Lorazepam

Registered South African indications:

• Pre-medication to relieve anxiety and tension, and to diminish recall of events associated with major or minor surgical and diagnostic procedures
• Symptomatic relief of acute anxiety
• Status epilepticus caused by various partial and generalised types

Contraindications

South African recommendations

• Pregnancy
• Known sensitivity or history of hypersensitivity to benzodiazepines, or to any ingredients contained in lorazepam injection
• Pre-existing central nervous system (CNS) depression or coma
• Respiratory insufficiency
• Sleep apnoea syndrome
• Myasthenia gravis
• Severe hepatic insufficiency
• Lorazepam is not recommended for out-patient use unless the patient is accompanied
• Children less than 12 years

Recommendations in other jurisdictions

• Hypersensitivity to the active substance, benzodiazepines or to any of the excipients
• Acute pulmonary insufficiency
• Sleep apnoea syndrome
• Myasthenia gravis
• Severe hepatic insufficiency
• Lorazepam is not recommended for out-patient use unless the patient is accompanied

Cautions

• Pregnancy (Recommendations in other jurisdictions)
• Breastfeeding
• Renal impairment 
• Mild to moderate hepatic impairment
• Elderly
• Depressive disorders
• Cardiovascular disease
• Cerebrovascular disease
• Psychotic disorders 
• Personality disorders 
• High doses
• Prolonged use 
• Abrupt withdrawal 
• History of alcoholism 
• Coma
• Shock
• History of drug abuse 
• Acute narrow angle glaucoma
• Chronic respiratory insufficiency
• Debilitated patients
• Impaired alcohol dehydrogenase enzyme systems

Forms avail. in SA and covered in this monograph: inj

Dosages below include:

• South African registered indications and dosages
• Indications and dosages registered in other jurisdictions

South African registered indications and dosages

Pre-medication to relieve anxiety and tension, and to diminish recall of events associated with major or minor surgical and diagnostic procedures

• IV: 0.05mg/kg (3.5mg for an average 70kg man), 30-45min prior to operative procedure

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Sedation will be evident after 5-10 minutes and maximal loss of recall will occur after 30-45 minutes. This dose will suffice for sedating most adult patients, and should not ordinarily be exceeded in those over 50 years

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• IM: 0.05mg/kg, 2hrs prior to operative procedure

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Sedation will be evident after 30-45 minutes and maximal loss of recall will occur after 60-90 minutes

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Administering lorazepam 1-2.5mg orally is recommended on the evening before surgery to relieve anxiety and promote sleep

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Symptomatic relief of acute anxiety
- In acute cases of anxiety with or without psychomotor agitation (and depending on its aetiology, severity, and the mass of the patient)

• IV: Initial: 0.025-0.03mg/kg (1.75-2.1mg for an average 70kg man); Repeat dose every 6hrs, if needed; Once the acute symptomatology has been controlled, switch to oral therapy if further treatment is required

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Lorazepam is indicated only when the disorder has not responded to non-medicine therapy, and is severe, disabling, or subjecting the individual to unacceptable distress. Anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic

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Status epilepticus caused by various partial and generalised types
- Generalised (tonic-clonic, “grand-mal”) seizures, generalised absence (“petit mal”) seizures or spike-wave stupor, partial elementary (focal motor) seizures, partial complex (psychomotor) seizures, and combinations such as generalised seizures with focal onset

• IV: Initial: 4mg, as a slow injection (2mg/min); If seizures continue or recur after 10-14min observation period: Repeat dose; If the 2nd dose does not result in seizure control after another 10-15min observation period: Other measures to control status epilepticus should be employed; Max: 8mg/12hr period

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All indications:
Dosage and duration of therapy should be individualised. The lowest effective dose should be prescribed for the shortest time possible. Treatment in all patients should be withdrawn gradually to minimise possible withdrawal symptoms

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Lorazepam can be given IV or IM. However, the IV route is to be preferred. Care should be taken to avoid injection into small veins and intra-arterial injection. Absorption from the injection site is considerably slower if the intramuscular route is used and as rapid an effect may be obtained by oral administration of lorazepam

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Lorazepam should not be used for long-term chronic treatment

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Indications and dosages registered in other jurisdictions

Pre-operative medication/ premedication for uncomfortable or prolonged investigations
- Examples are bronchoscopy, arteriography, endoscopy

• IV: 0.05mg/kg (3.5mg for an average 70kg man), 30-45min prior to operative procedure

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Sedation will be evident after 5-10 minutes and maximal loss of recall will occur after 30-45 minutes

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• IM: 0.05mg/kg, 60-90min prior to operative procedure

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Sedation will be evident after 30-45 minutes and maximal loss of recall will occur after 60-90 minutes

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Acute anxiety states, acute excitement or acute mania

• IV/IM: Initial: 0.025-0.03mg/kg (1.75-2.1mg for an average 70kg man); Repeat dose every 6hrs, if needed

Control of status epilepticus

• IV: 4mg

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All indications:
Dosage and duration of therapy should be individualised. The lowest effective dose should be prescribed for the shortest time possible. Treatment in all patients should be withdrawn gradually to minimise possible withdrawal symptoms

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Lorazepam can be given IV or IM. However, the IV route is to be preferred. Care should be taken to avoid injection into small veins and intra-arterial injection. Absorption from the injection site is considerably slower if the intramuscular route is used and as rapid an effect may be obtained by oral administration of lorazepam

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Lorazepam should not be used for long-term chronic treatment

Paed. forms avail. in SA an covered in this monograph: inj

Paed. dosages below include:

• South African registered indications and dosages
• Indications and dosages registered in other jurisdictions

South African registered indications and dosages

Pre-medication to relieve anxiety and tension, and to diminish recall of events associated with major or minor surgical and diagnostic procedures
Symptomatic relief of acute anxiety
- In acute cases of anxiety with or without psychomotor agitation (and depending on its aetiology, severity, and the mass of the patient)

Younger than 12 years

• Contraindicated

12 years and older

• See adult dosage

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Indications and dosages registered in other jurisdictions

Pre-operative medication/ premedication for uncomfortable or prolonged investigations
- Such as bronchoscopy, arteriography, endoscopy
Acute anxiety states, acute excitement or acute mania

Younger than 12 years

• No recommended for use

12 years and older

• See adult dosage

Control of status epilepticus

• IV: 2mg

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All indications:
Dosage and duration of therapy should be individualised. The lowest effective dose should be prescribed for the shortest time possible. Treatment in all patients should be withdrawn gradually to minimise possible withdrawal symptoms

---

Lorazepam should not be used for long-term chronic treatment

Pregnancy

South African recommendations

• Contraindicated 
• Safety in pregnancy has not been established
• Lorazepam should not be used during pregnancy. Lorazepam may cause foetal damage when administered to pregnant women
• An increased risk of congenital malformations associated with the use of benzodiazepines has been suggested in studies. Neonates born from women using benzodiazepines such as lorazepam may present with withdrawal symptoms during the postnatal period
• Symptoms such as hypoactivity, hypotonia, hypothermia, respiratory depression, apnoea, feeding problems, and impaired metabolic response to cold stress have been reported in neonates born of mothers who have received benzodiazepines during the late phase of pregnancy or at delivery
• Given during labour, it crosses the placenta and may cause the floppy-infant syndrome characterised by central respiratory depression, hypothermia and poor sucking
• Neonates appear to conjugate lorazepam slowly, the glucuronide being detectable in the urine for more than seven days. Glucuronidation of lorazepam may competitively inhibit the conjugation of bilirubin, leading to hyperbilirubinaemia in the newborn. Lorazepam is not recommended for obstetrical use

Recommendations in other jurisdictions

• Caution; positive evidence of risk
• Lorazepam should not be used during pregnancy, especially during the first and last trimesters, unless in the judgement of the physician such administration is clinically justifiable
• Benzodiazepines may cause foetal damage when administered to pregnant women. If the drug is prescribed to a woman of childbearing potential, she should be warned to contact her physician about stopping the drug if she intends to become, or suspects that she is, pregnant
• Use of lorazepam during the late phase of pregnancy may require ventilation of the infant at birth. If, for compelling medical reasons, the product is administered during the late phase of pregnancy, or during labour at high doses, effects on the neonate, such as hypothermia, hypotonia and moderate respiratory depression, can be expected, due to the pharmacological action of the compound
• Infants of mothers who ingested benzodiazepines for several weeks or more preceding delivery have been reported to have withdrawal symptoms during the postnatal period
• Symptoms such as hypotonia, hypothermia, respiratory depression, apnoea, feeding problems, and impaired metabolic response to cold stress have been reported in neonates born of mothers who have received benzodiazepines during the late phase of pregnancy or at delivery
• There are insufficient data regarding obstetrical safety of parenteral lorazepam, including use in caesarean section. Such use, therefore, is not recommended
• Benzyl alcohol can cross the placenta

Breastfeeding

South African recommendations

• Caution; not recommended
• Lorazepam injection should not be administered to breastfeeding women. Evidence to date indicates that lorazepam injection is excreted in breast milk
• Sedation and inability to suckle have occurred in neonates of lactating mothers taking benzodiazepines
• Infants of lactating mothers should be observed for pharmacological effects (including sedation and irritability)

Recommendations in other jurisdictions

• Caution; not recommended
• Since benzodiazepines are found in breast milk, lorazepam should not be given to breastfeeding mothers unless the expected benefit to the woman outweighs the potential risk to the infant

Renal Impairment

• eGFR 30-89 ml/min/1.73m²: No dose adjustment necessary
• eGFR ≤29 mL/min/1.73m²: Not recommended

Hepatic Impairment

• Mild to moderate: Caution; dose adjustment recommended
  Lower doses may be sufficient in these patients
• Severe: Contraindicated

Elderly

• Caution; dose adjustment recommended
  Initial dose should not exceed 2mg/day in divided doses; May respond to dose <50% of the normal adult dose

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Confusion
• Depression
• Unmasking of depression
• Disinhibition
• Euphoria
• Suicidal ideation or attempt
• Anxiety
• Agitation
• Excitation
• Hostility
• Aggression
• Sleep disturbances
• Sexual arousal
• Hallucinations
• Sedation
• Daytime drowsiness
• Ataxia
• Dizziness
• Extrapyramidal symptoms
• Tremor
• Vertigo
• Dysarthria
• Headache
• Numbed emotions 
• Appetite changes 
• Seizure
• Amnesia
• Coma
• Withdrawal symptoms 
• Dependence 
• Fatigue 
• Tremor
• Transient anterograde amnesia  

Cardiovascular Disorders

• Hypotension

Respiratory Disorders

• Respiratory depression
• Apnoea
• Worsening of obstructive pulmonary disease

Gastrointestinal Disorders

• Nausea
• Constipation
• Salivation changes

 Hepatobiliary Disorders

• Increase in hepatic function test values

Genitourinary Disorders

• Change in libido
• Impotence
• Decreased orgasm

Endocrine and Metabolic Disorders

• Syndrome of inappropriate antidiuretic hormone secretion
• Hyponatremia
• Hypothermia 

Musculoskeletal Disorders

• Muscle weakness

Skin and Subcutaneous Tissue Disorders

• Alopecia
• Rash
• Allergic dermatitis 
• Pain at injection site 

Immune, Blood and Lymphatic System Disorders

• Thrombocytopenia
• Agranulocytosis
• Pancytopenia
• Hypersensitivity reactions
• Anaphylactoid reactions
• Angioedema

Sensory Disorders

• Diplopia
• Blurred vision

• Central nervous system depressants
• Sodium oxybate
• Hydantoins
• Protease inhibitors 
• Probenecid
• Cisapride 
• Lofexidine 
• Nabilone
• Disulfiram 
• Baclofen
• Tizanidine 
• CYP450 inhibitors
• CYP450 inducers 
• Clozapine 
• Theophylline 
• Aminophylline 
• Haloperidol
• Adrenergic neurone blockers
• Beta-blockers
• Moxonidine
• Nitrates
• Hydralazine
• Minoxidil
• Sodium nitroprusside
• Diuretics
• Oestrogen-containing contraceptives
• Dopaminergics 
• Caffeine 
• Antacids

None routine. Specific cases may require

• Renal function 
• Hepatic function

Lorazepam enhances the effects of gamma aminobutyric acid, an inhibitory neurotransmitter in the central nervous system. 

 

Injection (per ml) 4mg

• Ativan (Pharmacare) originator