ATC categoryNeurology. Psychiatry
Each Lorazepam 1 mg tablet contains:
active ingredient: lorazepam – 1 mg
For a full list of excipients, see section List of excipients.
Lorazepam, 1 mg tablets
White or off white scored cylindrical tablets with a few small darker spots and with a risk on one side and a facet on both sides.
For short term (2-4 weeks only) use (adults only)
As Premedication (adults and children 5 years and above)
Before operative dentistry and general surgery
Not for use
Posology and method of administration
Route of administration: oral
Treatment to be given:
Doses should be individualized
Extension of use should not take place without further clinical evaluation
Chronic use not recommended (little is known of the long-term safety and efficacy; potential for dependence–see section Special warnings and precautions for use).
When treatment is started the patient should be informed that
Anxiety: 1-4mg daily in divided doses. Insomnia: 1-2mg before retiring
Premedication before operative dentistry or general surgery:
2-3mg the night before operation 2-4mg one to two hours before the procedure
Elderly and debilitated patients:
For elderly and debilitated patients reduce the initial dose by approximately 50% and adjust the dosage as needed and tolerated (see section Special warnings and precautions for use).
Children (aged 5-13 years):
Premedication: 0.5-2.5mg at 0.05mg/kg to the nearest 0.5mg according to weight, not less than one hour before operation.
Patients with Renal or Hepatic impairment:
Lower doses may be sufficient in these patients (See section Special warnings and precautions for use). Use in patients with severe hepatic insufficiency is contraindicated. (See section Fertility, pregnancy and lactation).
Benzodiazepines should not be used alone in depression or anxiety with depression (may precipitate suicide)
Patients should be advised that since their tolerance for alcohol and other CNS depressants will be diminished in the presence of Lorazepam, these substances should either be avoided or taken in reduced dosage.
Lorazepam is not intended for the primary treatment of psychotic illness or depressive disorders, and should not be used alone to treat depressed patients. The use of benzodiazepines may have a disinhibiting effect and may release suicidal tendencies in depressed patients. Therefore, large quantities of Lorazepam should not be prescribed to these patients.
Pre-existing depression may emerge during benzodiazepine use.
The use of benzodiazepines may lead to physical and psychological dependence. The risk of dependence on Lorazepam is low when used at the recommended dose and duration, but increases with higher doses and longer-term use. The risk of dependence is further increased in patients with a history of alcoholism or drug abuse, or in patients with significant personality disorders. Therefore, use in individuals with a history of alcoholism or drug abuse should be avoided.
Dependence may lead to withdrawal symptoms, especially if treatment is discontinued abruptly. (see Undesirable effects). Therefore, the drug should always be discontinued gradually.
It may be useful to inform the patient that treatment will be of limited duration and that it will be discontinued gradually. The patient should also be made aware of the possibility of “rebound” phenomena to minimize anxiety should they occur.
Abuse of benzodiazepines has been reported.
Some loss of efficacy to the hypnotic effects of short-acting benzodiazepines may develop after repeated use for a few weeks.
Anxiety or insomnia may be a symptom of several other disorders. The possibility should be considered that the complaint may be related to an underlying physical or psychiatric disorder for which there is more specific treatment.
Caution should be used in the treatment of patients with acute narrow-angle glaucoma.
Patients with impaired renal or hepatic function should be monitored frequently and have their dosage adjusted carefully according to patient response. Lower doses may be sufficient in these patients. The same precautions apply to elderly or debilitated patients and patients with chronic respiratory insufficiency.
As with all CNS-depressants, the use of benzodiazepines may precipitate encephalopathy in patients with severe hepatic insufficiency. Therefore, use in these patients is contraindicated.
Some patients taking benzodiazepines have developed a blood dyscrasia, and some have had elevations in liver enzymes. Periodic hematology and liver-function assessments are recommended where repeated courses of treatment are considered clinically necessary.
Transient anterograde amnesia or memory impairment has been reported in association with the use of benzodiazepines. This effect may be advantageous when Lorazepam is used as a premedicant. However, if Lorazepam is used for insomnia due to anxiety, patients should ensure that they will be able to have a period of uninterrupted sleep which is sufficient to allow dissipation of drug effect (e.g., 7-8 hours).
Paradoxical reactions have been occasionally reported during benzodiazepine use. Such reactions may be more likely to occur in children and the elderly. Should these occur, use of the drug should be discontinued (see Undesirable effects).
Although hypotension has occurred only rarely, benzodiazepines should be administered with caution to patients in whom a drop-in blood pressure might lead to cardiovascular or cerebrovascular complications. This is particularly important in elderly patients.
Risk from concomitant use of opioids:
Concomitant use of lorazepam and opioids may result in sedation, respiratory depression, coma and death. Because of these risks, concomitant prescribing of sedative medicines such as benzodiazepines or related drugs such as lorazepam with opioids should be reserved for patients for whom alternative treatment options are not possible. If a decision is made to prescribe lorazepam concomitantly with opioids, the lowest effective dose should be used, and the duration of treatment should be as short as possible (see also general dose recommendation in section Posology and method of administration).
The patients should be followed closely for signs and symptoms of respiratory depression and sedation. In this respect, it is strongly recommended to inform patients and their caregivers (where applicable) to be aware of these symptoms (see section Interaction with other medicinal products and other forms of interaction).
Contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium- free’. It is especially relevant to products used in children or in patients on a low sodium diet, to provide information to prescribers and reassurance to parents or patients concerning the low level of sodium in the product.
Lorazepam should be used with caution in elderly due to the risk of sedation and/or musculoskeletal weakness that can increase the risk of falls, with serious consequences in this population. Elderly patients should be given a reduced dose (see section Posology and method of administration).
Interaction with other medicinal products and other forms of interaction
Lorazepam should not be used together with alcohol (enhanced sedative effects; impaired ability to drive/operate machinery)
Avoid concomitant use (enhanced effects of sodium oxybate)
Avoid concomitant use (increased risk of prolonged sedation – see below for zidovudine Take into account
The concomitant use of sedative medicines such as benzodiazepines or related drugs such as lorazepam with opioids increases the risk of sedation, respiratory depression, coma and death because of additive CNS depressant effect. The dosage and duration of concomitant use should be limited (see section Special warnings and precautions for use).
Centrally acting drugs
Enhancement of the central depressive effect may occur if lorazepam is combined with drugs such as neuroleptics, antipsychotics, tranquillisers, antidepressants, hypnotics, analgesics, anaesthetics, barbiturates and sedative antihistamines. The elderly may require special supervision.
Pharmacokinetic studies on potential interactions between benzodiazepines and antiepileptic drugs have produced conflicting results. Both depression and elevation of drug levels, as well as no change have been reported.
Phenobarbital taken concomitantly may result in an additive CNS effect. Special care should be taken in adjusting the dose in the initial stages of treatment.
Side effects may be more evident with hydantoins or barbiturates
Valproate may inhibit the glucuronidation of lorazepam (increased serum levels: increased risk of drowsiness)
Enhancement of the euphoria may lead to increased psychological dependence
Reports of marked sedation, excessive salivation, hypotension, ataxia, delirium and respiratory arrest when given concurrently with lorazepam.
When taken with muscle relaxants, the overall muscle-relaxing effect may be increased (accumulative) therefore caution is advised, especially in elderly patients and at higher doses (risk of falling, see Section Special warnings and precautions for use)
Other drugs enhancing the sedative effect of diazepam
Cisapride, lofexidine, nabilone, disulfiram and the muscle relaxants – baclofen and tizanidine
Compounds that affect hepatic enzymes (particularly cyctochrome P450)
Antihypertensives, vasodilators and diuretics: Enhanced hypotensive effect with ACE-inhibitors, alpha-blockers, angiotensin-II receptor antagonists, calcium channel blockers, adrenergic neurone blockers, beta-blockers, moxonidine, nitrates, hydralazine, minoxidil, sodium nitroprusside and diuretics
Enhanced sedative effect with alpha-blockers or moxonidine.
Possible antagonism of the effect of levodopa
Concurrent use may delay absorption of lorazepam
Increased zidovudine clearance by lorazepam
Possible inhibition of hepatic metabolism of lorazepam
Increases metabolism of lorazepam which possibly reduces the effect
Concurrent use may result in reduced sedative and anxiolytic effects of lorazepam.
Inhibition of CYP3A4 may increase the plasma concentration of lorazepam (possible increased sedation and amnesia). This interaction may be of little significance in healthy individuals, but it is not clear if other factors such as old age or liver cirrhosis increase the risk of adverse events with concurrent use.
Benzodiazepines should not be used during pregnancy, especially during the first and last trimesters. 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.
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, 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.
Lorazepam is excreted in small amounts in breast milk. Mothers who are breast-feeding should not take benzodiazepines. Sedation and inability to suckle have occurred in neonates of lactating mothers taking benzodiazepines.
Patients should be advised that sedation, amnesia, impaired concentration, dizziness, blurred vision and impaired muscular function may occur and that, if affected, they should not drive or to use machines, or take part in other activities where this would put themselves or others at risk. If insufficient sleep duration occurs, the likelihood of impaired alertness may be increased. Concurrent medication may increase these effects (see section Interaction with other medicinal products and other forms of interaction)
This medicine can impair cognitive function and can affect a patient’s ability to drive safely. When prescribing this medicine, patients should be told:
Adverse reactions, when they occur, are usually observed at the beginning of therapy and generally decrease in severity or disappear with continued use or upon decreasing the dose.
Most frequently reported adverse reactions associated with benzodiazepines include daytime drowsiness, dizziness, muscle weakness, and ataxia.
Adverse reactions are listed by frequency:
Very common (≥1/10); Common (≥1/100 to <1/10); Uncommon (≥1/1,000 to <1/100); Rare (≥1/10,000 to <1/1,000); Very rare (<1/10,000); not known (cannot be estimated from the available data)
Blood and lymphatic system disorders
Very rare: Thrombocytopenia, leucopenia, agranulocytosis, pancytopenia
Immune system disorders
Very rare: Hypersensitivity including anaphylaxis/anaphylactoid reactions
Very rare: Inappropriate antidiuretic hormone secretion, hyponatraemia
Rare: Confusion, depression and unmasking of depression, numbed emotions, disinhibition, euphoria, appetite changes, sleep disturbance, change in libido, decreased orgasm.
Unknown: Dependence, Suicidal ideation/attempt
Paradoxical reactions such as restlessness, agitation, irritability, aggressiveness, delusion, rage, insomnia, nightmares, hallucinations, psychoses, sexual arousal, and inappropriate behaviour have been occasionally reported during use.
Nervous system disorders
Very common: Daytime drowsiness, sedation
Common: Dizziness, ataxia
Rare: headache, reduced alertness, dysarthria/slurred speech, transient anterograde amnesia or memory impairment.
Very rare: Tremor, extrapyramidal reactions, Coma (see Overdose)
Rare: Visual disturbances (diplopia, blurred vision)
Rare: Hypotension (see Special warnings and precautions)
Respiratory thoracic and mediastinal disorders:
Rare: Apnoea, worsening of sleep apnoea, worsening of obstructive pulmonary disease. Respiratory depression (see Overdose).
Rare: Nausea, constipation, salivation changes
Rare: Abnormal liver function test values (increases in bilirubin, transaminases, alkaline phosphatise), jaundice
Skin and subcutaneous tissue disorders
Rare: Rash, allergic dermatitis
Common: Muscle weakness
Reproductive system and breast disorders
Common: Asthenia, fatigue
Very rare: Hypothermia
Drug withdrawal symptoms (see Special warnings and precautions)
Symptoms reported following discontinuation of benzodiazepines include headaches, muscle pain, anxiety, tension, depression, insomnia, restlessness, confusion, irritability, sweating, and the occurrence of “rebound” phenomena whereby the symptoms that led to treatment with benzodiazepines recur in an enhanced form. These symptoms may be difficult to distinguish from the original symptoms for which the drug was prescribed.
In severe cases the following symptoms may occur: derealisation; depersonalisation; hyperacusis; tinnitus; numbness and tingling of the extremities; hypersensitivity to light, noise, and physical contact; involuntary movements; hyperreflexia, tremor, nausea, vomiting; diarrhoea, abdominal cramps, loss of appetite, agitation, palpitations, tachycardia, panic attacks, vertigo, short-term memory loss, hallucinations/delirium; catatonia; hyperthermia, convulsions. Convulsions may be more common in patients with pre-existing seizure disorders or who are taking other drugs that lower the convulsive threshold such as antidepressants.
Injury, poisoning and procedural complications Not known: Fall
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Arpimed “LLC” by going to www.arpimed.com and fill out the appropriate form ″Report an adverse reaction or inefficiency of drug″. Hotline number: (+374 55) 05 79 86. And by using Scientific Centre of Drug and Medical Technology Expertise after academician E. Gabrielyan ″CJSC ″, going to the site: www.pharm.am in ″Report about adverse effect of medicine″ section and fill out the ″Report of adverse reaction or manufacturing problem of medicinal product″. Hotline numbers: +37410200505; +37496220505.
In the management of overdose with any drug, it should be borne in mind that multiple agents may have been taken.
Overdose of benzodiazepines is usually manifested by degrees of central nervous system depression ranging from drowsiness to coma. In mild cases, symptoms include drowsiness, mental confusion, and lethargy. In more serious cases, and especially when other CNS-depressant drugs or alcohol are ingested, symptoms may include ataxia, hypotension, hypotonia, respiratory depression, coma, and very rarely, death.
If ingestion was recent, induced vomiting and/or gastric lavage should be undertaken followed by general supportive care, monitoring of vital signs and close observation of the patient. If there is no advantage in emptying the stomach, activated charcoal may be effective in reducing absorption. Hypotension, though unlikely, may be controlled with noradrenaline. Lorazepam is poorly dialysable.
The benzodiazepine antagonist, flumazenil may be useful in hospitalised patients for the management of benzodiazepine overdose. Flumazenil product information should be consulted prior to use.
Pharmacotherapeutic group: Anxiolytics. Benzodiazepine derivatives.
ATC code: NO5BA06
Lorazepam is a benzodiazepine with anxiolytic, sedative and hypnotic properties.
Lorazepam is almost completely absorbed from the gastrointestinal tract and peak serum levels are reached in 2 hours. It is metabolised by a simple one-step process to a pharmacologically inert glucuronide. There are no major active metabolites. The elimination half-life is about 12 hours and there is minimal risk of excessive accumulation
Preclinical safety data
Oesophageal dilation occurred in rats treated with lorazepam for more than one year at 6 mg/kg/day.
List of excipients
Lorazepam 1 mg and 2 mg tablets
maize (corn) starch
sodium starch glycolate
Do not use this medicine after the expiry date.
Lorazepam 1 mg tablets
Store at a temperature below 25°C, protect from light and moisture and out of the reach of children.
1 blister packet with 24 tablets with leaflet in the cardboard box.
Special precautions for disposal and other handling
No special requirements.