Lorazepam Prefilled Syringe 2mg/1ml Taj Pharma
- Name of the medicinal product
Lorazepam prefilled Syringe 2mg/1ml Taj Pharma.
- Qualitative and quantitative composition
Each Prefilled Syringe Contains
Lorazepam (INN, BAN) is chemically defined as 7-chloro-5-(o-chlorphenyl)-1,3-dihydro-3-hydroxy-2H-1,4-benzodiazepin-2-one.
Excipient(s) with known effect:
Lorazepam prefilled Syringe 2mg/1ml Injection contains 20.9mg/ml benzyl alcohol
For the full list of excipients, see section 6.1.
- Pharmaceutical form
Solution for injection
Clear, colourless solution supplied in clear glass Prefilled syringes.
- Clinical particulars
4.1 Therapeutic indications
Pre-operative medication or premedication for uncomfortable or prolonged investigations, e.g. bronchoscopy, arteriography, endoscopy.
The treatment of acute anxiety states, acute excitement or acute mania.
The control of status epilepticus.
4.2 Posology and method of administration
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Treatment in all patients should be withdrawn gradually to minimise possible withdrawal symptoms (See section 4.4).
Method of administration
Lorazepam prefilled Syringe 2mg/ml Injection can be given intravenously or intramuscularly. However, the intravenous 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.
Lorazepam prefilled Syringe 2mg/ml should not be used for long-term chronic treatment.
0.05mg/kg (3.5mg for an average 70kg man). By the intravenous route the injection should be given 30-45 minutes before surgery when sedation will be evident after 5-10 minutes and maximal loss of recall will occur after 30-45 minutes.
By the intramuscular route the injection should be given 1-11/2 hours before surgery when sedation will be evident after 30-45 minutes and maximal loss of recall will occur after 60-90 minutes.
Paediatric population: Lorazepam prefilled Syringe 2mg/ml Injection is not recommended in children under 12.
- Acute Anxiety
(1.75-2.1mg for an average 70kg man).
Repeat 6 hourly.
Paediatric population: Lorazepam prefilled Syringe 2mg/ml Injection is not recommended in children under 12.
- Status epilepticus
Paediatric population: 2mg intravenously
|Elderly:||The elderly may respond to lower doses and half the normal adult dose may be sufficient.|
Patients with Renal or Hepatic impairment:
Lower doses may be sufficient in these patients (See section 4.4). Use in patients with severe hepatic insufficiency is contraindicated.
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 4.4 Special warnings and precautions for use)
- Acute pulmonary insufficiency
- Hypersensitivity to benzodiazepines, including lorazepam or to any of the excipients listed in section 6.1.
- Sleep apnoea syndrome
- Myasthenia gravis
- Severe hepatic insufficiency
Lorazepam prefilled Syringe 2mg/ml Injection is not recommended for out-patient use unless the patient is accompanied.
4.4 Special warnings and precautions for use
Prior to use, Lorazepam prefilled Syringe 2mg/ml Injection may be used for IM administration and IV administration. Intravenous injection should be administered slowly except in the control of status epilepticus where rapid injection is required.
The possibility that respiratory arrest may occur or that the patient may have partial airway obstruction should be considered. Therefore, equipment necessary to maintain a patent airway and to support respiration/ventilation should be available and used where necessary.
The use of benzodiazepines, including lorazepam, may lead to physical and psychological dependence.
Severe anaphylactic/anaphylactoid reactions have been reported with the use of benzodiazepines. Cases of angioedema involving the tongue, glottis or larynx have been reported in patients after taking the first or subsequent doses of benzodiazepines. Some patients taking benzodiazepines have had additional symptoms such as dyspnoea, throat closing, or nausea and vomiting. Some patients have required medical therapy in the emergency department. If angioedema involves the tongue, glottis or larynx, airway obstruction may occur and be fatal. Patients who develop angioedema after treatment with a benzodiazepine should not be rechallenged with the drug.
It is recommended that patients receiving Lorazepam prefilled Syringe 2mg/ml Injection should remain under observation for at least eight hours and preferably overnight. When Lorazepam prefilled Syringe 2mg/ml Injection is used for short procedures on an outpatient basis, the patient should be accompanied when discharged.
Patients should be advised that their tolerance for alcohol and other CNS depressants will be diminished in the presence of Lorazepam prefilled Syringe 2mg/ml Injection. Alcoholic beverages should not be consumed for at least 24 to 48 hours after receiving Lorazepam prefilled Syringe 2mg/ml Injection.
Use of benzodiazepines, including lorazepam, may lead to potentially fatal respiratory depression. Extreme care must be taken in administering Lorazepam prefilled Syringe 2mg/ml Injection to elderly or very ill patients and to those with limited pulmonary reserve or compromised respiratory function (e.g. chronic obstructive pulmonary disease [COPD]), because of the possibility that apnoea and/or cardiac arrest may occur. Care should also be exercised when administering Lorazepam prefilled Syringe 2mg/ml Injection to a patient with status epilepticus, especially when the patient has received other central nervous system depressants.
Concomitant use of benzodiazepines 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 prefilled Syringe 2mg/ml with opioids should be reserved for patients for whom alternative treatment options are not possible. If a decision is made to prescribe Lorazepam prefilled Syringe 2mg/ml 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 4.2).
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 4.5).
There is no evidence to support the use of Lorazepam prefilled Syringe 2mg/ml Injection in coma or shock.
Lorazepam prefilled Syringe 2mg/ml 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.
Pre-existing depression may emerge during benzodiazepine use.
There are no clinical data available for Lorazepam prefilled Syringe 2mg/ml Injection with regard to abuse or dependence. However, based upon experience with oral benzodiazepines, doctors should be aware that repeated doses of Lorazepam prefilled Syringe 2mg/ml Injection over a prolonged period of time may lead to physical and psychological dependence. The risk of dependence on Lorazepam prefilled Syringe 2mg/ml 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. Therefore, the drug should always be discontinued gradually – using the oral preparation if necessary.
Symptoms reported following discontinuation of oral 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; vomiting; hallucinations; 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.
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 minimise anxiety should they occur.
Withdrawal symptoms (e.g. rebound insomnia) can appear following cessation of recommended doses after as little as one week of therapy.
There are indications that, in the case of benzodiazepines with a short duration of action, withdrawal phenomena can become manifest within the dosage interval, especially when the dosage is high.
When benzodiazepines with a long duration of action are being used, it is important to warn against changing to a benzodiazepine with a short duration of action, as withdrawal symptoms may develop.
Abuse of benzodiazepines has been reported.
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.
As with all benzodiazepines, the use of lorazepam may worsen hepatic encephalopathy.
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 haematologic 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 prefilled Syringe 2mg/ml is used as a premedicant.
Paradoxical reactions have been occasionally reported during benzodiazepine use (see section 4.8). Such reactions may be more likely to occur in children and the elderly. Should these occur, use of the drug should be discontinued.
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.
Lorazepam prefilled Syringe 2mg/ml Injection contains the excipients polyethylene glycol and propylene glycol. There have been reports of propylene glycol toxicity (e.g. lactic acidosis, hyperosmolality, hypotension) and polyethylene glycol toxicity (e.g. acute tubular necrosis) during administration of Lorazepam prefilled Syringe 2mg/ml Injection, including at higher than recommended doses. Central nervous system toxicity, including seizures, as well as unresponsiveness, tachypnoea, tachycardia and diaphoresis have also been associated with propylene glycol toxicity. Those prone to propylene glycol accumulation and its potential adverse effects include patients with impaired alcohol and aldehyde dehydrogenase enzyme systems, those with renal or hepatic disease; and paediatric patients.
Intravenous administration of the preservative benzyl alcohol has been associated with serious adverse event, and death in paediatric patients including neonates characterized by central nervous system depression, metabolic acidosis, gasping respirations, cardio-vascular failure and haematological anomalies (“gasping syndrome”). Although normal therapeutic doses of this product ordinarily deliver amounts of benzyl alcohol that are substantially lower than those reported in association with the “gasping syndrome”, the minimum amount of benzyl alcohol at which toxicity may occur is not known. Use only if it is necessary and if there are no alternatives possible. If given in high volumes, should be used with caution and preferably for short term treatment in subjects with liver or kidney impairment because of the risk of accumulation and toxicity (metabolic acidosis)
Premature and low-birth weight infants may be more likely to develop toxicity.
Benzyl Alcohol containing products should not be used in pre-term or full-term neonates unless strictly necessary.
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 4.2 Posology).
4.5 Interaction with other medicinal products and other forms of interaction
Not recommended: Concomitant intake with alcohol
The sedative effects may be enhanced when the product is used in combination with alcohol. This affects the ability to drive or use machines.
The benzodiazepines, including Lorazepam prefilled Syringe 2mg/ml Injection, produce additive CNS depressant effects including respiratory depression, when co-administered with other medications which themselves produce CNS depression, e.g. opioids, barbiturates, antipsychotics, sedatives/hypnotics, anxiolytics, antidepressants, narcotic analgesics, sedative antihistamines, anticonvulsants and anaesthetics (see section 4.4).
The concomitant use of sedative medicines such as benzodiazepines or related drugs such as Lorazepam prefilled Syringe 2mg/ml 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 4.4).
Concurrent administration of lorazepam with sodium valproate may result in reduced clearance (20 to 40%) and increased concentrations of lorazepam. Therefore clinical monitoring is advised and lorazepam dosage should be reduced when appropriate.
Concurrent administration of lorazepam with probenecid may result in reduced clearance, increased elimination half-life and increased concentrations of lorazepam. Therefore clinical monitoring is advised and lorazepam dosage should be reduced when appropriate.
An enhancement of the euphoria induced by narcotic analgesics may occur with benzodiazepine use, leading to an increase in psychic dependence.
Compounds which inhibit certain hepatic enzymes (particularly cytochrome P450) may enhance the activity of benzodiazepines. To a lesser degree this also applies to benzodiazepines which are metabolised only by conjugation.
The addition of scopolamine to Lorazepam prefilled Syringe 2mg/ml Injection is not recommended, since their combination has been observed to cause an increased incidence of sedation, hallucination and irrational behaviour.
Concomitant use of clozapine and lorazepam may produce marked sedation, excessive salivation, and ataxia.
Administration of theophylline or aminophylline may reduce the sedative effects of benzodiazepines, including lorazepam.
There have been reports of apnoea, coma, bradycardia, heart arrest and death with the concomitant use of lorazepam injection solution and haloperidol.
4.6 Fertility, pregnancy and lactation
Lorazepam prefilled Syringe 2mg/ml Injection 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 prefilled Syringe 2mg/ml Injection 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 prefilled Syringe 4mg/2ml, including use in caesarean section. Such use, therefore, is not recommended.
Benzyl alcohol can cross the placenta, see section 4.4..
Since benzodiazepines are found in breast milk, Lorazepam prefilled Syringe 2mg/ml Injection should not be given to breast- feeding mothers unless the expected benefit to the woman outweighs the potential risk to the infant.
4.7 Effects on ability to drive and use machines
This medicine can impair cognitive function and can affect a patient’s ability to drive safely. This class of medicine is in the list of drugs included in regulations under 5a of the Road Traffic Act 1988. When prescribing this medicine, patients should be told:
- The medicine is likely to affect your ability to drive
- Do not drive until you know how the medicine affects you
- It is an offence to drive while under the influence of this medicine
- However, you would not be committing an offence (called ‘statutory defence’) if:
o The medicine has been prescribed to treat a medical or dental problem and
o You have taken it according to the instructions given by the prescriber and in the information provided with the medicine and
o It was not affecting your ability to drive safely
Sedation, amnesia, impaired concentration and impaired muscular function may adversely affect the ability to drive or use machines. Therefore, patients should not drive or operate machinery within 24-48 hours of administration of Lorazepam prefilled Syringe 2mg/ml Injection and should be advised not to take alcohol (see section 4.5).
4.8 Undesirable effects
|System Organ Class||Very Common|
≥ 1/100 to < 1/10
≥ 1/1,000 to < 1/100
|Frequency not known|
(cannot be estimated from the available data)
|Blood and lymphatic system disorders||Thrombocytopenia, agranulocytosis, pancytopenia|
|Immune system disorders||Hypersensitivity reactions, anaphylactic/oid reactions|
|Metabolism and nutrition disorders||Hyponatremia|
|Psychiatric disorders||Confusion depression, unmasking of depression||Change in libido, decreased orgasm||Disinhibition, euphoria, suicidal ideation/attempt, paradoxical reactions, including anxiety, agitation, excitation, hostility, aggression, rage, sleep disturbances/insomnia, sexual arousal, hallucinations|
|Nervous system disorders ±||Sedation, drowsiness||Ataxia, dizziness||Extrapyramidal symptoms, tremor, dysarthria/slurred speech, headache, convulsions/seizures, amnesia, coma, impaired attention/concentration, balance disorder|
|Eye disorders||Visual disturbances (including diplopia and blurred vision)|
|Ear and labyrinth disorders||Vertigo|
|Vascular disorders||Hypotension, lowering in blood pressure|
|Respiratory, thoracic and mediastinal disorders||Respiratory depression, β apnea, worsening of sleep apnea, worsening of obstructive pulmonary disease|
|Skin and subcutaneous tissue disorders||Angioedema, allergic skin reactions, alopecia|
|Musculoskeletal and connective tissue disorders||Muscle weakness|
|Reproductive system and breast disorders||Impotence|
|General disorders and administration site conditions||Fatigue||Asthenia||Hypothermia|
|Investigations||Increase in bilirubin, increase in liver transaminases, increase in alkaline phosphatase|
± Benzodiazepine effects on the CNS are dose-dependent, with more severe CNS depression occurring with high doses.
β The extent of respiratory depression with benzodiazepines is dose–dependent, with more severe depression occurring with high doses.
Tolerance at the injection site is generally good although, rarely, pain and redness have been reported after Lorazepam prefilled Syringe 2mg/mlInjection.
Transient anterograde amnesia or memory impairment may occur using therapeutic doses, the risk increasing at higher doses (see section 4.4).
Paradoxical reactions may be more likely to occur in children and the elderly (see section 4.4).
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.
In the management of overdosage with any drug, it should be borne in mind that multiple agents may have been taken.
Overdosage 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, cardiovascular depression, coma and, very rarely, death.
Propylene glycol toxicity and polyethylene glycol toxicity have been reported following higher than recommended doses of Lorazepam prefilled Syringe 2mg/ml Injection (see section 4.4).
Treatment of overdosage is mainly supportive including monitoring of vital signs and close observation of the patient. An adequate airway should be maintained and assisted respiration used as needed. 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 overdosage. Flumazenil product information should be consulted prior to use. The physician should be aware of a risk of seizure in association with flumazenil treatment, particularly in long-term benzodiazepine users and in tricyclic antidepressant overdose.
- Pharmacological properties
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Benzodiazepine derivatives.
Lorazepam prefilled Syringe 2mg/mlis a benzodiazepine with anxiolytic, sedative, hypnotic, anticonvulsant and muscle relaxant properties.
5.2 Pharmacokinetic properties
Lorazepam prefilled Syringe 2mg/ml Injection is readily absorbed when given intramuscularly. Peak plasma concentrations occur approximately 60-90 minutes following intramuscular administration.
Lorazepam prefilled Syringe 2mg/ml is metabolised by a simple one-step process to a pharmacologically inactive glucuronide. There is minimal risk of accumulation after repeated doses, giving a wide margin of safety.
There are no major active metabolites.
The elimination half-life is about 12-16 hours when given intramuscularly or intravenously.
5.3 Preclinical safety data
Lorazepam glucuronide, the major metabolite of lorazepam, has no demonstrable CNS activity in animals.
No evidence of carcinogenic potential emerged in rats and mice during an 18-month study with oral lorazepam.
A study of the mutagenic activity of lorazepamon Drosophila melanogaster indicated that this agent was mutationally inactive.
Impairment of fertility
A pre-implantation study in rats was performed with oral lorazepam at a 20 mg/kg dose that showed no impairment of fertility.
Effect of anesthetic and sedative drugs
Nonclinical research has shown that administration of anesthetic and sedation drugs that block N-methyl-D-aspartate (NMDA) receptors and/or potentiate gamma-aminobutyric acid (GABA) activity can increase neuronal cell death in the brain and result in long term deficits in cognition and behavior of juvenile animals when administered during the period of peak brain development. Based on comparisons across nonclinical species, the window of vulnerability of the brain to these effects is believed to correlate with human exposures in the third trimester of pregnancy through the first year of life, but may extend to approximately 3 years of age. While there is limited information of this effect with lorazepam, since the mechanism of action includes potentiation of GABA activity, a similar effect may occur. The relevance of these nonclinical findings to human use is unknown.
- Pharmaceutical particulars
6.1 List of excipients
Polyethylene glycol 400
6.3 Shelf life
6.4 Special precautions for storage
Store and transport refrigerated (2°C to 8°C).
Keep Prefilled syringe in the outer carton to protect from light.
6.5 Nature and contents of container
1ml solution contains 2mg Lorazepam In a prefilled syringe.
6.6 Special precautions for disposal and other handling
No special requirements for disposal.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
- Manufactured in India by:
TAJ PHARMACEUTICALS LTD.
Unit No. 214.Old Bake House,
Maharashtra chambers of Commerce Lane,
Fort, Mumbai – 400001
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST