Lorazepam

Registered South African indications:

• Anxiety disturbances or anxiety states (tab)
  - General anxiety disturbances (tab)
  - Panic disturbances (tab)
  - Phobic anxiety disturbances (tab)
• Anxiety associated with and caused by organic disease (tab)
• Adjustment disturbances with anxiety or stress reactions (tab) 
• Acute anxiety episodes - severe (SL tab)
• Pre-medication to relieve anxiety and diminish recall of events associated with major or minor diagnostic procedure (SL tab)

Contraindications

South African recommendations

• Known hypersensitivity to benzodiazepines
• Pre-existing CNS depression or coma (tab)
• Porphyria (tab)
• Sleep apnoea (SL tab)
• Respiratory insufficiency (SL tab)
• Pregnancy (SL tab)

Recommendations in other jurisdictions

• Hypersensitivity to the active substance or to any of the excipients
• Hypersensitivity to benzodiazepines
• Acute pulmonary insufficiency: respiratory depression; sleep apnoea (risk of further respiratory depression)
• Obsessional states (inadequate evidence of safety and efficacy)
• Severe hepatic insufficiency (may precipitate encephalopathy)
• Planning a pregnancy
• Pregnancy (unless there are compelling reasons)
• Breastfeeding (unless there are compelling reasons) (0.5mg)
• Myasthenia gravis
• Benzodiazepines should not be used alone in depression or anxiety with depression (may precipitate suicide)

Cautions

• Pregnancy (tab) (South African recommendations)
• Breastfeeding (South African recommendations)
• Breastfeeding (Recommendations in other jurisdictions) (2.5mg)
• Renal impairment 
• Mild to moderate hepatic impairment (Recommendations in other jurisdictions)
• Elderly
• Children
• 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
• Patients sensitive to tartrazine (tab)
• Galactose intolerance (tab)
• Lapp lactase deficiency (tab)
• Glucose-galactose malabsorption (tab)

Forms avail. in SA and covered in this monograph: SL tab, tab

Dosages below include:

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

South African registered indications and dosages

Anxiety disturbances or anxiety states
- General anxiety disturbances
- Panic disturbances
- Phobic anxiety disturbances
Anxiety associated with and caused by organic disease
Adjustment disturbances with anxiety or stress reactions 

• Oral (tab): 2-3mg/day, in 2-4 divided doses; Range: 1-6mg/day

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Anxiety or tension associated with everyday life does not require treatment with an anxiolytic. It is recommended that the need for continued therapy with lorazepam be determined periodically

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Dosage should be individualised for optimal beneficial effect

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Acute anxiety episodes - severe

• Oral (SL tab): Recommended acute dosage: 4mg; Treatment duration: ≤8-12 weeks

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Duration of treatment should not exceed 8-12 weeks, including tapering. Extension of the treatment period should not take place without re-evaluation of the need for continued therapy. Treatment should be discontinued gradually

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Pre-medication to relieve anxiety and diminish recall of events associated with major or minor diagnostic procedure

• Oral (SL tab): 2mg, the night prior to procedure and/ OR 1-2hrs pre-procedure; If heightened sedative effect is required: 0.05mg/kg; Max: 4mg

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In case of local anaesthesia and diagnostic procedures requiring patient co-operation, concomitant use of an analgesic may be appropriate

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All indications:
Lorazepam sublingual tablets will dissolve in 20 seconds once placed under the tongue. The patient should not swallow for at least 2min to allow for sufficient time for absorption
Treatment should be started at the lowest recommended dose. The maximum dose should not be exceeded. Dosage and duration of therapy should be individualised. The lowest effective dose should be prescribed for the shortest time possible. Reassess regularly
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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Indications and dosages registered in other jurisdictions

Symptomatic relief of anxiety - severe
- Disabling or subjecting the individual to unacceptable distress occurring alone or in association with insomnia or short-term psychosomatic, organic or psychotic illness (short term therapy)

• Oral (tab): 1-4mg/day, in divided doses; Treatment duration: 2-4 weeks

Insomnia

• Oral (tab): 1-2mg, at night before bedtime; Treatment duration: 2-4 weeks

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Should not be used for long term therapy i.e. longer than 4 weeks and for mild/moderate anxiety

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Premedication
- Before operative dentistry and general surgery

• Oral (tab): 2-3mg, at night before operation; 2-4mg, 1-2hrs before the procedure

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Treatment to be given under close medical supervision, at the lowest effective dose and for the shortest possible duration (not exceeding 4 weeks). Doses should be individualised

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Extension of use should not take place without further clinical evaluation. Chronic use is not recommended (little is known of the long-term safety and efficacy, potential for dependence

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When treatment is started inform patient that treatment will be of limited duration, the dosage will be progressively decreased and there is a possibility of rebound phenomena

Paed. forms avail. in SA an covered in this monograph: SL tab, tab

Paed. dosages below include:

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

South African registered indications and dosages

Anxiety disturbances or anxiety states
- General anxiety disturbances
- Panic disturbances
- Phobic anxiety disturbances
Anxiety associated with and caused by organic disease
Adjustment disturbances with anxiety or stress reactions 

Oral (tab)

• Younger than 12 years: Not established for use
• 12 years and older: See adult dosage

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The safety and effectiveness of lorazepam sublingual tablets in children has not been established and as such is not recommended

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Indications and dosages registered in other jurisdictions
Premedication
- Before operative dentistry and general surgery

Oral (tab)

• Younger than 5 years: Not established for use
• Between 5-13 years: 0.5-2.5mg (0.05mg/kg to the nearest 0.5mg according to weight), >1hr before operation

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Not for use for insomnia or anxiety in children

Pregnancy

South African recommendations

• Contraindicated (SL tab)
• Benzodiazepines should not be used during pregnancy. If the medicine is prescribed to a woman of child bearing potential, she should be warned to contact her physician regarding discontinuance of the medicine if she intends to become or suspects that she is pregnant
• Benzodiazepines may cause foetal damage when administered to pregnant women. An increased risk of congenital malformation associated with the use of anxiolytic agents such as chlordiazepoxide, diazepam, and meprobamate has been suggested in several studies
• In humans, umbilical cord blood samples indicate placental transfer of benzodiazepines for several weeks or more preceding delivery and have been reported to have 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 to mothers who have received benzodiazepines during the late phase of pregnancy or at delivery
• Neonates appear to conjugate lorazepam slowly, the glucoronide being detectable in the urine for more than seven days. Glucoronidation of lorazepam may competitively inhibit the conjugation of bilirubin, leading to hyperbilirubinaemia in the newborn. Lorazepam sublingual tablets are not recommended for obstetrical use
   
• Caution; positive evidence of risk (tab)
• Lorazepam should be used judiciously during pregnancy and preferably avoided. In humans, blood levels obtained from umbilical cord indicate placental transfer of lorazepam and its glucuronide
• 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
• Given during labour, lorazepam crosses the placenta and my cause the floppy infant syndrome, characterised by central respiratory depression, hypothermia and poor sucking

Recommendations in other jurisdictions

• Contraindicated
• Benzodiazepines should not be used during pregnancy, especially during the first and last trimesters. Benzodiazepines may cause fetal 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
• There is a possibility that infants born to mothers who take benzodiazepines chronically during the later stages of pregnancy may develop physical dependence 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 hypoactivity, hypotonia, hypothermia, respiratory depression, apnea, 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

Breastfeeding

South African recommendations

• Caution; not recommended
• There is evidence that lorazepam is excreted in pharmacologically significant amounts in human breastmilk and should not be administered to nursing women

Recommendations in other jurisdictions

• 0.5mg (tab): Contraindicated
• 2.5mg (tab): Caution; not recommended
• Lorazepam is excreted in small amounts in breast milk. Mothers who are breastfeeding should not take benzodiazepines. Sedation and inability to suckle have occurred in neonates of lactating mothers taking benzodiazepines

Renal Impairment

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

Hepatic Impairment

South African recommendations

• Mild to moderate (Child-Pugh class A and B): No dose adjustment necessary
• Severe (Child-Pugh class C): Not recommended

Recommendations in other jurisdictions

• 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

South African recommendations

• Contraindicated (tab)

Recommendations in other jurisdictions

• 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. 

 

Tablet 0.5mg 

• Ativan (Pharmacare)

Tablet 1mg 

• Ativan (Pharmacare)
• Tranqipam (Pharmacare)

Tablet 2.5mg 

• Ativan (Pharmacare)
• Tranqipam (Pharmacare)

Tablet SL 1mg 

• Ativan SL (Pharmacare) originator