flurazepam into breast milk, but it should be expected based on data for other benzodiazepines, 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 or less than 10 mg diazepam/day) may be administered to nursing mothers, but high doses (equivalent to or greater than 10 mg 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. The CSM has recommended that benzodiazepines 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

Effects on Ability to Drive and Operate Machinery

This class of medicine is in the list of drugs included in regulations under 5a of the Road Traffic Act 1988 (England and Wales). When prescribing this medicine: Advise patient the medicine can affect cognitive function and is likely to affect ability to drive. Advise patient not to drive until they know how the medicine affects them.

Side Effects

Agitation
Amnesia
Ataxia
Bitter taste
Blood disorders
Changes in libido
Confusion
Delusions
Dependence
Depression
Dizziness
Double vision
Drowsiness and light-headedness (next day)
Excitement
Fatigue
Gastro-intestinal symptoms
Hallucinations
Headache
Hypotension
Increased hostility and aggression (paradoxical)
Irritability
Jaundice
Muscle weakness
Nightmares
Numbed emotions
Psychological changes
Psychosis
Rages
Rash
Reduced alertness
Restlessness
Suicidal tendencies
Urinary retention
Vertigo
Visual disturbances

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: September 2014

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press https://www.medicinescomplete.com Accessed on September 4, 2014.

Summary of Product Characteristics: Dalmane Capsules 15mg. Meda Pharmaceuticals Ltd. Revised February 2014.

Summary of Product Characteristics: Dalmane Capsules 30mg. Meda Pharmaceuticals Ltd. Revised February 2014.

Committee on Safety of Medicines/Medicines Control Agency. Current problems in Pharmacovigilance (1997); 23: 10
Available at: https://www.mhra.gov.uk/Publications/CON007479
Reminder: avoid benzodiazepines in pregnancy and lactation .
Last accessed on September 4, 2014.

UK Drugs in Lactation Advisory Service.
Available at: https://www.ukmicentral.nhs.uk/drugpreg/qrg_p1.asp
Last accessed on September 4, 2014.

Gov.uk. Government departments. Department for Transport. Publications. Drug driving and medicine: advice for healthcare professionals. Drug driving: Guidance for healthcare professionals on drug driving. Available at: https://www.gov.uk Last accessed: 6 January 2015 New drug driving offence implications for medicines packaging. Medicines Regulatory News. 10 December 2013. Available at: https://www.mhra.gov.uk Last accessed: 6 January 2015