Drugs List

Therapeutic Indications

Uses

Acute excitement
Acute mania
Anxiety state
Premedication - sedative
Status epilepticus

Preoperative medication or premedication for uncomfortable or prolonged investigations.

For the treatment of acute anxiety states, acute excitement or acute mania.

For the control of status epilepticus.

Administration

Injection can be administered intravenous (preferred route) in larger veins or intramuscularly.

Precautions should be considered to avoid injection into small veins and intra-arterial route.

Intravenous injection should be administered slowly except in the control of status epilepticus where rapid injection is required.

Contraindications

Hypersensitivity to benzyl alcohol
Acute respiratory impairment
Myasthenia gravis
Pregnancy
Severe hepatic impairment
Sleep apnoea

Precautions and Warnings

Debilitation
Elderly
Females of childbearing potential
Severe illness
Shock
Acute narrow angle glaucoma
Breastfeeding
Chronic obstructive pulmonary disease
Chronic respiratory impairment
Coma
Depression
History of alcohol abuse
History of drug misuse
History of seizures
Mild hepatic impairment
Personality disorder
Psychosis
Reduced respiratory reserve
Renal impairment

Advise patient ability to drive or operate machinery may be impaired
Advise patient not to drive or operate machinery within 24-48 hours of dose
Advise patient not to drive until they know how the medicine affects them
Advise patient this medicine is subject to driving restrictions
Not recommended for chronic administration
Not suitable as sole treatment of depression or anxiety with depression
Contains benzyl alcohol
Injection contains propylene glycol
A patent airway and adequate oxygenation must be maintained
Ventilatory support facilities must be immediately available
For intravenous or intramuscular administration only
May cause respiratory depression
Monitor haematological parameters regularly throughout treatment
Observe patient for at least 8 hours post injection
Potential for drug abuse
Prolonged or excessive use may result in dependence
Amnesia may occur
May cause anaphylactic / anaphylactoid reactions
Potential for withdrawal symptoms
Withdrawal symptoms may follow short courses at normal doses
Avoid abrupt withdrawal
Advise patient to seek advice at first indications of pregnancy
Discontinue if angioedema occurs
Discontinue if paradoxical reactions occur
Consider dose reduction in hepatic impairment
Consider dose reduction in renal impairment
Not licensed for all indications in all age groups
Reduce dose in elderly
Advise patient not to take alcohol during and for 48 hours after therapy
Advise that effects are potentiated by CNS depressants (including alcohol)
Advise patient on possible rebound phenomena on withdrawal

Although hypotension has been observed only rarely, benzodiazepines should be administered with caution to patients, like the elderly, in whom a drop in blood pressure might lead to cardiovascular or cerebrovascular complications.

Patients receiving lorazepam as an outpatient should be accompanied when discharged.

Care should be exercised to patients with status epilepticus, especially when the patient has received other central nervous system depressants.

Angioedema has been reported during treatment, some may experience additional symptoms such as dyspnoea, throat closing or nausea and vomiting. If angioedema involves the tongue, glottis or larynx, airway obstruction may be fatal.

Withdrawal symptoms can appear after as little as one week of therapy. Withdrawal symptoms may occur when treatment is changed from long duration of action to short duration of action.

Treatment may have a disinhibiting effect and can cause suicidal tendencies in depressed patients.

Consider a more specific treatment if anxiety or insomnia present.

Allergic reactions may be caused by benzyl alcohol, only if necessary should high volumes be used, particularly those at risk of accumulation and toxicity.

Medical monitoring is required in paediatric patients with liver or hepatic function impairment receiving more than or equal to 50mg/kg/day of propylene glycol because of renal failure, renal dysfunction and liver dysfunction.

Pregnancy and Lactation

Pregnancy

Lorazepam is contraindicated during pregnancy.

The manufacturer does not recommend the use of lorazepam during pregnancy, especially during the first and last trimesters unless administration is deemed clinically justifiable by a physician. Since there is not enough data regarding obstetrical safety of parenteral lorazepam (including use in caesarean section), its use is also not recommended.

Treatment may cause foetal damage when administered to pregnant women. The use of lorazepam during the late phase of pregnancy may require ventilation for the infant at birth. Using lorazepam during the late phase of pregnancy or during labour at high doses can lead to effects on the neonate such as hypothermia, hypotonia and moderate respiratory depression. Infants of mothers who ingested benzodiazepines for several weeks or more preceding delivery presented withdrawal symptoms during the postnatal period. Other symptoms presented in neonates born of mothers taking benzodiazepines during the late phase of pregnancy or at delivery are apnoea, feeding problems and impaired metabolic response to cold stress.

Briggs (2015) suggests that lorazepam crosses the placenta. High doses used near delivery may lead to the "floppy infant" syndrome.

Lactation

Use lorazepam with caution during breastfeeding.

The manufacturer does not recommend breastfeeding whilst taking lorazepam unless the expected benefit to the women outweighs the potential harm to the infant. Available data suggests lorazepam is present in breast milk.

LactMed (2021) indicates that lorazepam is found in low levels in breastmilk and can be safely administered directly to infants. Evidence suggests that lorazepam does not cause any adverse effects in breastfed infants with usual maternal dosages. No special precautions are required.

Briggs (2015) indicates that in prolonged exposures the effects of lorazepam can be of concern, according to the American Academy of Paediatrics.

Side Effects

Aggression
Agitation
Agranulocytosis
Allergic skin reactions
Alopecia
Amnesia
Anaphylaxis
Angioedema
Anxiety
Apnoea
Asthenia
Ataxia
Blood dyscrasias
Blurred vision
Cardiac arrest
Changes in libido
Coma
Concentration disturbances
Confusion
Constipation
Decrease in blood pressure
Dependence
Depression
Diplopia
Disinhibition
Dizziness
Drowsiness
Dysarthria
Euphoria
Exacerbation of obstructive pulmonary disease
Excitation
Extrapyramidal effects
Fatigue
Gastro-intestinal disturbances
Hallucinations
Headache
Hostility
Hypersensitivity reactions
Hyponatraemia
Hypotension
Hypothermia
Impotence
Inappropriate secretion of antidiuretic hormone
Increase in alkaline phosphatase
Increases in hepatic enzymes
Insomnia
Jaundice
Local pain (injection site)
Muscle weakness
Nausea
Orgasmic dysfunction
Pancytopenia
Paradoxical reactions
Pre-existing depression may be unmasked
Rages
Respiratory depression
Sedation
Seizures
Serum bilirubin increased
Sexual disturbances
Skin reactions
Sleep disturbances
Slurred speech
Suicidal tendencies
Throat tightness
Thrombocytopenia
Tremor
Vertigo
Visual disturbances
Vomiting
Withdrawal symptoms

Presentation

Injection of lorazepam.

Drugs List

Therapeutic Indications

Uses

Acute excitement
Acute mania
Anxiety state
Premedication - sedative
Status epilepticus

Preoperative medication or premedication for uncomfortable or prolonged investigations.

For the treatment of acute anxiety states, acute excitement or acute mania.

For the control of status epilepticus.

Dosage

Dosage and duration of therapy should be individualised. The lowest effective dose should be prescribed for the shortest time possible.

Adults

Elderly

Children

Neonates

Additional Dosage Information

Administration

Injection can be administered intravenous (preferred route) in larger veins or intramuscularly.

Precautions should be considered to avoid injection into small veins and intra-arterial route.

Intravenous injection should be administered slowly except in the control of status epilepticus where rapid injection is required.

Contraindications

Hypersensitivity to benzyl alcohol
Acute respiratory impairment
Myasthenia gravis
Pregnancy
Severe hepatic impairment
Sleep apnoea

Precautions and Warnings

Debilitation
Elderly
Females of childbearing potential
Severe illness
Shock
Acute narrow angle glaucoma
Breastfeeding
Chronic obstructive pulmonary disease
Chronic respiratory impairment
Coma
Depression
History of alcohol abuse
History of drug misuse
History of seizures
Mild hepatic impairment
Personality disorder
Psychosis
Reduced respiratory reserve
Renal impairment

Advise patient ability to drive or operate machinery may be impaired
Advise patient not to drive or operate machinery within 24-48 hours of dose
Advise patient not to drive until they know how the medicine affects them
Advise patient this medicine is subject to driving restrictions
Not recommended for chronic administration
Not suitable as sole treatment of depression or anxiety with depression
Contains benzyl alcohol
Injection contains propylene glycol
A patent airway and adequate oxygenation must be maintained
Ventilatory support facilities must be immediately available
For intravenous or intramuscular administration only
May cause respiratory depression
Monitor haematological parameters regularly throughout treatment
Observe patient for at least 8 hours post injection
Potential for drug abuse
Prolonged or excessive use may result in dependence
Amnesia may occur
May cause anaphylactic / anaphylactoid reactions
Potential for withdrawal symptoms
Withdrawal symptoms may follow short courses at normal doses
Avoid abrupt withdrawal
Advise patient to seek advice at first indications of pregnancy
Discontinue if angioedema occurs
Discontinue if paradoxical reactions occur
Consider dose reduction in hepatic impairment
Consider dose reduction in renal impairment
Not licensed for all indications in all age groups
Reduce dose in elderly
Advise patient not to take alcohol during and for 48 hours after therapy
Advise that effects are potentiated by CNS depressants (including alcohol)
Advise patient on possible rebound phenomena on withdrawal

Although hypotension has been observed only rarely, benzodiazepines should be administered with caution to patients, like the elderly, in whom a drop in blood pressure might lead to cardiovascular or cerebrovascular complications.

Patients receiving lorazepam as an outpatient should be accompanied when discharged.

Care should be exercised to patients with status epilepticus, especially when the patient has received other central nervous system depressants.

Angioedema has been reported during treatment, some may experience additional symptoms such as dyspnoea, throat closing or nausea and vomiting. If angioedema involves the tongue, glottis or larynx, airway obstruction may be fatal.

Withdrawal symptoms can appear after as little as one week of therapy. Withdrawal symptoms may occur when treatment is changed from long duration of action to short duration of action.

Treatment may have a disinhibiting effect and can cause suicidal tendencies in depressed patients.

Consider a more specific treatment if anxiety or insomnia present.

Allergic reactions may be caused by benzyl alcohol, only if necessary should high volumes be used, particularly those at risk of accumulation and toxicity.

Medical monitoring is required in paediatric patients with liver or hepatic function impairment receiving more than or equal to 50mg/kg/day of propylene glycol because of renal failure, renal dysfunction and liver dysfunction.

Pregnancy and Lactation

Pregnancy

Lorazepam is contraindicated during pregnancy.

The manufacturer does not recommend the use of lorazepam during pregnancy, especially during the first and last trimesters unless administration is deemed clinically justifiable by a physician. Since there is not enough data regarding obstetrical safety of parenteral lorazepam (including use in caesarean section), its use is also not recommended.

Treatment may cause foetal damage when administered to pregnant women. The use of lorazepam during the late phase of pregnancy may require ventilation for the infant at birth. Using lorazepam during the late phase of pregnancy or during labour at high doses can lead to effects on the neonate such as hypothermia, hypotonia and moderate respiratory depression. Infants of mothers who ingested benzodiazepines for several weeks or more preceding delivery presented withdrawal symptoms during the postnatal period. Other symptoms presented in neonates born of mothers taking benzodiazepines during the late phase of pregnancy or at delivery are apnoea, feeding problems and impaired metabolic response to cold stress.

Briggs (2015) suggests that lorazepam crosses the placenta. High doses used near delivery may lead to the "floppy infant" syndrome.

Lactation

Use lorazepam with caution during breastfeeding.

The manufacturer does not recommend breastfeeding whilst taking lorazepam unless the expected benefit to the women outweighs the potential harm to the infant. Available data suggests lorazepam is present in breast milk.

LactMed (2021) indicates that lorazepam is found in low levels in breastmilk and can be safely administered directly to infants. Evidence suggests that lorazepam does not cause any adverse effects in breastfed infants with usual maternal dosages. No special precautions are required.

Briggs (2015) indicates that in prolonged exposures the effects of lorazepam can be of concern, according to the American Academy of Paediatrics.

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). This medicine may be subject to police testing and has specified maximum blood levels for driving.
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.
It is an offence to drive while under the influence of this medicine. However, a patient is not committing an offence (called 'statutory defence') if: 1. The medicine has been prescribed to treat a medical or dental problem and 2. The medicine has been taken according to the instructions given by the prescriber and/or in the information provided with the medicine, and 3. The medicine was not affecting the ability to drive safely. For further guidance see https://www.gov.uk

Side Effects

Aggression
Agitation
Agranulocytosis
Allergic skin reactions
Alopecia
Amnesia
Anaphylaxis
Angioedema
Anxiety
Apnoea
Asthenia
Ataxia
Blood dyscrasias
Blurred vision
Cardiac arrest
Changes in libido
Coma
Concentration disturbances
Confusion
Constipation
Decrease in blood pressure
Dependence
Depression
Diplopia
Disinhibition
Dizziness
Drowsiness
Dysarthria
Euphoria
Exacerbation of obstructive pulmonary disease
Excitation
Extrapyramidal effects
Fatigue
Gastro-intestinal disturbances
Hallucinations
Headache
Hostility
Hypersensitivity reactions
Hyponatraemia
Hypotension
Hypothermia
Impotence
Inappropriate secretion of antidiuretic hormone
Increase in alkaline phosphatase
Increases in hepatic enzymes
Insomnia
Jaundice
Local pain (injection site)
Muscle weakness
Nausea
Orgasmic dysfunction
Pancytopenia
Paradoxical reactions
Pre-existing depression may be unmasked
Rages
Respiratory depression
Sedation
Seizures
Serum bilirubin increased
Sexual disturbances
Skin reactions
Sleep disturbances
Slurred speech
Suicidal tendencies
Throat tightness
Thrombocytopenia
Tremor
Vertigo
Visual disturbances
Vomiting
Withdrawal symptoms

Withdrawal Symptoms and Signs

Withdrawal symptoms may appear following the cessation of treatment and can occur after as little as one week of therapy. Patients should be informed that treatment will be of limited duration and that discontinuation of treatment will be gradual.

Symptoms of withdrawal include, headaches, muscle pain, anxiety, tension, depression, insomnia, restlessness, confusion, irritability, sweating, and a rebound phenomena. In severe cases derealisation, depersonalisation, hyperacusis, tinnitus, numbness and tingling of the extremities, hypersensitivity to light, noise and physical contact, involuntary movements, vomiting, hallucinations and convulsions may occur.

Patients should be aware of the 'rebound' phenomena to reduce anxiety should symptoms occur.

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 2021

Reference Sources

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

Summary of Product Characteristics: Lorazepam Macure 4mg/ml solution for injection. Macure Pharma UK Ltd. Revised March 2021.

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: 10 September 2021

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 10 September 2021

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://www.ncbi.nlm.nih.gov/books/NBK501922/
Lorazepam Last revised: 21 June 2021
Last accessed: 07 October 2021