Lorazepam

Anxiolytic and Hypnotic Drugs

Drug class: Benzodiazepine, BDZs

Lorazepam (Ativan)(中文:勞拉西泮 ) is a short-acting benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant properties. It is used:

• In the short-term treatment of severe anxiety disorders;
• As a hypnotic in the short-term treatment of insomnia;
• As an anticonvulsant (particularly in the management of status epilepticus and febrile convulsions)
• As a sedative for those who are being mechanically ventilated
• Chemotherapy-induced nausea and vomiting

Pronunciation

Lorazepam 0.5mg

Lorazepam 1mg

Drug Names

Generic Name 藥名	HA Code 藥物代碼	Classification藥物分類
Lorazepam Tablet 0.5 mg	LORA01	P1S1S3 & Part 1 Dangerous Drug
Lorazepam Tablet 1 mg	LORA02	P1S1S3 & Part 1 Dangerous Drug
Lorazepam Tablet 2 mg	LORA03	P1S1S3 & Part 1 Dangerous Drug

Drug Usage

• Anxiety disorders
• Insomnia due to anxiety or stress
• Status epilepticus
• Pre-operative sedation

Mechanism of Action

• Lorazepam is a benzodiazepine.
• Gama-Aminobutyric acid (GABA) is an inhibitory neurotransmitter, acting on the GABA receptors in the central nervous system (CNS), thus inhibiting the nerve impulses.
• It acts on the benzodiazepine receptors in the brain and the spinal cord. Benzodiazepine receptors in the CNS are linked with GABA receptors as a complex.
• Lorazepam by binding to the benzodiazepine receptors results in activation of the GABA-benzodiazepine receptor complex, resulting in inhibition of nerve impulses, overall depression of brain and spinal cord.
• The anticonvulsant properties of lorazepam come from binding to sodium channels.

Route of Administration

Oral (tablets, solution), intramuscular injection, intravenous injection

Dosage

Anxiety	By mouth ADULT: 1 – 4 mg daily in divided doses ELDERLY: 0.5 – 2 mg daily in divided doses
Insomnia associated with anxiety	By mouth ADULT: 1 – 2 mg daily, to be taken at bedtime
Acute panic attacks	By mouth ADULT: 25 – 30 micrograms/kg every 6 hours if required; Usual dose: 1.5 – 2.5 mg every 6 hours if required
Conscious sedation for procedures	By mouth ADULT: 2 – 3 mg to be taken the night before operation 2 – 4 mg to be taken 1 – 2 hours before operation
Premedication	By mouth 2 – 3 mg to be taken the night before operation 2 – 4 mg to be taken 1 – 2 hours before operation
Status epilepticus Febrile convulsions Convulsions due to poisoning	By slow intravenous injection CHILD 1 month – 11 years: 100 micrograms/kg (max. per dose 4 mg) for 1 dose, then 100 micrograms/kg after 10 minutes (max. per dose 4 mg) if required for 1 dose, to be administered into a large vein CHILD 12 – 17 years: 4 mg for 1 dose, then 4 mg after 10 minutes if required for 1 dose, to be administered into a large vein ADULT: 4 mg for 1 dose, then 4 mg after 10 minutes if seizures continue or recur
Chemotherapy-induced nausea and vomiting	By mouth ADULTS: 1 to 2 mg may be added to antiemetic therapy with domperidone or metoclopramide for the prophylaxis of nausea and vomiting. The addition of lorazepam may be helpful in the prevention of anticipatory symptoms because of its anxiolytic, sedative and amnestic effects.

Side Effects

Sedative drugs, including alprazolam, have been associated with an increased risk of death.

Possible side effects include:

Very common (>10% of incidence) or Common(1-10% of incidence)	Shakiness and unsteady walk (especially in the elderly) Trembling, and other problems with muscle control or coordination Confusion (especially in the elderly) Amnesia Drowsiness the next day sedation Muscle weakness Paradoxical increase in aggression
Infrequent (0.1 -1% of incidence)	Dysarthria Gastro-intestinal disturbances Gynaecomastia Low blood pressure Incontinence Urinary retention Slurred speech Tremor Vertigo Visual disturbances
Rare (<0.1% of incidence)	Apnoea Blood disorders Jaundice Respiratory depression hypersensitivity reactions

Overdosage can produce CNS depression and coma.

Paradoxical reactions (the opposite of what is to be expected) may occur. Symptoms include

• aggression, rage
• mania, agitation, and restlessness
• hallucinations, inappropriate behavior
• twitches and tremor

Pharmacokinetics

Oral bioavailability	Lorazepam is well absorbed after oral doses.
Onset of action	Peak plasma concentrations occur about 2 hours after an oral dose; and after 10 to 30 minutes when given as a rectal solution.
Metabolism	Lorazepam is metabolized in the liver
Elimination half-life	Lorazepam is excreted in the urine. The half-life of Lorazepam ranges from 10 – 20 hours.

Drug Management

Monitoring

• Blood pressure, pulse and respiratory rate are recommended
• Elderly may be sensitivity to diazepam’s effects. Impairment of memory, cognitive function, and psychomotor performance and behavior disinhibition may be common. Long-term use commonly exacerbates underlying dementia in elderly patients.
• Diazepam may make elderly patients feel dizzy, increasing risk of falls, so fall prevention is needed
• Some patients develop blood dyscrasias, and have raised liver enzymes, so periodic blood counts and liver function tests are recommended
• changes in mood, the development or worsening depression, and/or any thoughts or behaviour of suicide.

Dependence and Withdrawal

• One-third of individuals treated with benzodiazepines for longer than 4 weeks develop a dependence on the drug and experience a withdrawal syndrome on cessation.
• Withdrawal symptoms can range from insomnia and anxiety to more serious symptoms, including seizures and psychosis.
• Lorazepam should therefore be withdrawn by tapering the dose to minimize occurrence of withdrawal symptoms.

Drug interaction

Medicines that interact with diazepam may either

• Decrease its effect
• Affect how long it works for
• Increase side effects

Common medications that may interact with diazepam include:

Drugs given with lorazepam	Potential Effect
Alcohol, Hypnotics/sedative (e.g. barbiturates) Antidepressants (e.g. fluoxetine, amitriptyline) Sedative histamines (e.g. promethazine) Antipsychotic (e.g. chlorpromazine, clozapine)	May worsens the side effects such as drowsiness , dizziness and respiratory depression
Valproate	Valproate inhibits the metabolism of lorazepam and thus prolong its action.
Carbamazepine Lamotrigine Phenobarbitone Phenytoin rifampicin	All these drugs increase metabolism of lorazepam, thus decreasing its plasma levels and effects
Alcohol	May cause a synergistic enhancement of the hypotensive effect of lorazepam and alcohol
Oral contraceptives	Plasma concentration of lorazepam reduced by estrogens
Steroid (e.g. Dexamethasone) St John’s wort	Increase the metabolism of lorazepam, thus decreasing its plasma levels and effects
Steroid (e.g. Dexamethasone) St John’s wort	Increase the metabolism of diazepam, thus decreasing diazepam plasma levels and effects
Theophylline	May inhibit the action of lorazepam
Levodopa (e.g. Sinemet)	Lorazepam may block the action of levodopa used in the treatment of Parkinson’s disease.

Caution

• particular care in pregnancy,
• elderly, due to increased susceptibility to side-effects, especially loss of coordination and drowsiness
• in patients with hepatic or renal impairment, who may require reduced doses
• people with history of alcohol dependence or abuse
• people with history of drug dependence or abuse
• people with psychiatric disorders
• avoid prolonged use and abrupt withdrawal thereafter

Contra-indications

Use of diazepam should be avoided, when possible, in individuals with:

• severe hepatic impairment
• sleep apnoea
• chronic obstructive airways disease (COPD)
• Myasthenia gravis
• Acute narrow-angle glaucoma
• Chronic schizophrenia

Hepatic impairment

• Start with smaller initial doses or reduce dose.
• Can precipitate coma.
• Avoid in severe impairment.

Renal impairment

• Start with small doses in severe impairment.

Pregnancy

Possible adverse effects of use of benzodiazepines such as diazepam during pregnancy include: miscarriage, malformation, intrauterine growth retardation, and function deficits.

Breast-feeding

Use during breast feeding is not recommended.

Driving and skilled tasks

May impair judgment and increase reaction time, and so affect ability to drive or operate machinery. Patients should be warned not to operate dangerous machinery or motor vehicles until it is known that they do not become drowsy from diazepam therapy.

FAQ

How should I take the tablet?

May be taken with or without food. Swallow whole with a glass of water.

What should I avoid while taking?

Do not eat grapefruit or drink grapefruit juice as it may increase blood levels of diazepam.

Avoid drinking alcohol while taking diazepam because it may enhance the side effects of sedation and respiratory depression.

Avoid driving or hazardous activity until you know how diazepam will affect you.

What happen if I overdose?

Contact your primary care doctor. If emergency situation, call 999

What happen if I miss a dose?

Take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.