Drugs List

Therapeutic Indications

Uses

Insomnia (short-term treatment)

Short-term treatment of insomnia, including difficulty in falling asleep and/or frequent nocturnal awakenings. Only for use when insomnia is severe or disabling, or subjecting the individual to extreme distress.

Contraindications

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

Precautions and Warnings

Debilitation
Elderly
Suicidal ideation
Cerebrovascular disorder
Depression
Glucose-galactose malabsorption syndrome
Hepatic impairment
History of alcohol abuse
History of drug misuse
Lactose intolerance
Muscle weakness
Personality disorder
Pregnancy
Psychiatric disorder
Renal impairment
Respiratory disease

Advise impaired alertness may affect ability to drive or operate machinery
Advise patient ability to drive or operate machinery may be impaired
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
Some formulations contain lactose
Monitor closely suicidal subjects
Monitor for rebound insomnia following withdrawal
Neonate exposed in utero: Monitor for neonatal withdrawal syndrome
Prolonged or excessive use may result in dependence
Discontinue if psychiatric disturbances develop
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
Not recommended for use longer than 4 weeks
Only recommended for short term use
Advise patient to avoid alcohol during treatment

Suicide may be precipitated in patients who are depressed and who exhibit aggressive behaviour towards self and others.

Dosage should be decreased gradually to avoid withdrawal symptoms. These are more likely if physical dependence has developed during usage. However, withdrawal symptoms can occur even with normal therapeutic doses given for short periods of time. Patients receiving benzodiazepines should be regularly monitored.

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.

Pregnancy and Lactation

Pregnancy

Loprazolam should be used with caution in 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 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 (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.

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

Loprazolam is contraindicated during breastfeeding.

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

Anterograde amnesia
Ataxia
Blood dyscrasias
Blurred vision
Changes in libido
Confusion
Dependence
Depression (with risk of suicide)
Dizziness
Drowsiness and light-headedness (next day)
Excitement
Gastro-intestinal symptoms
Headache
Hypotension
Increased hostility and aggression (paradoxical)
Jaundice
Muscle hypotonia
Nausea
Rash
Urinary retention
Visual disturbances

Presentation

Tablets containing loprazolam

Drugs List

Therapeutic Indications

Uses

Insomnia (short-term treatment)

Short-term treatment of insomnia, including difficulty in falling asleep and/or frequent nocturnal awakenings. Only for use when insomnia is severe or disabling, or subjecting the individual to extreme distress.

Dosage

The lowest dose which can control the symptoms should be used.

If possible, treatment should be intermittent; long term chronic use is not recommended. Treatment should not normally be continued beyond 4 weeks.

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.

Adults

Elderly

Contraindications

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

Precautions and Warnings

Debilitation
Elderly
Suicidal ideation
Cerebrovascular disorder
Depression
Glucose-galactose malabsorption syndrome
Hepatic impairment
History of alcohol abuse
History of drug misuse
Lactose intolerance
Muscle weakness
Personality disorder
Pregnancy
Psychiatric disorder
Renal impairment
Respiratory disease

Advise impaired alertness may affect ability to drive or operate machinery
Advise patient ability to drive or operate machinery may be impaired
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
Some formulations contain lactose
Monitor closely suicidal subjects
Monitor for rebound insomnia following withdrawal
Neonate exposed in utero: Monitor for neonatal withdrawal syndrome
Prolonged or excessive use may result in dependence
Discontinue if psychiatric disturbances develop
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
Not recommended for use longer than 4 weeks
Only recommended for short term use
Advise patient to avoid alcohol during treatment

Suicide may be precipitated in patients who are depressed and who exhibit aggressive behaviour towards self and others.

Dosage should be decreased gradually to avoid withdrawal symptoms. These are more likely if physical dependence has developed during usage. However, withdrawal symptoms can occur even with normal therapeutic doses given for short periods of time. Patients receiving benzodiazepines should be regularly monitored.

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.

Pregnancy and Lactation

Pregnancy

Loprazolam should be used with caution in 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 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 (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.

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

Loprazolam is contraindicated during breastfeeding.

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.

Counselling

Advise women of childbearing potential to contact their physician if they intend to become, or suspect they may be pregnant.

Advise patients not to drive or operate machinery if affected by sedation, amnesia, impaired concentration or impaired muscle function.

Advise patients that impairment may be intensified by alcohol and that they should not drink alcohol during treatment with loprazolam.

Side Effects

Anterograde amnesia
Ataxia
Blood dyscrasias
Blurred vision
Changes in libido
Confusion
Dependence
Depression (with risk of suicide)
Dizziness
Drowsiness and light-headedness (next day)
Excitement
Gastro-intestinal symptoms
Headache
Hypotension
Increased hostility and aggression (paradoxical)
Jaundice
Muscle hypotonia
Nausea
Rash
Urinary retention
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: October 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.

Joint Formulary Committee. British National Formulary(online) London: BMJ Group and Pharmaceutical Press Accessed on 3 October, 2014.

Paediatric Formulary Committee. BNF for Children (online) London: BMJ Group, Pharmaceutical Press, and RCPCH Publications Accessed on 3 October, 2014.

Summary of Product Characteristics: Loprazolam 1mg tablets. Zentiva. Revised September 2014.

Clinical Knowledge Summaries - Insomnia - Management
Scenario: Managing short-term insomnia (less than 4 weeks)
Available at: https://cks.nice.org.uk/insomnia#!scenario
Last accessed: 3 October, 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: 3 October, 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